text:
Exposure to chronic stress is a reliable predictor of depressive disorders, and social stress is a common ethologically relevant stressor in both animals and humans. However, many animal models of depression were developed in males and are not applicable or effective in studies of postpartum females. Recent studies have reported significant effects of chronic social stress during lactation, an ethologically relevant and effective stressor, on maternal behavior, growth, and behavioral neuroendocrinology. This manuscript will describe this chronic social stress paradigm using repeated exposure of a lactating dam to a novel male intruder, and the assessment of the behavioral, physiological, and neuroendocrine effects of this model. Chronic social stress (CSS) is a valuable model for studying the effects of stress on the behavior and physiology of the dam as well as her offspring and future generations. The exposure of pups to CSS can also be used as an early life stress that has long term effects on behavior, physiology, and neuroendocrinology.
24 Related JoVE Articles!
Creating Dynamic Images of Short-lived Dopamine Fluctuations with lp-ntPET: Dopamine Movies of Cigarette Smoking
Institutions: Yale University, Yale University, Yale University, Yale University, Massachusetts General Hospital, University of California, Irvine.
We describe experimental and statistical steps for creating dopamine movies of the brain from dynamic PET data. The movies represent minute-to-minute fluctuations of dopamine induced by smoking a cigarette. The smoker is imaged during a natural smoking experience while other possible confounding effects (such as head motion, expectation, novelty, or aversion to smoking repeatedly) are minimized.
We present the details of our unique analysis. Conventional methods for PET analysis estimate time-invariant kinetic model parameters which cannot capture short-term fluctuations in neurotransmitter release. Our analysis - yielding a dopamine movie - is based on our work with kinetic models and other decomposition techniques that allow for time-varying parameters 1-7
. This aspect of the analysis - temporal-variation - is key to our work. Because our model is also linear in parameters, it is practical, computationally, to apply at the voxel level. The analysis technique is comprised of five main steps: pre-processing, modeling, statistical comparison, masking and visualization. Preprocessing is applied to the PET data with a unique 'HYPR' spatial filter 8
that reduces spatial noise but preserves critical temporal information. Modeling identifies the time-varying function that best describes the dopamine effect on 11
C-raclopride uptake. The statistical step compares the fit of our (lp-ntPET) model 7
to a conventional model 9
. Masking restricts treatment to those voxels best described by the new model. Visualization maps the dopamine function at each voxel to a color scale and produces a dopamine movie. Interim results and sample dopamine movies of cigarette smoking are presented.
Behavior, Issue 78, Neuroscience, Neurobiology, Molecular Biology, Biomedical Engineering, Medicine, Anatomy, Physiology, Image Processing, Computer-Assisted, Receptors, Dopamine, Dopamine, Functional Neuroimaging, Binding, Competitive, mathematical modeling (systems analysis), Neurotransmission, transient, dopamine release, PET, modeling, linear, time-invariant, smoking, F-test, ventral-striatum, clinical techniques
Induction and Clinical Scoring of Chronic-Relapsing Experimental Autoimmune Encephalomyelitis
Institutions: University of California, Irvine (UCI).
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that commonly affects young adults. It is characterized by demyelination and glial scaring in areas disseminated in the brain and spinal cord. These lesions alter nerve conduction and induce the disabling neurological deficits that vary with the location of the demyelinated plaques in the CNS (e.g. paraparesis, paralysis, blindness, incontinence).
Experimental autoimmune encephalomyelitis (EAE) is a model for MS. EAE was first induced accidentally in humans during vaccination against rabies, using viruses grown on rabbit spinal cords. Residues of spinal injected with the inactivated virus induced the CNS disease. Following these observations, a first model of EAE was described in non-human primates immunized with a CNS homogenate by Rivers and Schwenther in 1935. EAE has since been generated in a variety of species and can follow different courses depending on the species/strain and immunizing antigen used. For example, immunizing Lewis rats with myelin basic protein in emulsion with adjuvant induces an acute model of EAE, while the same antigen induces a chronic disease in guinea pigs.
The EAE model described here is induced by immunizing DA rats against DA rat spinal cord in emulsion in complete Freund's adjuvant. Rats develop an ascending flaccid paralysis within 7-14 days post-immunization. Clinical signs follow a relapsing-remitting course over several weeks. Pathology shows large immune infiltrates in the CNS and demyelination plaques. Special considerations for taking care for animals with EAE are described at the end of the video.
Immunology, Issue 5, Autoimmune Disease, Animal Model, EAE, Experimental Allergic Encephalomyelitis, Multiple Sclerosis, Immunology, Clinical Scoring, Disease Model, Inflammation, Central Nervous System
Rapid Determination of the Thermal Nociceptive Threshold in Diabetic Rats
Institutions: Wright State University, Universidade São Judas Tadeu.
Painful diabetic neuropathy (PDN) is characterized by hyperalgesia i.e.
, increased sensitivity to noxious stimulus, and allodynia i.e.,
hypersensitivity to normally innocuous stimuli1
. Hyperalgesia and allodynia have been studied in many different rodent models of diabetes mellitus2
. However, as stated by Bölcskei et al
, determination of "pain
" in animal models is challenging due to its subjective nature3
. Moreover, the traditional methods used to determine behavioral responses to noxious thermal stimuli usually lack reproducibility and pharmacological sensitivity3
. For instance, by using the hot-plate method of Ankier4
, flinch, withdrawal and/or licking of either hind- and/or fore-paws is quantified as reflex latencies at constant high thermal stimuli (52-55 °C). However, animals that are hyperalgesic to thermal stimulus do not reproducibly show differences in reflex latencies using those supra-threshold temperatures3,5
. As the recently described method of Bölcskei et al.6
, the procedures described here allows for the rapid, sensitive and reproducible determination of thermal nociceptive thresholds (TNTs) in mice and rats. The method uses slowly increasing thermal stimulus applied mostly to the skin of mouse/rat plantar surface. The method is particularly sensitive to study anti-nociception during hyperalgesic states such as PDN. The procedures described bellow are based on the ones published in detail by Almási et al 5
and Bölcskei et al 3
. The procedures described here have been approved the Laboratory Animal Care and Use Committee (LACUC), Wright State University.
Neuroscience, Issue 63, Diabetes, painful diabetic neuropathy, nociception, thermal nociceptive threshold, nocifensive behavior
Comprehensive Analysis of Transcription Dynamics from Brain Samples Following Behavioral Experience
Institutions: The Hebrew University of Jerusalem.
The encoding of experiences in the brain and the consolidation of long-term memories depend on gene transcription. Identifying the function of specific genes in encoding experience is one of the main objectives of molecular neuroscience. Furthermore, the functional association of defined genes with specific behaviors has implications for understanding the basis of neuropsychiatric disorders. Induction of robust transcription programs has been observed in the brains of mice following various behavioral manipulations. While some genetic elements are utilized recurrently following different behavioral manipulations and in different brain nuclei, transcriptional programs are overall unique to the inducing stimuli and the structure in which they are studied1,2
In this publication, a protocol is described for robust and comprehensive transcriptional profiling from brain nuclei of mice in response to behavioral manipulation. The protocol is demonstrated in the context of analysis of gene expression dynamics in the nucleus accumbens following acute cocaine experience. Subsequent to a defined in vivo
experience, the target neural tissue is dissected; followed by RNA purification, reverse transcription and utilization of microfluidic arrays for comprehensive qPCR analysis of multiple target genes. This protocol is geared towards comprehensive analysis (addressing 50-500 genes) of limiting quantities of starting material, such as small brain samples or even single cells.
The protocol is most advantageous for parallel analysis of multiple samples (e.g.
single cells, dynamic analysis following pharmaceutical, viral or behavioral perturbations). However, the protocol could also serve for the characterization and quality assurance of samples prior to whole-genome studies by microarrays or RNAseq, as well as validation of data obtained from whole-genome studies.
Behavior, Issue 90,
Brain, behavior, RNA, transcription, nucleus accumbens, cocaine, high-throughput qPCR, experience-dependent plasticity, gene regulatory networks, microdissection
The 5-Choice Serial Reaction Time Task: A Task of Attention and Impulse Control for Rodents
Institutions: Oberlin College.
This protocol describes the 5-choice serial reaction time task, which is an operant based task used to study attention and impulse control in rodents. Test day challenges, modifications to the standard task, can be used to systematically tax the neural systems controlling either attention or impulse control. Importantly, these challenges have consistent effects on behavior across laboratories in intact animals and can reveal either enhancements or deficits in cognitive function that are not apparent when rats are only tested on the standard task. The variety of behavioral measures that are collected can be used to determine if other factors (i.e
., sedation, motivation deficits, locomotor impairments) are contributing to changes in performance. The versatility of the 5CSRTT is further enhanced because it is amenable to combination with pharmacological, molecular, and genetic techniques.
Neuroscience, Issue 90, attention, impulse control, neuroscience, cognition, rodent
A New Approach for the Comparative Analysis of Multiprotein Complexes Based on 15N Metabolic Labeling and Quantitative Mass Spectrometry
Institutions: University of Münster, Carnegie Institution for Science.
The introduced protocol provides a tool for the analysis of multiprotein complexes in the thylakoid membrane, by revealing insights into complex composition under different conditions. In this protocol the approach is demonstrated by comparing the composition of the protein complex responsible for cyclic electron flow (CEF) in Chlamydomonas reinhardtii
, isolated from genetically different strains. The procedure comprises the isolation of thylakoid membranes, followed by their separation into multiprotein complexes by sucrose density gradient centrifugation, SDS-PAGE, immunodetection and comparative, quantitative mass spectrometry (MS) based on differential metabolic labeling (14
N) of the analyzed strains. Detergent solubilized thylakoid membranes are loaded on sucrose density gradients at equal chlorophyll concentration. After ultracentrifugation, the gradients are separated into fractions, which are analyzed by mass-spectrometry based on equal volume. This approach allows the investigation of the composition within the gradient fractions and moreover to analyze the migration behavior of different proteins, especially focusing on ANR1, CAS, and PGRL1. Furthermore, this method is demonstrated by confirming the results with immunoblotting and additionally by supporting the findings from previous studies (the identification and PSI-dependent migration of proteins that were previously described to be part of the CEF-supercomplex such as PGRL1, FNR, and cyt f
). Notably, this approach is applicable to address a broad range of questions for which this protocol can be adopted and e.g.
used for comparative analyses of multiprotein complex composition isolated from distinct environmental conditions.
Microbiology, Issue 85, Sucrose density gradients, Chlamydomonas, multiprotein complexes, 15N metabolic labeling, thylakoids
A Procedure to Observe Context-induced Renewal of Pavlovian-conditioned Alcohol-seeking Behavior in Rats
Institutions: Concordia University.
Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate drug-seeking behavior and prompt relapse in abstinent drug users. We have developed a procedure to study the behavioral and neural processes that mediate the impact of context on alcohol-seeking behavior in rats. Following acclimation to the taste and pharmacological effects of 15% ethanol in the home cage, male Long-Evans rats receive Pavlovian discrimination training (PDT) in conditioning chambers. In each daily (Mon-Fri) PDT session, 16 trials each of two different 10 sec auditory conditioned stimuli occur. During one stimulus, the CS+, 0.2 ml of 15% ethanol is delivered into a fluid port for oral consumption. The second stimulus, the CS-, is not paired with ethanol. Across sessions, entries into the fluid port during the CS+ increase, whereas entries during the CS- stabilize at a lower level, indicating that a predictive association between the CS+ and ethanol is acquired. During PDT each chamber is equipped with a specific configuration of visual, olfactory and tactile contextual stimuli. Following PDT, extinction training is conducted in the same chamber that is now equipped with a different configuration of contextual stimuli. The CS+ and CS- are presented as before, but ethanol is withheld, which causes a gradual decline in port entries during the CS+. At test, rats are placed back into the PDT context and presented with the CS+ and CS- as before, but without ethanol. This manipulation triggers a robust and selective increase in the number of port entries made during the alcohol predictive CS+, with no change in responding during the CS-. This effect, referred to as context-induced renewal, illustrates the powerful capacity of contexts associated with alcohol consumption to stimulate alcohol-seeking behavior in response to Pavlovian alcohol cues.
Behavior, Issue 91, Behavioral neuroscience, alcoholism, relapse, addiction, Pavlovian conditioning, ethanol, reinstatement, discrimination, conditioned approach
Quantitative Analysis of Chromatin Proteomes in Disease
Institutions: David Geffen School of Medicine at UCLA, David Geffen School of Medicine at UCLA, David Geffen School of Medicine at UCLA, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah.
In the nucleus reside the proteomes whose functions are most intimately linked with gene regulation. Adult mammalian cardiomyocyte nuclei are unique due to the high percentage of binucleated cells,1
the predominantly heterochromatic state of the DNA, and the non-dividing nature of the cardiomyocyte which renders adult nuclei in a permanent state of interphase.2
Transcriptional regulation during development and disease have been well studied in this organ,3-5
but what remains relatively unexplored is the role played by the nuclear proteins responsible for DNA packaging and expression, and how these proteins control changes in transcriptional programs that occur during disease.6
In the developed world, heart disease is the number one cause of mortality for both men and women.7
Insight on how nuclear proteins cooperate to regulate the progression of this disease is critical for advancing the current treatment options.
Mass spectrometry is the ideal tool for addressing these questions as it allows for an unbiased annotation of the nuclear proteome and relative quantification for how the abundance of these proteins changes with disease. While there have been several proteomic studies for mammalian nuclear protein complexes,8-13
there has been only one study examining the cardiac nuclear proteome, and it considered the entire nucleus, rather than exploring the proteome at the level of nuclear sub compartments.15
In large part, this shortage of work is due to the difficulty of isolating cardiac nuclei. Cardiac nuclei occur within a rigid and dense actin-myosin apparatus to which they are connected via multiple extensions from the endoplasmic reticulum, to the extent that myocyte contraction alters their overall shape.16
Additionally, cardiomyocytes are 40% mitochondria by volume17
which necessitates enrichment of the nucleus apart from the other organelles. Here we describe a protocol for cardiac nuclear enrichment and further fractionation into biologically-relevant compartments. Furthermore, we detail methods for label-free quantitative mass spectrometric dissection of these fractions-techniques amenable to in vivo
experimentation in various animal models and organ systems where metabolic labeling is not feasible.
