Showing papers by "University of Maryland, Baltimore published in 2008"
TL;DR: This report provides the best available prevalence estimates for the US for osteoarthritis, polymyalgia rheumatica, gout, fibromyalgia, and carpal tunnel syndrome as well as the symptoms of neck and back pain.
Abstract: Objective
To provide a single source for the best available estimates of the US prevalence of and number of individuals affected by osteoarthritis, polymyalgia rheumatica and giant cell arteritis, gout, fibromyalgia, and carpal tunnel syndrome, as well as the symptoms of neck and back pain. A companion article (part I) addresses additional conditions.
4,813 citations
Daniel J. Klionsky1, Hagai Abeliovich2, Patrizia Agostinis3, Devendra K. Agrawal4 +232 more•Institutions (137)
TL;DR: A set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes are presented.
Abstract: Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms Recent reviews have described the range of assays that have been used for this purpose(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi) Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response
2,310 citations
TL;DR: In this article, an automated eukaryotic gene structure annotation tool, EVM, is presented as a weighted consensus of all available evidence, combined with the Program to Assemble Spliced Alignments (PASA), yields a comprehensive, configurable annotation system that predicts protein coding genes and alternatively spliced isoforms.
Abstract: EVidenceModeler (EVM) is presented as an automated eukaryotic gene structure annotation tool that reports eukaryotic gene structures as a weighted consensus of all available evidence. EVM, when combined with the Program to Assemble Spliced Alignments (PASA), yields a comprehensive, configurable annotation system that predicts protein-coding genes and alternatively spliced isoforms. Our experiments on both rice and human genome sequences demonstrate that EVM produces automated gene structure annotation approaching the quality of manual curation.
1,996 citations
University of Alberta1, Harvard University2, Johns Hopkins University3, Mayo Clinic4, University of São Paulo5, University of Maryland, Baltimore6, Vanderbilt University7, University of Manitoba8, University of Paris9, Wake Forest University10, Katholieke Universiteit Leuven11, National Institutes of Health12, University of Basel13, Westmead Hospital14, University of North Carolina at Chapel Hill15, University of Pittsburgh16, University of Vienna17, University of Oxford18, University of Padua19
TL;DR: Emerging research data led to the establishment of collaborative working groups addressing issues like isolated ‘v’ lesion and incorporation of omics‐technologies, paving the way for future combination of graft biopsy and molecular parameters within the Banff process.
1,700 citations
University of Michigan1, National Institutes of Health2, University of Oxford3, University of Bristol4, National Research Council5, University of Maryland, Baltimore6, French Institute of Health and Medical Research7, University of Paris8, National Institute for Health and Welfare9, University of Southern California10, University of London11, University of Helsinki12, University of North Carolina at Chapel Hill13
TL;DR: In this paper, the authors used genotype imputation and meta-analysis to identify genetic variants influencing plasma lipid concentrations, using three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to their study.
Abstract: To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls.
1,616 citations
TL;DR: In this paper, the authors presented the first characterization of terrestrial biomes based on global patterns of sustained, direct human interaction with ecosystems and identified the anthropogenic biomes through empirical analysis of global population, land use, and land cover.
Abstract: Humans have fundamentally altered global patterns of biodiversity and ecosystem processes. Surprisingly, existing systems for representing these global patterns, including biome classifications, either ignore humans altogether or simplify human influence into, at most, four categories. Here, we present the first characterization of terrestrial biomes based on global patterns of sustained, direct human interaction with ecosystems. Eighteen “anthropogenic biomes” were identified through empirical analysis of global population, land use, and land cover. More than 75% of Earth's ice-free land showed evidence of alteration as a result of human residence and land use, with less than a quarter remaining as wildlands, supporting just 11% of terrestrial net primary production. Anthropogenic biomes offer a new way forward by acknowledging human influence on global ecosystems and moving us toward models and investigations of the terrestrial biosphere that integrate human and ecological systems.
1,452 citations
TL;DR: Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology are intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient.
Abstract: Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to these guidelines and recommendations to be voluntary, with the ultimate determination regarding their application to be made by the physician in light of each patient’s individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed or endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice.
1,447 citations
TL;DR: Future research into the effects of robot-assisted therapy should distinguish between upper and lower robotics arm training and concentrate on kinematical analysis to differentiate between genuine upper limb motor recovery and functional recovery due to compensation strategies by proximal control of the trunk and upper limb.
