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Many heritable anemias are caused by mutations in genes encoding globins, red blood cell (RBC) membrane proteins, or enzymes in the glycolytic and hexose monophosphate shunt pathways. association studies and the rapidly expanding use of global genome sequencing for human diagnostics. Findings obtained through such studies of RBCs Phloridzin supplier and associated diseases are likely generalizable to many human diseases and quantitative traits. Introduction The most common hereditary forms of anemia arise from mutations in genes that encode globins, red bloodstream cell (RBC) membrane proteins, or enzymes. Nevertheless, mutations in RBC transcription element (TF) genes, or the components by which they bind to modify gene expression, take into account a uncommon, but educational subset of anemias. Megakaryocytes (MEGs) and RBCs are based on a common bipotential MEG-erythroid progenitor (MEP), and Rabbit Polyclonal to TAF15 their advancement is controlled by a few common TFs, such as for example GATA binding proteins 1 (GATA1) (Shape 1). Appropriately, gene mutations can present with anemia, thrombocytopenia, or both. Likewise, T-cell severe lymphoblastic leukemia 1 (TAL1), FOG relative 1 (FOG1), and nuclear element, erythroid 2 (NF-E2) are erythro-megakaryocytic TFs that could hypothetically become modified in hereditary anemia/thrombocytopenia. On the other hand, Fli-1 proto oncogene (FLI1) and Kruppel-like element 1 (KLF1) travel mono-lineage creation of MEGs and RBCs, respectively, and determined mutations in these genes affect just the single related lineage.1,2 Extensive study over greater than a 10 years offers defined the biological properties of the and several additional erythro-megakaryocytic TFs. Mutations that alter their framework and/or manifestation to cause human being blood diseases offer valuable insights in to the biology of hematopoiesis and hemoglobin switching. Further investigations in to the mechanisms of the mutations should determine new strategies for treating more common congenital anemias, for example, by manipulating fetal hemoglobin expression in the setting of sickle cell anemia or thalassemia. Open in a separate window Physique 1 TFs that drive erythromegakaryopoiesis. RBCs and MEGs derive from the bipotential MEP. KLF1 and FLI1 regulate lineage determination of the MEP and subsequent erythroid or MEG maturation, respectively. GATA1, TAL1, FOG1, NF-E2, and GFI1B regulate the maturation of both lineages. Germ-line mutations in KLF1 (shown in blue) cause isolated congenital anemia, whereas mutations in the TFs indicated in red affect RBCs and MEGs. Candidate TFs for which no germ-line human mutations have yet been discovered to be associated with anemia or thrombocytopenia are shown in black. Deficiency of FLI1 (shown in green) is usually associated with thrombocytopenia, but not anemia in Paris-Trousseau syndrome.112 Etiologies of hereditary anemias Hereditary anemia encompasses a wide spectrum of RBC disorders that typically present in infants and children. These disorders can be subclassified according to the RBC developmental stage most profoundly affected. Shortened lifespan of circulating erythrocytes (hemolysis). Phloridzin supplier This group includes the most common causes of Phloridzin supplier hereditary anemia and is typically caused by defects in hemoglobin (sickle cell anemia and other hemoglobin variants), RBC membrane proteins (hereditary spherocytosis, elliptocytosis), or enzymatic pathways (glucose 6 phosphate dehyrogenase (G6PD] deficiency, glycolytic flaws). Congenital dyserythropoietic anemia type II (CDA II) can be connected with early devastation of erythrocytes in the spleen. Faulty maturation of erythroid precursors. Thalassemia syndromes are connected with impaired erythroid precursor maturation, termed inadequate erythropoiesis. The CDAs are connected with deposition of erythroid precursors that type RBCs inefficiently.3 Affected erythroblasts display bizarre dysplastic morphologies including multinuclearity often, internuclear bridging, and megaloblastic features. Historically, CDAs have already been categorized into 3 types (I, II, and III) predicated on the looks of erythroid precursors and serological research. Causal mutations for these traditional CDAs have already been determined in (CDA I), (CDA I), (CDA II), and (CDA III).3,4 These genes usually do not encode typical hematopoietic TFs, although CDAN1 is reported to modify the transportation of histones5 and it is implicated in the impaired localization of HP1, an essential component of heterochromatin.6 However, it really is now clear the fact that CDAs are heterogeneous plus some variant forms are due to mutations in and (discover below). Decreased erythroid precursors (natural reddish colored cell aplasia/hypoplasia). The traditional example is Gemstone Blackfan anemia (DBA), a congenital anemia that displays in early years as a child, with associated developmental anomalies frequently. 7 DBA is certainly heterogeneous genetically, with about two-thirds of cases caused by dominantly inherited heterozygous loss-of-function mutations in 1 of 12 large or small ribosomal subunit proteins. It Phloridzin supplier is not certain how ribosomal protein haploinsufficiency causes selective defects in the accumulation of erythroid precursors. This may occur in part via perturbation of TF networks. For example, imbalanced ribosome assembly may activate p53, a TF that induces apoptosis and/or cell cycle arrest. In addition, gene mutations are associated with an X-linked form of DBA8 (discussed.
Data Availability StatementAll relevant data are within the paper. in the frequency of IL-2+ CXCR3+ TH1 cells as a significant increase in the frequency of IL-4+ CCR4+ TH2 cells. Finally, septic CD43-/- animals contained significantly fewer CD25+ Foxp3+ TReg cells as compared to WT septic animals. buy Alvocidib Importantly, depleting CD25+ Treg eliminated the increased mortality observed in CD43-/- mice. Taken together, these data demonstrate an important role of CD43 in modulating immune dysregulation and mortality following sepsis. Introduction Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection . Despite an annual incidence of to 3 millions cases in the U up.S. and a reported 42.5% mortality in severe cases , buy Alvocidib effective therapy once and supportive care fails continues to be deficient antibiotics. Once regarded as a problem of extreme swelling mainly, the immunological derangements within sepsis pathology are actually understood to change from a hyper-inflammatory stage to 1 of continual, long-term immunosuppression [3C5]. For instance, aberrant T cell activation [6, 7], upregulation of inhibitory protein [8, 9], and intensive lymphocyte apoptosis  in the establishing of high antigen publicity due to inadequate infection control bring about sponsor defense incompetence. These modifications in immunity in the later on stage of sepsis place the individual in danger for opportunistic pathogens and supplementary infections, leading to increased long-term mortality and morbidity. Some studies show that as much as 60% of individuals succumb to these supplementary infections of these later on stages of sepsis . Characterizing the immune system incompetence of sepsis can be vital to further Rabbit Polyclonal to AKR1CL2 defining this disease procedure aswell as enabling development of feasible immunomodulatory therapies. Intensive lymphocyte apoptosis can be a well-known feature of sepsis. Many postmortem research possess verified wide-spread apoptosis of lymphocytes most observed in lymphoid organs frequently, like the spleen, aswell as gastrointestinal lymphoid connected cells (GALT) [10, 12]. The system for apoptosis initiation appears to be multifactorial as multiple cell loss of life pathways are activated in sepsis, including both extrinsic and intrinsic pathways . Significant cellular depletion occurs across a multitude of lineages within both the adaptive and the innate immune systems, notably in CD4+ and CD8+ T cells, B cells, buy Alvocidib and dendritic cells [14C16]. This buy Alvocidib resultant lymphopenia significantly alters host response to subsequent infection, which often manifests as reactivation of latent viral infections such as CMV and EBV . Not only is there a significant decrease in the number of circulating lymphocytes during sepsis, but the functionality of the remaining T cells is also dramatically altered. In particular, the balance of T helper cell populations, specifically TH1, TH2, T regulatory cells (Treg cells), and TH17, is modified during sepsis. The axis of TH1/ TH2 cells, the two major subtypes of effector T cells, is implicated in a multitude of disease pathways. TH1 cells are a subset of T helper cells most commonly implicated in clearance of intracellular bacteria and cell-mediated immunity, while TH2 cells are associated with the humoral immune system and providing help for antibody production . Evaluation of circulating lymphocytes in septic patients has shown an imbalance of TH1/ TH2 effector cells towards a TH2 skew , as well as decreasing frequency of TH1 cells associated with increased sepsis severity [20, 21]. Further, expansion of buy Alvocidib TReg cells was associated with T cell anergy in human septic patients , but more mechanistic studies using both loss- and gain-of-function approaches in murine models have revealed that Foxp3+ Treg are likely beneficial in the setting of sepsis [23, 24]. Additionally, blockade of IL-17A total results in improved survival, recommending that Th17 cells may donate to sepsis mortality  negatively. Glycosylation of T cell surface area receptors also takes on an important part in changing activation and function in the inflammatory establishing. Compact disc43 is a big, glycosylated transmembrane protein highly, abundant on T cells, and continues to be implicated in a number of lymphocytic procedures. Blockade of Compact disc43 led to reduced trafficking of lymphocytes to lymphoid cells, implicating a job for Compact disc43 in T cell trafficking both at baseline with sites of swelling [26, 27]. Additionally, Compact disc43 continues to be connected with T helper cell differentiation. Ex-vivo excitement of Compact disc43-/- lymphocytes demonstrated these cells generate even more IL-4 in comparison to WT cells considerably, suggesting these are skewed towards a.