Medicine, Issue 70, Molecular Biology, Immunology, Genetics, Genomics, Physiology, Protein, DNA, Chromatin, cardiovascular disease, proteomics, mass spectrometry
Isolation of CA1 Nuclear Enriched Fractions from Hippocampal Slices to Study Activity-dependent Nuclear Import of Synapto-nuclear Messenger Proteins
Institutions: Leibniz Institute for Neurobiology, Utrecht University.
Studying activity dependent protein expression, subcellular translocation, or phosphorylation is essential to understand the underlying cellular mechanisms of synaptic plasticity. Long-term potentiation (LTP) and long-term depression (LTD) induced in acute hippocampal slices are widely accepted as cellular models of learning and memory. There are numerous studies that use live cell imaging or immunohistochemistry approaches to visualize activity dependent protein dynamics. However these methods rely on the suitability of antibodies for immunocytochemistry or overexpression of fluorescence-tagged proteins in single neurons. Immunoblotting of proteins is an alternative method providing independent confirmation of the findings. The first limiting factor in preparation of subcellular fractions from individual tetanized hippocampal slices is the low amount of material. Second, the handling procedure is crucial because even very short and minor manipulations of living slices might induce activation of certain signaling cascades. Here we describe an optimized workflow in order to obtain sufficient quantity of nuclear enriched fraction of sufficient purity from the CA1 region of acute hippocampal slices from rat brain. As a representative example we show that the ERK1/2 phosphorylated form of the synapto-nuclear protein messenger Jacob actively translocates to the nucleus upon induction of LTP and can be detected in a nuclear enriched fraction from CA1 neurons.
Neuroscience, Issue 90, Hippocampal slices, long-term potentiation LTP, nucleus, NMDA receptors, NLS, immunoblotting, Jacob, nuclear enriched protein preparations
A Procedure for Studying the Footshock-Induced Reinstatement of Cocaine Seeking in Laboratory Rats
Institutions: University of Toronto Scarborough.
The most insidious aspect of drug addiction is the high propensity for relapse. Animal models of relapse, known as reinstatement procedures, have been used extensively to study the neurobiology and phenomenology of relapse to drug use. Although procedural variations have emerged over the past several decades, the most conventional reinstatement procedures are based on the drug self-administration (SA) model. In this model, an animal is trained to perform an operant response to obtain drug. Subsequently, the behavior is extinguished by withholding response-contingent reinforcement. Reinstatement of drug seeking is then triggered by a discrete event, such as an injection of the training drug, re-exposure to drug-associated cues, or exposure to a stressor 1
Reinstatement procedures were originally developed to study the ability of acute non-contingent exposure to the training drug to reinstate drug seeking in rats and monkeys 1, 2
. Reinstatement procedures have since been modified to study the role of environmental stimuli, including drug-associated cues and exposure to various forms of stress, in relapse to drug seeking 1, 3, 4
Over the past 15 years, a major focus of the reinstatement literature has been on the role of stress in drug relapse. One of the most commonly used forms of stress for studying this relationship is acute exposures to mild, intermittent, electric footshocks. The ability of footshock stress to induce reinstatement of drug seeking was originally demonstrated by Shaham and colleagues (1995) in rats with a history of intravenous heroin SA5
. Subsequently, the effect was generalized to rats with histories of intravenous cocaine, methamphetamine, and nicotine SA, as well as oral ethanol SA 3, 6
Although footshock-induced reinstatement of drug seeking can be achieved reliably and robustly, it is an effect that tends to be sensitive to certain parametrical variables. These include the arrangement of extinction and reinstatement test sessions, the intensity and duration of footshock stress, and the presence of drug-associated cues during extinction and testing for reinstatement. Here we present a protocol for footshock-induced reinstatement of cocaine seeking that we have used with consistent success to study the relationship between stress and cocaine seeking.
Neuroscience, Issue 47, Relapse, Reinstatement, Cocaine, Rat, Footshock, Stress, Intravenous, Self-administration, Operant Conditioning
A General Method for Evaluating Incubation of Sucrose Craving in Rats
Institutions: Western Washington University.
For someone on a food-restricted diet, food craving in response to food-paired cues may serve as a key behavioral transition point between abstinence and relapse to food taking 1
. Food craving conceptualized in this way is akin to drug craving in response to drug-paired cues. A rich literature has been developed around understanding the behavioral and neurobiological determinants of drug craving; we and others have been focusing recently on translating techniques from basic addiction research to better understand addiction-like behaviors related to food 2-4
As done in previous studies of drug craving, we examine sucrose craving behavior by utilizing a rat model of relapse. In this model, rats self-administer either drug or food in sessions over several days. In a session, lever responding delivers the reward along with a tone+light stimulus. Craving behavior is then operationally defined as responding in a subsequent session where the reward is not available. Rats will reliably respond for the tone+light stimulus, likely due to its acquired conditioned reinforcing properties 5
. This behavior is sometimes referred to as sucrose seeking or cue reactivity. In the present discussion we will use the term "sucrose craving" to subsume both of these constructs.
In the past decade, we have focused on how the length of time following reward self-administration influences reward craving. Interestingly, rats increase responding for the reward-paired cue over the course of several weeks of a period of forced-abstinence. This "incubation of craving" is observed in rats that have self-administered either food or drugs of abuse 4,6
. This time-dependent increase in craving we have identified in the animal model may have great potential relevance to human drug and food addiction behaviors.
Here we present a protocol for assessing incubation of sucrose craving in rats. Variants of the procedure will be indicated where craving is assessed as responding for a discrete sucrose-paired cue following extinction of lever pressing within the sucrose self-administration context (Extinction without cues) or as responding for sucrose-paired cues in a general extinction context (Extinction with cues).
Neuroscience, Issue 57, addiction, craving, cue-reactivity, extinction, reinstatement, relapse, sucrose seeking
Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD
Institutions: Uniformed Services University of the Health Sciences, Bethesda, Maryland, GenProMarkers, Inc..
Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for objective diagnosis but also for the evaluation of therapeutic efficacy and resilience to trauma. Ongoing research is directed at identifying molecular biomarkers for PTSD, including traumatic stress induced proteins, transcriptomes, genomic variances and genetic modulators, using biologic samples from subjects' blood, saliva, urine, and postmortem brain tissues. However, the correlation of these biomarker molecules in peripheral or postmortem samples to altered brain functions associated with psychiatric symptoms in PTSD remains unresolved. Here, we present an animal model of PTSD in which both peripheral blood and central brain biomarkers, as well as behavioral phenotype, can be collected and measured, thus providing the needed correlation of the central biomarkers of PTSD, which are mechanistic and pathognomonic but cannot be collected from people, with the peripheral biomarkers and behavioral phenotypes, which can.
Our animal model of PTSD employs restraint and tail shocks repeated for three continuous days - the inescapable tail-shock model (ITS) in rats. This ITS model mimics the pathophysiology of PTSD 17, 7, 4, 10
. We and others have verified that the ITS model induces behavioral and neurobiological alterations similar to those found in PTSD subjects 17, 7, 10, 9
. Specifically, these stressed rats exhibit (1) a delayed and exaggerated startle response appearing several days after stressor cessation, which given the compressed time scale of the rat's life compared to a humans, corresponds to the one to three months delay of symptoms in PTSD patients (DSM-IV-TR PTSD Criterian D/E 13
), (2) enhanced plasma corticosterone (CORT) for several days, indicating compromise of the hypothalamopituitary axis (HPA), and (3) retarded body weight gain after stressor cessation, indicating dysfunction of metabolic regulation.
The experimental paradigms employed for this model are: (1) a learned helplessness paradigm in the rat assayed by measurement of acoustic startle response (ASR) and a charting of body mass; (2) microdissection of the rat brain into regions and nuclei; (3) enzyme-linked immunosorbent assay (ELISA) for blood levels of CORT; (4) a gene expression microarray plus related bioinformatics tools 18
. This microarray, dubbed rMNChip, focuses on mitochondrial and mitochondria-related nuclear genes in the rat so as to specifically address the neuronal bioenergetics hypothesized to be involved in PTSD.
Medicine, Issue 68, Genetics, Physiology, Neuroscience, Immunology, PTSD, biomarker, stress, fear, startle, corticosterone, animal model, RNA, RT-PCR, gene chip, cDNA microarray, oligonucleotide microarray, amygdala, prefrontal cortex, hippocampus, cingulate cortex, hypothalamus, white blood cell
Setting-up an In Vitro Model of Rat Blood-brain Barrier (BBB): A Focus on BBB Impermeability and Receptor-mediated Transport
Institutions: VECT-HORUS SAS, CNRS, NICN UMR 7259.
The blood brain barrier (BBB) specifically regulates molecular and cellular flux between the blood and the nervous tissue. Our aim was to develop and characterize a highly reproducible rat syngeneic in vitro
model of the BBB using co-cultures of primary rat brain endothelial cells (RBEC) and astrocytes to study receptors involved in transcytosis across the endothelial cell monolayer. Astrocytes were isolated by mechanical dissection following trypsin digestion and were frozen for later co-culture. RBEC were isolated from 5-week-old rat cortices. The brains were cleaned of meninges and white matter, and mechanically dissociated following enzymatic digestion. Thereafter, the tissue homogenate was centrifuged in bovine serum albumin to separate vessel fragments from nervous tissue. The vessel fragments underwent a second enzymatic digestion to free endothelial cells from their extracellular matrix. The remaining contaminating cells such as pericytes were further eliminated by plating the microvessel fragments in puromycin-containing medium. They were then passaged onto filters for co-culture with astrocytes grown on the bottom of the wells. RBEC expressed high levels of tight junction (TJ) proteins such as occludin, claudin-5 and ZO-1 with a typical localization at the cell borders. The transendothelial electrical resistance (TEER) of brain endothelial monolayers, indicating the tightness of TJs reached 300 ohm·cm2
on average. The endothelial permeability coefficients (Pe) for lucifer yellow (LY) was highly reproducible with an average of 0.26 ± 0.11 x 10-3
cm/min. Brain endothelial cells organized in monolayers expressed the efflux transporter P-glycoprotein (P-gp), showed a polarized transport of rhodamine 123, a ligand for P-gp, and showed specific transport of transferrin-Cy3 and DiILDL across the endothelial cell monolayer. In conclusion, we provide a protocol for setting up an in vitro
BBB model that is highly reproducible due to the quality assurance methods, and that is suitable for research on BBB transporters and receptors.
Medicine, Issue 88, rat brain endothelial cells (RBEC), mouse, spinal cord, tight junction (TJ), receptor-mediated transport (RMT), low density lipoprotein (LDL), LDLR, transferrin, TfR, P-glycoprotein (P-gp), transendothelial electrical resistance (TEER),
Using the Threat Probability Task to Assess Anxiety and Fear During Uncertain and Certain Threat
Institutions: University of Wisconsin-Madison.
Fear of certain threat and anxiety about uncertain threat are distinct emotions with unique behavioral, cognitive-attentional, and neuroanatomical components. Both anxiety and fear can be studied in the laboratory by measuring the potentiation of the startle reflex. The startle reflex is a defensive reflex that is potentiated when an organism is threatened and the need for defense is high. The startle reflex is assessed via electromyography (EMG) in the orbicularis oculi muscle elicited by brief, intense, bursts of acoustic white noise (i.e.
, “startle probes”). Startle potentiation is calculated as the increase in startle response magnitude during presentation of sets of visual threat cues that signal delivery of mild electric shock relative to sets of matched cues that signal the absence of shock (no-threat cues). In the Threat Probability Task, fear is measured via startle potentiation to high probability (100% cue-contingent shock; certain) threat cues whereas anxiety is measured via startle potentiation to low probability (20% cue-contingent shock; uncertain) threat cues. Measurement of startle potentiation during the Threat Probability Task provides an objective and easily implemented alternative to assessment of negative affect via self-report or other methods (e.g.
, neuroimaging) that may be inappropriate or impractical for some researchers. Startle potentiation has been studied rigorously in both animals (e.g
., rodents, non-human primates) and humans which facilitates animal-to-human translational research. Startle potentiation during certain and uncertain threat provides an objective measure of negative affective and distinct emotional states (fear, anxiety) to use in research on psychopathology, substance use/abuse and broadly in affective science. As such, it has been used extensively by clinical scientists interested in psychopathology etiology and by affective scientists interested in individual differences in emotion.
Behavior, Issue 91,
Startle; electromyography; shock; addiction; uncertainty; fear; anxiety; humans; psychophysiology; translational
Getting to Compliance in Forced Exercise in Rodents: A Critical Standard to Evaluate Exercise Impact in Aging-related Disorders and Disease
Institutions: Louisiana State University Health Sciences Center.
There is a major increase in the awareness of the positive impact of exercise on improving several disease states with neurobiological basis; these include improving cognitive function and physical performance. As a result, there is an increase in the number of animal studies employing exercise. It is argued that one intrinsic value of forced exercise is that the investigator has control over the factors that can influence the impact of exercise on behavioral outcomes, notably exercise frequency, duration, and intensity of the exercise regimen. However, compliance in forced exercise regimens may be an issue, particularly if potential confounds of employing foot-shock are to be avoided. It is also important to consider that since most cognitive and locomotor impairments strike in the aged individual, determining impact of exercise on these impairments should consider using aged rodents with a highest possible level of compliance to ensure minimal need for test subjects. Here, the pertinent steps and considerations necessary to achieve nearly 100% compliance to treadmill exercise in an aged rodent model will be presented and discussed. Notwithstanding the particular exercise regimen being employed by the investigator, our protocol should be of use to investigators that are particularly interested in the potential impact of forced exercise on aging-related impairments, including aging-related Parkinsonism and Parkinson’s disease.
Behavior, Issue 90, Exercise, locomotor, Parkinson’s disease, aging, treadmill, bradykinesia, Parkinsonism
Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Institutions: Université de Strasbourg.
Opioid-induced hyperalgesia and tolerance severely impact the clinical efficacy of opiates as pain relievers in animals and humans. The molecular mechanisms underlying both phenomena are not well understood and their elucidation should benefit from the study of animal models and from the design of appropriate experimental protocols.