Abstract: Objective. The aim of the study was to present a systematic review of studies that investigate the effects of robot-assisted therapy on motor and functional recovery in patients with stroke. Method...
1,360 citations
Michigan State University1, J. Craig Venter Institute2, National Institutes of Health3, Wellcome Trust Sanger Institute4, Plymouth Marine Laboratory5, University of Maryland, Baltimore6, University of Cambridge7, University of York8, United States Department of Energy9, Ghent University10, Pennsylvania State University11, Argonne National Laboratory12, University of California, San Diego13, Jacobs University Bremen14, University of Colorado Boulder15, National Science Foundation16, Edinburgh Napier University17, Boston Children's Hospital18, University of Georgia19, University of California, Berkeley20, Newcastle University21, Lawrence Berkeley National Laboratory22, University of California, Irvine23, University of Oxford24, Howard University25, Abertay University26, University of Manchester27, Technical University of Denmark28, University of Wyoming29, University of Pennsylvania30, University of New Mexico31
TL;DR: Here, the minimum information about a genome sequence (MIGS) specification is introduced with the intent of promoting participation in its development and discussing the resources that will be required to develop improved mechanisms of metadata capture and exchange.
Abstract: With the quantity of genomic data increasing at an exponential rate, it is imperative that these data be captured electronically, in a standard format. Standardization activities must proceed within the auspices of open-access and international working bodies. To tackle the issues surrounding the development of better descriptions of genomic investigations, we have formed the Genomic Standards Consortium (GSC). Here, we introduce the minimum information about a genome sequence (MIGS) specification with the intent of promoting participation in its development and discussing the resources that will be required to develop improved mechanisms of metadata capture and exchange. As part of its wider goals, the GSC also supports improving the 'transparency' of the information contained in existing genomic databases.
1,097 citations
University of California, Los Angeles1, University of North Carolina at Chapel Hill2, Bangor University3, United States Department of Veterans Affairs4, University of Maryland, Baltimore5, University of Düsseldorf6, University of Pennsylvania7, University of California, Berkeley8, Vanderbilt University9, University of Medicine and Dentistry of New Jersey10, National Institutes of Health11
TL;DR: A consensus-building meeting on social cognition in schizophrenia was held at the National Institute of Mental Health in March 2006, and agreement was reached on several points, including definitions of terms, the significance of social cognition for schizophrenia research, and suggestions for future research directions.
Abstract: Social cognition has become a high priority area for the study of schizophrenia. However, despite developments in this area, progress remains limited by inconsistent terminology and differences in the way social cognition is measured. To address these obstacles, a consensus-building meeting on social cognition in schizophrenia was held at the National Institute of Mental Health in March 2006. Agreement was reached on several points, including definitions of terms, the significance of social cognition for schizophrenia research, and suggestions for future research directions. The importance of translational interdisciplinary research teams was emphasized. The current article presents a summary of these discussions.
860 citations
TL;DR: The simple SOF index predicts risk of falls, disability, fracture, and death as well as the more complex CHS index and may provide a useful definition of frailty to identify older women at risk of adverse health outcomes in clinical practice.
Abstract: BACKGROUND: Frailty, as defined by the index derived from the Cardiovascular Health Study (CHS index), predicts risk of adverse outcomes in older adults. Use of this index, however, is impractical in clinical practice. METHODS: We conducted a prospective cohort study in 6701 women 69 years or older to compare the predictive validity of a simple frailty index with the components of weight loss, inability to rise from a chair 5 times without using arms, and reduced energy level (Study of Osteoporotic Fractures [SOF index]) with that of the CHS index with the components of unintentional weight loss, poor grip strength, reduced energy level, slow walking speed, and low level of physical activity. Women were classified as robust, of intermediate status, or frail using each index. Falls were reported every 4 months for 1 year. Disability (>/=1 new impairment in performing instrumental activities of daily living) was ascertained at 4(1/2) years, and fractures and deaths were ascertained during 9 years of follow-up. Area under the curve (AUC) statistics from receiver operating characteristic curve analysis and -2 log likelihood statistics were compared for models containing the CHS index vs the