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Mutations in the coding sequence of SOX9 cause campomelic dysplasia (CD), a disorder of skeletal development associated with 46,XY disorders of sex development (DSDs). Translocations, deletions and duplications within a ~2 Mb region upstream of SOX9 can recapitulate the CD-DSD phenotype fully or partially, suggesting the existence of an unusually large cis-regulatory control region. Pierre Robin sequence (PRS) is a craniofacial disorder that is frequently an endophenotype of CD and a locus for isolated PRS at ~1.2-1.5 Mb upstream of SOX9 has been previously reported. The craniofacial regulatory potential within this locus, and within the greater genomic domain surrounding SOX9, remains poorly defined. We report two novel deletions upstream of SOX9 in families with PRS, allowing refinement of the regions harbouring candidate craniofacial regulatory elements. In parallel, ChIP-Seq for p300 binding sites in mouse craniofacial tissue led to the identification of several novel craniofacial enhancers at the SOX9 locus, which were validated in transgenic reporter mice and zebrafish. Notably, some of the functionally validated elements fall within the PRS deletions. These studies suggest that multiple non-coding elements contribute to the craniofacial regulation of SOX9 expression, and that their disruption results in PRS.
SOX9; craniofacial; enhancer; Pierre Robin; long-range regulation; campomelic dysplasia
The GNE gene encodes the rate-limiting, bifunctional enzyme of sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). Biallelic GNE mutations underlie GNE myopathy, an adult-onset progressive myopathy. GNE myopathy-associated GNE mutations are predominantly missense, resulting in reduced, but not absent, GNE enzyme activities. The exact pathomechanism of GNE myopathy remains unknown, but likely involves aberrant (muscle) sialylation. Here we summarize 154 reported and novel GNE variants associated with GNE myopathy, including 122 missense, 11 nonsense, 14 insertion/deletions and 7 intronic variants. All variants were deposited in the online GNE variation database (http://www.dmd.nl/nmdb2/home.php?select_db=GNE).
We report the predicted effects on protein function of all variants as well as the predicted effects on epimerase and/or kinase enzymatic activities of selected variants. By analyzing exome sequence databases, we identified three frequently occurring, unreported GNE missense variants/polymorphisms, important for future sequence interpretations. Based on allele frequencies, we estimate the world-wide prevalence of GNE myopathy to be ~ 4–21/1,000,000. This previously unrecognized high prevalence confirms suspicions that many patients may escape diagnosis. Awareness among physicians for GNE myopathy is essential for the identification of new patients, which is required for better understanding of the disorder’s pathomechanism and for the success of ongoing treatment trials.
distal myopathy with rimmed vacuoles (DMRV); GNE myopathy; hereditary inclusion body myopathy (HIBM); adult onset muscular dystrophy; N-acetylmannosamine (ManNAc); disease prevalence; sialic acid
Three causal genes for Idiopathic Basal Ganglia Calcification (IBGC) have been identified. Most recently, mutations in PDGFRB, encoding a member of the platelet-derived growth factor receptor family type β, and PDGFB, encoding PDGF-B, the specific ligand of PDGFRβ, were found implicating the PDGF-B/PDGFRβ pathway in abnormal brain calcification. In this study we aimed to identify and study mutations in PDGFRB and PDGFB in a series of 26 patients from the Mayo Clinic Florida Brain Bank with moderate to severe basal ganglia calcification (BCG) of unknown etiology. No mutations in PDGFB were found. However, we identified one mutation in PDGFRB, p.R695C located in the tyrosine kinase domain, in one BGC patient. We further studied the function of p.R695C mutant PDGFRβ and two previously reported mutants, p.L658P and p.R987W PDGFRβ in cell culture. We show that, in response to PDGF-BB stimulation, the p.L658P mutation completely suppresses PDGFRβ autophosphorylation whereas the p.R695C mutation results in partial loss of autophosphorylation. For the p.R987W mutation, our data suggest a different mechanism involving reduced protein levels. These genetic and functional studies provide the first insight into the pathogenic mechanisms associated with PDGFRB mutations and provide further support for a pathogenic role of PDGFRB mutations in BGC.
Basal Ganglia Calcification; BGC; IBGC; Fahr disease; PDGFRB; PDGFB
During the last years, next-generation sequencing (NGS) technologies have accelerated the detection of genetic variants resulting in the rapid discovery of new disease-associated genes. However, the wealth of variation data made available by NGS alone is not sufficient to understand the mechanisms underlying disease pathogenesis and manifestation. Multidisciplinary approaches combining sequence and clinical data with prior biological knowledge are needed to unravel the role of genetic variants in human health and disease. In this context, it is crucial that these data are linked, organized and made readily available through reliable online resources. The Swiss-Prot section of the Universal Protein Knowledgebase (UniProtKB/Swiss-Prot) provides the scientific community with a collection of information on protein functions, interactions, biological pathways, as well as human genetic diseases and variants, all manually reviewed by experts. In this article, we present an overview of the information content of UniProtKB/Swiss-Prot to show how this knowledgebase can support researchers in the elucidation of the mechanisms leading from a molecular defect to a disease phenotype.
UniProtKB/Swiss-Prot; database; manual curation; genetic variants; disease; functional annotation; controlled vocabulary
As whole genome sequencing (WGS) uncovers variants associated with rare and common diseases, an immediate challenge is to minimize false positive findings due to sequencing and variant calling errors. False positives can be reduced by combining results from orthogonal sequencing methods, but costly. Here we present variant filtering approaches using logistic regression (LR) and ensemble genotyping to minimize false positives without sacrificing sensitivity. We evaluated the methods using paired WGS datasets of an extended family prepared using two sequencing platforms and a validated set of variants in NA12878. Using LR or ensemble genotyping based filtering, false negative rates were significantly reduced by 1.1- to 17.8-fold at the same levels of false discovery rates (5.4% for heterozygous and 4.5% for homozygous SNVs; 30.0% for heterozygous and 18.7% for homozygous insertions; 25.2% for heterozygous and 16.6% for homozygous deletions) compared to the filtering based on genotype quality scores. Moreover, ensemble genotyping excluded > 98% (105,080 of 107,167) of false positives while retaining > 95% (897 of 937) of true positives in de novo mutation (DNM) discovery, and performed better than a consensus method using two sequencing platforms. Our proposed methods were effective in prioritizing phenotype-associated variants, and ensemble genotyping would be essential to minimize false positive DNM candidates.
whole-genome sequencing; ensemble genotyping; logistic regression; false positive; incidental finding; de novo mutation discovery
Genotyping efforts in hemophilia A (HA) populations in many countries have identified large numbers of unique mutations in the Factor VIII gene (F8). To assist HA researchers conducting genotyping analyses, we have developed a listing of F8 mutations including those listed in existing locus-specific databases as well as those identified in patient populations and reported in the literature. Each mutation was reviewed and uniquely identified using Human Genome Variation Society (HGVS) nomenclature standards for coding DNA and predicted protein changes as well as traditional nomenclature based on the mature, processed protein. Listings also include the associated hemophilia severity classified by International Society of Thrombosis and Haemostasis (ISTH) criteria, associations of the mutations with inhibitors, and reference information. The mutation list currently contains 2,537 unique mutations known to cause HA. HA severity caused by the mutation is available for 2,022 mutations (80%) and information on inhibitors is available for 1,816 mutations (72%). The CDC Hemophilia A Mutation Project (CHAMP) Mutation List is available at http://www.cdc.gov/hemophiliamutations for download and search and will be updated quarterly based on periodic literature reviews and submitted reports.
hemophilia A; mutation database; locus-specific database; F8 gene
Glycine substitutions in the conserved Gly-X-Y motif in the triple helical domain of collagen VI are the most commonly identified mutations in the collagen VI myopathies including Ullrich congenital muscular dystrophy, Bethlem myopathy, and intermediate phenotypes. We describe clinical and genetic characteristics of 97 individuals with glycine substitutions in the triple helical domain of COL6A1, COL6A2, or COL6A3 and add a review of 97 published cases, for a total of 194 cases. Clinical findings include severe, intermediate, and mild phenotypes even from patients with identical mutations. Intermediate phenotypes were most common, accounting for almost half of patients, emphasizing the importance of intermediate phenotypes to the overall phenotypic spectrum. Glycine substitutions in the triple helical domain are heavily clustered in a short segment N-terminal to the 17th Gly-X-Y triplet, where they are acting as dominants. The most severe cases are clustered in an even smaller region including Gly-X-Y triplets 10 to 15, accounting for only 5% of the triple helical domain. Our findings suggest that clustering of glycine substitutions in the N-terminal region of collagen VI is not based on features of the primary sequence. We hypothesize that this region may represent a functional domain within the triple helix.
collagen VI; Ullrich congenital muscular dystrophy; Bethlem myopathy; genotype-phenotype correlation
The discovery of novel disease-associated variations in genes is often a daunting task in highly heterogeneous disease classes. We seek a generalizable algorithm that integrates multiple publicly available genomic data sources in a machine-learning model for the prioritization of candidates identified in patients with retinal disease. To approach this problem, we generate a set of feature vectors from publicly available microarray, RNA-seq, and ChIP-seq datasets of biological relevance to retinal disease, to observe patterns in gene expression specificity among tissues of the body and the eye, in addition to photoreceptor-specific signals by the CRX transcription factor. Using these features, we describe a novel algorithm, positive and unlabeled learning for prioritization (PULP). This article compares several popular supervised learning techniques as the regression function for PULP. The results demonstrate a highly significant enrichment for previously characterized disease genes using a logistic regression method. Finally, a comparison of PULP with the popular gene prioritization tool ENDEAVOUR shows superior prioritization of retinal disease genes from previous studies.
machine learning; data integration; gene prioritization; prediction