Supplementary MaterialsAdditional file 1: Table S1. S5. Univariate and Multivariate Cox Regression Analyses of URRCC. (XLSX 11 kb) 12943_2019_998_MOESM6_ESM.xlsx (11K) GUID:?175B291E-DE22-4157-AA4F-B3A3E25FC9D8 Additional file 7: Figure S2. A and B: qRT-PCR assays for the URRCC mRNA level in 786-O and OSRC-2 cells after transfection of sh-control, sh-URRCC-1, and sh-URRCC-2. C: MTT assays after transfection of sh-URRCC compared with sh-control in 786-O cells. D: Representative images and the numbers of invasive cells per high-power field reduced by the transfection of sh-URRCC in 786-O compared to sh-control groups. (PDF 96 kb) 12943_2019_998_MOESM7_ESM.pdf (97K) GUID:?F3736E46-4445-49C5-BB75-F752BB5AF77C Additional file 8: Figure S3. A: Heatmaps of dysregulated mRNAs expression between sh-control and sh-URRCC groups in the treated A498 cells. B: Volcano plots of the differentially expressed mRNAs. Green and red spots represent value less than 0.05. Red spots represent fold change more than 2.0. Green spots represent fold change less than 0.5. C: JMY mRNA level in ccRCC tissues compared with normal renal tissues from TCGA KIRC dataset. D: KaplanCMeier analyses of the correlations between URRCC expression and overall survival of 530 ccRCC patients from TCGA KIRC dataset. Log-rank test was used to calculate values.?E: Correlation between URRCC and EGFL7 in mRNA level in cell lines. F: mRNA level of EGFL7 in different treatment groups. G and H: ChIP analyses of A498 and OSRC-2 cells treated with sh-control, sh-URRCC or sh-URRCC+TSA(100 nM) were conducted on the EGFL7 promoter regions using anti-acetyl-histone H3 and anti-acetyl-histone H4. Enrichment was determined relative to input controls. I: Representative Ki67 IHC staining of xenograft tumors from sh-control, sh-URRCC, mock, and oe-URRCC groups (200, 400). (ZIP 220 kb) 12943_2019_998_MOESM8_ESM.zip (221K) GUID:?1061DA72-0133-4DD0-BA06-E9A6CCEF61DF Additional file 9: Table S6. Small mRNA array data. (XLSX 147 kb) 12943_2019_998_MOESM9_ESM.xlsx (147K) GUID:?B4FCC07B-6366-4AE7-952E-C3DB6838C962 Additional file 10: Table S7. JMY expression in ccRCC and normal renal samples from TCGA KIRC dataset. (XLS 27 kb) 12943_2019_998_MOESM10_ESM.xls (27K) GUID:?376F8729-6AFE-4D71-A3CD-0FC5A583F0A0 Additional file 11: Table S8. JMY expression and paitients survival time from TCGA KIRC dataset. (XLS 19 kb) 12943_2019_998_MOESM11_ESM.xls (19K) GUID:?981A3489-AEF6-4AD2-A007-3A05A0E5E859 Additional file 12: Table S9. EGFL7 expression Rabbit Polyclonal to MGST3 in ccRCC and normal renal samples from Nocodazole inhibition TCGA KIRC dataset. (XLS 26 kb) 12943_2019_998_MOESM12_ESM.xls (27K) GUID:?584773C0-5B0E-4F7D-A94A-B042A29A68A2 Additional file 13: Figure S4. A: Bioinformatics analysis of potential FOXO3 binding site on URRCC promoter by online software RegRNA 2.0. B: Correlation between URRCC and FOXO3 in mRNA level in cell lines. C and D: The mRNA level of URRCC and EGFL7 were detected by qRT-PCR in A498 and OSRC-2 cells after transfection with si-NC or si-FOXO3. E and F: The mRNA level of URRCC and EGFL7 were detected by qRT-PCR in A498 and OSRC-2 cells after transfection with NC or oe-FOXO3. G and H: Cell apoptosis assays by flow cytometry in A498 cell lines.?(ZIP 209 kb) 12943_2019_998_MOESM13_ESM.zip (210K) GUID:?3DE379B7-58A2-48C1-9CA7-2FD4DE765971 Additional file 14: Table S10. FOXO3 expression and paitients’ survival time from TCGA KIRC dataset. (XLS 19 kb) 12943_2019_998_MOESM14_ESM.xls (19K) GUID:?96C1A6C7-3C51-4019-B755-55D66622D254 Data Availability StatementData and materials are available from website of Molecular Cancer. Abstract Background The aberrant expression of Nocodazole inhibition long noncoding RNAs (lncRNAs) has recently emerged as key molecules in human cancers; however, whether lncRNAs are implicated in Nocodazole inhibition the progression of clear cell renal cell carcinoma (ccRCC) remains unclear. Methods Candidate lncRNAs were selected using microarray analysis and quantitative real-time PCR (qRT-PCR) was performed to detect.
Solid tumors grow at a higher speed resulting in insufficient blood circulation to tumor cells. a tumor suppressive Th17 phenotype. From many studies, the concept is definitely growing that hypoxia and ROS are mutually dependent effectors on DC function in the tumor micro-environment. Understanding their exact tasks and interplay is definitely important given that an adaptive immune response is required to obvious tumor cells. methods using artificial membranes transporting ROS might help to overcome this problem. Another problem is definitely that resolving the physiological effects of specific sources and types of ROS remains demanding, because of the highly transient nature and the lack of specific probes that offer adequate spatiotemporal resolution. Controlling specific redox signaling and antioxidant pathways would be a valid approach to this problem, since these guidelines can be revised with genetic techniques. In addition, ROS can be induced with organellar precision using fusion constructs of proteins with known cellular location with photosensitizer proteins like SuperNova . Similarly, culture media can be supplemented with a wide range of antioxidants or radical-generating systems. Another key question is definitely whether ROS can be used to treat cancer. A possible avenue would be local administration of pro-oxidants in the TME. Tumor cells screen a faulty Nrf2 pathway frequently, rendering them even more vunerable to oxidative tension , while DC maturation could be improved by ROS as referred to above. Inside a xenograft mouse style of chronic lymphocyte leukemia, pro-oxidative treatment decreased tumor burden  strongly. However, since ROS offers pro-tumorigenic results also, the contrary approach of administrating anti-oxidants can be done also. There were several randomized managed trials where prophylactic ramifications of such antioxidant supplementation was looked into. However, for occurrence of prostate and total tumor in males, supplemental supplement E got no results [121C123] and in a GS-1101 price single study even considerably increased prostate tumor incidence . Because the ramifications of ROS on tumor and immune GS-1101 price system cells are complicated and reliant on the website of ROS era as well as the interplay with hypoxia and immune system signaling, focusing on ROS by administering pro- or antioxidants on is probably not sufficient simply. Targeting antioxidants or ROS to a particular cell type might provide a even more successful plan to fight tumor. For instance, advertising ROS development in the lumen of endo/phagosomes of DCs is actually a technique to promote antigen cross-presentation [55C57, 60, 61, 63, 125], whereas blockage of mitochondrial ROS formation might increase T cell activation in the lymph nodes . In the paper by Dingjan is still very challenging. An alternative approach would be to target DCs with nanoparticles carrying a ROS-inducer [127C129], for example an iron core that promotes generation of highly reactive hydroxyl radicals through Fenton chemistry [130, 131]. In a similar fashion, cancer cells might be specifically targeted with antioxidants to block the pro-tumorigenic effects of ROS. GS-1101 price While, as described above, systemic antioxidant therapy proved unsuccessful in cancer, localized interventions are still worth considering. Endosomal Rabbit polyclonal to PHACTR4 NOX2 activity was recently shown to play an important role in progression of prostate cancer , which could be targeted (for instance with antibodies) with antioxidant-carrying small particles for special uptake via endocytosis by tumor cells . Another interesting focusing on approach can be ROS-responsive nanoparticles for targeted delivery of hydrophilic and cationic medicines in ROS-producing cells . In this scholarly study, Meng demonstrated that MnO2-centered nanoparticles selectively launch the HIF-1 inhibitor acriflavine in tumor cells after oxidation by H2O2 and in a mouse style of colon cancer. Even though the authors didn’t investigate uptake by phagocytic cells, chances are that technique is with the capacity of releasing substances in phagosomes also. Finally, it could be highly good for sequester lipid peroxidation items such as for example MDA and 4-HNE because of the negative effect on DC function, as referred to above. Doing this would shield DCs against these results without interfering with ROS-induced DC and cross-presentation maturation. Many potential substances have already been determined lately that warrant additional analysis, of which histidine-containing dipeptides are currently the most promising [135C137]. Given that cancer cells use hypoxia and ROS to reprogram immune and stromal cells in the TME to prevent an immune response and augment GS-1101 price tumor progression, while.
Supplementary Materialsnn200182x_si_001. had been quickly internalized into professional APCs (dendritic cells and macrophages) within a few minutes in mice. We also showed which the nanotube scaffold itself is normally noncytotoxic to individual dendritic cells and it is nonimmunogenic. Outcomes Synthesis and Characterization of SWNTC4FB The artificial system for the nanotubeCpeptide conjugates found in this research is proven TAK-375 price (?(1).1). SWNTs covalently functionalized with principal amines (SWNTCNH2) had been produced as defined previously.(27) In prior research(28) we characterized the physical properties of identically ready SWNTCNH2 material as well as the chromatographic strategies used to get ready it. This synthetic scheme produces functionalized SWNTs in the scale selection of 50C400 nm reproducibly. The SWNTCNH2 materials was a darkish solid whose amine content material was 0.4C0.6 mmol/g, as quantified through the Kaiser ninhydrin assay and in agreement with previous syntheses. The purity was 90%, as confirmed by reverse stage HPLC (?(1b).1b). The solid SWNTCNH2 was analyzed using Raman spectroscopy which showed which the nanotubes were extremely functionalized, evidenced by a growth in the disorder music group at 1360 Rabbit Polyclonal to BID (p15, Cleaved-Asn62) cmC1, aswell as the main tangential setting peak at 1580 cmC1, quality of CNTs. The broadening of the peaks plus a broad upsurge in history signal also verified which the SWNTs were extremely dispersed. The SWNTCNH2 was reacted with succinimidyl-4-formyl-benzoate after that, as well as the causing aldehyde functionalized nanotubes (SWNTC4FB) had been examined by reverse stage HPLC (?(2b)2b) that confirmed the high purity ( 90%) from the material aswell as very similar retention time for you to the beginning SWNTCNH2. The transformation to aldehyde groupings was also noticeable in the reduced amount of obtainable amines to significantly less than 0.05 mmol/g as measured with the Kaiser ninhydrin assay. The SWNTC4FB solid was also examined by transmitting electron microscopy (TEM) (?(2c)2c) to roughly determine nanotube measures and TAK-375 price present aggregates of nanotubes in the number in 50C400 nm, with high variability in nanotube duration. This finding is at good relationship with sizes computed from powerful light scattering measurements on likewise functionalized SWNTs.(28) We also noticed that individualized side-wall functionalized SWNTs had poor contrast in TEMs, likely because of decreased electron density upon covalent modification, rendering it difficult to see individual tubes. Open up in another window Amount 1 Synthetic system for the creation of SWNTCpeptide conjugates and adjustment of WT1Pep-427 TAK-375 price with aromatic hydrazine groupings. Open in another window Amount 2 Characterization of functionalized SWNTs. (a) UVCvis spectral range of SWNTCWT1Pep427 (solid series) demonstrates a growth in absorbance at 354 nm within the SWNTC4FB range (dashed series). This top is characteristic from the bis-aryl hydrazone connection formed between your modified peptide as well as the SWNTC4FB. (b) Change phase HPLC from the beginning materials SWNTCNH2 (dark), TAK-375 price the SWNTC4FB intermediate (crimson), as well as the SWNTCWT1Pep427 conjugate (blue) demonstrate the purity from the three constructs. All peaks overlaid, as well as the spectral range of the main peak of SWNTCWT1Pep427 was in keeping with the spectral range of the SWNTCWT1Pep427 proven above in -panel a. (c) TEM from the SWNTC4FB found in these research displays a polydisperse combination with features characteristic of nanotubes. Changes of WT1Pep427 A WT1 epitope bearing peptide (WT1Pep427, sequence: NH2-RSDELVRHHNMHQRNMTKL-COOH) was chosen based on earlier studies that demonstrated the peptide consists of sequences capable of binding to MHC class II proteins (observe above). The peptide was reacted with succinimidyl hydrazino nicotinamide at mildly fundamental pH (?(1)1) to introduce aromatic hydrazines in the amino terminus of the peptide, while avoiding modification of the lysine side chains (p(?(6A).6A). This suggests that once the T cell receptor (TCR) signaling reached a sustained level for its activation, increasing the density.