SOF index. RESULTS: Increasing evidence of frailty as defined by either the CHS index or the SOF index was similarly associated with an increased risk of adverse outcomes. Frail women had a higher age-adjusted risk of recurrent falls (odds ratio, 2.4), disability (odds ratio, 2.2-2.8), nonspine fracture (hazard ratio, 1.4-1.5), hip fracture (hazard ratio, 1.7-1.8), and death (hazard ratio, 2.4-2.7) (P < .001 for all models). The AUC comparisons revealed no differences between models with the CHS index vs the SOF index in discriminating falls (AUC = 0.61 for both models; P = .66), disability (AUC = 0.64; P = .23), nonspine fracture (AUC = 0.55; P = .80), hip fracture (AUC = 0.63; P = .64), or death (AUC = 0.72; P = .10). Results were similar when -2 log likelihood statistics were compared. CONCLUSION: The simple SOF index predicts risk of falls, disability, fracture, and death as well as the more complex CHS index and may provide a useful definition of frailty to identify older women at risk of adverse health outcomes in clinical practice. Language: en
Missouri Baptist Medical Center1, Stanford University2, University of Pennsylvania3, Baylor College of Medicine4, University of Maryland, Baltimore5, University of Duisburg-Essen6, Yale University7, University of Pittsburgh8, Cleveland Clinic9, University of Rostock10, University of Texas Health Science Center at Houston11, University of California, Los Angeles12, Washington University in St. Louis13, Mayo Clinic14, Arizona Heart Institute15
TL;DR: The natural history of aortic disease, indications for repair, outcomes after conventional open surgery, currently available devices, and insights from outcomes of randomized studies using stent-grafts for abdominal aorti aneurysm surgery are reviewed; a suggestion for treatment is offered.
TL;DR: Pangenomic calculations indicate that E. coli genomic diversity represents an open pangenome model containing a reservoir of more than 13,000 genes, many of which may be uncharacterized but important virulence factors, which should provide the basis for future functional work on this important group of pathogens.
Abstract: Whole-genome sequencing has been skewed toward bacterial pathogens as a consequence of the prioritization of medical and veterinary diseases. However, it is becoming clear that in order to accurately measure genetic variation within and between pathogenic groups, multiple isolates, as well as commensal species, must be sequenced. This study examined the pangenomic content of Escherichia coli. Six distinct E. coli pathovars can be distinguished using molecular or phenotypic markers, but only two of the six pathovars have been subjected to any genome sequencing previously. Thus, this report provides a seminal description of the genomic contents and unique features of three unsequenced pathovars, enterotoxigenic E. coli, enteropathogenic E. coli, and enteroaggregative E. coli. We also determined the first genome sequence of a human commensal E. coli isolate, E. coli HS, which will undoubtedly provide a new baseline from which workers can examine the evolution of pathogenic E. coli. Comparison of 17 E. coli genomes, 8 of which are new, resulted in identification of ∼2,200 genes conserved in all isolates. We were also able to identify genes that were isolate and pathovar specific. Fewer pathovar-specific genes were identified than anticipated, suggesting that each isolate may have independently developed virulence capabilities. Pangenome calculations indicate that E. coli genomic diversity represents an open pangenome model containing a reservoir of more than 13,000 genes, many of which may be uncharacterized but important virulence factors. This comparative study of the species E. coli, while descriptive, should provide the basis for future functional work on this important group of pathogens.
TL;DR: A new model of broad applicability is suggested, including examples of its implementation, and the size of the gene repertoire accessible to any given species is characterized together with an estimate of the number of whole genome sequences required for proper analysis.
J. Craig Venter Institute1, New York University2, University of South Florida3, University of Maryland, Baltimore4, University of Maryland, College Park5, World Health Organization6, Burnet Institute7, University of Pennsylvania8, University of Barcelona9, Walter and Eliza Hall Institute of Medical Research10, Hood College11, Heidelberg University12, University of Queensland13, Emory University14, Macquarie University15, University of Melbourne16, University of São Paulo17, Centers for Disease Control and Prevention18
TL;DR: The synteny and isochore structure of P. vivax chromosomes are described, and it is shown that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously.
Abstract: The human malaria parasite Plasmodium vivax is responsible for 25-40% of the approximately 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.
TL;DR: The introduction of endocrine disrupting compounds into the environment that mimic or alter the actions of estradiol has generated considerable concern, and the developing brain is a particularly sensitive target.