The greatest interpretive challenge of modern medicine may be to functionally annotate the vast variation of human genomes. Demonstrating a proposed approach, we created a library of BRCA2 exon 27 shotgun-mutant plasmids including solitary and multiplex mutations to generate human knockin clones using homologous recombination. This 55-mutation, 13-clone syngeneic variance library (SyVaL) comprised severely affected clones having early-stop nonsense mutations, functionally hypomorphic clones having multiple missense mutations emphasizing the potential to identify and assess hypomorphic mutations in novel proteomic and epidemiologic studies, and neutral clones having multiple missense mutations. Efficient coverage of nonessential amino acids was provided by mutation multiplexing. Severe mutations were distinguished from hypomorphic or neutral changes by chemosensitivity assays (hypersensitivity to mitomycin C and acetaldehyde), by analysis of RAD51 focus formation, and by mitotic multipolarity. A multiplex unbiased approach of generating all-human SyVaLs in medically important genes, with random mutations in native genes, would provide databases of variants that could be functionally annotated without concerns arising from exogenous cDNA constructs or interspecies interactions, as a basis for subsequent proteomic domain mapping or clinical calibration if desired. Such gene-irrelevant approaches could be scaled up for multiple genes of clinical interest, providing distributable cellular libraries linked to public-shared functional databases.
BRCA2; shotgun library; hypomorphs; homologous recombination
Facioscapulohumeral dystrophy (FSHD) is one of the most prevalent muscular dystrophies. The majority of FSHD cases are linked to a decreased copy number of D4Z4 macrosatellite repeats on chromosome 4q (FSHD1). Less than 5% of FSHD cases have no repeat contraction (FSHD2), most of which are associated with mutations of SMCHD1. FSHD is associated with the transcriptional derepression of DUX4 encoded within the D4Z4 repeat, and SMCHD1 contributes to its regulation. We previously found that the loss of heterochromatin mark (i.e., histone H3 lysine 9 trimethylation (H3K9me3)) at D4Z4 is a hallmark of both FSHD1 and FSHD2. However, whether this loss contributes to DUX4 expression was unknown. Furthermore, additional D4Z4 homologs exist on multiple chromosomes, but they are largely uncharacterized and their relationship to 4q/10q D4Z4 was undetermined. We found that the suppression of H3K9me3 results in displacement of SMCHD1 at D4Z4 and increases DUX4 expression in myoblasts. The DUX4 open reading frame (ORF) is disrupted in D4Z4 homologs and their heterochromatin is unchanged in FSHD. The results indicate the significance of D4Z4 heterochromatin in DUX4 gene regulation and reveal the genetic and epigenetic distinction between 4q/10q D4Z4 and the non-4q/10q homologs, highlighting the special role of the 4q/10q D4Z4 chromatin and the DUX4 ORF in FSHD.
FSHD1; FSHD2; DUX4; H3K9me3; SMCHD1; D4Z4; heterochromatin
Primary ciliary dyskinesia (PCD) is an autosomal-recessive disorder characterized by impaired ciliary function that leads to subsequent clinical phenotypes such as chronic sinopulmonary disease. PCD is also a genetically heterogeneous disorder with many single gene mutations leading to similar clinical phenotypes. Here, we present a novel PCD causal gene, coiled-coil domain containing 151 (CCDC151), which has been shown to be essential in motile cilia of many animals and other vertebrates but its effects in humans was not observed until currently. We observed a novel nonsense mutation in a homozygous state in the CCDC151 gene (NM_145045.4:c.925G>T:p.[E309*]) in a clinically diagnosed PCD patient from a consanguineous family of Arabic ancestry. The variant was absent in 238 randomly selected individuals indicating that the variant is rare and likely not to be a founder mutation. Our finding also shows that given prior knowledge from model organisms, even a single whole-exome sequence can be sufficient to discover a novel causal gene.
primary ciliary dyskinesia; CCDC151; respiratory cilia; ciliopathy
Severe congenital neutropenia (SCN) is a rare hematopoietic disorder, with estimated incidence of 1 in 200,000 individuals of European descent, many cases of which are inherited in an autosomal dominant pattern. Despite the fact that several causal genes have been identified, the genetic basis for >30% of cases remains unknown. We report a five generation family segregating a novel single nucleotide variant (SNV) in TCIRG1. There is perfect co-segregation of the SNV with congenital neutropenia in this family; all 11 affected, but none of the unaffected, individuals carry this novel SNV. Western blot analysis show reduced levels of TCIRG1 protein in affected individuals, compared to healthy controls. Two unrelated patients with SCN, identified by independent investigators, are heterozygous for different, rare, highly conserved, coding variants in TCIRG1.
TCIRG1; Congenital neutropenia; SCN; V-ATPase
Laing early onset distal myopathy and myosin storage myopathy are caused by mutations of slow skeletal/β-cardiac myosin heavy chain encoded by the gene MYH7, as is a common form of familial hypertrophic/dilated cardiomyopathy. The mechanisms by which different phenotypes are produced by mutations in MYH7, even in the same region of the gene, are not known. To explore the clinical spectrum and pathobiology we screened the MYH7 gene in 88 patients from 21 previously unpublished families presenting with distal or generalised skeletal muscle weakness, with or without cardiac involvement. Twelve novel mutations have been identified in thirteen families. In one of these families the grandfather of the proband was found to be a mosaic for the MYH7 mutation. In eight cases de novo mutation appeared to have occurred, which was proven in three. The presenting complaint was footdrop, sometimes leading to delayed walking or tripping, in members of 17 families (81%), with other presentations including cardiomyopathy in infancy, generalised floppiness and scoliosis. Cardiac involvement as well as skeletal muscle weakness was identified in 9 of 21 families. Spinal involvement such as scoliosis or rigidity was identified in 12 (57%). This report widens the clinical and pathological phenotypes, and the genetics of MYH7 mutations leading to skeletal muscle diseases.
MYH7; Laing distal myopathy; MPD1
Mutations affecting skeletal muscle isoforms of the tropomyosin genes may cause nemaline myopathy, cap myopathy, core-rod myopathy, congenital fiber-type disproportion, distal arthrogryposes, and Escobar syndrome. We correlate the clinical picture of these diseases with novel (19) and previously reported (31) mutations of the TPM2 and TPM3 genes. Included are altogether 93 families: 53 with TPM2 mutations and 40 with TPM3 mutations. Thirty distinct pathogenic variants of TPM2 and 20 of TPM3 have been published or listed in the Leiden Open Variant Database (http://www.dmd.nl/). Most are heterozygous changes associated with autosomal-dominant disease. Patients with TPM2 mutations tended to present with milder symptoms than those with TPM3 mutations, DA being present only in the TPM2 group. Previous studies have shown that five of the mutations in TPM2 and one in TPM3 cause increased Ca2+ sensitivity resulting in a hypercontractile molecular phenotype. Patients with hypercontractile phenotype more often had contractures of the limb joints (18/19) and jaw (6/19) than those with nonhypercontractile ones (2/22 and 1/22), whereas patients with the non-hypercontractile molecular phenotype more often (19/22) had axial contractures than the hypercontractile group (7/19). Our in silico predictions show that most mutations affect tropomyosin–actin association or tropomyosin head-to-tail binding.
congenital myopathy; genotype–phenotype correlation; TPM2; TPM3; actin; hypercontractile phenotype
Central serous chorioretinopathy (CSC) is characterized by leakage of fluid from the choroid into the subretinal space and, consequently, loss of central vision. The disease is triggered by endogenous and exogenous corticosteroid imbalance and psychosocial stress and is much more prevalent in men. We studied the association of genetic variation in 44 genes from stress response and corticosteroid metabolism pathways with the CSC phenotype in two independent cohorts of 400 CSC cases and 1,400 matched controls. The expression of cadherin 5 (CDH5), the major cell–cell adhesion molecule in vascular endothelium, was downregulated by corticosteroids which may increase permeability of choroidal vasculature, leading to fluid leakage under the retina. We found a significant association of four common CDH5 SNPs with CSC in male patients in both cohorts. Two common intronic variants, rs7499886:A>G and rs1073584:C>T, exhibit strongly significant associations with CSC; P = 0.00012; odds ratio (OR) = 1.5; 95%CI [1.2;1.8], and P = 0.0014; OR = 0.70; 95%CI [0.57;0.87], respectively. A common haplotype was present in 25.4% male CSC cases and in 35.8% controls (P = 0.0002; OR = 0.61, 95% CI [0.47–0.79]). We propose that genetically predetermined variation in CDH5, when combined with triggering events such as corticosteroid treatment or severe hormonal imbalance, underlie a substantial proportion of CSC in the male population.
CDH5; Cadherin 5; central serous chorioretinopathy; genetic association; retinal disease
Hereditary hearing loss (HHL) is extremely heterogeneous. Over 70 genes have been identified to date, and with the advent of massively parallel sequencing, the pace of novel gene discovery has accelerated. In a family segregating progressive autosomal dominant non-syndromic hearing loss (ADNSHL) we used OtoSCOPE® to exclude mutations in known deafness genes and then performed segregation mapping and whole exome sequencing (WES) to identify a unique variant, p.Ser178Leu, in TBC1D24 that segregates with the hearing loss phenotype. TBC1D24 encodes a GTPase-activating protein expressed in the cochlea. Ser178 is highly conserved across vertebrates and its change is predicted to be damaging. Other variants in TBC1D24 have been associated with a panoply of clinical symptoms including autosomal recessive NSHL (ARNSHL), syndromic hearing impairment associated with onychodystrophy, osteodystrophy, mental retardation and seizures (DOORS syndrome), and a wide range of epileptic disorders.
TBC1D24, autosomal dominant; non-syndromic; hearing loss; hearing impairment; pleiotropy; OtoSCOPE ®
ATP-sensitive potassium (KATP) channels, composed of inward-rectifying potassium channel subunits (Kir6.1 and Kir6.2, encoded by KCNJ8 and KCNJ11, respectively) and regulatory sulfonylurea receptor (SUR1 and SUR2, encoded by ABCC8 and ABCC9, respectively), couple metabolism to excitability in multiple tissues. Mutations in ABCC9 cause Cantú syndrome, a distinct multi-organ disease, potentially via enhanced KATP channel activity. We screened KCNJ8 in an ABCC9 mutation-negative patient who also exhibited clinical hallmarks of Cantú syndrome (hypertrichosis, macrosomia, macrocephaly, coarse facial appearance, cardiomegaly, and skeletal abnormalities). We identified a de novo missense mutation encoding Kir6.1[p.Cys176Ser] in the patient. Kir6.1[p.Cys176Ser] channels exhibited markedly higher activity than wild-type channels, as a result of reduced ATP sensitivity, whether co-expressed with SUR1 or SUR2A subunits. Our results identify a novel causal gene in Cantú syndrome, but also demonstrate that the cardinal features of the disease result from gain of KATP channel function, not from Kir6-independent SUR2 function.