Supplementary MaterialsSupplementary Figures srep23865-s1. thereby enabled the movement from the S4 -helix to mediate a fluorescent response. With this age group of imaging neuronal activity, current variations of genetically encoded voltage signals (GEVI) provide potential of monitoring inhibition and activation in one neuron1,2,3,4,5,6,7. Nevertheless, the best objective can be to optically map the experience of multicellular, neuronal circuits involving the fluorescent imaging of tens to potentially thousands of cells. Since the nervous system uses voltage in many different ways to convey and process information, the membrane potential of neuronal cells can vary from hyperpolarizations during neuronal inhibition to depolarizations from synaptic activity and the firing of action potentials. These differing says of membrane potential during the imaging of neuronal circuits complicate the optical signals from fluorescent voltage sensors since it is likely that integrated light signals will come from several cells potentially experiencing different neuronal activities. Restricting the optical response of a GEVI to one type of activity (search strategy was developed to identify potential voltage-sensing Sirt7 proteins since new genomes are routinely being sequenced. The use of a conserved amino acid motif in the second transmembrane segment of the voltage-sensing phosphatase (VSP) gene family enabled the identification of distantly related voltage-sensing proteins including voltage-gated calcium channels (Cav), voltage-gated sodium channels (Nav), voltage-gated potassium channels (Kv), and voltage-gated proton channels (Hv). One VSD identified from this strategy was an uncharacterized Hv from Chinese Liver Fluke, VSP. These results indicate that this mechanism of fluorescence change in response to voltage for Pado consists of the movement of S4 altering the conversation/dimerization from the FP. Outcomes A conserved theme in the S2 transmembrane portion from the VSD can recognize book, voltage-sensing proteins The S2 transmembrane helix from the VSP gene family members contains an extremely conserved structural structures consisting of a proper conserved phenylalanine, a poor residue three proteins downstream accompanied by an optimistic residue four proteins downstream (Fxx[E,D]xxx[R,K], where x is certainly any amino acidity)8,15. This S2 theme is situated in various Axitinib small molecule kinase inhibitor other voltage-sensing protein16 also,17,18,19,20,21,22. Using the VSD series through the Zebrafish VSP proteins, a pattern-initiated-hit BLAST search23 needing the current presence of the Fxx[E,D]xxx[R,K] theme determined potential VSDs using a different distribution of favorably billed proteins in the S4 transmembrane -helix. Further analyses of these potential VSDs revealed homologies to Hv, Cav, Nav, and Kv as well as two putative mechanosensitive ion channels. Loosening the stringency at the phenylalanine position to be tyrosine or tryptophan ([F,Y,W]xx[E,D]xxx[R,K]) broadened the range of potential VSDs to plants. For demonstration purposes the labels of the nodes in the circular cladogram in Fig. 1 have been removed. Expanded views of the voltage-sensing proteins identified via this Axitinib small molecule kinase inhibitor search strategy are shown in supplemental Physique 1 demonstrating the range of organisms from mammals to bacteria, algae, and plants. Dendrograms were created using the program, Dendroscope 324. All proteins identified by this search can be found in the datasets 1 and 2 in the supplemental materials. Open in a separate window Physique 1 Identification of diverse VSDs.Partial dendrogram of distantly related proteins discovered using the Axitinib small molecule kinase inhibitor VSD in the zebrafish VSP and requiring the sequence [FYW]xx[DE]xxx[RK]. The Hv category of proteins is within crimson. The Kv category of channels is within crimson. The Cav proteins are denoted in green. The Cav nodes finishing with a gemstone are from plant life. Nav stations are in blue. The VSP family members & most hypothetical proteins except from plant life were taken out for demonstration reasons. Comparison from the S2 and S4 transmembrane sequences for the VSP (zebrafish), Hv (individual), Cav (mouse), Shaker (Kv C drosophila), NaChBac (Nav – bacterias), Cav seed (search yielding known and potential book VSDs from the next microorganisms and accession quantities: (freshwater protozoan), “type”:”entrez-protein”,”attrs”:”text message”:”EGR29338″,”term_id”:”340502671″,”term_text message”:”EGR29338″EGR29338; (moss), “type”:”entrez-protein”,”attrs”:”text message”:”XP_001766478.1″,”term_id”:”168027922″,”term_text message”:”XP_001766478.1″XP_001766478.1; (metazoa), “type”:”entrez-protein”,”attrs”:”text message”:”XP_002110559.1″,”term_id”:”196001383″,”term_text message”:”XP_002110559.1″XP_002110559.1; (ciliated protozoa), “type”:”entrez-protein”,”attrs”:”text message”:”EJY83098.1″,”term_id”:”403366591″,”term_text message”:”EJY83098.1″EJY83098.1; (pelagic tunicate), “type”:”entrez-protein”,”attrs”:”text message”:”CBY37723.1″,”term_id”:”313216408″,”term_text message”:”CBY37723.1″CBY37723.1; (choanoflagellate), Axitinib small molecule kinase inhibitor “type”:”entrez-protein”,”attrs”:”text message”:”EGD72607.1″,”term_id”:”326427037″,”term_text message”:”EGD72607.1″EGD72607.1; (Chinese language liver organ fluke), “type”:”entrez-protein”,”attrs”:”text message”:”GAA49235.1″,”term_id”:”358341604″,”term_text”:”GAA49235.1″GAA49235.1; and (starlet sea anemone), “type”:”entrez-protein”,”attrs”:”text”:”XP_001627761.1″,”term_id”:”156368561″,”term_text”:”XP_001627761.1″XP_001627761.1. The heavy, hydrophobic amino acid in the S2 transmembrane segment is in green. Negatively charged residues in the required bait sequence are in blue, positively charged proteins are crimson as will be the potential positive fees in the S4 transmembrane portion that react to voltage. A GEVI using the VSD.
In this study, we investigated the partnership between sarcopenia (evaluated in term of fibres atrophy), vitamin d receptor proteins appearance and VDR genotypes within an Italian cohort of osteoporosis(n=44) and osteoarthritis (n=55) sufferers. sarcopenia. Altogether these data open up brand-new potential for TAK-375 biological activity the get rid of and prevention of age-related muscle disorders. experiment confirmed that supplement D can induce calcium mineral influx, intracellular gene and signaling appearance in muscle tissue stem cells [13,14]. Perhaps one of the most researched applicant genes for sarcopenia is certainly Supplement D receptor (VDR) broadly, due to its important regulatory role in calcium homeostasis and skeletal muscle mass function . Endo et al. found that the muscle mass fibers of VDR null mice were smaller and experienced persistently increased expression of early markers of myogenic differentiation compared with controls . The identification of the VDR on muscle mass cells provided further support for a direct effect of vitamin D on muscle tissue . In this context, for the first-time Bischoff-Ferrari et al. reported the expression of VDR in skeletal muscle mass, demonstrating that older age was significantly associated with decreased of nuclear expression of VDR, impartial of biopsy location . Nevertheless, the molecular mechanism in which vitamin D regulate musculoskeletal function by VDR activation is usually longstanding. The VDR is usually a nuclear receptor of 50 kDa, TAK-375 biological activity belonging to class 2 of the family of steroid receptors. The gene is located on chromosome 12q.13.1 and contains nine exons [19-21]. The gene has several polymorphic sites that TAK-375 biological activity have been examined in relation to skeletal muscle mass traits such as and and variants are in and significant haplotype associations with skeletal muscle TAK-375 biological activity mass strength have been observed [22,23]. The polymorphism affects the translational start site of polymorphism is usually polymorphism, which is a functional binding site for the intestinal specific transcription factor in the promoter region of the gene. polymorphisms have been associated with increased BMD and decreased risk of fracture in Caucasian and Japanese populations [25-28]. Recently, Ling et al. (2016) examined the relationship between polymorphism and serum 25(OH)D levels, bone mineral density (BMD) and fracture in Chinese people [29,30]. They discovered that the A allele in polymorphism in the gene was connected with serum 25(OH)D amounts, elevated BMD and reduced threat of fracture in females [29,30]. In this scholarly study, we investigated the partnership between sarcopenia (examined in term of fibres atrophy), VDR proteins appearance and genotypes within an Italian cohort of osteoporosis(n=44) and osteoarthritis (n=55) sufferers. MATERILAS AND Strategies Sufferers We enrolled 99 sufferers who underwent hip Rabbit polyclonal to LOX medical procedures in the Orthopedic Section of Tor Vergata School Hospital in the time June 2013-Feb 2016. Particularly, we enrolled 44 consecutive sufferers who underwent hip arthroplasty for subcapital fractures from the femur (39 females and 5 guys), and 55 consecutive sufferers who underwent hip arthroplasty for osteoarthritis (OA) (40 females and 15 guys). Exclusion requirements were background of cancers, myopathies or various other neuromuscular illnesses or chronic administration of corticosteroid for autoimmune illnesses (a lot more than four weeks), diabetes, alcoholic beverages mistreatment, and Hepatitis B trojan, Individual Immunodeficiency Trojan or Hepatitis C computer virus infections. All experiments explained in the present study were authorized by the ethics committee of Policlinico Tor Vergata (authorization reference quantity# 85/12). All experimental methods were carried out according to The Code of Ethics of the World Medical Association (Declaration of Helsinki). Informed consent was from all individuals prior to surgery treatment. Specimens were dealt with and carried out in accordance with the authorized recommendations. Bone mineral denseness evaluation DXA was performed having a Lunar DXA apparatus (GE Healthcare, Madison, WI, USA). Lumbar spine (L1-L4) and femoral (neck and total) scans were performed, and BMD was measured according to manufacture recommendations . Dual-energy X-ray absorption-metry (DXA) steps BMD (in grams per square centimeter), having a coefficient of variance of 0.7 %. For individuals with fragility fractures, BMD was measured within the uninjured limb. For OA individuals, measurements had been performed over the nondominant side, using the individuals supine with an evaluation table using their limbs somewhat abducted . DXA test was performed one.
Cortical actin patches will be the most prominent actin structure in budding and fission yeast. were relatively normal. Our results are consistent with Arp2/3 complex-mediated actin polymerization traveling candida actin patch assembly and motility, as described by a Prostaglandin E1 small molecule kinase inhibitor variance of the dendritic nucleation model. exposed branched thin filaments, but filament polarity was not determined and many branch Prostaglandin E1 small molecule kinase inhibitor angles were not characteristic of Arp2/3 complicated (Medalia et al., 2002). Actin-based motility could be reconstituted with purified Arp2/3 complicated, capping proteins, and ADF/cofilin (Loisel et al., 1999). This observation as well as the biochemical and structural research above have resulted in the dendritic nucleation model (Pollard and Borisy, 2003), which is normally proposed to take into account actin-based motility in vertebrate cells on the industry leading and comet tails of pathogens such as for example (Loisel et al., 1999). The dendritic nucleation super model tiffany livingston might connect with yeast actin patches. Activators of Arp2/3 complicated Prostaglandin E1 small molecule kinase inhibitor appear to immediate the development and maturation of actin areas (Kaksonen et al., 2003). Nevertheless, although capping proteins colocalizes with Arp2/3 complicated at sites of actin set up generally in most systems (Use and Cooper, 2004), and capping proteins is normally a fungus actin patch element, fungus strains missing capping proteins are practical, and their actin areas assemble and move (Kim et al., 2004). Furthermore, cofilin could be needless for patch motility (Lappalainen and Drubin, 1997). Hence, the dendritic nucleation model may not connect with actin patches. Actin patch motion and set up in fungus have already been well examined by hereditary, cell natural, and biochemical strategies. However, an integral little bit of the puzzle is normally lacking: how are actin filaments within a patch arranged? Ultrastructural research of the fungus actin cytoskeleton have already been challenging due to the high thickness of fungus Prostaglandin E1 small molecule kinase inhibitor cytosol. A thin-section EM research found actin areas at plasma membrane invaginations with filaments around some invaginations (Mulholland et al., 1994). Rapid-freeze, deep-etch