Abstract: Estradiol is the most potent and ubiquitous member of a class of steroid hormones called estrogens. Fetuses and newborns are exposed to estradiol derived from their mother, their own gonads, and synthesized locally in their brains. Receptors for estradiol are nuclear transcription factors that regulate gene expression but also have actions at the membrane, including activation of signal transduction pathways. The developing brain expresses high levels of receptors for estradiol. The actions of estradiol on developing brain are generally permanent and range from establishment of sex differences to pervasive trophic and neuroprotective effects. Cellular end points mediated by estradiol include the following: 1) apoptosis, with estradiol preventing it in some regions but promoting it in others; 2) synaptogenesis, again estradiol promotes in some regions and inhibits in others; and 3) morphometry of neurons and astrocytes. Estradiol also impacts cellular physiology by modulating calcium handling, immediate-early-gene expression, and kinase activity. The specific mechanisms of estradiol action permanently impacting the brain are regionally specific and often involve neuronal/glial cross-talk. The introduction of endocrine disrupting compounds into the environment that mimic or alter the actions of estradiol has generated considerable concern, and the developing brain is a particularly sensitive target. Prostaglandins, glutamate, GABA, granulin, and focal adhesion kinase are among the signaling molecules co-opted by estradiol to differentiate male from female brains, but much remains to be learned. Only by understanding completely the mechanisms and impact of estradiol action on the developing brain can we also understand when these processes go awry.
TL;DR: Research focusing on the pathogenesis of CAUTIs will lead to a better understanding of the disease process and will subsequently lead to the development of new diagnosis, prevention, and treatment options.
Abstract: Catheter-associated urinary tract infections (CAUTIs) represent the most common type of nosocomial infection and are a major health concern due to the complications and frequent recurrence. These infections are often caused by Escherichia coli and Proteus mirabilis. Gram-negative bacterial species that cause CAUTIs express a number of virulence factors associated with adhesion, motility, biofilm formation, immunoavoidance, and nutrient acquisition as well as factors that cause damage to the host. These infections can be reduced by limiting catheter usage and ensuring that health care professionals correctly use closed-system Foley catheters. A number of novel approaches such as condom and suprapubic catheters, intermittent catheterization, new surfaces, catheters with antimicrobial agents, and probiotics have thus far met with limited success. While the diagnosis of symptomatic versus asymptomatic CAUTIs may be a contentious issue, it is generally agreed that once a catheterized patient is believed to have a symptomatic urinary tract infection, the catheter is removed if possible due to the high rate of relapse. Research focusing on the pathogenesis of CAUTIs will lead to a better understanding of the disease process and will subsequently lead to the development of new diagnosis, prevention, and treatment options.
University of Oregon1, Stanford University2, Northwestern University3, National Institute of Genetics4, J. Craig Venter Institute5, Harvard University6, South African National Bioinformatics Institute7, Bosch8, United States Department of Agriculture9, University of Missouri10, Medical College of Wisconsin11, University of Maryland, Baltimore12, Carnegie Institution for Science13
TL;DR: To thrive, the field that links biologists and their data urgently needs structure, recognition and support.
Abstract: To thrive, the field that links biologists and their data urgently needs structure, recognition and support.
TL;DR: A cross-sectional study of military personnel following deployment to conflicts in Iraq or Afghanistan ascertained histories of combat theater injury mechanisms and mild traumatic brain injury (TBI) and current prevalence of posttraumatic stress disorder (PTSD) and postconcussive symptoms as discussed by the authors.
Abstract: A cross-sectional study of military personnel following deployment to conflicts in Iraq or Afghanistan ascertained histories of combat theater injury mechanisms and mild traumatic brain injury (TBI) and current prevalence of posttraumatic stress disorder (PTSD) and postconcussive symptoms. Associations among injuries, PTSD, and postconcussive symptoms were explored. In February 2005, a postal survey was sent to Iraq/Afghanistan veterans who had left combat theaters by September 2004 and lived in Maryland; Washington, DC; northern Virginia; and eastern West Virginia. Immediate neurologic symptoms postinjury were used to identify mild TBI. Adjusted prevalence ratios and 95% confidence intervals were computed by using Poisson regression. About 12% of 2,235 respondents reported a history consistent with mild TBI, and 11% screened positive for PTSD. Mild TBI history was common among veterans injured by bullets/shrapnel, blasts, motor vehicle crashes, air/water transport, and falls. Factors associated with PTSD included reporting multiple injury mechanisms (prevalence ratio = 3.71 for three or more mechanisms, 95% confidence interval: 2.23, 6.19) and combat mild TBI (prevalence ratio = 2.37, 95% confidence interval: 1.72, 3.28). The strongest factor associated with postconcussive symptoms was PTSD, even after overlapping symptoms were removed from the PTSD score (prevalence ratio = 3.79, 95% confidence interval: 2.57, 5.59).