KCNJ8; Kir6.1; Cantú syndrome; KATP; hypertrichosis
Diamond-Blackfan Anemia (DBA) is characterized by a defect of erythroid progenitors and, clinically, by anemia and malformations. DBA exhibits an autosomal dominant pattern of inheritance with incomplete penetrance. Currently nine genes, all encoding ribosomal proteins (RP), have been found mutated in approximately 50% of patients. Experimental evidence supports the hypothesis that DBA is primarily the result of defective ribosome synthesis. By means of a large collaboration among six centers, we report here a mutation update that includes nine genes and 220 distinct mutations, 56 of which are new. The DBA Mutation Database now includes data from 355 patients. Of those where inheritance has been examined, 125 patients carry a de novo mutation and 72 an inherited mutation. Mutagenesis may be ascribed to slippage in 65.5% of indels, whereas CpG dinucleotides are involved in 23% of transitions. Using bioinformatic tools we show that gene conversion mechanism is not common in RP genes mutagenesis, notwithstanding the abundance of RP pseudogenes. Genotype–phenotype analysis reveals that malformations are more frequently associated with mutations in RPL5 and RPL11 than in the other genes. All currently reported DBA mutations together with their functional and clinical data are included in the DBA Mutation Database.
Diamond-Blackfan anemia; ribosomal protein; erythropoiesis; ribosome biogenesis
A high density comparative genomic hybridization array was designed to evaluate CNVs in the genomic region of six familial PD genes in 181 PD cases and 67 controls. No CNV was found in PARK7, ATP13A2, PINK1, and LRRK2. Intronic-only CNVs were found in SNCA and PARK2 but were not associated with PD risk. A whole-gene duplication of SNCA was found in one case. The allele frequency of PARK2 exonic CNV is significantly higher in cases than in controls (P = 0.02), higher in early-onset (AAO ≤ 40) than in late-onset cases (P = 0.001), and higher in familial than in sporadic cases (P = 0.005). Except for single exon 2 duplications, all PARK2 exonic CNVs have different breakpoints, even when the same exon(s) were involved. In conclusion, except for SNCA and PARK2, CNVs are not a major contributing mechanism for the familial PD genes examined. The majority of PARK2 exonic CNVs are not recurrent.
CNV; CGH; Parkinson; PARK2
Tumor-derived cell lines play an important role in the investigation of tumor biology and genetics. Across a wide array of studies, they have been tools of choice for the discovery of important genes involved in cancer and for the analysis of the cellular pathways that are impaired by diverse oncogenic events. They are also invaluable for screening novel anticancer drugs. The TP53 protein is a major component of multiple pathways that regulate cellular response to various types of stress. Therefore, TP53 status affects the phenotype of tumor cell lines profoundly and must be carefully ascertained for any experimental project. In the present review, we use the 2014 release of the UMD TP53 database to show that TP53 status is still controversial for numerous cell lines, including some widely used lines from the NCI-60 panel. Our analysis clearly confirms that, despite numerous warnings, the misidentification of cell lines is still present as a silent and neglected issue, and that extreme care must be taken when determining the status of p53, because errors may lead to disastrous experimental interpretations. A novel compendium gathering the TP53 status of 2,500 cell lines has been made available (http://p53.fr). A stand-alone application can be used to browse the database and extract pertinent information on cell lines and associated TP53 mutations. It will be updated regularly to minimize any scientific issues associated with the use of misidentified cell lines (http://p53.fr).
TP53; cancer cell line; cross-contamination; misidentification; recommendation
The wild-type human p53 (TP53) tumor suppressor can be posttranslationally modified at over 60 of its 393 residues. These modifications contribute to changes in TP53 stability and in its activity as a transcription factor in response to a wide variety of intrinsic and extrinsic stresses in part through regulation of protein-protein and protein-DNA interactions. The TP53 gene frequently is mutated in cancers, and in contrast to most other tumor suppressors the mutations are mostly missense often resulting in the accumulation of mutant protein, which may have novel or altered functions. Most mutant TP53s can be posttranslationally modified at the same residues as in wild-type TP53. Strikingly, however, codons for modified residues are rarely mutated in human tumors, suggesting that TP53 modifications are not essential for tumor suppression activity. Nevertheless, these modifications might alter mutant TP53 activity and contribute to a gain-of-function leading to increased metastasis and tumor progression. Furthermore, many of the signal transduction pathways that result in TP53 modifications are altered or disrupted in cancers. Understanding the signaling pathways that result in TP53 modification and the functions of these modifications in both wild-type TP53 and its many mutant forms may contribute to more effective cancer therapies.
TP53; p53; phosphorylation; acetylation; methylation; ubiquitylation; transcription
Methylmalonyl-CoA mutase (MUT) is an essential enzyme in propionate catabolism that requires adenosylcobalamin as a cofactor. Almost 250 inherited mutations in the MUT gene are known to cause the devastating disorder methylmalonic aciduria; however, the mechanism of dysfunction of these mutations, more than half of which are missense changes, has not been thoroughly investigated. Here, we examined 23 patient missense mutations covering a spectrum of exonic/structural regions, clinical phenotypes, and ethnic populations in order to determine their influence on protein stability, using two recombinant expression systems and a thermostability assay, and enzymatic function by measuring MUT activity and affinity for its cofactor and substrate. Our data stratify MUT missense mutations into categories of biochemical defects, including (1) reduced protein level due to misfolding, (2) increased thermolability, (3) impaired enzyme activity, and (4) reduced cofactor response in substrate turnover. We further demonstrate the stabilization of wild-type and thermolabile mutants by chemical chaperones in vitro and in bacterial cells. This in-depth mutation study illustrates the tools available for MUT enzyme characterization, guides future categorization of further missense mutations, and supports the development of alternative, chaperone-based therapy for patients not responding to current treatment.
methylmalonic aciduria; methylmalonyl-CoA mutase; MUT; cobalamin; thermolability
Next generation sequencing (NGS) technologies have been rapidly applied in biomedical and biological research since its advent only a few years ago, and they are expected to advance at an unprecedented pace in the following years. To provide the research community with a comprehensive NGS resource, we have developed the database Next Generation Sequencing Catalog (NGS Catalog, http://bioinfo.mc.vanderbilt.edu/NGS/index.html), a continually updated database that collects, curates and manages available human NGS data obtained from published literature. NGS Catalog deposits publication information of NGS studies and their mutation characteristics (SNVs, small insertions/deletions, copy number variations, and structural variants), as well as mutated genes and gene fusions detected by NGS. Other functions include user data upload, NGS general analysis pipelines, and NGS software. NGS Catalog is particularly useful for investigators who are new to NGS but would like to take advantage of these powerful technologies for their own research. Finally, based on the data deposited in NGS Catalog, we summarized features and findings from whole exome sequencing, whole genome sequencing, and transcriptome sequencing studies for human diseases or traits.
next generation sequencing (NGS); exome sequencing; whole genome sequencing; RNA sequencing; disease genome; gene fusion; database
Assessment of the functional consequences of variants near splice sites is a major challenge in the diagnostic laboratory. To address this issue, we created expression minigenes (EMGs) to determine the RNA and protein products generated by splice site variants (n = 10) implicated in cystic fibrosis (CF). Experimental results were compared with the splicing predictions of eight in silico tools. EMGs containing the full-length Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) coding sequence and flanking intron sequences generated wild-type transcript and fully processed protein in Human Embryonic Kidney (HEK293) and CF bronchial epithelial (CFBE41o-) cells. Quantification of variant induced aberrant mRNA isoforms was concordant using fragment analysis and pyrosequencing. The splicing patterns of c.1585−1G>A and c.2657+5G>A were comparable to those reported in primary cells from individuals bearing these variants. Bioinformatics predictions were consistent with experimental results for 9/10 variants (MES), 8/10 variants (NNSplice), and 7/10 variants (SSAT and Sroogle). Programs that estimate the consequences of mis-splicing predicted 11/16 (HSF and ASSEDA) and 10/16 (Fsplice and SplicePort) experimentally observed mRNA isoforms. EMGs provide a robust experimental approach for clinical interpretation of splice site variants and refinement of in silico tools.
expression minigene; splicing; CFTR; in silico tools
Whole genome sequencing (WGS) studies are uncovering disease-associated variants in both rare and non-rare diseases. Utilizing the next-generation sequencing for WGS requires a series of computational methods for alignment, variant detection, and annotation, and the accuracy and reproducibility of annotation results are essential for clinical implementation. However, annotating WGS with up to date genomic information is still challenging for biomedical researchers. Here we present one of the fastest and highly scalable annotation, filtering, and analysis pipeline –gNOME – to prioritize phenotype-associated variants while minimizing false positive findings. Intuitive graphical user interface of gNOME facilitates the selection of phenotype associated variants, and the result summaries are provided at variant-, gene-, and genome-levels. Moreover, the enrichment results of specific variants, genes, and gene sets between two groups or compared to population scale WGS datasets that is already integrated in the pipeline can help the interpretation. We found a small number of discordant results between annotation software tools in part due to different reporting strategies for the variants with complex impacts. Using two published whole exome datasets of uveal melanoma and bladder cancer, we demonstrated gNOME's accuracy of variant annotation and the enrichment of loss of function variants in known cancer pathways. gNOME web-server and source codes are freely available to the academic community.
whole genome sequences; variant annotation; disease gene discovery; analysis pipeline