We describe here a methodological approach for inducing, recording and quantifying morphine-induced hyperalgesia as well as for evidencing analgesic tolerance, using the tail-immersion and tail pressure tests in wild-type mice. As shown in the video, the protocol is divided into five sequential steps. Handling and habituation phases allow a safe determination of the basal nociceptive response of the animals. Chronic morphine administration induces significant hyperalgesia as shown by an increase in both thermal and mechanical sensitivity, whereas the comparison of analgesia time-courses after acute or repeated morphine treatment clearly indicates the development of tolerance manifested by a decline in analgesic response amplitude. This protocol may be similarly adapted to genetically modified mice in order to evaluate the role of individual genes in the modulation of nociception and morphine analgesia. It also provides a model system to investigate the effectiveness of potential therapeutic agents to improve opiate analgesic efficacy.
Neuroscience, Issue 89, mice, nociception, tail immersion test, tail pressure test, morphine, analgesia, opioid-induced hyperalgesia, tolerance
Analysis of Tubular Membrane Networks in Cardiac Myocytes from Atria and Ventricles
Institutions: Heart Research Center Goettingen, University Medical Center Goettingen, German Center for Cardiovascular Research (DZHK) partner site Goettingen, University of Maryland School of Medicine.
In cardiac myocytes a complex network of membrane tubules - the transverse-axial tubule system (TATS) - controls deep intracellular signaling functions. While the outer surface membrane and associated TATS membrane components appear to be continuous, there are substantial differences in lipid and protein content. In ventricular myocytes (VMs), certain TATS components are highly abundant contributing to rectilinear tubule networks and regular branching 3D architectures. It is thought that peripheral TATS components propagate action potentials from the cell surface to thousands of remote intracellular sarcoendoplasmic reticulum (SER) membrane contact domains, thereby activating intracellular Ca2+
release units (CRUs). In contrast to VMs, the organization and functional role of TATS membranes in atrial myocytes (AMs) is significantly different and much less understood. Taken together, quantitative structural characterization of TATS membrane networks in healthy and diseased myocytes is an essential prerequisite towards better understanding of functional plasticity and pathophysiological reorganization. Here, we present a strategic combination of protocols for direct quantitative analysis of TATS membrane networks in living VMs and AMs. For this, we accompany primary cell isolations of mouse VMs and/or AMs with critical quality control steps and direct membrane staining protocols for fluorescence imaging of TATS membranes. Using an optimized workflow for confocal or superresolution TATS image processing, binarized and skeletonized data are generated for quantitative analysis of the TATS network and its components. Unlike previously published indirect regional aggregate image analysis strategies, our protocols enable direct characterization of specific components and derive complex physiological properties of TATS membrane networks in living myocytes with high throughput and open access software tools. In summary, the combined protocol strategy can be readily applied for quantitative TATS network studies during physiological myocyte adaptation or disease changes, comparison of different cardiac or skeletal muscle cell types, phenotyping of transgenic models, and pharmacological or therapeutic interventions.
Bioengineering, Issue 92, cardiac myocyte, atria, ventricle, heart, primary cell isolation, fluorescence microscopy, membrane tubule, transverse-axial tubule system, image analysis, image processing, T-tubule, collagenase
Training Rats to Voluntarily Dive Underwater: Investigations of the Mammalian Diving Response
Institutions: Midwestern University.
Underwater submergence produces autonomic changes that are observed in virtually all diving animals. This reflexly-induced response consists of apnea, a parasympathetically-induced bradycardia and a sympathetically-induced alteration of vascular resistance that maintains blood flow to the heart, brain and exercising muscles. While many of the metabolic and cardiorespiratory aspects of the diving response have been studied in marine animals, investigations of the central integrative aspects of this brainstem reflex have been relatively lacking. Because the physiology and neuroanatomy of the rat are well characterized, the rat can be used to help ascertain the central pathways of the mammalian diving response. Detailed instructions are provided on how to train rats to swim and voluntarily dive underwater through a 5 m long Plexiglas maze. Considerations regarding tank design and procedure room requirements are also given. The behavioral training is conducted in such a way as to reduce the stressfulness that could otherwise be associated with forced underwater submergence, thus minimizing activation of central stress pathways. The training procedures are not technically difficult, but they can be time-consuming. Since behavioral training of animals can only provide a model to be used with other experimental techniques, examples of how voluntarily diving rats have been used in conjunction with other physiological and neuroanatomical research techniques, and how the basic training procedures may need to be modified to accommodate these techniques, are also provided. These experiments show that voluntarily diving rats exhibit the same cardiorespiratory changes typically seen in other diving animals. The ease with which rats can be trained to voluntarily dive underwater, and the already available data from rats collected in other neurophysiological studies, makes voluntarily diving rats a good behavioral model to be used in studies investigating the central aspects of the mammalian diving response.
Behavior, Issue 93, Rat, Rattus norvegicus, voluntary diving, diving response, diving reflex, autonomic reflex, central integration
Viability Assays for Cells in Culture
Institutions: Duquesne University.
Manual cell counts on a microscope are a sensitive means of assessing cellular viability but are time-consuming and therefore expensive. Computerized viability assays are expensive in terms of equipment but can be faster and more objective than manual cell counts. The present report describes the use of three such viability assays. Two of these assays are infrared and one is luminescent. Both infrared assays rely on a 16 bit Odyssey Imager. One infrared assay uses the DRAQ5 stain for nuclei combined with the Sapphire stain for cytosol and is visualized in the 700 nm channel. The other infrared assay, an In-Cell Western, uses antibodies against cytoskeletal proteins (α-tubulin or microtubule associated protein 2) and labels them in the 800 nm channel. The third viability assay is a commonly used luminescent assay for ATP, but we use a quarter of the recommended volume to save on cost. These measurements are all linear and correlate with the number of cells plated, but vary in sensitivity. All three assays circumvent time-consuming microscopy and sample the entire well, thereby reducing sampling error. Finally, all of the assays can easily be completed within one day of the end of the experiment, allowing greater numbers of experiments to be performed within short timeframes. However, they all rely on the assumption that cell numbers remain in proportion to signal strength after treatments, an assumption that is sometimes not met, especially for cellular ATP. Furthermore, if cells increase or decrease in size after treatment, this might affect signal strength without affecting cell number. We conclude that all viability assays, including manual counts, suffer from a number of caveats, but that computerized viability assays are well worth the initial investment. Using all three assays together yields a comprehensive view of cellular structure and function.
Cellular Biology, Issue 83, In-cell Western, DRAQ5, Sapphire, Cell Titer Glo, ATP, primary cortical neurons, toxicity, protection, N-acetyl cysteine, hormesis
Strategies for Study of Neuroprotection from Cold-preconditioning
Institutions: The University of Chicago Medical Center.
Neurological injury is a frequent cause of morbidity and mortality from general anesthesia and related surgical procedures that could be alleviated by development of effective, easy to administer and safe preconditioning treatments. We seek to define the neural immune signaling responsible for cold-preconditioning as means to identify novel targets for therapeutics development to protect brain before injury onset. Low-level pro-inflammatory mediator signaling changes over time are essential for cold-preconditioning neuroprotection. This signaling is consistent with the basic tenets of physiological conditioning hormesis, which require that irritative stimuli reach a threshold magnitude with sufficient time for adaptation to the stimuli for protection to become evident.
Accordingly, delineation of the immune signaling involved in cold-preconditioning neuroprotection requires that biological systems and experimental manipulations plus technical capacities are highly reproducible and sensitive. Our approach is to use hippocampal slice cultures as an in vitro
model that closely reflects their in vivo
counterparts with multi-synaptic neural networks influenced by mature and quiescent macroglia / microglia. This glial state is particularly important for microglia since they are the principal source of cytokines, which are operative in the femtomolar range. Also, slice cultures can be maintained in vitro
for several weeks, which is sufficient time to evoke activating stimuli and assess adaptive responses. Finally, environmental conditions can be accurately controlled using slice cultures so that cytokine signaling of cold-preconditioning can be measured, mimicked, and modulated to dissect the critical node aspects. Cytokine signaling system analyses require the use of sensitive and reproducible multiplexed techniques. We use quantitative PCR for TNF-α to screen for microglial activation followed by quantitative real-time qPCR array screening to assess tissue-wide cytokine changes. The latter is a most sensitive and reproducible means to measure multiple cytokine system signaling changes simultaneously. Significant changes are confirmed with targeted qPCR and then protein detection. We probe for tissue-based cytokine protein changes using multiplexed microsphere flow cytometric assays using Luminex technology. Cell-specific cytokine production is determined with double-label immunohistochemistry. Taken together, this brain tissue preparation and style of use, coupled to the suggested investigative strategies, may be an optimal approach for identifying potential targets for the development of novel therapeutics that could mimic the advantages of cold-preconditioning.
Neuroscience, Issue 43, innate immunity, hormesis, microglia, hippocampus, slice culture, immunohistochemistry, neural-immune, gene expression, real-time PCR
Survivable Stereotaxic Surgery in Rodents
Institutions: Tufts University.
The ability to measure extracellular basal levels of neurotransmitters in the brain of awake animals allows for the determination of effects of different systemic challenges (pharmacological or physiological) to the CNS. For example, one can directly measure how the animal's midbrain dopamine projections respond to dopamine-releasing drugs like d-amphetamine or natural stimuli like food. In this video, we show you how to implant guide cannulas targeting specific sites in the rat brain, how to insert and implant a microdialysis probe and how to use high performance liquid chromatography coupled with electrochemical detection (HPLC-EC) to measure extracellular levels of oxidizable neurotransmitters and metabolites. Local precise introduction of drugs through the microdialysis probe allows for refined work on site specificity in a compound s mechanism of action. This technique has excellent anatomical and chemical resolution but only modest time resolution as microdialysis samples are usually processed every 20-30 minutes to ensure detectable neurotransmitter levels. Complementary ex vivo tools (i.e., slice and cell culture electrophysiology) can assist with monitoring real-time neurotransmission.
Neuroscience, Issue 20, microdialysis, nucleus accumbens, catecholamines, dopamine, rats. mice, brain
Creation of Reversible Cholestatic Rat Model
Institutions: Providence Hospital and Medical Centers.
Cholestasis is a clinical condition commonly encountered by both surgeons and gastroenterologists. Cholestasis can cause various physiological changes and affect the nutritional status and surgical outcomes. Study of the pathophysiological changes occurring in the liver and other organs is of importance. Various studies have been done in cholestatic rat models.
We used a reversible cholestatic rat model in our recent study looking at the role of methylprednisolone in the ischemia reperfusion injury. Various techniques for creation of a reversible cholestatic model have been described. Creation of a reversible cholestatic rat model can be challenging in view of the smaller size and unique hepatopancreatobiliary anatomy in rats. This video article demonstrates the creation of a reversible cholestatic model.
This model can be used in various studies, such as looking at the changes in nutritional, physiological, pathological, histological and immunological changes in the gastrointestinal tract. This model can also be used to see the effects of cholestasis and various therapeutic interventions on major hepatic surgeries.
Medicine, Issue 51, Cholestasis, Rat model, Reversible cholestasis, Choledochoduodenostomy, Bile duct obstruction, Cholestasis
The Resident-intruder Paradigm: A Standardized Test for Aggression, Violence and Social Stress
Institutions: University Groningen, Radboud University Nijmegen.
This video publication explains in detail the experimental protocol of the resident-intruder paradigm in rats. This test is a standardized method to measure offensive aggression and defensive behavior in a semi natural setting. The most important behavioral elements performed by the resident and the intruder are demonstrated in the video and illustrated using artistic drawings. The use of the resident intruder paradigm for acute and chronic social stress experiments is explained as well. Finally, some brief tests and criteria are presented to distinguish aggression from its more violent and pathological forms.
Behavior, Issue 77, Neuroscience, Medicine, Anatomy, Physiology, Genetics, Basic Protocols, Psychology, offensive aggression, defensive behavior, aggressive behavior, pathological, violence, social stress, rat, Wistar rat, animal model
The Structure of Skilled Forelimb Reaching in the Rat: A Movement Rating Scale
Institutions: University of Lethbridge.
Skilled reaching for food is an evolutionary ancient act and is displayed by many animal species, including those in the sister clades of rodents and primates. The video describes a test situation that allows filming of repeated acts of reaching for food by the rat that has been mildly food deprived. A rat is trained to reach through a slot in a holding box for food pellet that it grasps and then places in its mouth for eating. Reaching is accomplished in the main by proximally driven movements of the limb but distal limb movements are used for pronating the paw, grasping the food, and releasing the food into the mouth. Each reach is divided into at least 10 movements of the forelimb and the reaching act is facilitated by postural adjustments. Each of the movements is described and examples of the movements are given from a number of viewing perspectives. By rating each movement element on a 3-point scale, the reach can be quantified. A number of studies have demonstrated that the movement elements are altered by motor system damage, including damage to the motor cortex, basal ganglia, brainstem, and spinal cord. The movements are also altered in neurological conditions that can be modeled in the rat, including Parkinson's disease and Huntington's disease. Thus, the rating scale is useful for quantifying motor impairments and the effectiveness of neural restoration and rehabilitation. Because the reaching act for the rat is very similar to that displayed by humans and nonhuman primates, the scale can be used for comparative purposes. from a number of viewing perspectives. By rating each movement element on a 3-point scale, the reach can be quantified. A number of studies have demonstrated that the movement elements are altered by motor system damage, including damage to the motor cortex, basal ganglia, brainstem, and spinal cord. The movements are also altered in neurological conditions that can be modeled in the rat, including Parkinson's disease and Huntington's disease. Thus, the rating scale is useful for quantifying motor impairments and the effectiveness of neural restoration and rehabilitation.
Experiments on animals were performed in accordance with the guidelines and regulations set forth by the University of Lethbridge Animal Care Committee in accordance with the regulations of the Canadian Council on Animal Care.
Neuroscience, Issue 18, rat skilled reaching, rat reaching scale, rat, rat movement element rating scale, reaching elements