22 Sep 2008
TL;DR: It is shown that individual mitochondria undergo spontaneous bursts of superoxide generation, termed "superoxide flashes", and proposed that superoxide flashes could serve as a valuable biomarker for a wide variety of oxidative stress-related diseases.
TL;DR: Mutation carriers compared with noncarriers had lower fasting and postprandial serum triglycerides, higher levels of HDL-ch cholesterol and lower levels of LDL-cholesterol, which suggests that lifelong deficiency of apoC-III has a cardioprotective effect.
Abstract: Apolipoprotein C-III (apoC-III) inhibits triglyceride hydrolysis and has been implicated in coronary artery disease. Through a genome-wide association study, we have found that about 5% of the Lancaster Amish are heterozygous carriers of a null mutation (R19X) in the gene encoding apoC-III (APOC3) and, as a result, express half the amount of apoC-III present in noncarriers. Mutation carriers compared with noncarriers had lower fasting and postprandial serum triglycerides, higher levels of HDL-cholesterol and lower levels of LDL-cholesterol. Subclinical atherosclerosis, as measured by coronary artery calcification, was less common in carriers than noncarriers, which suggests that lifelong deficiency of apoC-III has a cardioprotective effect.
Duke University1, Fred Hutchinson Cancer Research Center2, Los Alamos National Laboratory3, University of North Carolina at Chapel Hill4, University of California, Irvine5, University of Alabama at Birmingham6, Centre for the AIDS Programme of Research in South Africa7, University of Maryland, Baltimore8
TL;DR: It is demonstrated that the first IgM and IgG antibodies induced by transmitted HIV-1 are capable of binding virions but have little impact on acute-phase viremia at the timing and magnitude that they occur in natural infection.
Abstract: A window of opportunity for immune responses to extinguish human immunodeficiency virus type 1 (HIV-1) exists from the moment of transmission through establishment of the latent pool of HIV-1-infected cells. A critical time to study the initial immune responses to the transmitted/founder virus is the eclipse phase of HIV-1 infection (time from transmission to the first appearance of plasma virus), but, to date, this period has been logistically difficult to analyze. To probe B-cell responses immediately following HIV-1 transmission, we have determined envelope-specific antibody responses to autologous and consensus Envs in plasma donors from the United States for whom frequent plasma samples were available at time points immediately before, during, and after HIV-1 plasma viral load (VL) ramp-up in acute infection, and we have modeled the antibody effect on the kinetics of plasma viremia. The first detectable B-cell response was in the form of immune complexes 8 days after plasma virus detection, whereas the first free plasma anti-HIV-1 antibody was to gp41 and appeared 13 days after the appearance of plasma virus. In contrast, envelope gp120-specific antibodies were delayed an additional 14 days. Mathematical modeling of the earliest viral dynamics was performed to determine the impact of antibody on HIV replication in vivo as assessed by plasma VL. Including the initial anti-gp41 immunoglobulin G (IgG), IgM, or both responses in the model did not significantly impact the early dynamics of plasma VL. These results demonstrate that the first IgM and IgG antibodies induced by transmitted HIV-1 are capable of binding virions but have little impact on acute-phase viremia at the timing and magnitude that they occur in natural infection.
TL;DR: Tissue-specific gene deletion studies reveal an important contribution of LRP1 in the vasculature, central nervous system, macrophages, and adipocytes, revealing a critical, but as of yet, undefined role in development.
Abstract: The LDL receptor-related protein (originally called LRP, but now referred to as LRP1) is a large endocytic receptor that is widely expressed in several tissues. LRP1 is a member of the LDL receptor...
Johns Hopkins University1, Harvard University2, Broad Institute3, University of Maryland, Baltimore4, University of Texas Health Science Center at San Antonio5, University of California, Los Angeles6, Wake Forest University7, Case Western Reserve University8, National Institutes of Health9, Loyola University Chicago10, University of Chicago11, University of California, Irvine12, University of Alabama at Birmingham13, Science Applications International Corporation14
TL;DR: Multiple common SNPs in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic E SRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans.
Abstract: Linda Kao and colleagues use admixture mapping to identify risk variants in MYH9 associated with nondiabetic end-stage renal disease in African Americans. The risk variants are more common in populations with West African ancestry and contribute to the excess burden of end-stage kidney diseases in these populations. A similar finding is reported in an accompanying paper by Cheryl Winkler and colleagues. As end-stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans, we hypothesized that susceptibility alleles for ESRD have a higher frequency in the West African than the European gene pool. We carried out a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and found a highly significant association between excess African ancestry and nondiabetic ESRD (lod score = 5.70) but not diabetic ESRD (lod = 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% CI = 0.39–0.63) compared to African ancestry. Multiple common SNPs (allele frequencies ranging from 0.2 to 0.6) in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans.