domain: medical


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MT. PLEASANT, SC (WCSC) - A Southern-style emporium featuring cooking classes, a specialty grocery store, a restaurant, and more is now open for business in Mt. Pleasant.
Southern Season, located at 730 Coleman Boulevard, is holding a grand opening celebration September 5-22. The festivities will include live music, cooking demos, tastings, and a Southern Happy Hour beginning at 4 p.m.
The 44,000-square-foot storefront will offer an assortment of local and international gourmet foods. Southern Season's cheese section boast over 380 varieties, while its wine and beer section will be packed with over 3,000 wines from around the world more than 300 craft beers.
After checking out Southern Season's specialty grocery store and kitchen and housewares section, patrons can make their way over to the attached Southerly Restaurant, which features an open-air patio and bar.
This is Southern Season's second location, with a storefront currently open in Chapel Hill, North Carolina.
The store will be open Monday through Saturday from 7 a.m. to 9 p.m., and on Sundays from 9 a.m. to 7 p.m.

domain: food


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If you feel fear, anxiety, or discomfort when confronted with the task of speaking in front of an audience, you are not alone national polls consistently show that public speaking is among americans' top fears (bodie, 2010. Manage public speaking anxiety using self-hypnosis - an efficient, effective way to swap fear for confidence. Glossophobia, or the fear of public speaking, is surprisingly common it can also be extremely life-limiting, but it can also be treated with therapy. The abcs of giving presentations without palpitations strategies for overcoming fear of public speaking. Fear of public speaking is the #1 fear in america powerful coaching techniques can and have produced near to full recovery and help you manage the anxiety. Upon mingling, i learned that many of the people in the room were hoping to conquer their fear of public speaking, either for personal or professional reasons.
5 steps on how to reduce public speaking anxiety. Public speaking (also called oratory or oration) is the process or act of performing a speech to a live audience this type of speech is deliberately structured with three general purposes: to inform, to persuade and to entertain. How many of us fear public speaking more than death: four out of five, nine out of ten, 99 out of 100 we've all heard a variety of statistics, all of them suggesting the formidability perceived or real of the task of getting up and talking in front of other people but perhaps you'll get an. Public speaking without fear you can reduce your fear of public speaking to almost nothing in five or less one hour sessions with the lefkoe method. Celebrities with anxiety: harrison ford: fear of public speaking the fear of public speaking is a specific phobia many people with specific phobias will try to avoid any situation that may cause anxiety or panic.
The average person ranks the fear of public speaking above death is this you follow these steps to crush your fears and get your point across. A fear of public speaking is considered the number one fear among societies population it is also considered to be a social anxiety disorder where individuals suffer from performance anxiety the medical term referring to the fear of public speaking is called glossophobia the following. Social anxiety public speaking tips for social anxiety sufferers, because combining public speaking with social anxiety can trigger overwhelming stress. Better public speaking becoming a confident this is why public speaking causes so much anxiety and concern the good news is that, with thorough preparation and practice, you can overcome your nervousness and perform exceptionally well. Tired of nerves tripping you up when you speak in front of an audience this writer overcame her fear and so can you. People most likely to suffer from speaking anxiety are those who care most about their careers the reason is that overachievers are highly aware of the importance of presentation skills in climbing the corporate ladder and becoming successful.
How can i overcome my fear of public speaking answers from craig n sawchuk, phd, lp fear of public speaking is a common form of anxiety it can range from slight nervousness to paralyzing fear and panic many people with this fear avoid public speaking situations altogether, or they suffer.
News about public speaking commentary and archival information about public speaking from the new york times. A few days before i have to talk in front a lot of people, i get this queasy feeling in my stomach that won't go away i don't want to eat i just want to cancel so i don't have to deal with the stress my hands get sweaty before i get on stage i feel like i want to run away and then i. The most evidence based clinical success for social anxiety since 1978 treatment available worldwide. Overcoming fear: the ultimate cure guide for how to overcome fear forever ((anxiety, worry, fear of failure, fear of death, fear of flying, public speaking.

domain: health


An add-on component of a Thule rack system, the Short Roofline Adapter allows you to increase the bar spread on 2-door vehicles with short rooflines.
- Ensures correct weight distribution for increased carrying capacity
- Thule One-Key System lock cylinder (not included) compatible
- Thule Car Fit Guide
|Country of Origin||Imported|


Piano Lessons Book 1 Hal Leonard Student Piano Library 2021
Luckily, thanks to the modern technology of today’s technical world, it no more requires to be similar to this. If you plan on teaching on your own to play the piano in the future, the best online piano instruction offers a lot more palatable and also cost effective choices for all budgets. As well as these programs instruct you how to discover piano online the method it was suggested to be discovered – online. That implies no more struggling through lessons that are difficult to comprehend, or struggling to stay on top of the fast lane of a class room environment. You can discover piano on-line exactly like you would certainly in an actual class setting. Piano Lessons Book 1 Hal Leonard Student Piano Library
For many people that pick to learn to play piano online, their very first issue is keeping their focus when they are practicing. Exercising is an essential part of finding out to play piano. While sheet music can be delightful to study and also play, it does not hold any weight in the affordable globe of playing sheet music for a living. Piano Lessons Book 1 Hal Leonard Student Piano Library
Piano Lessons Book 1 Hal Leonard Student Piano Library
The quickest method to maintain your concentration when examining is to discover to play piano using sheet music. Sheet music is merely strings of notes that are created on paper. When you are finding out piano, you will discover that there are generally a selection of songs that can be played. These songs will certainly be utilized in order to educate you the numerous designs of playing that prevail among specialists. Piano Lessons Book 1 Hal Leonard Student Piano Library
In many cases, you will certainly use the sheet music as an overview while you exercise what you have actually just checked out. This coincides kind of technique that is made use of when learning to play any type of instrument. You need to know just how an instrument is made so that you can determine the various components that make it up. In this instance, you will be making use of the piano to play a tune in a style comparable to music designs. Piano Lessons Book 1 Hal Leonard Student Piano Library
There are many individuals that take piano lessons since they want to discover to play. These are generally individuals that are more curious about playing than analysis. These kinds of people usually start off taking novice lessons because they can obtain really interesting tunes with a piano. However, many people tend to learn better when they begin with innovative lessons. Piano lessons for novices include numerous things that are similar to other types of lessons.
If you are trying to find the fastest and also finest way to discover piano, you must think about taking lessons from a tutor. Some individuals are not comfortable with this concept. As mentioned above, it is not constantly easy to get along with someone that you do not know very well. This is especially true if the lessons are done on the phone. Consequently, lots of people prefer to take private lessons. Whether you choose to hire a person to educate you is totally your option.
For people that are not thinking about spending all their downtime at a piano, there are several options available for them as well. There are online tutorials that you can locate and also utilize. Much of these on the internet tutorials are more affordable than having a tutor to find to your house. Along with being more affordable, many of these online tutorials have high quality graphics and music that can really aid you out. You can also discover video tutorials that will permit you to see just how playing piano jobs, in addition to seeing the secrets as well as whatever related to playing.
One type of tutorial that many individuals favor is ones that reveal you the fundamentals of playing a piano. These tutorials will generally give you the secrets and how to use them. They might likewise reveal you exactly how to review the musical notation, just how to read musical arrangements and so forth. When you discover the piano, it is very important that you comprehend all the different kinds of points that you need to recognize in order to play piano.


One of only three built and the only example finished in black, this 2007 Shelby Series II prototype CSX5505 was actually built in 2005 and made its public debut at the August 2006 Concorso Italiano in Monterey, California. Clear away the debate that swirled around the Shelby Series 1 and one is left with the simple truth that it was a terrific “sports car” with ample power and superb handling. The first-and-only car designed, developed and produced by Shelby American, its sophisticated extruded-aluminum and honeycomb chassis and competition-proven double-wishbone suspension were highly advanced for a contemporary road car, featuring pushrod-actuated rocker arms working on inboard remote-reservoir coilover shock absorbers. Oldsmobile’s excellent Aurora 4.0L V-8 was packaged behind the front axle line and mated to a ZF 6-speed transaxle through a carbon-fiber driveshaft. To maximize the advantage of its almost perfect 49/51 front-to-rear weight distribution, the Series I combined quick-ratio power rack-and-pinion steering with Goodyear Eagle F1 tires and 4-wheel power disc brakes. The first American production car to feature carbon-fiber and fiberglass-laminate body panels, the Series I offered a leather interior with power seats embroidered with Carroll Shelby’s signature, power windows and locks, air conditioning and a factory sound system. After Series I production ended in 2005, new investors approached Shelby with a plan to produce a Series II incorporating styling and performance refinements. Deposits were taken for all 50 cars slated for production, but new DOT safety and emissions standards increased costs to the breaking point. Only three prototypes were completed: two finished in blue, and this one in black with silver Lemans stripes. Driven just 22 test miles and powered by a supercharged 4.0L 550 HP Oldsmobile Aurora V-8 engine backed by a 6-speed transmission, it is a unique example of the Shelby that never came to be.