This is both a very serious and light-hearted episode as Kamijace and Twylark talk about the recent shooting in Jacksonville, Florida and discuss how gamers can do better for the community. As well as gun rights and other “political” ideas. We talk both as friends and as concerned gamers.
Remember: Any and all media is political.
Check out Sunday September 2 episode for links to Facebook, Twitter, and the Humble Bundle.
Support this podcast: https://anchor.fm/wkcooldown/support


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Raised blood glucose levels (more than 10mmol/l)
The amount of a substance (solute) in a solution
The biochemical process by which the cells in the body releases energy
A polysaccharide, (C6H10O5)n, that is stored in the liver and in muscles and can be converted back into glucose when needed by the body.
A hormone produced by the pancreas. It causes the liver to convert glycogen back to glucose and to release glucose into the bloodstream.
To confirm diabetes, a person will normally take a glucose tolerance test in a hospital.
Patients do not eat for 12 hours before the test. This gets their blood glucose to its lowest level. They are then given a drink containing 75g of glucose and their blood glucose level is monitored over the next two hours.
Diabetics will rapidly become hyperglycaemic. Their blood glucose level rises and remains above normal.
Healthy individuals will release insulin to store the excess glucose. Their blood glucose level rises but then returns to normal.
Blood glucose in the diabetic rises and stays above normal.
The healthy person regulates their glucose back to normal.
Every cell in the body needs a supply of glucose to maintain respiration and generate energy for all of its processes. Levels of glucose (sugar) in the blood are closely controlled by two hormones; insulin and glucagon.
Use the animation to see how the body responds to high and low blood sugar levels:
Drag the responses into the correct columns
|Blood sugar too high||Blood sugar too low|