EM from the plasma membrane’s cytoplasmic encounter revealed structures filled with short actin filaments and several actin-binding patch parts (A. Rodal, B. Goode, D. Drubin, and J. Hartwig, personal communications). In this work, we isolated and partially purified GFP-labeled actin patches and correlated fluorescence and EM images to identify actin patches in the EM. Patches contained networks of branched actin filaments. The network characteristics in wild-type and mutant cells have implications for patch assembly and movement and the applicability of the dendritic nucleation model in candida. Results and conversation Purification of actin patches Actin patches are at the cell cortex, but when candida are lysed, patches are expelled with the cytoplasm (Fig. 1 A). To purify actin patches, we GFP-labeled them and adopted them by fluorescence microscopy. Unless stated normally, we GFP-labeled the Cap1 subunit of capping protein. GFP-labeled patches in cell lysates did not correlate with any constructions observed with DIC or phase contrast optics and were absent in preparations from strains lacking GFP. Actin patches were stable at 4C inside a concentrated cell lysate for 24 h, but disassembled in 2 h at 25C or when diluted into a variety of buffers. We found that KS buffer, which contains 1 M sorbitol and 0.2 M potassium phosphate, stabilized patches to dilution for hours. Because patches in vivo turn over in moments, we asked if Prostaglandin E1 small molecule kinase inhibitor KS stabilized actin filaments. Pure actin filaments disassembled in 100 s when diluted into control buffers, but only 5% of actin depolymerized within 10 min when diluted into KS. Phosphate only prevented depolymerization (Fig. S1, available at http://www.jcb.org/cgi/content/full/jcb.200404159/DC1), and it stabilizes Arp2/3 complex-mediated actin branches (Blanchoin et al., 2000). However, stabilizing actin patches required both phosphate and sorbitol. Open CED in a separate window Number 1. Assessment of isolated actin patches with patches in.
Idiopathic pulmonary fibrosis (IPF) is a progressive and often fatal lung disease for which there is no known treatment. pathway; see below) (Armanios, 2012). It Kenpaullone inhibition now appears that 10C15% of FIP instances are due to mutations in the telomerase pathway, in the lack of traditional manifestations of DC. Oddly enough, short telomeres are generally found in people with sporadic IPF (Alder et al., 2008), recommending that telomere dysfunction can be a common feature of fibrotic lung disease actually in the lack of telomerase mutations. Desk 1. IPF-associated genes Open up in another window Package 2. Cell types involved with IPF pathogenesis Type II alveolar epithelial Kenpaullone inhibition cells (AECs): epithelial cells surviving in the edges of alveoli; in charge of the creation of surfactant proteins; considered to serve as progenitors of type I AECs, which will make in the respiratory gas exchange surface area. Fibroblasts: mesenchymal cells that have a home in the pulmonary interstitium and make collagen and extracellular matrix (ECM). Myofibroblasts: contractile mesenchymal cells expressing alpha-smooth muscle tissue actin; it really is thought these cells come with an triggered phenotype, and donate to exuberant ECM and collagen creation in IPF. Subsequent work discovering the effects of the genetic mutations offers implicated many unanticipated pathways in IPF pathogenesis, including endoplasmic reticulum (ER) tension as well as the unfolded proteins response (UPR), mobile senescence, the DNA-damage response, and WntC-catenin signaling potentially. Once we discuss with this review, these pathways appear to converge in epithelial cells, recommending that epithelial cell dysfunction and damage are necessary in the evolution of lung fibrosis. Clarifying the part of the pathways in epithelial cells should help answer a number of the many exceptional questions linked to IPF. Research study A 53-year-old guy with obstructive rest apnea and gastroesophageal reflux disease shown to a pulmonary center having a 6-month background of progressive exertional dyspnea and nonproductive cough. He previously been treated for community-acquired pneumonia in the preceding weeks without improvement of his symptoms. He previously retired carrying out a 20-season profession in the refused and armed service contact with asbestos, silica or additional particulates. He reported a 30 pack/season background of using tobacco but have been abstinent for 9 years. His genealogy was remarkable for just two sisters with idiopathic pulmonary fibrosis (IPF) diagnosed at age group 46 and 52. Another sibling was deceased from problems of myelodysplasia, and a niece got passed away from aplastic anemia at age group 24. His air saturation was 97% deep breathing ambient air. There have been faint bilateral inspiratory crackles and gentle clubbing. Pulmonary function testing demonstrated a gentle restrictive defect having a Rabbit Polyclonal to PTX3 reasonably reduced diffusing convenience of carbon monoxide (DLCO). High-resolution CT from the upper body demonstrated scattered regions of basilar predominant peripheral interstitial prominence with many small regions of honeycomb modification. Serological testing for connective cells disease was adverse. A prominent genealogy of pulmonary fibrosis in conjunction with his medical program and radiographic design suggested he probably got familial interstitial pneumonia (FIP), the inherited type of IPF. Hereditary sequencing determined a heterozygous mutation in telomerase invert transcriptase (mutation (L188Q) that was connected with interstitial lung disease in 14 Kenpaullone inhibition people from a single huge FIP kindred (Thomas et al., 2002). Individuals with this cohort demonstrated irregular localization of SP-C pro-peptide (discover below), that was distributed in the cytoplasm of atypical-appearing type II AECs diffusely. Transfection of L188Q into mouse lung epithelial cells decreased mobile proliferation and improved cytotoxicity in vitro, recommending how the deleterious aftereffect of mutant SP-C was mediated through a gain-of-function system. Subsequent function indicated that ER tension with activation from the UPR was most likely a key system in interstitial lung disease connected with mutations (evaluated by Tanjore et al., 2012). SFTPC mutations trigger ER tension SP-C is a little secreted hydrophobic protein produced exclusively by type II AECs. SP-C is translated as a 21 kDa pro-peptide and requires the C-terminus for initial folding steps in the ER before undergoing multiple proteolytic cleavages prior to secretion of the highly hydrophobic mature peptide. Truncated forms of pro-SP-C lacking the C-terminus, including the exon4 variant originally described by Nogee and colleagues (Nogee et al., 2001), fail to undergo appropriate proteolytic cleavage for targeting to cytoplasmic vesicles and remain in the ER (Beers et al., 1998; Wang et al., 2003). In.
Hypertrophic cardiomyopathy is certainly a human cardiovascular disease characterized by improved ventricular mass, focal regions of fibrosis, myocyte, and myofibrillar disorganization. R403Q, Clozapine N-oxide inhibition had been competent to put together into heavy filaments creating myofibrils with well described I rings, A rings, and H zones. Coexpression and detection of wild-type MHC and either R249Q or R403Q proteins in the same myocyte showed these proteins are equally able to assemble into the sarcomere and provided no discernible differences in subcellular localization. Thus, human MHC R249Q and R403Q mutant proteins were readily incorporated into NRC sarcomeres and did not disrupt myofilament formation. This study indicates that this phenotype of myofibrillar disarray seen in HCM patients which harbor either of these two mutations may not be directly due to the failure of the mutant myosin heavy chain protein to assemble and form normal sarcomeres, but may rather be a secondary effect possibly resulting from the chronic stress of decreased MHC function. A sarcomere, the functional unit of muscle, is composed of a precise arrangement of at least 20 known proteins ordered in nearly crystalline fashion. Complex interactions of a few of these proteins, mainly actin and myosin, produce the force necessary for muscular contraction (for review see Squire, 1986). The association of actin and myosin is usually tightly regulated by the troponin complex, tropomyosin, and flux of Ca2+ ions. Productive muscular contraction depends upon correct spatial interactions of muscle tissue structural protein inside the sarcomere. Hereditary evaluation in and shows that mutations in a number of from the sarcomeric protein disrupt myofibrillar firm and affect muscle tissue function (for review discover Epstein and Bernstein, 1992). Nevertheless, for most of the mutations the root biochemical/useful defect is not elucidated. Thick and thin filaments can form independently of one another, yet apparently equal stoichiometric quantities of actin and myosin are required for proper sarcomeric order (Beall et al., 1989). The discovery that mutations in sarcomeric proteins cause an inherited form of human heart disease has brought significant attention towards understanding muscle protein function. Familial hypertrophic cardiomyopathy (HCM)1 is an autosomal dominant, genetically heterogeneous heart disease with variable penetrance and an assortment of clinical phenotypes ranging from moderate syncope to sudden death. The hallmark of this disease is usually unexplained left ventricular hypertrophy in which dilation of the ventricular chamber is usually absent (Maron, 1988) and an increase in myocyte disarray associated with abnormal myofilament structure in hearts with HCM is usually apparent. Genetic mapping has identified a minimum of six loci which cosegregate with the disease, any of which can be responsible for the dominant phenotype. The genes identified as responsible for HCM all encode different structural components of the sarcomere, myosin heavy chain (MHC; Geisterfer-Lowrance et al., 1990), cardiac troponin T, tropomyosin (Thierfelder et al., 1994), C protein (Bonne et al., 1995; Watkins et al., 1995muscle MHC displays dominant phenotypes that dramatically disrupt sarcomere business (Bejsovec and Anderson, 1988, 1990). Although none of the mutations correspond to those described in HCM, it is possible that the individual MHC mutant protein have an identical deleterious affect on myofibril set up and/or structure. To handle this relevant issue, we have created an in vivo competition assay which will allow the immediate evaluation of the power of the epitope tagged mutant individual cardiac MHC proteins to effectively contend with a wild-type MHC proteins for set up into endogenous sarcomeric products in living myocardial cells. Within this paper we survey the cloning and structure of full duration individual MHC cDNAs encoding wild-type and mutant protein. Expression of the clones either independently Clozapine N-oxide inhibition or in mixture within transiently transfected principal civilizations of neonatal rat ventricular cardiomyocytes (NRC) was utilized to analyze the result of MHC mutations on subcellular localization and myofibril set up. A missense mutation in the consensus ATP binding Rabbit Polyclonal to PPP2R3C series affected sarcomere framework significantly, disrupting myofibril set up at an early on stage. Nevertheless, MHC with either of two HCM mutations, R403Q or R249Q, assemble normally. This means that the myofibrillar disarray seen in HCM sufferers may possibly not be the direct result of mutant contractile proteins altering myofilament assembly. Furthermore, the data presented here support previous information suggesting that biochemical defects in Clozapine N-oxide inhibition the human MHC proteins produce physiological dysfunction and pathological alterations in the heart. Materials and Methods Isolation of Human MHC cDNA Clones A human heart (ventricular) specific cDNA library (Stratagene, La Jolla, CA) was screened with end labeled oligonucleotide probes derived from the MHC published sequence (Jaenicke et al., 1990; Liew et al., 1990). End.