text:
The Cell DoctrineIts History And Present State
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MilSuite provides a collection of social business tools for Department of Defense (DoD) personnel that facilitates professional networking, learning, and innovation through knowledge sharing and collaboration.
The CELL THEORY, or cell doctrine, states that all organisms are composed of similar units of organization, called cells. The concept was formally articulated in by Schleiden & Schwann and has remained as the foundation of modern biology.
The idea predates other great paradigms of biology including Darwin's theory of evolution (), Mendel's laws of inheritance (), and the. Excerpt from The Cell Doctrine: Its History and Present State, for the Use of Students in Medicine and Dentistry, Also, a Copious Bibliography of the Subject Fig.
Formation of Pus from subcutaneous connective tissue. From Virchow. Fig. Formation of Pus from interstitial connective tissue of mus cle.
Details The Cell Doctrine PDF
From Virchow. Fig. Author: James Tyson. Cell is a five-star read all the way up to the halfway mark. You got crazies running around, nom nom nomming on tender bits, and a likable crew of misfits trying to stay alive. Underneath it all, King is stoking the fires of 9/11, trying to keep the fear alive a full five years after the towers fell in a half-ass attempt to scare you with real /5.
The cell doctrine: its history and present state. For the use of students in medicine and dentistry. Also, a copious bibliography of the subject.
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Table of Contents. Cover Illustration Text Text Text Text Text Text Text Illustration Title Page Text Text Text Text Text Text Text Text Text Text Text Text Text Text Text Text Text Text Text Text.
The neuron doctrine is the concept that the nervous system is made up of discrete individual cells, a discovery due to decisive neuro-anatomical work of Santiago Ramón y Cajal and later presented by, among others, H.
Waldeyer-Hartz. The term neuron (spelled neurone in British English) was itself coined by Waldeyer as a way of identifying the cells in question. Title. The cell doctrine: its history and present state.
Tyson, James, Type. Book Material. Published material. The Cell Doctrine [James Tyson] on *FREE* shipping on qualifying offers. This work has been selected by scholars as being culturally important, and is part of the knowledge base of civilization as we know it. This work was reproduced from the original artifact.
Cell Theory is one of the basic principles of for the formulation of this theory is given to German scientists Theodor Schwann (–), Matthias Schleiden (–), and Rudolph Virchow (–).Author: Regina Bailey.
The Reisch-Brunschwig diagram of medieval cell doctrine was one of the most frequently copied throughout this period; this one is from a book printed in In these, fantasy and imagination are in the first cell right behind the common sensory input, to which three senses by: 5.
"The Birth of the Cell is a thorough, scholarly, and informative book on the development and establishment of the theory of cellular structure in plants and animals. It covers the 17th, 18th, and 19th centuries and parallels the development of the light microscope and techniques of preparing biologic tissues for microscopical examination.
The cell theory, or cell doctrine, states that all organisms are composed of similar units of organization, called cells. The concept was formally The idea predates other great paradigms of biology including Darwin's theory of evolution (), Mendel's laws of inheritance (), and the establishment of comparative biochemistry ().Author: Dan Rhoads.
The chapter elaborates on the medieval cell doctrine (MCD). In 11th century, MCD became the standard in medical practice. Besides furnishing the standard model of brain function, MCD became a Author: Harry Whitaker.
Joint Doctrine Hierarchy Chart, March The current status of Joint Publications presented in a hierarchical format. New Joint Staff Insights and Best Practices Focus Papers for Mission Command, CCIRs, Chief of Staff Roles at Joint HQ, JTF C2 and Organization, Command Senior Enlisted Leader, and Sustainment.
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Description The Cell Doctrine EPUB
Get this from a library. The cell doctrine: its history and present state. For the use of students in medicine and dentistry.
Also, a copious bibliography of the subject. [James Tyson; Milwaukee Academy of Medicine. ǂb Book Collection ǂ5 WMMCW.]. A Tactical Approach to Consolidating Gains in a Post-Caliphate Iraq, The author discusses efforts to adjust support in Iraq to ensure the Islamic State does not gain an opportunity for a new foothold in the region.
The new operational approach focuses primarily on the utility and effects of using an integrated target cell to work with and support Iraqi Security Forces. Robert Turner, Daniel De Haan, in Progress in Brain Research, The Neuron Doctrine of Cajal.
The neuron doctrine is the universally accepted concept that the nervous system is made up of discrete individual cells, the neurons, supported by astrocytes and by other glial cells. This discovery was due to the brilliant neuroanatomical work of Santiago Ramón y Cajal (Finger, ).
Free 2-day shipping. Buy The Cell Doctrine: Its History and Present State at nd: James L Tyson. That's generally why I liked The Birth of the Cell so much when I read it.
Dissatisfied by the standard accounts of the origin of the cell doctrine, Henry Harris read the original writings of the relevant early cytologists from the first visualization of animalcules to the identification of the cell nucleus and binary : Dan Rhoads.
Church Growth Through Cell Groups: A Consideration of Four Books on Cell Church Methodology Print/Download: PDF DOC The following is an adaptation of a work concerning the church growth movement that was written to a specific audience in January of List the basic tenets of the cell doctrine.
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This theory of 'free cell formation' was reminiscent of the old 'spontaneous generation' doctrine (although as an intracellular variant), but was refuted Cited by: This book works towards identifying the gaps between international ambitions, present doctrine, principles, operational procedures and actual practice, reappraises the doctrinal deficit and presents options for a UN doctrine for future missions.
COVID Resources. Reliable information about the coronavirus (COVID) is available from the World Health Organization (current situation, international travel).Numerous and frequently-updated resource results are available from this ’s WebJunction has pulled together information and resources to assist library staff as they consider how to handle coronavirus.
Cell doctrine is the foundational paradigm of Euro-American medicine and biology. Even without stepping outside that tradition, one may imagine alternate models of the body such as a fluid model Author: Neil David Theise.
In powerful, accessible language the book showcases a wide array of emerging adult stem cell breakthroughs, including their ability to repair damaged hearts and organs, restore sight, kill cancer, cure diabetes, heal burns and stop the march of degenerative diseases, such as Alzheimer's, multiple sclerosis and Lou Gehrig's disease.
This banner text can have markup. web; books; video; audio; software; images; Toggle navigation. Karen Robards' Guardian Series, #3. Edition description: Product dimensions: (w) x (h) x (d) About the Author. Karen Robards is the New York Times, USA TODAY and Publishers Weekly bestselling author of fifty novels and one novella.
She is the winner of six Silver Pen awards and numerous other awards. Read an : MIRA Books. (G12) is a cell church model founded by Pastor Cesar Castellanos which is thestrong (International Charismatic Mission in Bogota, Colombia).
Wanting to see growth in his church 'In He (Cesar Castellanos) went to Korea and adopted the principles of cell church as taught by Dr Yonggi Cho. By the end of there were 70 cells. This book surveys the impact of the Monroe Doctrine on United States relations with Latin America, with a particular focus on the Caribbean Basin, since its proclamation in It explores the historical role of the Monroe Doctrine as the instrument to foreclose future European colonial adven.; concluded that all living things are made of cells struck by the structural similarities between plant and animal cells; after concluding that all living things are made of cells, he published the first statement of the cell theory (had to be refined over the years as additional data led to new conclusions).“Where a cell arises, there must be a previous cell, just as animals can only arise from animals and plants from plants.” This cell doctrine, proposed by the German pathologist Rudolf Virchow incarried with it a profound message for the continuity of life.
Cells are generated from cells, and the only way to make more cells is by division of those that already by:
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domain: library


text:
Thursday, June 17, 2010
To Montserrat and Back Again
Hello world! I'm back from my inaugural trip to both the East Coast AND the 4th Annual Encaustic Conference at Montserrat College of Art. And what a wonderful trip it was!
I had three days filled with conference fun such as demos, talks, meeting other amazing artists, seeing their work...and did I mention buying art supplies in the vendors' rooms? Oh my. It's a miracle that my bank didn't drag me out of those rooms before I could do more damage. But, really, how is a girl supposed to say no to all that color?
I will admit that I do have a short limit of the amount of gallery mingling I can handle...so I went on a little "walkabout" during one of the openings...and I stumbled upon some students' studio spaces on campus. Which is where I snapped the above photo with the quote from Degas. It was a beautiful studio space with an equally striking quote. I love it when we stumble upon just what we need to hear.
Here is my newest work, and one included in the conference's "Best Foot Forward" exhibit. If I was going to show all of the other attendees something that was "me" it better have a bit of green in it!
I will share other photos from the conference as I try to get this blog up and running again. Oh, and to the lovely woman (I am SO VERY bad at remember names) who came up to me (while I was trying not to buy MORE paint from R&F) and who told me she reads my blog and how much she enjoyed it....thank you! You rocked my world and I promise I'll try sneak away from the dreaded Facebook enough to actually put posts on my blog more often!