domain: chemistry


text:
Smooth Lapis and Diamond Earringssa-508rL
Round, smooth spheres of lapis hang below Gabrielle's signature 18K yellow gold flyers to create a pair of earrings with vibrant, versatile color. Pair them with your weekend wear for a punch of color, or down-play something more formal by adding them as a touch of earthy elegance.
total length : 3/4"
lapis : 12mm diameter each
18K yellow gold flyer ear wires
NEW YORK - Gabrielle's stunning jewelry has always evolved directly from the essence of the natural materials she chooses. Her fascination with pearls as completely organic gems has led her to create a collection of luscious jewels with stunning refined elegance. Faceted stones in vibrant, saturated, and subtle colors and with smooth and faceted surfaces add a lively, distinctive visual dimension to her collection. Topped with her signature 18K gold flyers, Gabrielle's earrings are collected by many for their sophisticated, easy-to-wear earthiness and splash of color.
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domain: artistic


If you’re a Verizon customer, expect to pay a little more for your phone bill soon. But at least you’ll get some more data for streaming Netflix and checking Facebook.
According to CNET, the nation’s largest wireless carrier’s plans will go up between $5 and $10 a month, depending on the plan.
Plans will see data bumps between one and six gigabytes.
Here’s the breakdown:
- “S” plan is $35 a month for 2GB (originally $30 for 1GB)
- “M” is $50 a month for 4GB (originally $45 for 3GB)
- “L” is $70 a month for 8GB (originally $60 for 6GB)
- “XL” is $90 a month for 16GB (originally $80 for 12GB)
- “XXL” is $110 a month for 24GB (originally $100 for 18GB)
Verizon is expected to unveil “Carryover Data,” a rollover plan that allows customers to keep unused data from one month to the next. Another anticipated change is called “Safety Mode,” something that will protect customers from overage fees. Instead of getting socked with a fee for using too much data, customers would see their data connection slowed down until the end of the billing cycle.
CNET reports that existing customers won’t be forced to change to the new plans but will instead get to opt in if they choose. Verizon is expected to unveil the new plans during a news conference Wednesday afternoon.


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If you’re into all things sweet and savory, you should definitely snatch up a bottle of Salted Belgian Chocolate Stout, our most recent Lips of Faith collaboration with St. Louis’ Perennial Artisan Ales. It’s rich, chocolaty, slightly fruity and kissed with hints of spice and salt. In a word: delicious. You know what else is delicious? Cake, especially chocolate cake made with the beer.
Just down the street from the brewery is Little Bird Bakeshop, where owner and pastry chef Amy Marsh whipped up an intensely luscious chocolate cake featuring the stout. Now Friday production’s come to a halt as we’re all just sitting around nomming on beer cake.
Amy Marsh of Little Bird Bakeshop.
If you’re looking for a new holiday dessert to bake this winter, pick up a bottle of Salted Belgian Chocolate Stout and check out the recipe below. If you live in town, swing by Little Bird, where this recipe is likely to pop up again soon along with other beer-baked goodness.
Salted Chocolate Stout Cake with Ginger Stout Glaze
1 cup Salted Belgian Chocolate Stout
2 sticks unsalted butter
¾ cup cocoa powder (preferably Dutch processed)
2 cups all purpose flour
2 cups sugar
¾ teaspoon baking soda
¾ teaspoon kosher salt
2 large eggs
2/3 cup sour cream
2 cups powdered sugar
1 pinch kosher salt
1 ounce (2 tablespoons) unsalted butter, softened
¼ cup Salted Belgian Chocolate Stout
2 tablespoons minced crystallized ginger
Cheers — Chris

domain: food


text:
Krakatoa's Eruption - The
One of the most cataclysmic events of recent history may not
have just a geological impact but a geopolitical one, as suggested by
renowned author Simon Winchester.
Winchester's premise is twofold: that the blasting out of
existence of the island of Krakatoa was a catastrophe that gave birth to the
concept of global village while triggering a revolt that gave birth to
modern-day Islamic fundamentalism.
The eruption, in August 1883, was not only of a volcano but
an explosion of social, political, religious and economic forces in the
Dutch colony of Java. Krakatoa set the
scene for the rise of such entrenched anti-colonial and anti-Christian
sentiment that it is intrinsically linked to the fanaticism of Osama bin
The anti-colonial mullahs used Krakatoa as a sign to the
peasantry of the revenge of Allah against not only the infidel Dutch and
their allies, but also those Muslims who supported them.
Some 24 European civilians were massacred in a revolt that erupted five years
later. Although ruthlessly put down by the Dutch in one of the world's first wars on terror, the Bantan
Peasants' Revolt of 1888 is still regarded as the first step leading to the expulsion of Europeans and the creation
of the modern state of Indonesia in 1949. The revolt was inspired by letters from Arabia (Yemen, apparently), which
may be the dim outlines of the first global terrorist network.
More immediately plausible is Krakatoa's relationship to the global village. The tectonic
collision that gave rise to the volcanic blast caused the first tremors on May 10, and first serious concerns that
something terrible was afoot on May 15. London knew all about it on May 24.
The speed of communication - you could actually get a Morse message between Asia and London in
just three hours by the quickest route - was a product of the newly invented electric telegraph and submarine
The telegraph arrived in the East Indies in 1856 and submarine cable - the fastest means of
getting a message around the world - in 1870.
By 1872, London could speak directly to Sydney.
To give an idea of the improvement in speed of message transmission, just 50 years earlier it
had taken two months for news of Napoleon's death on St Helena to reach London.
While the physical tremors from Krakatoa were felt as far as 4500km from the source, the
emotional tremors were felt around the civilized world.
The news must have been received with the same trepidation as that sparked by the Chernobyl
nuclear accident 100 years later. The scale of the disaster is still awesome.
At 10.02am on August 27, more than nine cubic kilometers of
rock were literally blasted out of existence, a massive ash plume headed
skyward, some reaching the fringes of space. The noise was heard more than
4500km away, including in parts of western and northern Australia.
More than 160 villages ceased to exist as a series of
volcano-inspired tidal waves up to 35m high swept across the coast. Such was
the force of the waves that the steamer Berouw was lifted and unceremoniously
dumped more than 2km up the Koeripan River from its original position in its
The human toll was staggering for the time: the final death
count was 36,417. The world's atmospheric temperature dropped by one
It sparked weeks of blood-red sunsets from China to South
Africa and by its vividness tricked firemen at Poughkeepsie on the Hudson River
into thinking the bush outside town was alight.
Read some other interestng Facts about Krakatoa.