domain: medical


A Winter Storm Warning has been issued for our area, prompting the declaration of a Snow Emergency in Upper Nyack. This emergency will be in effect from midnight tonight until midnight Tuesday.
During this time:
- No vehicles are permitted to be parked in the public right of way or on a public street, except in designated parking places for homes without driveways on the South side of School Street and the West side of Front Street north of Highmount Avenue.
- The Superintendent of Public Works or the Police Department is authorized to remove and store any vehicle parked or left standing on any public street or highway within the Village during any snowstorm, flood, fire, or other public emergency.
- Residents must remove snow from their sidewalks within 24 hours after the snow ceases.
- It is prohibited to shovel or plow snow into a public street.
- If there is ice on the sidewalk that cannot be removed, residents must spread sand or other material on the sidewalk for safety.
It is urged that all residents adhere to these guidelines for their safety and the efficient clearing of snow from our streets.


A typical embedded system including the Bridge core is shown in . Some additional components to this system in the Vivado® IP integrator can include the need to connect the MicroBlaze™ ™ processor or Zynq® device Arm® processor peripheral to communicate with PCI Express® (in addition to the AXI4-Lite register port on the PCIe bridge). The AXI Interconnect provides this capability and performs the necessarily conversions for the various AXI ports that might be connected to the AXI Interconnect IP (see AXI to AXI Connector Data Sheet (DS803)).
The Bridge core can be configured with each port connection for an AXI Vivado IP integrator system topology. When instantiating the core, ensure the following bus interface tags are defined.
BUS_INTERFACE M_AXI BUS_INTERFACE S_AXI BUS_INTERFACE S_AXI_CTL


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In 2012, Lakeside Companies began actively managing operations for PetrolinkUSA – today known as RIG – turning it into a profitable investment with substantial growth. In 2018, Lakeside acquired Cogen Cleaning Technologies and Energy Services International (ESI) to form Reliable Industrial Group. A North America partnership with ExxonMobil followed in 2019. In early 2022 RIG added in Hydrocarbon Filtration and Elden Consulting to the RIG portfolio.
The Blue Wolf acquisition announcement was made by Tim Hennigan, CEO: “We are very excited to welcome RIG to the Blue Wolf platform. RIG’s capabilities will support our efforts in expanding our service offerings into lube oil flushing and other related service lines as well as establishing a turnkey pre-commissioning offering.”

domain: economics


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Virgin Galactic — billionaire Richard Branson's space tourism company — has agreed to charter its new private spaceliner SpaceShipTwo, to NASA for research purposes.
Under the $4.5 million deal, NASA engineers, technologists and scientific researchers will make up to three flights on the SpaceShipTwo, an air-launched spacecraft designed to carry eight people on trips to suborbital space, the company has announced on its website.
Check out this spectacular video of the SpaceShipTwo in action:
Earlier this week, Virgin Galactic announced also announced that the former deputy chief of NASA's now-retired space shuttle program, Mike Moses, had joined the company as vice president of operations.
Moses will, according to Fox News, work out of Spaceport America, Virgin Galactic's base for its "commercial suborbital spaceflight program" in New Mexico. The company is slated to dedicate its headquarters at the spaceport this coming Monday (Oct. 17).
Virgin Galactic's statement about the NASA deal read:
This arrangement dramatically increases the access researchers currently have to space. Each mission allows for up to 1300 lbs of scientific experiments, which could enable up to 600 experimental payloads per flight. Virgin Galactic will provide a Flight Test Engineer on every flight to monitor and interact with experiments as necessary, a capability that has never before been available on suborbital vehicles. If requested, these experiments can be quickly accessed after landing, a feature critical to many types of experiments.
George Whitesides, president and CEO of Virgin Galactic, said that previously, space "research opportunities have been rare and expensive."
He continued: "At Virgin Galactic, we are fully dedicated to revolutionizing access to space, both for tourist astronauts and, through programs like this, for researchers."
(GlobalPost reports: Not a giant leap)

domain: news


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World Bank President chides west for Bio-Fuels program
Just about every time we do an article or blog post about the bio fuels boondoggle here at American Thinker, we hear it from supporters of ethanol that the program does not affect the price of food.
Well, the President of the World Bank doesn't think so. Robert Zoellick criticized Europeans and Americans for diverting agricultural land away from growing food in order to pursue the elusive goal of saving energy and reducing greenhouse gas emissions.
The problem is that there is a food crisis in the world, although you'd never know it if you lived in America. The price of food has skyrocketed:
He said the price of wheat had risen by 120% in the past year, more than doubling the cost of a loaf of bread. Rice prices were up by 75% in just two months.There have been food riots in Mexico and India because of scarcity. Land used to grow corn or other base bio-fuel crops could be used to grow wheat and some of that land could be used to grow rice. Clearly, the massive committment of America and Europe to bio fuels is having the effect of raising food prices to the point that real harm is being felt by poor people around the world.
On average, the Bank calculates that food prices have risen by 83% in the past three years.
"In Bangladesh a 2kg bag of rice now consumes almost half of the daily income of a poor family. With little margin for survival, rising prices too often means fewer meals," he said. Poor people in Yemen were now spending more than a quarter of their income on bread.
"This is not just about meals forgone today, or about increasing social unrest, it is about lost learning potential for children and adults in the future, stunted intellectual and physical growth. Even more, we estimate that the effect of this food crisis on poverty reduction worldwide is in the order of seven lost years."
If farmers want to grow food for bio fuels, fine. But let's stop subsidizing this wasteful and ultimately futile process which only benefits farmers and causes hardship for those who cannot afford it.

domain: food


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via Lobe Log
The Asian Law Caucus (ALC), in collaboration with the Public Affairs Alliance of Iranian Americans (PAAIA) and several other Iranian-American organizations, has released a publication titled “Unintended Victims: The Impact of the Iran Sanctions on Iranian Americans.”
News reports continue to spell out something that the US government claims it’s trying to avoid: sanctions are harming average Iranians, many of whom are the most vulnerable. Now it’s also clear that Iranians inside Iran aren’t the only ones who are suffering from America’s apparently incoherent Iran policy.
The sanctions and the deeply complicated, burdensome and stressful process of obtaining exemptions from the mammoth sanctions-regulatory/enforcement body, OFAC, are impeding ordinary Iranian-Americans from a wide range of routine activities essential to their personal lives. According to the report, this isn’t by accident, and can be remedied:
Both proponents and opponents of the sanctions must agree that U.S. persons should not be unfairly targeted by a set of laws and regulations simply because of their nationality or country of origin. And yet, that is precisely the situation the Iranian American community finds itself in. As illustrated in this report, it is clear that the Iran Sanctions have had intended and collateral consequences for the Iranian American community. Lawmakers and those in the Executive Branch, including the President and the Office of Foreign Assets Control, should work closely with the Iranian American community and community and legal organizations to understand the community’s concerns, and should take the proactive steps outlines above to ensure that this disproportionate burden is lifted.
- Obama Narrows Scope of Terror War
- Advocates Cheer Tightening of Extractives Transparency Standards
- Where Law Enforcement Goes Bad
- Indian Gov’t on Collision Course With Civil Society
- OP-ED: The Nexus Between Women and Development
- Life Terms Urged in Bangladesh Building Collapse
- Groaning Under Power Cuts, Scorching Temps in Pakistan
- Hungary Losing Its Best and Brightest
- Gazans Dying to Enter Israel
- OP-ED: A Global Goal on Gender Equality, Women’s Rights and Women’s Empowerment


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The Okanagan Rail Trail has a new logo that incorporates the essential elements of the 49-kilometre recreation trail between Kelowna and Coldstream.
It includes symbolic references to the trail’s environment: the Okanagan Valley, the surrounding mountains, its wildlife, trees, beaches, the sky and sun.
“The Okanagan Rail Trail logo encapsulates the many benefits and experiences the trail has to offer its users and communities,” says the official announcement. The containing shape is an ‘O’ representing the Okanagan as well as an oval train track.
“The graphic elements combine in a cohesive way to signify the connection of communities, environment, history, heritage and future of the Okanagan Rail Trail.”
It also reflects the heritage and history of this region.
“The traditional and continuing use of the land by the syilx Okanagan people has created a history that is synonymous with the land. The logo design is inspired by traditional syilx pictographs. Kilowna (grizzly) claws are representative of the traditional syilx name for the Kelowna area.
“Railway ties represent the history of railway that visually transforms into the trail. These two elements work in unison and signify the partnership and the transformation to the Okanagan Rail Trail.
“The trail winds through the mountains/valley, serving as a conduit for recreation, commuting and connecting communities.
“The trail leads the eye through the environment and into the sunny horizon signifying a positive and bright future.”
Several volunteers from the trail-building fundraising society, the Okanagan Rail Trail Initiative, have now established a foundational Friends of Okanagan Rail Trail Society, or FORT for short.
FORT is a non-profit society, volunteer-driven, and the official non-government partner to the rail trail owner jurisdictions.
The new organization has adopted the new logo and added the words “Friends of” at the top.
FORT core values are: user experience, environment, inspiration and stewardship which will be accomplished through three main programs: trail ambassadors, trail improvement and fundraising, says the website: okanaganrailtrail.ca.
With the trail construction now fully funded, trail ambassadors have been trained to help with trail operations.
The role of trail ambassadors will be to support the trail user experience, inspire users by sharing information on the trail environment and history, solicit feedback and information from users, be a visible presence on the trail to enhance user safety, report to managing authorities on conditions and issues, and encourage compliance with trail etiquette and rules.