domain: artistic


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Bless is really excited to support and partner with other local churches to host Love Hanwell in 2012
What is Love Hanwell?
Love Hanwell is the collective name for a series of events that will be run by the churches of Hanwell in West London in 2012. Through these events, we plan to bring the message of hope that Jesus brings right into the heart of Hanwell.
All kinds of events are being planned: drama, serving the community in practical ways, delivery of a gospel to every household, social events and more. Most of these events will take place between Easter 2012 and November 2012 but keep watching for earlier events, some of which will even occur this year.
Find out more on the Love Hanwell website
Bless Community Church
Based in west London
Contact us: email@example.com

domain: sociology


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All eyes will be on Kenya over the coming months as Access Now and civil society from across the globe urge authorities to uphold their commitment to ensuring a fair, open, and accessible internet throughout the presidential elections scheduled for August 9.
“Democracy means information, participation, and communication. Democracy means internet accessibility,” said Felicia Anthonio, #KeepItOn Campaign Manager at Access Now. “Kenya votes on August 9, and Access Now is calling on authorities to stand by their commitment, and #KeepItOn when it counts — always!”
At least three times this year — first in May, then again twice this month — authorities have committed to keeping the country connected during this cornerstone moment in the nation’s democracy. Chief Justice Martha Koome has also highlighted the importance of digitization and access to the internet, and committed the judiciary to ensuring that the law is upheld in internet governance efforts.
Although there have been no recorded cases of Kenyan authorities shutting down the internet, they have made several attempts to exert control over information flow in the country during election periods, such as during the 2007 elections by imposing a ban on live broadcasts, leading some broadcasters to suspend news coverage of the disputed elections.
“Authorities are implementing internet shutdowns across the region and causing serious harm to fundamental rights and democracy,” said Grace Githaiga, CEO & Convenor at Kenya ICT Network (KICTANet). “Kenya continues to set an example of not restricting internet and social media use during elections. The 2022 general election should be no different. #KeepItOn in Kenya this election.”
Access Now and the coalition of organizations are calling on authorities to:
- Publicly assure the people of the Republic of the Kenya that the internet, including social media and other digital communication platforms, will remain open, accessible, inclusive and secure across Kenya before, during and after the election;
- Refrain from ordering the interruption of telecommunications services, social media platforms, and other digital communication platforms;
- Ensure that telecommunications and internet service providers implement all necessary measures to provide high-quality, secure, unrestricted and uninterrupted internet access; and,
- Ensure that telecommunication and internet service providers inform internet users of any potential disruptions, and to take all reasonable steps to fix any identified disruptions.
Increasingly, civil society from across the globe and international actors such as the United Nations are uniting in the fights to #KeepItOn, as outlined in a recent RightsCon summit conversation.
Read the full statement.


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Basic controls consist of stop, start, reverse. A push button box incorporating a flying lead and plug to accommodate the electrical socket within the machine tool.
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domain: design


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Denise Jones is Editor-in-Chief at Hubwav.
The 10-track album features Frank Ocean, JAY-Z’s mom and Damian Marley.
Chasing the ghost of Jordan’s past.
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In many Western diets, the role of plants has been reduced in favour of more animal-based products and this is now being cited more widely as being the cause of increases in the incidence of diseases such as cancer and cardiovascular disease. This important book covers the biochemistry and nutritional importance of a wide range of phytonutrients, including all the major macronutrients as well as the micronutrients and 'non-essential' nutrients.
Phytonutrients is divided into three parts. The first deals with the role of plants in the human diet. Part II, representing the major part of the book covers in turn each of the major phytonutrient groups. Chapters include: non-lipid micronutrients, lipids and steroids, carotenoids, phenolics, vitamins C, E, folate/vitamin B12, phytoestrogens, other phytonutrients and minerals, and anti-nutritional factors. The final part of the book covers the methods used to manipulate levels of phytonutrients in the diet, such as fortification, supplementation and the use of genetically modified plants.
Phytonutrients is an essential purchase for nutritionists, food scientists and plant biochemists, particularly those dealing with nutrients from plants, and their use in the human diet.

domain: biology


text:
Posted 9/2/2010 12:48:02 PM
I added fresh mushrooms and had ground chicken instead of turkey. My husband and one year old loved this! It was so quick to make, and while I usually use whole wheat noodles, it was a nice break from the ordinary and took no time. Play around with it- add veggies, spices, etc. Good as is, though.


Endorsements for AISD board of trustees
The following are the Chronicle's recommendations for the Austin Independent School District board of trustees, where a dramatic changeover in policy leadership will follow the not unexpected but abrupt departure to Atlanta of Superintendent Meria Carstarphen. The district faces increasing pressure from the state's inadequate public school finance system – again ruled unconstitutional even while it continues to "recapture" many millions in resources from the "property wealthy" AISD that yet serves a majority of poor, minority students. The new, mostly freshmen trustees will have to get up to speed very quickly, hire a new superintendent with a more collaborative style, and develop policies that maximize school resources while also working with other districts to reverse the state's historical inequities. It's a tall order, and in making our endorsements, we tried to keep those challenges in mind.
At Large (position 9): Kendall Pace
Incumbent Tamala Barksdale's departure from her seat after only one term is a sad loss, especially since she finally seemed to be getting her bearings in this thankless position. In a packed race to replace her, there is a lot of commitment to the principles of public education. However, Pace, with broad experience in both nonprofits and district bodies, shows by far the broadest, deepest, and most nuanced understanding of the nuts and bolts of both AISD, and Texas education in general. We are also impressed, however, with Kazique Prince's obvious intelligence and commitment to equity and inclusion, areas too often overlooked in AISD. Whatever the result of this election, we hope he will stay engaged in district policies and decisions moving forward.
District 1: Ted Gordon
The Northeast area of Austin has historically been AISD's most segregated and institutionally neglected section. However, the district's problems are far from unique citywide.Yet retiring incumbent Cheryl Bradley often promulgated an "Us vs. Them" approach that served to cause further tensions and create reflexive administrative responses – making District 1 almost an island for experimentation, rather than part of an integrated whole. On a slate of candidates that propose fixes for its specific campuses, UT African and African Diaspora Studies Chair Gordon is best poised to make D1 more than just an education reform laboratory. Should he be elected, it will be a test of the nostrum, "If you wish to get something done, ask a busy person" – but he's consulted with predecessors on the trustee workload, and intends to convene a group of collaborators from both the district and the university – where there is indeed plenty of expertise relevant to district needs. His work on the city's African-American Quality of Life Initiative shows broad, out-of-the-box thinking that, if implemented with enough energy and commitment, could result in real social change, and turn D1 into a role model for the rest of AISD.
District 4: Julie Cowan
In 2010, when Cowan opposed Tamala Barksdale for the board's At-Large seat (position 9), we were torn between two highly qualified candidates. In the end, we endorsed Barksdale, but we are pleased to see Cowan return to the ballot. After her loss, her work both within district schools and on the legislative staff of that rarest of birds – a pro-public education Republican – has reinforced our belief that she understands the big policy needs of the district. She has already done much good work for the district, and enjoys a broad range of support for her candidacy. And, much as in 2010, we find ourselves applauding the passion of her opponent, Karen Zern Flanagan. We would suggest that the district call on her expertise and commitment to the often unaddressed health and wellbeing needs of AISD students.
District 6: Paul Saldaña
This South-Central zone of AISD has the potential to be a model for the entire school district. For example, community-led projects like the Travis Heights Elementary in-district charter (which builds on public school experience without trying to cherry-pick the most readily teachable students), could help rebuild the public trust largely lost under former Superintendent Meria Carstarphen, whose replacement will be a major responsibility of the incoming trustees. Kate Mason-Murphy has a teacher's perspective and instincts – and should be an invited asset on district policies, especially regarding classroom teaching. But Saldaña's experience as an advocate for families, especially the growing Hispanic student body, is broadly based, and his extensive community connections should leverage his presence on the board. His long experience on educational issues and his understanding of both the operations and the legal strictures affecting AISD are strong. Now he must make a personal transition from critical advocate on public education to culpable decision maker – inside the tent, as it were – in a context of making the case for public schools to the whole community. We're confident he can do the job.
District 7: Robert Schneider
Cantankerous. Obstructionist. Critical. And those are his good qualities. Detail-oriented, and willing to take unpopular stances when the facts support it, retired UT computing researcher Schneider was one of the first trustees to demand accountability from former Superintendent Meria Carstarphen. As he runs for a fourth term, he is a known quantity on a slate of otherwise new faces. Over the next two years, AISD will select a new superintendent, and traverse the minefield of school finance reform. While his challenger Yasmin Wagner (a second opponent, Theresa Bastian, dropped out after filing) seems committed to increasing outcomes and reducing outflows in the district, Schneider's experience will be vital on a board on which no other member has more than two years tenure.


text: Baufloor™ laminate flooring is technologically state-of-the-art and consists almost entirely of wood, an element classified as renewable raw material. Our decor fits perfectly in modern and traditional rooms. Laminate flooring is FSC certified, which means that they are made using products from forests managed in a correct and sustainable way, while respecting environmental standards. Moreover, the Baufloor™ laminate flooring is an environmentally friendly and sustainable product and can even be recycled. Baufloor™ laminate flooring has a hard and compact surface that prevents dust and dirt from penetrating. Our floors are hygienic, easy to clean and particularly suitable for allergy sufferers. We apply to our floors an antibacterial superficial treatment that does not allow the bacteria to find a material where they can nourish and reproduce. The laminate flooring is undergoing a number of rigorous testing before being put on the market, our production standards are very rigid and for this reason, we can grant very extensive guarantees for all residential uses.