domain: history


text:
There are many reasons why dating a married female is a bad idea. Not only can it result in a unpleasant breakup, additionally, it may cause clash between a married female and her partner. A hitched woman is more likely to put her family’s needs prior to her fan. However , when you are the type of individual who values spouse and children more than anything at all otherwise, then online dating a married woman is excellent.
Online dating a married female will not be easy. It will make you feeling puzzled and emotionally drained. You may also acquire stuck in a lurch, while she might not exactly want to leave her husband. Besides, it’s not uncommon for a betrothed woman to have multiple love-making partners.
Dating a married woman will likewise expose you to emotional manipulation. If she actually is sad in her marriage, she’ll try to get your sympathy by simply telling you about her husband’s problems. Whilst she could possibly be telling you the fact, she’ll make an effort to manipulate you to acquire sympathy on her situation.
Even though the notion of dating a married female may seem important, the end result might leave you with broken minds and a broken house. Whether the woman is looking for thrills outside of her matrimony, searching for anyone to lean on, or looking for revenge for your cheating husband, it could wrong in every single way.
Although a married woman may be appealing and alluring, she has a hard deadline. In cases where her partner or her children find out about your marriage, she’ll most probably leave. Even if your woman stays in the relationship, she will most likely be low and her family may not forgive you. This is why it’s important https://steveharvey.com/how-to-beat-the-online-dating-game/ to make sure you’re here ready for this sort of relationship before you take the plunge.
Although married women may be physically attractive and get steady personalities, they’re generally as well busy balancing their lives to be genuinely tender-hearted. This makes it difficult to spend quality time together. As a result, they may become isolated, possessive, and damaging. In addition , they’re not likely to allow for their partners to pursue their marriage.
In addition , dating a married girl can be a difficult situation just for the woman’s husband. After the affair, he may end up being trying to train his better half a lesson, but this can prove to be complex. It may take a lot of makes an attempt before the female’s husband can understand https://married-dating.org/sweetdiscreet-review/ that his wife comes with another gentleman. If this lady doesn’t response, he may have a second woman in mind.

domain: sociology


Lost in the endless swirl of Elon related news was just how fast the electric vehicle industry is growing. While still just a speck compared to the overall vehicle market some recently released numbers should have major automakers running for the hills. The end of days for traditional gas-powered vehicles isn't here yet but things aren't looking up and if things continue the way they are electric vehicles are going to take over the auto industry much faster than anticipated.
The Numbers Keep Growing
Globally the EV market share is tiny, just surpassing the 4 million mark and making up roughly one-half a percent of the total vehicle count. By looking at things this way its easy to write EVs off as a passing fancy rather then a growing trend. However, this would be a mistake as global electric vehicle sales over the past two years have been rapidly accelerating.
Global electric vehicle sales:
1st million: ~20 years
2nd million: 18 months
3rd million: 8 months
4th million: 6 months
5th million: 5 months (projected)
It doesn't take a genius to look at the trend to see where this is all headed. People want EVs and with the continued push by most major nations to hit certain adoption milestones things are starting to rev up even faster. The demand is clearly there, the only thing slowing down adoption is the supply. While Tesla has gone to great lengths to speed its output many of the other auto OEMs are content with simply dragging their feet. With Audi going so far as to limit the sale of their new e-tron line to 'special order' only. It seems extremely short-sighted to do this as Tesla continues to eat away at their market share.
Tesla, The King of Luxury
Tesla, by any measure, is not a large automaker yet. By years end they'll produce roughly 200,000 vehicles which doesn't even come close to cracking the top 20 largest automakers in the world. Once again these numbers are deceiving, as Tesla will nearly double its output from last year, but more importantly they have started to dominate their individual classes and taken over two of the luxury class markets.
Their overall market share is nothing near that of Volkswagen, but the simple fact remains that they are dominating their like-for-like counter parts. If they could scale to the size of a GM or VW and had vehicles in every market class odds are good they would own those markets too. The Model 3 is dominating the competition across the board and that doesn't even include the original Model S or X.
Its clear that Tesla is not only the undisputed king of EVs but they are well on their way to owning the all the luxury car market as well. Which should make the likes of Audi, BMW, and Mercedes very nervous.
China Loves Electrics
Quiet possibly the strongest headwind for electric vehicles is their ever increasing popularity in the world's largest car market. China has done quiet a lot to grow their EV market over the past three years instituting lots of incentives to new car buyers in order to bring air pollution under control. The thing to remember is that just three years ago the Chinese EV market didn't really exist.
China's EV Market Share Growth
2018:5% (through August)
While the trend of doubling every year isn't likely to continue its easy to see that the EV market in China is strong. Especially when taking into account commercial vehicles like city buses. All these roads lead the same place, electric vehicles are starting to take over the auto industry and if traditional automakers don't step up in a big way they'll end up left behind.


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A gifted child, A. Sooryagayathri juggles her studies, music and travel with an acrobat’s finesse.
On YouTube, she is nothing short of a sensation. Search for Sooryagayathri and you come across a flawless rendering of a Ganesha bhajan, not one swara or syllable out of place. A figure in seven digits on the bottom right of the screen denotes the number of views the video had earned for the rendition by the little genius. A sixth grader from Kozhikode district in Kerala, the 11-year-old was even younger when accolades came her way for singing devotional songs and albums. It was in 2015 that she first shot to fame through the devotional albums of Kuldeep M. Pai. Her latest, Vishnu Sahasranamam recorded in January, has already garnered over two lakh views.
“I want to be like M.S. Subbulakshmi Amma, and spread my music across the globe,” comes the reply when she is prodded on what she wants to do when she grows up. Kuldeep, who creates his own tunes for traditional bhajans, is a friend of the young singer’s father and records his tunes in his own studio in Chennai. Prior to every YouTube release, he posts a teaser on Facebook.
The girl, clad in a traditional silk skirt and top with her hair parted at the centre, conjures up an image similar to that of the little singer in the Tamil movie Saivam. A gifted child, A. Sooryagayathri juggles her studies, music and travel with an acrobat’s finesse.
Surprisingly, this busy schedule has no impact on her studies. “When I’m away for programmes, my friends write notes for me. My teachers are so helpful in getting my doubts cleared. My mother is there to help me cover lessons I miss in class as well,” says the 11-year-old. Despite her busy schedule, Sooryagayathri’s scorecard has A-grades against all subjects, informs her mother.
Having learned Indian classical music from the age of five, Sooryagayathri is under the tutelage of two teachers in Carnatic vocals. She does a lot of homework when she has to sing songs in languages other than her mother tongue. She finds out about the audience’s taste before selecting the songs. For instance, the North Indian audience loves bhajans in Hindi and Sanskrit while South Indians prefer songs in their languages.
There were rumours that the young prodigy was the late legend MS Subbulakshmi’s grandchild. “It happened when her Hanuman Chalisa went viral. Somehow her style of presentation invited such a comparison,” says her mother. Perhaps also because she received the M.S. Subbulakshmi Fellowship for music and shows an unusual wealth of talent.


text:
Listed in: English, as ENGL-213
Formerly listed as: ENGL-08 | ENGL-10
Barry O'Connell (Section 01)
In the years 1830 to 1860 Emerson dominates. He is known throughout the entire United States, widely read, yet more widely heard, an inspiration to many writers, a curse to a few. Melville and Thoreau are little known for the most part. Until Harriet Beecher Stowe’s Uncle Tom’s Cabin, none of the many women writers achieved comparable stature, though many were popular.
Political and social struggle marked these times: Indian Rights, abolitionism, women’s rights, utopian communities, the continuing efforts of black people to become free in the North as well as in the South, and the sectional antagonisms that led to the Civil War. These pervade every form of literature and support the emergence of Indian writers, a substantial number of black writers (most notably Frederick Douglass) and slave narratives, a whole new genre, and more writing by women. For the first time in American history something like the full range of voices in the society could be heard and read.
The readings in the course focus on Emerson, Thoreau, Whitman, Douglass, Apess, and Stowe.
Limited to 40 students. Spring semester. Professor Emeritus O’Connell.
If Overenrolled: Preference will be given to seniors and then juniors.

domain: library


text:
SAMUEL ROY-BOIS / ELSPETH PRATT / JACK JEFFREY
Opening: Friday May 31, 7:00 p.m. | Exhibition: May 29 – June 29, 2019
Trapp Projects | 274 East 1 Ave., Vancouver
Please join the SCA's Elspeth Pratt and Samuel Roy-Bois and Jack Jeffrey for an exhbiiton at Patrik Andersson's upstart Trapp Projects space, located at 274 East 1 Avenue (entrance from alley). Trapp Projects is open Saturdays from 12:00 – 5:00 pm or by appointment.
Trapp Projects was initiated by Patrik Andersson in 1997 as a curatorial platform on which to introduce local and international artists to as wide an audience as possible, while not being limited by the mandates of traditional exhibition spaces. Over the years, this project has led to collaborations with a wide range of people and spaces to highlight both emerging and established practices. One of the best examples of this collaboration has been the support of graphic designer Judith Steedman, as well as patrons such as Dr. Zenon Trylowsky who has allowed Trapp Projects to turn his downtown Vancouver dental office into a temporary art gallery on seven different occasions. Other collaborations have led Trapp to open exhibitions internationally in shopping malls, artist’s studios, grain silos, museums, artist-run spaces, commercial galleries, books, magazines and boxes. In each case, the characteristics of the particular site has helped to shape the exhibition’s outcome.