domain: geography


Home Media Segment 17: A Butthurt Band Member, Grandfathered VIPs And Facts Of The... MediaVideo Segment 17: A Butthurt Band Member, Grandfathered VIPs And Facts Of The Day February 28, 2019 106 Share Facebook Twitter Pinterest WhatsApp ReddIt Email During today’s Segment 17, we talked about a variety of topics that we didn’t get to on the regular radio show. They included: A butthurt band member Some info for grandfathered VIPs Facts of the day and (maybe) more! https://vimeo.com/320532626… Hey, sorry! This content is for Fancy Idiot (Monthly), Fancy Idiot (Annual) and Lucky Idiot only.Become an Idiot Today! Log In RELATED ARTICLESMORE FROM AUTHOR Blog Orlando Woman Goes Viral For Squeaky-Oven Video Media Webcam Feed: Monday, August 19, 2019 Media Segment 17: Kidney Stone Babies And Facts Of The Day Media A Round Of Name That Tune Turns Into Garth Brooks Karaoke And Bob Dylan Impressions Media Webcam Feed: Friday, August 16, 2019 Media Segment 17: Joe’s Poop Pants, Underdogs Update, Pee Ice Cream And Facts Of The Day MOST POPULAR Orlando Woman Goes Viral For Squeaky-Oven Video August 20, 2019 A Listener Is Naming Their Baby After One Of Us! August 20, 2019 THE LATEST Blog Tussle Over Neighbor’s Trash Ends In Sword Fight Blog Orlando Woman Goes Viral For Squeaky-Oven Video Blog Survey Shows Nearly Half Of Americans Do This And It’s Nasty Blog What Two States Border Arkansas Across The Mississippi River?


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Last March, the chief of the world’s largest fund management company – BlackRock – announced in a letter to his shareholders that it was “the end of the globalisation we have known for the past three decades”. The catalyst for this letter was the conflict in Ukraine, which suddenly disrupted the world order that had prevailed since the 1990s and, with it, many of the trade links that had existed between nations.
Larry Fink’s announcement came almost two years to the day, after the start of another major global crisis that had put many of the established rules and institutions of the world to the test, and had also profoundly challenged the long-held acceptance of globalised, capitalist models – COVID-19.
The common factor? The sudden awareness of the risk inherent in dependence on single markets or monopoly providers of goods: be it energy dependence, food dependence, health dependence or economic dependence. The world is experiencing the flaws of a system which, although virtuous in many respects, is nevertheless based on what has become an increasingly fragile balance over the last decade.
REORGANISATION, RESILIENCE AND SECURITY
Resilience and security have become bywords for an environment of increasing complexity and instability. While some people have advocated the need to onshore manufacturing processes and supply chain networks, this does not necessarily mean protectionism and unilateralism are the right answers. Rather, a new balance needs to be established, and that is what is happening today.
In just two years, a millisecond in the recent history of international trade, many companies have reorganised to secure production lines, supply networks and (somehow) maintain costs at a level that, despite heightened global inflation, have remained relatively manageable. This is a real organisational and logistical tour de force, the enormity of which is not always fully appreciated by consumers.
More than the capacity to adapt, perhaps the speed with which this adaptation is required is such a remarkable feat. How many years, or even decades, would it have taken companies at the end of the last century to reorganise their operating streams in a similar global crisis? Would it have even been possible without the connected systems, digitised processes and rapid innovation cycles we now have at our disposal today? The answer is almost certainly, no.
SILVER LININGS IN ANY CLOUD
It would be a mistake to think that the current symptoms (product and staffing shortages, inflationary pressure, etc.) are simply cyclical accidents. The globalisation of commerce, along with the supply chains that underpin it, not to mention the increase in political, technological and cyber risk, are all areas that create complexity, fragility and uncertainty and have been increasing for many years.
In the face of such risks, it is vital that organisations and governments, societies and individuals have the tools at their disposal to be able to adapt quickly by building and having access to networks that are resilient, innovative and adaptable.
Globalisation as we know it has been shaken to its foundations over the past two years, and repeated (if not) differing crises are causing the model to break. While the short-term stresses caused by this schism are being felt by billions around the globe, it is a process that we must look to seize upon if we are to build a new more resilient, sustainable and adaptable approach to global commerce in the long-term.
To be clear, this is not the end of globalisation or capitalism; it may well, however, represent the beginning of a new phase in its evolution, one that will see unified supply chains play an increasingly important role in the flow of global commerce.

domain: politics


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Doctor insights on:
SEVERE pain w liver bx. Admitted.Dx multi organ serositis. CRP 284.Sed50,ddimer1680. Hi ferr,myoglobin. Lo rbc,plat,lymph. Lo prot, HG. Ascites,eff,fever,brn urine. What was trigger? Bile leak,bleed?
Urine is the product of the kidneys, which is produced to eliminate the waste products of metabolism, manage body fluid balance, &maintain acid-base balance. The blood is first filtered by the kidneys, and the composition of the resulting fluid is then altered depending on the body's needs. It is composed of mostly water, and breakdown products from blood cells impart ...Read more
Myoglobin high. Drk brown urine. Dr said myositis. If kidneys ok at discharge is there a good chance they will stay ok or would damage be delayed?
7 weeks out on recovering from rhabdomyolysis. Consuming 2-3 liters of water a day, urine is dark amber. myoglobin not present. Should I be concerned?
Bmp, myoglobin, 5 hiaa 24hr urine are test neurologist ordered. He seemed to think tremors, fast heart rate, chest pain are all related. He said something about serotonin to nurse. What could it be?
Is coq10 (ubiquinol 50 mg) safe for chf/ckd patient? Was on statin, discontinued 6 months ago due to neuropathic issues, myoglobin in urine, but muscle loss persist. What is a good test for cariomyopathy and which specialist treats myog/muscle loss?
Yes: Studies of coenzyme Q10 use in patients with CHF were dosed at 100 mg 3 times a day and studies showed improved exercise tolerance. Studies of coenzyme Q10 for statin-induced muscle aches are typically dosed around 200 mg once a day. Testing for cardiomyopathy requires a full cardiac workup by a cardiologist, treating muscle loss depends on the cause, consult your internist ...Read moreSee 2 more doctor answers
Skeletal muscle loss/ischemia evident by high myoglobin in urine (25). What are the markers for myalgia vs neuropathy? Patient on gabapentin and decreased gfr (20), cymbalta was discontinued for low gfr. Which specialist would be best for the issue?
Need more informatio: What are the muscle enzymes CPK and Aldolase. Are they elevated sicne there is urine myoglobin. If the myoglobin is elevated this suggests that the myalgia may be a myositis. Neuropathy is something different. Ask your physician about seeing a neurologist for the neuropathy and a nephrologist for the kidney. You may need others. ...Read moreSee 1 more doctor answer
Abdominal pain, fever, raised wbc. On cipro but symptoms persist. Chf and inflammatory markers with esr sed rate 88 and myoglobin in urine. Can it be rheumatic fever, untreated strep?
No: You don't satisfy the Jones Criteria for Rheumatic Fever: Here they are: http://reference.medscape.com/calculator/jones-criteria-diagnosis-rheumatic. There are many possibilities but connective tissue disease is on the short list. You're sick and need an early full evaluation. ...Read moreSee 1 more doctor answer
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domain: biology


text:
Last year was the second-most difficult in the past five years for salary increases in South Africa, according to a BankservAfrica report released on Wednesday - meaning at the current rate, it would take 180 years to double a salary in real terms.
BankservAfrica's Take-home pay Index tracks about 3 million salary earners via about 4 million monthly payments made into the national payments system.
The overall data shows that real take-home pay increased by just 0.4% in the SA economy in 2018.
With inflation averaging 4.6% for 2018, the average employee's increase was above the price level changes as measured by the inflation basket, according to Shergeran Naidoo, head: stakeholder engagements at BankservAfrica.
A total increase of 1% after tax and pension in take-home pay over five years indicates that, in essence, salaries were adjusted just for inflation on average, according to Mike Schüssler, chief economist at Economists.co.za.
In December 2018 the average banked real-take home pay was R14 094, showing a 0.5% year-on-year (y/y) change and a slight improvement from November, according to Naidoo. The nominal value was R15 045 or a 5.5% change y/y.
The average real take-home pay for the whole of 2018 was R13 990 per month for the person receiving their salary via a bank account. Before inflation, the average was R15 018 per month.
"The worst year for real take-home pay was 2016, where there was a 1.1% decline in take-home pay after inflation, while all the other years showed an increase of which 2018 was the smallest," said Naidoo.
According to Schüssler, the weak economy is not helping South Africans get salary increases, although the average increase for 2018 was just above inflation.
Some salary increases were above 7%, which, after tax and inflation, would have resulted in an estimated 1.8% increase in real after-inflation terms.
"Many private sector firms remain under pressure, resulting in less-than-inflation increases. Many employees are struggling to maintain their standard of living," said Schüssler.
He added that take-home pay did at least result in higher retail sales, as retail inflation was just about half the headline inflation rate for 2018.

domain: finance


The 2019/20 L League league can be categorized into three categories: AZ Alkmaar is committed to promoting and marketing talents in the European football market, and Manchester United is one of the clubs that skims over the cream of the proposed Astana product "With "Partizan" they are located somewhere in the middle – they are not averse to sell and buy, but in most cases goods are not bought from the first freshness Today in Prosports.kz – about the cost of the composition of the clubs of Only Sultan and Belgrade after the portal transfer market.
"Astana": the total value of the players – 25.4 million euros
The most expensive football player: Marine Thomasov – 3.8 million euros
In the application of the strongest club in the country there are immediately 12 "millionaires"! The most important is Marin Tomasov. Horvath is truly a one-of-a-kind player for KPL, the only legionary in the history of domestic football who reached the peak of its market value at the age of 30.
Since the arrival of Marina in Astana its price has more than doubled, and now Thomasov is the most expensive capital of the entire Premier League. In the list of the rich, Kazakhstan's Dmitry Shomko and Roman Murtazaev and the Congolese company Mubele share 2-4 places – each of them has a transfer value of 2.5 million euros.
Partizan: the total value of the players – 25,825 million euros
The most expensive football player: Lazar Markovich – 4 million
One of the two best rated Serbian clubs is only marginally superior to the Kazakh champion in terms of transfer value – less than half a million euros.
And the principle of occupation is similar in many ways to what Astana practices. Partizan in competition with Red Star weakens other clubs in the country and attracts young talents from across the country under his wing.
The black and white clip of local students is watered down with legionnaires who are not in demand in the strongest European leagues and often leave the fair.
However, in view of the higher skills of Serbian players compared to Kazakhstan, they are much higher on the football market.
The then 19-year-old midfielder Lazar Markovich was sold in 2013 for 10 million euros to Benfica. In 2014, his transfer price increased twice and the midfielder of the Balkans moved to Liverpool.
However, in the Merseysiders camp, Lazar could not reach its full potential. On the basis of the "Reds", he spent only 19 games in five years and was able to lease five times.
And this summer Markovic returned to Partizan, who was plagued by life and has long lost a place in the Serbian national team. Its price is now only 4 million euros.
In total there are 10 football players in Belgrade, whose market price is measured in numbers with six zeroes, including two former Moscow "army men" – Zoran Tosic and Bibras Natho.