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Area: Historic District
|Jul 8, 19 - Jan 1, 70||$536|
|Aug 1, 19 - Jan 1, 70||$577|
|Aug 10, 19 - Jan 1, 70||$556|
|Aug 25, 19 - Jan 1, 70||$556|
|Aug 30, 19 - Jan 1, 70||$795|
|Sep 21, 19 - Jan 1, 70||$795|
|Nov 20, 19 - Jan 1, 70||$935|
|Dec 18, 19 - Jan 1, 70||$1,650|
|Dec 19, 19 - Jan 1, 70||$1,815|
|Dec 26, 19 - Jan 1, 70||$2,628|
|Jan 3, 20 - Jan 1, 70||$1,015|
|Feb 1, 20 - Jan 1, 70||$1,125|
|Feb 13, 20 - Jan 1, 70||$1,237|
|Feb 18, 20 - Jan 1, 70||$1,125|
|Feb 28, 20 - Jan 1, 70||$1,125|
|Mar 21, 20 - Jan 1, 70||$1,125|
|Apr 3, 20 - Jan 1, 70||$835|
A five bedroom with five and a half baths – which sleeps twelve – and has a beautiful interior, plenty of windows and sunshine as well as an unobstructed view of the gorgeous Tenmile Range!
This beautiful, modern home will blow you away with its unique architecture, massive windows and nooks! It features expansive ceilings, walls of windows, plenty of sunshine, hardwood, granite and plush carpet flooring. Located just east of Main Street, this home is walking distance to the ice rink and free shuttle bus stop, and is a short walk to Main Street. It has unbelievable views from all around the house of the Tenmile Range.
The kitchen has stainless steel Viking appliances including a large gas stove enclosed by native river rock, granite countertops with an eat-in table with seating for six. Attached to the kitchen is the laundry room with washer and dryer as well as a desk. There is additional seating for six plus two side chairs in the formal dining room and an additional table with seating for six near the entryway to the deck. There is also an office on the main floor with TV, cable and printer.
This home has two living rooms, each with a flatscreen TV with cable and DVD player, and the upstairs living room also has a VCR. A gas fireplace travels from the main floor living room up to the upstairs living room, so there is a warm fire in both rooms. The main floor has seating for seven with a sectional and two additional chairs, while the upstairs living room has seating for five with a couch and two additional chairs that recline and have a foot stool. The upstairs couch is also a full-sized sleeper sofa.
For the bedrooms, on the main floor, you will find the gorgeous master suite. It has a king-sized bed, large windows with views of the Tenmile Range and an amazing ensuite bath. The bathroom has a large walk-in closet, his and hers vanity, makeup station, shut-off toilet and spacious, beautifully tiled three-head shower with Jacuzzi tub within.
The next three bedrooms are found upstairs. Walk up the stairs over the loft and you will find the twin bedroom. This bedroom has two twin beds and an ensuite bath with single vanity, toilet and shower/tub combo. The next bedroom has a queen-sized bed and ensuite bath with single vanity, toilet and stand-up shower; the last bedroom found upstairs also has a queen-sized bed and ensuite bath with single vanity, toilet and stand-up shower. Additionally, it has a window with views of the mountains! All bathrooms are very well-appointed and modern.
The fifth bedroom is found on the lower-level. This bedroom has a king-sized bed and a couch that pulls out to a sleeper sofa. It has a large, mounted flatscreen TV with cable and has an attached room with poker table and lighting. The bath is located next door with single vanity, toilet and stand-up shower and there are games on the hallway shelving.
This home has a one-car garage and space to park on the driveway. It is built-into the hill which allows the guests staying in the upstairs bedrooms and living room to observe wildlife as well. The home also has a large two-story deck with entrance from the upstairs level to the private hot tub and stairs that bring you down to the main floor deck with grill, table, chairs and unbelievable views!
If you are looking for a spacious private home to accommodate up to twelve guests with great shared spaces to enjoy your group as well as many nooks to enjoy your own time, this beautiful home may be a great fit for your next Breckenridge escape!
AWD/4WD VEHICLE RECOMMENDED DURING WINTER MONTHS
Renters must be a minimum of 25 years old
• Breckenridge Business License No. 658580001
- Property Type
- Bedrooms 5 Bedroom , Sleeps 12

domain: geography


text:
IN TALK WITH JENNY YOHANA KANSIL
Jenny Yohana Kansil shared her views on young local designers and her hope for the future fashion industry.
The Samarinda born entepreneur Jenny Yohana Kansil is coming to our short interview. Ten years ago, she moved from Surabaya to Jakarta to create one of the best fashion schools in Indonesia, Istituto di Moda Burgo Indonesia.
Some of her best graduates are Janice Pradipta Setyawan and Benita Pradipta Setyawan, who founded MAQUINN. They have been known to have a successful show in Milan. Jenny also shared how proud she is of the twins' accomplishments. Jenny, who lives in Jakarta, is planning to create another fashion collection around September 2021.
Jenny also told us that becoming a fashion designer has been her long-time dream, but she never thought she could make it. She defined that she loves something elegant, simple yet eye-catching. It was shown when The S Media interviewed her via Zoom. She wore this white t-shirt with an eye-catching necklace.
The S Media talked with Jenny about many things, from her favorite fashion designers to her hope for the Indonesian fashion industry. Jenny, who is Roberto Cavalli's fan, is an open-minded, fun-loving woman who shared her most honest thoughts.
Hi, Jenny. You were the founder of Instituto di Moda Burgo Indonesia. Could you please tell us about how you built this fashion school?
It started when I went to Istituto di Moda Burgo in Italy to pursue my dream to become a designer. After three months Fernando Burgo offered me to open a branch in Indonesia. Because there were a lot of inquiries from people in Indonesia. But, not everyone was able to go to Milan, Italy.
Why are you interested in having a career in the fashion industry? Do you have any favorite designers from Indonesia or any other country?
I feel it was meant to be. I was into clothes since I was a kid. I really love to draw and play with dolls. Back then, fashion in my era is different from fashion in your era. Right now, fashion has established itself.
I have a lot of favorite designers, and they are quite inspiring me. Starting with the local designer, I love Ali Charisma. I am really into a designer that could attract the international market. I think Ali Charisma is one of the Indonesian designers who could do that. He got a lot of clients in Australia, the U.S, and Europe. He is super creative as well. He is just like a chameleon. He is also the founder of the Indonesian Fashion Chamber.
I also like Deden Siswanto. I never thought that we could be friends. He is really genius in the way he plays with the fabric and pattern.
What do you think about the current talents in Indonesia? What should young people do to be great designers?
If I see the new talents right now, I'm very optimistic about the future of Indonesian fashion. Because they are very talented and have such an authentic and unique taste. I think in this era, they are provided with technology.
With the presence of technology, they could explore more, and they could see more. They were brilliant and got inspired by many things, maybe because they were traveling a lot. I really hope they could be the future of Indonesian fashion.
What do they need to be the best designer?
First is mastery, the primary skills of a fashion designer. And then in our fashion school, you could learn how to do fashion illustration, pattern making, and we have Burgo Method with one on one individual lesson using Books issued by Burgo Milan and everyone without talent can mastery the skills with this method
A young designer also needs to have a vision for the next five, ten, or twenty years from now. From what I see, this young generation tends to give up on something easily.
If you want to be a great designer, you have to know what you want, and you should know your next plan after you get what you want. So when you feel you want to give up, you should remember that vision once again. Just remember the outcome that you dreamed of.
So I think, from this young generation, I only see that they lack consistency. It's not about how good you are. It is about how good you want to be. No one gets the result from an instant time. Louis Vuitton started his business in the 18th century.
The pandemic has actually changed the local fashion industry. I felt that right now, the local brands have more opportunities. More people are interested in a fashion brand with a lot of heritage or even cultural background.
Without a doubt, the fashion industry in Indonesia has a lot of potentials. We need to support young, local talented designers, or maybe just taking a class at Instituto di Moda Burgo Indonesia.
#THE S MEDIA #Media Milenial #fashion #jenny yohana kansil #burgo #fashion school


text:
As I’m sure you guys can tell from my Instagram lately, I am VERY VERY VERY excited for fall! Literally put pumpkin on or in anything and I will eat it. Its like a 3 month addiction I have. For the past week I have had pumpkin smoothies for breakfast, a coconut flour pumpkin muffin with my lunch and then pumpkin avocado mousse after dinner. Like I just can’t be stopped…
This recipe I bring you is very pumpkin spicy and was concocted with my newest wellness friend! I met Macey at a local health cafe in Calgary and I knew after chatting with her about how much we love Crosby Taylor, ghee and paleo baking our friendship was going to be very valuable one.
Last week I was hankering for a nice cup of hot chocolate and of course some pumpkin spice to ring in the fall season so, I messaged Macey to bring her expertise into the FoodGlow kitchen to help me create a super nutritious, low sugar and super cozy elixir! It gets its creamy touch from the pumpkin puree, coconut butter and pumpkin seed butter and gets its sweetness from monk fruit sweetener so this baby scores 10/10 in terms of taste but a 0 on the glycemic index scale. If you are sensitive to stimulants I would not advise drinking this before bed because the red maca and chaga have slight stimulant properties and could ruin your sleep! Other than that get your flannel, a nice mug, a friend and your blender and get ready to spice up your fall a little bit!
Pumpkin Spice Adaptogen Hot Chocolate
1 tsp chaga powder
1 tsp upgraded collagen
1 tsp red maca
2 tbsp cacao powder
1 1/4 tsp pumpkin spice blend
1 tbsp coconut butter
3 tbsp pumpkin puree
1 tbsp pumpkin seed butter
3 tbsp Lakanto Monkfruit Sweetner
2 cups boiling water
1/2 cup homemade pumpkin seed and hemp mylk
Throw all ingredients into your blender and blend until frothy! Pour into one large mug or two small ones and drink up!