TL;DR: Pregestational diabetes mellitus was associated with a wide range of birth defects; GDM wasassociated with a limited group ofBirth defects.
TL;DR: This work highlights the importance of SOPs for genome annotation and endorse an online repository of Sops and highlights the need for a central repository to store and disseminate procedures and protocols for annotation.
Abstract: The methodologies used to generate genome and metagenome annotations are diverse and vary between groups and laboratories. Descriptions of the annotation process are helpful in interpreting genome annotation data. Some groups have produced Standard Operating Procedures (SOPs) that describe the annotation process, but standards are lacking for structure and content of these descriptions. In addition, there is no central repository to store and disseminate procedures and protocols for genome annotation. We highlight the importance of SOPs for genome annotation and endorse an online repository of SOPs.
TL;DR: Placebo and nocebo effects are associated with opposite responses of DA and endogenous opioid neurotransmission in a distributed network of regions and form part of the circuit typically implicated in reward responses and motivated behavior.
Abstract: Context Placebo and nocebo effects, the therapeutic and adverse effects, respectively, of inert substances or sham procedures, represent serious confounds in the evaluation of therapeutic interventions. They are also an example of cognitive processes, particularly expectations, capable of influencing physiology. Objective To examine the contribution of 2 different neurotransmitters, the endogenous opioid and the dopaminergic (DA) systems, to the development of placebo and nocebo effects. Design and Setting Using a within-subject design, subjects twice underwent a 20-minute standardized pain challenge, in the absence and presence of a placebo with expected analgesic properties. Studies were conducted in a university hospital setting. Participants Twenty healthy men and women aged 20 to 30 years recruited by advertisement. Main Outcome Measures Activation of DA and opioid neurotransmission by a pain stressor with and without placebo (changes in the binding potential of carbon 11 [ 11 C]–labeled raclopride and [ 11 C] carfentanil with positron emission tomography) and ratings of pain, affective state, and anticipation and perception of analgesia. Results Placebo-induced activation of opioid neurotransmission was detected in the anterior cingulate, orbitofrontal and insular cortices, nucleus accumbens, amygdala, and periaqueductal gray matter. Dopaminergic activation was observed in the ventral basal ganglia, including the nucleus accumbens. Regional DA and opioid activity were associated with the anticipated and subjectively perceived effectiveness of the placebo and reductions in continuous pain ratings. High placebo responses were associated with greater DA and opioid activity in the nucleus accumbens. Nocebo responses were associated with a deactivation of DA and opioid release. Nucleus accumbens DA release accounted for 25% of the variance in placebo analgesic effects. Conclusions Placebo and nocebo effects are associated with opposite responses of DA and endogenous opioid neurotransmission in a distributed network of regions. The brain areas involved in these phenomena form part of the circuit typically implicated in reward responses and motivated behavior.
Journal Article•
TL;DR: Get comprehensive, current information on every aspect (including behavioral and psychologic concomitants) of all common and uncommon movement disorders, including Parkinson's disease, other neurodegenerative diseases, tremors, dystonia, Tourette's syndrome, Huntington’s disease, and ataxias.
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TL;DR: An intuitive description of the complex physics of plasmons and near-field interactions is provided and how these effects will result in new classes of experimental procedures, novel probes, bioassays and devices are suggested.
Abstract: Fluorescence spectroscopy is widely used in biological research. Until recently, essentially all fluorescence experiments were performed using optical energy which has radiated to the far-field. By far-field we mean at least several wavelengths from the fluorophore, but propagating far-field radiation is usually detected at larger macroscopic distances from the sample. In recent years there has been a growing interest in the interactions of fluorophores with metallic surfaces or particles. Near-field interactions are those occurring within a wavelength distance of an excited fluorophore. The spectral properties of fluorophores can be dramatically altered by near-field interactions with the electron clouds present in metals. These interactions modify the emission in ways not seen in classical fluorescence experiments. In this review we provide an intuitive description of the complex physics of plasmons and near-field interactions. Additionally, we summarize the recent work on metal-fluorophore interactions and suggest how these effects will result in new classes of experimental procedures, novel probes, bioassays and devices.