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Chuck Arista, the last Elk territory manager before the hostile, um, merger by, er, between GAF and Elk, gave me the news. For those old enough to remember when Elk (Elcor) introduced the Prestique II, GAF's big announcement should harken those days. GAF started a war today by making all of its shingle, sans the 25 year Royal Sovereign Thee tab, lifetime products. That means 50 years with the last 2% never going away, thus lifetime.
GAF had already killed the Sentinel because it wasn't willing to compete with Owens Corning for how thin a shingle could be made. Elk had made that decision back in the 80's and I think we tore off the last Elk 25 year Sunseal in Irving a few weeks ago. It had six hail storms on it and it was still heavier than the Owens Corning 20 year three tab, a product that so thin nobody could find it anymore.
The reason I hark the Prestique II birth is that rather than increase dollar sales by getting more people to move up from the three tab to the new light weight laminate shingle, the new roofing product caused people to downgrade from the 30 year laminate, the Prestique 30 year, to the 25 year version. But the damage had been done.
This marked the beginning of an explosion in different types of roofing. GAF made a new Timberline, going through name changes every few months until they got back to the original Timberline name and adding the number 25 for it's warranty. Those names were Woodline, Woodline Plus, some other name that lasted a few weeks, and ultimately Timberline.
The manufacturers were playing leap frog with their warranties. The 25 year became 30, the 30 became 40, and then Elk tried to bring balance to the universe by creating the Prestique Plus 40 year, that became a 50 year when the leap frogging ceremony began.
Always the gamer, Atlas always just added five more years than everybody else.
Back at the supply house, where Chuck hangs out now having quit Elk for the job of outside sales for the Roofing Supply Group, or RSG as everything in roofing has an acronym, they'll have the old wrappers and sample boards for months to come and we'll get the inevitable irate phone calls from customers saying "the wrapper says 30 year and you said it was lifetime." We warned them in advance but I guess it'll be part of that 80% they forget after the presentation. They'll be suspicious anyway until they get the warranty. Here it is if you want to see for yourself: NEW BIG FAT WARRANTY.
So rather than buy 40 year or Lifetime or AmorShield II Lifetime Class IV roofing, all people will buy is the Timberline 30, er, lifetime.
I just took a break to read the news and saw that the 40 year is "while supplies last." The heavy duty is now the Timberline Ultra HD and the Timberline 30 is Timberline Lifetime, the name the old Timberline Ultra had before it became the Timberline Lifetime, the name the 30 year has now. And if you think that is a mouthful, for the last couple of years the 30 year product was called the GAF ELK Timberline Prestique High Definition 30 year. Gasp for air. The extra ink on the packages alone made the product seem heavier and caused the price to go up.
I will miss the Armorhield II Timberline Prestique seems to have exited the building. It doesn't even qualify for the "while supplies last" tombstone. The original ArmorShield (I) was only in business for a few months before it was changed. (I was wrong, They still make the ArmorShield II)
The System Plus warranty will become 50 years on materials and labor. Period. 100%. Period. The Golden Pledge will be the same as the System Plus with a 20 year leak protection that we Master Elite roofers are honored with the privilege to offer.
Still the hostile, er, merger, was one of the few great moves I've ever seen in the roofing industry. The better and bigger behemoth merged all over the pretty Elk roofing. I always hated it when a customer said "but I want one that looks like that." Then the sell went Elk. Now GAF wears an Elk skin but is the biggest baddest roofing manufacturer out there, except in the Class IV tournaments. GAF has only one product at this time but soon it will have more, or so I've been told.
Now if I were the Big Kahuna at GAF, I would have sprung this on the enemy in April when national sales go up, not now when roofing jobs are at their year low point. That way CertainTeed, Tamko, and Owens Corning would not have been able to make an adequate response until harvest season was over. I know what Atlas is going to do. They are going to come out with lifetime plus 5 years on all their products. They always leap the frog last. But the paper is as worthless as a Greek Drachma, Spanish peseta, or an Irish pound.
By the way, an Irish pound is a fifth.
Jon Alan Wright
Jon Wright Roofing, Siding, and Windows
1915 Peters Rd., Suite 310
Irving, TX 75061
Master Elite Roofer: (Scroll to the bottom)


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When a team makes significant changes to its roster during an offseason it becomes a lot of fun for fans to play fantasy hockey and start mixing and matching players together as they try and predict who will be paired with who.
One team that has had drastic rate of turnover in the past year has been the Minnesota Wild organization. The Wild have not only gone through 2 general managers in about 2 seasons but the second of those general managers, Paul Fenton, traded away some of the organization's core players in a series of moves that has left the roster looking dramatically different than it did just a year ago. The head coach, Bruce Boudreau, find himself in a rather odd position given the fact that he will now be playing under his third general manager since joining the ranks of the Wild, but he appears to be taking it all in stride.
In fact in a recent interview with Minnesota Wild insider Mike Russo Boudreau appeared to be in pretty good spirits and was even in good enough of a mood to give Russo a preview of what the Minnesota Wild's line up might look like this season once it hits the ice. To be clear training camp as well as the offseason training of all these players could have a major impact on how the lines end up once we are ready for the start of the 2019 - 2020 NHL regular season, but Boudreau seemed pretty confident about the direction he was moving in.
Here's what Boudreau had to say about his line combinations for this upcoming season as per The Athletic(emphasis our own):
You know, I’ve been looking at a couple things that I put on the board. I guess before I answer that, I should make clear that a lot of it depends on how Mikko’s (Koivu) health is, how his leg is. In other words, are we going to have to start him slow or is he ready to go off the bat? So I’ll preface everything that a lot of this depends on Mikko and that these are things that are just going through my head in early August. Anything can change next month. But (Eric) Staal will start as the No. 1 center, and I’m looking at him with (Jason) Zucker and (Mats) Zuccarello. On the board, I really like the look and sound of Parise, Kunin and Fiala. And then, Mikko’s health will probably determine the other combinations. It’ll probably start with Mikko or (Joel Eriksson) Ek with (Ryan) Donato and (Jordan) Greenway and then (Marcus) Foligno with the other center (Ek or Mikko) and Hartman with J.T. Brown and Victor Rask pushing.
What do you think of Boudreau's vision for the future of the team? Would you keep things the same or would you prefer to shuffle the lines in a different manner moving forward?

domain: sports


text:
Secondhand. Good condition. Ex library copy with stickers, stamps and white-out on the inside cover. Some edgewear including a small tear to dust jacket. There is a small tear to the top of the inside cover.
This book provides a detailed account of the history of Upper Preston, from its settlement and administration, its early setters, industries and schools. The history of the local pubs including the famous Forrest Hotel are also discussed.

domain: history


text:
The COVID-19 pandemic may have affected production and sales but this hasn’t stopped Davao City-based chocolate manufacturer Malagos Chocolate from adding a few more feathers to its cap at the recently concluded Schokoladen Gourmet Festival in Hannover, Germany.
In the festival’s World Drinking Chocolate Competition, Malagos Chocolate won 4 golds for Plain/Origin Dark Drinking Chocolate (made with water), Growing Country, Chocolate Maker, and Direct Traded categories, and a bronze for Plain/Origin Dark Drinking Chocolate (made with milk) category.
The World Drinking Chocolate Competition celebrates the origins of chocolate as a drink and comes with a revival of high-quality drinking chocolate within the craft chocolate movement. The results were announced during the virtual holding of the festival last October 25, 2020.
“What makes our latest victory even sweeter is that our Unsweetened Chocolate is the base throughout our entire product line. It is our purest with only one ingredient, the fermented dried cacao bean. This is a validation of our never-ending quest for excellence in the field of cacao farming and chocolate-making,” said Rex Victor P. Puentespina of Malagos Chocolate/Malagos Agri-Ventures Corporation.
With their latest triumph, Puentespina said that their multi-awarded chocolate has gone full circle.
“Back in 2015, it was in this same category that we were able to claim our first international award, which placed the spotlight on Malagos and Philippine cacao,” he expounded.
Aside from receiving acclaims from different prestigious global chocolate experts, their cacao farm in Davao City’s Baguio District was also recognized as one of the producers of the Best 50 Beans in the World at the 2017 Cocoa Excellence Programme in France.
“We share and dedicate these international recognitions to the hardworking Filipino farmers. Truly grateful as well to those who continue to support and cheer us on during these tough times,” Puentespina said.
He also recognized all Filipino chocolate makers “who make great chocolates and help place the Philippines on the chocolate map of the world” while strengthening the country’s role as a major player in the global cacao industry.
In spite of the challenges of the times, Puentespina further said that they continue to improve their products especially their fermentation processes as they learned that it is in this level of chocolate making that heavily influences the flavor.
“Traditional sales methods may have slowed down but we’re thankful that we were able to ride the shift to digital and e-commerce early on,” he shared.
According to the chocolate maker, a number of people have become more enterprising during quarantine, creating a massive influx of new customers for the brand, particularly chefs and home bakers who have taken to social media to vend homemade products using Malagos Chocolate.
“These shifts have definitely become the new normal as people say, and we have no choice but to adapt to safer and more efficient ways of doing business the Malagos way,” said Puentespina.
The Schokoladen (German for chocolate) Gourmet Festival is an event that gathers the world’s finest chocolate manufacturers and chocolates and celebrates good and fine chocolates. The competition was organized by the International Chocolate Awards in partnership with the Schokoladen Gourmet Festival, powered by Germany-based Chocolats-de-luxe.de.