text:
A genetic study published on Sunday raised the question on whether or not a super snake could emerge in the Florida Everglades after it was revealed a small number of Burmese and Indian pythons have been breeding.
The journal Ecology and Evolution reported that experts examined tail tissue of 400 captured snakes from South Florida and found 13 had some genetic indicators that point to Indian pythons, according to The Miami Herald.
The Indian pythons, unlike the Burmese pythons, prefer high and dry grounds, the report said.
Margaret Hunter, a geneticist at the U.S. Geological Survey and lead author of the report, said the Indian pythons have a “wider range.”
Hunter said seeing the Indian marker was “unexpected,” and she had to keep looking at the data “to make sure what she was seeing was correct.”
Tens of thousands of pythons are estimated to be slithering through the Everglades. Scientists say the giant constrictor snakes, which can grow over 20 feet long, have eliminated 99 percent of the native mammals in the Everglades, decimating food sources for native predators such as panthers and alligators.
The area also was habitat for American crocodiles, one of the protected native species in the Everglades that officials say are losing ground to the invasive pythons.
Hunter said in the report that it is unclear how the species got crossed, but scientists believe that the snakes could head north due to the warming planet.
"Such a large population allows them to rapidly adapt," she said. "If some animals die out because of climatic issues, there are other animals that may not die out."
The Associated Press contributed to this report

domain: geography


The Los Angeles County Office of the Assessor, led by Jeffrey Prang, received a near-perfect rating of 99.67 in the most recent survey of its practices and performance by the California State Board of Equalization.
The rating reflects the completeness and accuracy of the Assessment Roll, which is the...
Los Angeles County homeowners whose properties have been damaged or destroyed by the Woolsey, Hill, or Pike fires may be eligible for property tax relief.
The offices of Los Angeles County Assessor Jeffrey Prang, Treasurer and Tax Collector Joseph Kelly, Auditor-Controller John Naimo, and Executive...
LOS ANGELES, CA – Assessor Jeffrey Prang urges homeowners and owners of other property damaged or destroyed by the recent wildfires to seek tax relief.
By filing a claim for “Misfortune & Calamity” relief (available at assessor.lacounty.gov) within one year, property owners who have suffered...
Santa Clarita ranks No. 5 among Los Angeles County’s 88 cities in the assessed value of all taxable real property and business personal property, according to the 2017 Annual Report released by County Assessor Jeffrey Prang today.
Santa Clarita’s taxable property is $30.7 billion, a 7.1...
The most prestigious recognition for government assessment agencies has been awarded to the Office of the Assessor in Los Angeles County. Assessor Jeffrey Prang will be presented with the Certificate of Excellence in Assessment Administration (CEAA) by the International Association of Assessing Officers...
With COVID-19 vaccine appointments booked at Los Angeles County sites through the end of the week, Public Health officials assured those who received their first dose are guaranteed their second — but confusion over the scheduling process prompted officials to clarify the situation Tuesday.
The Santa Clarita Community College District Board of Trustees will hold a video/teleconferencing special meeting via Zoom on Wednesday, Jan. 27, beginning with a closed session at 4:00 p.m., followed immediately by open session at 5:00 p.m.
Five Point Holdings, LLC recently announced the sale of additional homesites at its Valencia community, previously known as Newhall Ranch, and the lineup of homebuilders for the first phase of the community.
As COVID-19 vaccination continues for health care workers and those over 65, Gov. Gavin Newsom announced Monday California is looking to prioritize the next phases of vaccination efforts by age, rather than occupation.
Tejon Ranch Co. declared victory for its 8,000-acre Grapevine mixed-use development after a Kern County Superior Court judge ruled against an Arizona-based environmental group that dubbed the project “damaging.”
California Public Health officials lifted the regional Stay at Home Order statewide on Monday as Los Angeles County Public Health officials confirmed 43 new deaths and 6,642 new cases of confirmed COVID-19 countywide, and Henry Mayo Newhall Hospital in Valencia reported five new deaths on Saturday and Monday.
Los Angeles County is set to align its health order with California's by the end of the week, as the state lifted its regional stay-at-home order statewide Monday, green-lighting the reopening of in-person outside dining and hair and nail salons, among other businesses.
Officials with the California Department of Public Health on Monday ordered the Regional Stay at Home Order lifted for all regions statewide, including the three regions that had still been under the order – San Joaquin Valley, Bay Area, and Southern California.
As another winter storm hit the Santa Clarita Valley and surrounding areas, Interstate 5 was shut down through the Grapevine in "Operation Snowflake" Monday morning, with some lanes reopened by Monday afternoon.
Because of the recent rainfall, Los Angeles County Health Officer Muntu Davis, MD, MPH, is cautioning residents about beach water use due to bacteria, chemicals, debris, trash, and other public health hazards from city streets and mountain areas that are likely to contaminate ocean waters at and around discharging storm drains, creeks, and rivers.
Citing the case of a convicted child rapist, Los Angeles County Supervisor Kathryn Barger said Friday she’s concerned there is a growing trend that the rights of victims of some of the most violent crimes are not being protected under District Attorney George Gascón’s administration.
Medical examiners with the Los Angeles County Coroner’s Office identified Benjamin Marquez IV, 31, of Castaic, as the man killed in a solo-vehicle crash that left one dead and sent another to the hospital Saturday.
The COVID-19 crisis has trashed recycling efforts and instead generated an increase in plastic waste, according to a recent study, but Los Angeles County restaurants could soon be required to make adjustments related to disposable food ware in an effort to reduce waste.
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Prominent female wrestlers in India, including Vinesh Phogat, Sakshi Malik, and Bajrang Punia, are protesting against Wrestling Federation of India chief Brij Bhushan Sharan Singh, whom they accuse of sexually harassing them for years, at Jantar Mantar in New Delhi.
Brij Bhushan Sharan Singh, the BJP member of parliament for Kaiserganj in Uttar Pradesh, is a powerful figure in Indian politics. He has, however, stated that he is “willing to be hanged” if the allegations against him are proven true.
“How did he get here?” is the question. What effect do these allegations have on his political standing? In what follows, I’ll go over a few of these aspects.
A SEVEN-TIME MEMBER OF PARLIAMENT IS SUSPECTED IN THE DESTRUCTION OF THE BABRI MASJID.
Brij Bhushan Sharan Singh, 65, is a Thakur from Uttar Pradesh’s Gonda district who has been elected to Parliament six times. He has represented the constituencies of Gonda, Kaiserganj, and Balrampur in parliament. With the exception of the 2009 election, in which he ran for the Samajwadi Party, he has won every election on the BJP ticket.
His son Prateek Bhushan Singh is the current MLA for Gonda Sadar, and his wife Ketki Devi Singh is the president of the Gonda Zila Panchayat.
Singh is one of those accused of being involved in the destruction of the Babri Masjid in Ayodhya on December 6, 1992.
Singh, a former wrestler, rose to the status of Bahubali in the 1990s.
Subhash Singh Thakur, Jayendra Thakur alias Bhai Thakur, Paresh Desai, and Shyam Kishore Garikapatti were among the alleged associates of underworld don Dawood Ibrahim who were charged under the Terrorist and Disruptive Activities (TADA) Act in the mid-1990s. He was also accused of giving the suspects access to his phone so they could contact Dawood. He was eventually exonerated of all charges.
Singh reported four open cases in Ayodhya and Gonda for the 2019 Lok Sabha elections. Dacoity, attempted murder, and rioting are among the numerous charges levelled against him.
FROM A POLITICAL POINT OF VIEW, ACCUSATIONS OF SEXUAL MISCONDUCT
Brij Bhushan, the Golden Fleece Brahmin Sharan Singh has presided over the WFI as its president for more than ten years. His leadership of the federation has been criticised, but he has maintained it. He once slapped a wrestler on stage at an event, according to reports.
His political clout is widely regarded as a key factor in his federation-wide dominance.
Nonetheless, he has recently run into problems within the BJP. In 2022, he chastised the Uttar Pradesh government for its “shoddy arrangements” in the Gonda district during the floods.
When questioned about the situation, he stated, “I have never seen such bad arrangements in my life,” adding that he might be labelled a “rebel” for “speaking the truth.”
Before Raj Thackeray’s MNS joined the BJP, he threatened to punish him if he entered Ayodhya.
According to BJP insiders, the sexual misconduct allegations against him would not have been made public in this manner without the tacit support of powerful BJP elements, and he has several detractors in the BJP’s central and Uttar Pradesh leadership.
“Take a look at how things are going. Some of sports’ biggest names are expected to attend. They’ve congregated at Jantar Mantar. Some of them have a lot riding on the outcome. This would not have been possible without the support of influential people “The BJP’s internal information was leaked.
With this issue, the BJP faces a challenge. Sandeep Singh, their Haryana minister, resigned after being accused of sexual misconduct by a coach. Brij Bhushan Sharan Singh cannot be fired because he does not hold a ministerial position. The government’s legal strategy in this case is unknown. It may only be a matter of time before opposition parties speak out against Singh.
The Hindustan Herald Is Your Source For The Latest In Business, Entertainment, Lifestyle, Breaking News, And Other News. Please Follow Us On Facebook, Instagram, Twitter, And LinkedIn To Receive Instantaneous Updates. Also, Don’t Forget To Subscribe To Our Telegram Channel @Heraldhindustan

domain: news


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(FOX 11) Richard Thompson is a singer songwriter who's been performing in the music business for more than 40 years. He's also been named one of the 20 best guitarists of all time by Rolling Stone magazine.
Thompson is performing Friday night at the John Anson Ford Amphitheater and talked beforehand with Good Day LA.
Richard opened up about his guitar influences and when steve put him to the test to play some of their stuff, you can see he passed with flying colors.
He also gives a surprising answer when asked if he could only listen to one piece of music, what would it be? Richard also discussed his latest album, "Electric" and how he hit the scene as a teen guitarist and songwriter with the groundbreaking "fairport convention", the band that essentially invented the term "english folk-rock."