text:
297 Bella's Redemption » by Butterfly Betty Dancing with the Devil cost Bella a piece of her soul. Will she earn her redemption? Or be lost forever. Sequel to Carlisle's Gift.
Twilight, M, English, Angst & Tragedy, chapters: 34, words: 76k+, favs: 121, follows: 178, updated: 8/27 published: 2/2/2020, Bella, Edward
73The Sun and the Moon » by Vampire By Day Wolf By Night Bella Swan was facing death when she was saved by her own personal sun. Jacob Black was pinning after a certain brunette for as long as he could remember. For some unknown reason, his imprinting did not happen right away. Follow along as Bella and Jacob grow into the wonderful couple that runs the wolf pack.
Twilight, M, English, Romance & Supernatural, chapters: 14, words: 40k+, favs: 175, follows: 264, updated: 3/13 published: 1/1/2017, [Bella, Jacob]
735Of Wolves and Vampires » by Saiyon Bella Black was raised on La Push, and has been causing trouble wherever she goes. Only one day she suddenly shifted into a wolf, and finds out she's suddenly destined to be the alpha of the La Push pack. What's in store for her next? Tanya comes in much later, but Bella/Rosalie/Tanya ending.
Twilight, M, English, Supernatural & Romance, chapters: 25, words: 91k+, favs: 1k+, follows: 1k+, updated: 1/9 published: 3/28/2016, [Bella, Rosalie, Tanya]
549The Alpha Twins » by laura-maeve Roughly two years have passed since the Witch's War. Maddox and Ash Black have lived in bliss with their siblings and mates. Dox has been learning the intricacies of leading the Children while Ash quietly worries over the fate of his human mate. But drama stirs once again when Ryell, Dox's mate, is threatened. Dox, with Ash's help, will do anything to protect her. Rated M.
Twilight, M, English, Drama & Romance, chapters: 32, words: 324k+, favs: 96, follows: 94, updated: 8/21/2021 published: 6/6/2016, Jacob, Renesmee C./Nessie, OC
564The Witch Girl's Human » by Saiyon Jane happens to meet Bella as a child, but what happens when she makes one different decision? A decision that changes both girl's lives forever? Warning: First chapter is nearly identical to my other Jane/Bella story, but it'll take off in a whole different direction.
Twilight, M, English, Romance & Supernatural, chapters: 21, words: 48k+, favs: 1k+, follows: 1k+, updated: 4/28/2021 published: 12/3/2015, [Bella, Jane]
168From Across the Water » by Saiyon Bella loves to swim, and finding places to do so only gets harder when she moves to Forks. But when Bella finds a nice lake to swim in, she happens to come across something she never could have imagined. Thrust into the vampire world, her life is changed forever. Rosalie/Bella endgame.
Twilight, M, English, Romance & Supernatural, chapters: 3, words: 6k+, favs: 627, follows: 973, updated: 3/2/2021 published: 8/19/2016, [Rosalie, Bella]
29Through It All- Episode III » by Yxtchel Ryan sensed many eyes on him as he stepped up to the take out counter. A new face was always noticed around these parts and a six plus tall native man would be noticed even more. The attention was making him anxious and he rushed out with his food, almost running a little girl over in the process and found himself looking down into the prettiest set of grey eyes he'd ever seen.
Twilight, M, English, Drama & Hurt/Comfort, chapters: 13, words: 66k+, favs: 17, follows: 23, updated: 10/25/2020 published: 9/25/2016, Paul, OC
4k+Summer Vacation: Happily Ever After » by Twireader81 The third in the Summer Vacation series. Bella and Edward's dream wedding has finally arrived. Join their celebration of life and love and family. Discover what their future holds and share in their happily ever after.
Twilight, M, English, Romance & Family, chapters: 359, words: 560k+, favs: 786, follows: 797, updated: 6/30/2020 published: 2/21/2014, Bella, Edward
182We Have Each Other, and That's Enough Rewritten » by Iridescent Thilbo Bagginshield After Bella catches Edward cheating on her with Tanya, she is heartbroken. Carlisle comes to comfort her, and they immediately fall in love. Together, they fight every obstacle that comes their way. Rated M for language, lemons, rape, and character death. I do NOT own Twilight or anything else of Stephenie Meyer's.
Twilight, M, English, Romance & Drama, chapters: 21, words: 85k+, favs: 408, follows: 411, updated: 6/4/2020 published: 4/8/2012, Bella, Carlisle
30The Valley of Our Love SPIN-OFF » by Iridescent Thilbo Bagginshield What if Bella and Carlisle discovered that they WERE bisexual and decided to explore their sexuality more? A story for those who wanted both slash and femslash in the original story and to those who are interested in reading this. Rated M for LEMONS, language, threesomes, foursomes, and possible orgies. Bella/Carlisle because they are the main pair. OOC.
Twilight, M, English, Romance & Humor, chapters: 6, words: 33k+, favs: 136, follows: 123, updated: 5/7/2020 published: 10/21/2012, Bella, Carlisle, Edward, Esme
22 Prove d'Amore (Trials of Love) » by MiAiMo The humans are being kept in concentration camps built by the Volturi and guarded by mutated vampire hybrids with terrible strength and an even worse thirst. All those who oppose them are dead, too afraid, or joined the guard. A prisoner of Volterra goes back in time to train the Coven and the Pack for their destined day. Can she bring them together? Or will she tear herself apart?
Twilight, M, English, Adventure & Romance, chapters: 23, words: 161k+, favs: 38, follows: 42, updated: 5/2/2020 published: 11/11/2016, [Jacob, Edward] OC
251The Valley of Our Love » by Iridescent Thilbo Bagginshield Set in New Moon. While Bella is getting stitched up in Carlisle's office, they discover that they have feelings for each other, which soon blossoms into love. Rated M for later chapters. LEMONS. OOC! I do NOT own Twilight or anything of Stephenie Meyer's. Mainly Bella and Carlisle's POVs, but there are other POVs from time to time as well.
Twilight, M, English, Romance & Humor, chapters: 20, words: 129k+, favs: 597, follows: 591, updated: 3/27/2020 published: 11/20/2011, Bella, Carlisle
117 Carlisle's Gift » by Butterfly Betty Charlie Swan made a deal with the devil. Owing a debt he couldn't repay, he took the cowardly way out and offered his daughter's services to pay off his tab. The rich and powerful Carlisle Cullen greedily accepts, and Bella finds herself at the mercy of a dark and violent man. Will she survive? Or will he beat the life out of her? Dark themes. NC-17 for violence and language. AU.
Twilight, M, English, Angst & Tragedy, chapters: 15, words: 39k+, favs: 125, follows: 121, updated: 1/29/2020 published: 1/12/2020, Bella, Carlisle
161Follow Your Heart » by Iridescent Thilbo Bagginshield Formerly titled I Touched Myself ADOPTED. Bella was supposed to be alone for the weekend, but there's been a change of plans. The result of the plans leads to a confrontation, which will cause both Bella and Carlisle to make important decisions. The outcome of them will lead to a revelation that shocks not only them, but their family as well. Rated M for smut and lemons.
Twilight, M, English, Romance, chapters: 17, words: 43k+, favs: 331, follows: 407, updated: 1/15/2020 published: 5/1/2013, Bella, Carlisle
10We WILL Overcome » by Iridescent Thilbo Bagginshield The sequel to Held Captive. Bella, JC, and Tanya are struggling to heal from the wounds of their past. However, JC decides to take certain matters into his own hands after push finally comes to shove one day. As a result, he walks down the path of darkness, leaving a trail of destruction behind him. Can he be stopped before it is too late? More details inside.
Twilight, M, English, Romance & Hurt/Comfort, chapters: 3, words: 15k+, favs: 32, follows: 22, updated: 11/22/2019 published: 10/29/2014, [Bella, Carlisle] OC
99 Saved From Terror By An Angel (DISCONTINUED) » by Iridescent Thilbo Bagginshield On September 11th, the World Trade Center, where Charlie, Renee, and Phil work in the North Tower, is attacked. 14-year-old Bella rushes to save them, but it collaspes before she can get inside. Carlisle Cullen rescues her from the falling debris. Read about their journey together as Carlisle helps Bella find her parents and stepfather, who are presumed dead. Rated M for later
Twilight, M, English, Romance & Drama, chapters: 21, words: 85k+, favs: 136, follows: 149, updated: 9/10/2019 published: 7/27/2012, Bella, Carlisle
316 Beneath The Dark Corner » by Joy12908 Her self-worth had been stripped away, layer by layer, until nothing remained. But she never forgot who she used to be, the girl who lived inside her caged soul, waiting for the day to be set free. He can clip her wings and tell her lies of how fragile birds were never meant to fly, but she cannot be confined. Her wings will grow and she'll find the sky. *Timeline Set Mid New-Moon*
Twilight, M, English, Romance & Hurt/Comfort, chapters: 56, words: 108k+, favs: 178, follows: 189, updated: 8/28/2019 published: 6/7/2018, Bella, Billy, Charlie S., Jacob
67 Immortal Love » by ButterflyWhisperer A short story and the final epilogue to the Sunrise Saga. Renesmee and Jacob are preparing for the wedding of their daughter, Sarah, and the entire family is coming to Forks from all parts of the globe to meet up for the joyful occasion. Find out what happened to everyone 23 years after the final battle in Eternal Dawn. Takes place in 2041.
Twilight, T, English, Family & Romance, chapters: 11, words: 25k+, favs: 33, follows: 26, updated: 7/7/2019 published: 5/27/2019, Jacob, Renesmee C./Nessie, OC
60Love in unexpected places » by Romantific Edward Masen has just moved to Forks Washington with his dad after the death of his mother. Edward is socially awkward and gay and quickly befriends equally socially awkward Isabella Swan after her failed attempt at flirting. After a mysterious run in with a giant wolf during a walk in the woods Edward soon finds his life changed forever.
Twilight, M, English, Romance & Fantasy, chapters: 28, words: 32k+, favs: 86, follows: 108, updated: 7/4/2019 published: 8/17/2015, [Paul, Edward] [Jacob, Bella]
187Chameleon » by Always an Edward fan "But Carlisle we want to meet her now." Alice whined. "Does she have to smell like strawberries? It's almost syrupy sweet." Rosalie hissed. "Strawberries and chocolate, and it's absolutely perfect!" Edward called out while Emmett and Jasper both nodded their heads. "Oh she is so adorable my love, is she staying permanently? Please Carlisle?" Esme pleaded.
Twilight, M, English, Romance & Supernatural, chapters: 17, words: 40k+, favs: 335, follows: 470, updated: 4/10/2019 published: 2/21/2013, Bella, Edward, Emmett, Jasper

domain: literature