text:
If one lives in the western world, or lives on a western diet, one thing that’s just about be guaranteed is that one will have an issue with tooth decay.
But does it have to be this way, what if tooth decay was a result of the diet and the food and drink that one was consuming, would that begin to make one start looking differently at the way we look at tooth decay?
Cure for Tooth Decay? – Ramiel Nagel
For the more and more that one searches, it is a deficiency in the food we consume that is leading to the biggest cause of tooth decay, for the body is a self-healing organism, so if we are missing things in the food that we eat, it only stands to reason that the body won’t be able to repair itself.
Nutritional deficiencies Hidden In Your Teeth
How to treat cavities naturally and reverse tooth decay
And it doesn’t matter who explains it, the same 3 minerals and 4 vitamins are the common theme.
Minerals for building teeth strength
Fat Soluble Vitamins for building teeth strength
So if one is having tooth decay issues, like most other health problems, ones diet is always a good place to start

domain: health


text:
Servings: 6 Start to Finish 10 mins
- 1/2 cup walnut oil
- 1/4 cup apple cider vinegar
- 1 tablespoon molasses
- 1/2 teaspoon salt
- 1/4 teaspoon black pepper
- 1 bag (12 ounces) baby spinach, washed and dried
- 12 pitted dates, sliced
- 3 apples (about 1 pound), cored and thinly sliced (any combination such as Gala, Golden Delicious, McIntosh, Fuji)
- 1/2 cup walnuts, toasted and coarsely chopped
1. To make the salad dressing, whisk together walnut oil, vinegar, molasses, salt and pepper in small bowl until well blended.
2. Toss together spinach, dates, apples and 1/4 cup walnut-oil dressing in large salad bowl.
3. Serve salad immediately with the toasted walnuts sprinkled over top. Serve the remaining dressing alongside the salad.
Nutrition Facts Servings Per Recipe: 6; Amount Per Serving: cal. (kcal): 325, Fat, total (g): 24, chol. (mg): , sat. fat (g): 2, carb. (g): 29, fiber (g): 4, pro. (g): 3, sodium (mg): 241, Percent Daily Values are based on a 2,000 calorie diet.


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A popular Indian restaurant where illegal workers were paid with diners' leftover food has had its licence to operate revoked.
Council chiefs heard how desperate, fleeing illegal workers striped off their kitchen attire, hid in toilets and posed as customers during immigration raids at Akbar Dynasty, off the A66 at Sadberge.
The restaurant, launched in 2009 on the former Little Chef premises, had been repeatedly raided by immigration officers, Darlington Council's licensing committee heard.
In 2019, a man was found hiding in the toilets and another was discovered sitting in the restaurant area, pretending to be a customer, with red-stained hands and curry sauce on his clothes.
For that and another similar incident the following year, director Abdul Mannan Shabul Ali was fined £35,000, which he had yet to pay.
A Home Office immigration enforcement officer said the ability to work illegally, as Mr Ali had allowed to happen at the 50-cover restaurant rated by TripAdvisor as 15th best of Darlington's 190 eateries, is a key driver of illegal migration.
He said: "Continuing to employ people without making the legal required checks and not making improvements to prevent such allegations goes to demonstrate that the premises licence holder is not robust and does not take their responsibility towards the licensing objectives seriously."
The officer added: "It encourages people to take risks in trying to enter the UK illegally by putting their lives in the hands of unscrupulous people smugglers and leaves them vulnerable to exploitative employers."
Mr Ali, representing himself, claimed he was completely unaware of the circumstances surrounding the 2019 incident, despite having had responsibility for the restaurant.
He said he had only recently taken over the restaurant's running in 2020 when it was raided.
He claimed a worker had turned up for an interview on the day that officers raided the restaurant.
Mr Ali told the committee: "He didn't tell me at the time that he didn't have his work permit.
"He wasn't an immigrant, he had the legality to stay in this country. He was just waiting for his work permit permission, which was granted just two months later."
However, immigration officers said the worker in question had been "wearing a waiter's costume and attending a table when officers entered the premises".
When pressed over what he had done to check the worker's suitability for employment, Mr Ali claimed the illegal worker had showed an immigration identity card.
However, the immigration officers dismissed this, saying the card clearly stated the holder had no right to work.
Mr Ali, of Keighley, West Yorkshire, made no response when he was told his licence had been revoked.
Following the meeting, councillors said the ruling would send shockwaves around the region.
The committee's chairman, councillor Brian Jones said: "I think we have done the right thing in highlighting what has been going on.
"I would certainly hope it's a warning shot because clearly no longer are they just taking jobs from people in this country, they are taking jobs from legal immigrants that are entitled to be here and look for work.
"I understand the restaurant has been very popular. I'm sorry for the people who would be going there for a nice meal."


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3D printers touting high-quality "linear rails" have sprouted up all over the market. Find out if a linear rail 3D printer is legitimately better or just a marketing sham.
The Printrun Suite (Pronterface, Pronsole, and Printcore) has been around for a long time but is still a valuable go-to resource for creating great prints. Find out the basics of this useful tool, and how to get started with it.
Nylon (polyamide) is well-suited for 3D printing functional parts, with superior tensile strength compared to PLA. Find out more about 3D printing nylon.
The Anet A8 was the most popular 3D printer until fall 2018. Check out our Anet A8 review, the most important upgrades, and how it differs from the Anet A6. It has since been overtaken by the Creality Ender 3.
Want to create multicolor 3D prints? Check out this multicolor 3D printer guide to discover the full spectrum of 3D printing.
3D printed joints may seem intimidating, but they don't need to be hard. Learn how to 3D print joints with this simple guide!
Take control of your 3D printer's firmware and discover a world of possibilities. We show you how to set up Marlin, one of the most popular firmware options among 3D printing enthusiasts!
Converting SLDPRT to STL can be hard if you don't have the right tools. Here's a handy list of tools you can use to convert your files. Choose the one that works for you!
If you consider yourself a kitchen whizz, you can never have enough cool kitchen gadgets. Here are some cool 3D printed kitchen utensils.
How much does a 3D printer cost in 2020? Check out our overview to 3D printer price ranges, covering everything from beginner to industrial 3D printers.
Nipped, tucked, and upgraded for a little more money, the Elegoo Mars Pro outclasses the original Elegoo Mars in many ways. But should you upgrade? Read our review to find out.
The Anycubic Mega X is the largest printer in the Mega family, but is it the best? Read on for our full review.
The updated Creality CR-10 S5 offers gigantic build possibilities for a competitive price. Join us for our hands-on review.
The Anycubic Photon is our summer 2019 pick for the "Best Budget Resin 3D Printer". Check out our review to find out why it's a great choice if you want to spend $500 or less.
Check out our selection of the best CAM software for SolidWorks, AutoCAD, and other CAD software. Plus, how to choose the right program for your needs!
Among the most popular slicers, Simplify3D and Cura split opinions and hearts in the 3D printing community. Find out which is best for you!
Vanquish those layer lines and make your 3D printed part look more professional! Learn all about ABS vapor smoothing!

domain: hobby


text:
Lampbrush Chromosomes of Rana nigromaculata, R. brevipoda, R. plancyi chosenica, R. p. fukienensis and their Reciprocal Hybrids
KJ00000016952.pdf 4.67 MB
Landmarks and chiasmata of lampbrush chromosomes were observed in the oocytes of female Rana nigromaculata, (N) NN, R. brevipoda, (B) BB, R. plancyi chosenica, (C) CC, and R. p. fukienensis, (F) FF, and in those of 12 kinds of hybrids produced from these species and subspecies. The lampbrush chromosomes of the three species and one subspecies are not always parallel to their mitotic chromosomes in morphological characters. The lampbrush chromosomes of Rana plancyi chosenica are peculiar in extreme scarcity of landmarks and remarkably differ from the conspecific R. p. fukienensis at nearly the same degree as the other two species. (N) NN, (B) BB, (C) CC and (F) FF had all 13 bivalents in each of 50 oocytes and were 38.5,38.7,42.5 and 38.2,respectively, in the mean number of chiasmata of the 13 bivalents. When compared with the parental species and subspecies, all the 12 kinds of hybrids among them were fewer in the number of oocytes having 13 bivalents as well as in the mean number of chiasmata found in the 13 pairs of homologous chromosomes. These fewer numbers in bivalents and chiasmata are attributable to the differences between the lampbrush chromosomes of the two parental species or subspecies. On the other hand, the difference between reciprocal hybrids in the number of oocytes having 13 bivalents and the mean number of chiasmata in the 13 pairs of homologous chromosomes seems to be attributable to a difference in cytoplasm between the two parental species or subspecies.
Scientific report of the Laboratory for Amphibian Biology
Institute for Amphibian Biology, Hiroshima University

domain: literature


text:
Dare Viva Puffs Strawberry Cookies - 300g
Soft mallow cookies with a delectable chocolatey coating and bursting with tangy strawberry flavour in every bite!
Peanut free, Source of energy, Low in sodium, Flavoured with real fruit.
Baked in a peanut free facility, Contains wheat, soya and milk.
Chocolatey coating (sugar, hydrogenated palm kernel oil, cocoa, salt, sorbitan tristearate, soya lecithin, artificial flavour), corn syrup, wheat flour, sugar, vegetable oil shortening (contains modified palm oil and canola oil), apple puree, corn starch, salt, strawberry puree, whey powder, gelatin, glycerin, baking soda, baking powder, pectin, ammonium bicarbonate, citric acid, potassium sorbate, locust bean gum, natural and artificial flavour, sulphites, colour.


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this tutorial is in 2 separate posts, keep scrolling to get the rest.
last year i had so many compliments on my nicely wrapped gifts that i decided to do my first ever tutorial. how to wrap a pretty package.
start out by measuring out how much paper you need. i normally err on the side of caution and cut a LITTLE extra not too much extra though.
bring the other side around, pull it taut, but not too tight and fold the end of the wrapping paper under, this creates a nice clean edge.
use one piece of tape in the middle.
heres where it tends to get messy, nothing a little practice wont cure. trim off any excess paper from the ends, the paper should extend no further than the edge of the box or a little less.

domain: artistic


text:
I used to go to musicals every birthday - that was my birthday present. We'd go to London, me and my two brothers and mum and dad. I think I saw 'Mamma Mia' about five times.
|Born||April 5, 1989|
Lily James (Lily Chloe Ninette Thomson) is an English actress, best known for her role as Lady Rose MacClare in the period drama Downton Abbey. She began her professional acting career as Ethel Brown in the 2010 BBC production Just William.
She earned warm reviews in several London theatre productions and she began to appear in Hollywood films in 2012, with roles in 'Wrath of the Titans' and 'Fast Girls', and was seen in further television roles. She starred in the title role of the 2015 Disney film 'Cinderella'.