domain: celebrity


Subsidized infant milk will only be available in 1,005 outlets throughout the country, Egypt's health minister said on Thursday
كتب: Aswat MasriyaThursday 01-09-2016 06:21 PM
An Egyptian court extended on Thursday the detention of an advisor to the health minister for 15 days on charges of receiving a bribe.
كتب: Aswat MasriyaThursday 16-06-2016 05:12 PM
Egyptian prosecution ordered on Tuesday the detention of an advisor to health minister for four days on charges of receiving a bribe worth EGP 4.5 million.
كتب: Aswat MasriyaTuesday 31-05-2016 06:13 PM


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Tiny Harris just posted a cute video of her God baby showing off her singing and dancing skills. The Xscape singer wished everybody a Merry Christmas. Check out the lovely video.
‘Look at my God baby @laiyahbrown she know to make her TT feel good!! I’m in love for Christmas ? Merry Christmas Everyone! May it be filled with love & happiness ???❤’ Tiny captioned the video which got tons of appreciation from her fans.
Everyone was in love with Tiny’s God baby and the cute way that she sings and dances.
Tiny’s holidays are filled with love and gratitude, and she recently posted a video of her daughter Zonnique Pullins holding baby Heiress while they were both attending one of their mom’s concerts.
It seems that this Christmas is all about family for Tiny and that’s the way it should be.
She has had quite a tough year after the whole scandal with T.I.’s cheating scandal involving young grandma Bernice Burgos.
Her daughter is pregnant at 21, and Bernice will become a grandmother really soon.
Despite the fact that lots of critics slammed her for having her daughter at only 15 years old, Bernice couldn’t be happier these days.
Fortunately, that story is behind Tiny and Tip, and these two seem to have managed to get past it and make things better.
They have been trying really hard to rekindle their relationship, and it seems that it worked. Overall, this year ends happily for Tiny, and her loved ones.

domain: entertainment


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Plans for up to 50 sheltered apartments in Arundel were unveiled to the public this afternoon.
The plans would see an existing industrial site and vacant neighbouring property in Fitzaland Road demolished to make room for accommodation for the elderly.
Artist impressions of what the development could look like as well as information were displayed at the Norfolk Arms Hotel in Arundel this afternoon.
Retirement homes specialist Renaissance Retirement limited is seeking to build up to 50 sheltered apartments for elderly people on the land.
The site has previously been identified by Arundel Town Council for possible future development in the town’s Neighbourhood Plan.
Peter Tanner, planning director for Renaissance Retirement, said: “From our research we have indentified that the significant growth in the elderly population projected over the next ten to 20 years clearly demonstrates a need for specialist accommodation to meet the needs of the local elderly population.
“One of the significant advantages of this form of development is that older people downsizing into special accommodation for the elderly releases under-occupied family houses back into the market.”
However concerns were raised at the meeting that the need for more affordable housing for young people is greater than the need for sheltered housing.
More on the plans will be on the Littlehampton Gazette website next week.


text: This book features the artwork of William Luberoff and includes full color illustrations. Size: 5" x 7". Includes 14 prayers that every young Catholic will learn. Also lists The Sacraments, Beatitudes, Works of Mercy, The Ten Commandments, Stations of the Cross, and Joyful, Sorrowful, and Glorious Mysteries of The Rosary. Reading Level: Ages 4-8 years. Format: Softcover, 32 pages, color. Editors: Victor Hoagland, Karen Cavanagh.


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Santosh Kumar Singh, Fund Manager, Motilal Oswal AMC, says “there is no fixed criteria for cash holding. It is just that I am not so bullish on the markets and that is why our prop model shows our exposure to be somewhere and I am not so bullish, so we have kept some cash there. But generally, we do not keep more than 1% or 2% cash in the fund. Generally, we are a fully deployed fund. But as of today, we are slightly higher cash in the fund.”
Can we dive deep into your Balanced Advantage Fund returns? It has given great returns of almost 23% and it is very interesting to note that out of the four funds that you are part of, most of the allocation that we can see in the mid and the small end of the market is in the Balanced Advantage Fund. Is that the strategy that you have been following since the inception and because of the boom that we have seen in this end of the market?
Balanced Advantage Fund is an asset allocator fund. First we need to understand that it is an asset allocator fund where what we are trying to do is trying to reduce the standard deviation of the fund. So the standard deviation of this fund will be significantly lower than Nifty standard deviation.
The first thing we are trying to do is allocate between equity and debt. As a strategy, we are very active investors. We do not passivize any bit of either the equity part or the debt part or sort of hedging in this particular fund. So we do not do any passivization. What has worked for the fund is that it is not about mid, small or large.
Our allocation in the smallcap space will be closer to 20-25% to 20-30%. So the idea has been simple to find stocks where we can generate money rather than sort of track the market. So with that basic idea we are trying to run the fund. The equity allocation strategy is also very simple. We get into profitable segments with high profit growth rate and low PE ratios. This is the basic strategy we run the fund with.
But since it is a Balanced Advantage Fund, as you rightly mentioned, the main focus is actually to get that standard deviation in control and you have that debt component as well as a part of your Balanced Advantage Fund. Amongst the equity and the debt side, what sort of a ratio do you try to maintain for the Balanced Advantage Fund and how do you rebalance the same when there are variations?
Our allocation between equity and debt is based on our own proprietary model which we call Motilal Oswal Value Index and that is published daily on our website. So you can actually go and see there if any investors want to see what our allocations would be… So I was explaining that we use our own proprietary quant model for allocation between equity and debt. That is the core for the allocation part and that model is based on three fundamental criteria that is price to book, price to earnings and dividend yield. We use all the three to see how the markets are positioned.
Based on that, we actually try to position our fund between debt and equity. If you look at the fund, current equity allocation will be closer to 55-56%. And that is based on the MOVI Index, the Motilal Oswal Value Index, as well as the discretion which I have. If I find that the markets are directionally getting into some area where I might want a lower or a higher allocation. So that is how we determine the equity and debt allocation.
The allocations can move from normal circumstances from 30-35% to 75-80%. This is the range in normal circumstances it moves into. And for the last one year, the markets have been rebalancing. So we were talking about rebalancing quite frequently because we use derivatives for rebalancing.
I was audible when I talked about the Motilal Oswal Value Index which we use for our allocations. Current allocation between equity, net equity is around 55 to 56%. This is the current allocation of equity based on the indications from our proprietary model.
Apart from that, you have exposures in pharma, transport, IT services and more. We wanted to know if going ahead any sector that you believe can have more allocation in your portfolio or has the potential to perform in a better manner? What is your sector specific approach at this point in time?
I run with slightly contra views. What you will find is that the most underperforming segment of the market might be the highest weight in my portfolio. That is why what you will find is a company called Star Health will be the largest weight in the portfolio because it has been a stark underperformer in the year.
What we try to do is we try to find companies, some of the great companies, where the markets have turned negative and we try to sort of get exposure to that. So currently, if you ask me, I am bullish on financials, but not lenders because the fund is quite underweight on lenders. I am bullish on all other parts of the financials. So we have a large exposure to insurance, we have large exposure to capital markets through Bombay Stock Exchange. IT is another sector for where I am quite positive and that is an area where we have incrementally become overweight. That is why you could see one of the largest weights there.
What is the strategy regarding the cash holding because I could see that almost 4% of the total AUM you are holding in cash as of now. Is that some percentage near to that? We always see you holding this much cash in your portfolio or it gets skewed when you find better opportunities as well?
There is no fixed criteria for cash holding. It is just that I am not so bullish on the markets and that is why our prop model shows our exposure to be somewhere and I am not so bullish, so we have kept some cash there. But generally, we do not keep more than 1% or 2% cash in the fund. Generally, we are a fully deployed fund. But as of today, we are slightly higher cash in the fund.
You are not that bullish and still looking out for opportunities and not much opportunities left in IT now?
That is why the fund has some contra contours to it. The areas where we are invested our highest overweights are the areas which have not performed at all in the market. Even in the past, if you look at the fund performance it has come from some seven, eight stocks, which were not being bought by anyone. So we have a slightly contra mindset while running the fund. And that is why we find opportunities in the market.
I might not be bullish on the market, but I have a lot of stocks where I am quite bullish and tend to buy and wait for our time because we are buying some of the best companies in the industry.
(What’s moving Sensex and Nifty Track latest market news, stock tips and expert advice on ETMarkets. Also, ETMarkets.com is now on Telegram. For fastest news alerts on financial markets, investment strategies and stocks alerts, subscribe to our Telegram feeds.)
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domain: finance


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Birth Name: Martijn Gerard Garritsen
Place of Birth: Amstelveen, North Holland, Netherlands
Date of Birth: 14 May, 1996
Martin Garrix is a Dutch DJ, record producer, and musician. His father is Gerard Garritsen. His mother is said to be named Karin van Nieuwkerk.
Photo by Prphotos


Aldrich Building facts for kids
Quick facts for kids
|Location||98 Monroe Center, NW, Grand Rapids, Michigan|
|Area||less than one acre|
|NRHP reference No.||82000536|
|Added to NRHP||November 12, 1982|
The Aldrich Building was built in 1869 by druggists Edward Wilson and John Harvey, who operated their business from the first floor and rented out the upper floors. It was significant at the time for being the first building in Grand Rapids constructed with large plate glass windows in the storefronts. Wilson and Harvey owned the building until 1885, when it was purchased by Euphrasia Alcrich, whose family owned the buildings on either side. In 1887, a pair of physicians began practicing out of the building, and in 1910 the first dentist began practicing in the building. A dentistry practice operated in the building until at least the 1980s. In 1936, a Fannie Farmer Candies store moved into the first floor space, and remained there into the 21st century. They were replaced with a coffee shop in 2008. The building was renovated in 2013.
The Aldrich Building is a three-story brick commercial Italianate building, shaped like a wedge due to its location at the corner of two streets which form an obtuse angle. The first-floor facade was likely modernized in the early 20th century. Brick pilasters run from the street level up to a cornice line at the top of the building, where they merge with a brick frieze. The upper stories contain eight-foot-tall, one-over-one windows framed with brick molding. The window heads are semi-circular on the second floor and semi-hexagonal on the third. Decorative elements on the upper floors are constructed of brick, stone, and wood.
Aldrich Building Facts for Kids. Kiddle Encyclopedia.