Showing papers by "McGill University published in 2003"
Baylor College of Medicine1, Chinese Academy of Sciences2, Chinese National Human Genome Center3, University of Hong Kong4, The Chinese University of Hong Kong5, Hong Kong University of Science and Technology6, Illumina7, McGill University8, Washington University in St. Louis9, University of California, San Francisco10, Wellcome Trust Sanger Institute11, Beijing Normal University12, Health Sciences University of Hokkaido13, Shinshu University14, University of Tsukuba15, Howard University16, University of Ibadan17, Case Western Reserve University18, University of Utah19, Cold Spring Harbor Laboratory20, Johns Hopkins University21, University of Oxford22, North Carolina State University23, National Institutes of Health24, Massachusetts Institute of Technology25, Chinese Academy of Social Sciences26, Kyoto University27, Nagasaki University28, Wellcome Trust29, Genome Canada30, Foundation for the National Institutes of Health31, University of Maryland, Baltimore32, Vanderbilt University33, Stanford University34, New York University35, University of California, Berkeley36, University of Oklahoma37, University of New Mexico38, Université de Montréal39, University of California, Los Angeles40, University of Michigan41, University of Wisconsin-Madison42, London School of Economics and Political Science43, Genetic Alliance44, GlaxoSmithKline45, University of Washington46, Harvard University47, University of Chicago48, Fred Hutchinson Cancer Research Center49, University of Tokyo50
TL;DR: The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance the ability to choose targets for therapeutic intervention.
Abstract: The goal of the International HapMap Project is to determine the common patterns of DNA sequence variation in the human genome and to make this information freely available in the public domain. An international consortium is developing a map of these patterns across the genome by determining the genotypes of one million or more sequence variants, their frequencies and the degree of association between them, in DNA samples from populations with ancestry from parts of Africa, Asia and Europe. The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance our ability to choose targets for therapeutic intervention.
5,926 citations
TL;DR: The emphasis is on outlining the biochemical properties of the brown algae that set them apart from other algal biosorbents, including alginate and fucoidan, which are chiefly responsible for heavy metal chelation.
2,191 citations
Mayo Clinic1, Leeds Teaching Hospitals NHS Trust2, University of Arkansas3, University of Nantes4, University of Turin5, University of South Florida6, National and Kapodistrian University of Athens7, University of Birmingham8, Lille University of Science and Technology9, Harvard University10, Cleveland Clinic11, University of Pittsburgh12, University of Salamanca13, Nagoya University14, McGill University15, Erasmus University Rotterdam16, Lund University17, University of Minnesota18, Medical College of Wisconsin19
TL;DR: The International Myeloma Working Group has reviewed the criteria for diagnosis and classification with the aim of producing simple, easily used definitions based on routinely available investigations to facilitate comparison of therapeutic trial data.
Abstract: The monoclonal gammopathies are a group of disorders associated with monoclonal proliferation of plasma cells. The characterization of specific entities is an area of difficulty in clinical practice. The International Myeloma Working Group has reviewed the criteria for diagnosis and classification with the aim of producing simple, easily used definitions based on routinely available investigations. In monoclonal gammopathy of undetermined significance (MGUS) or monoclonal gammopathy, unattributed/unassociated (MG[u]), the monoclonal protein is < 30 g/l and the bone marrow clonal cells < 10% with no evidence of multiple myeloma, other B-cell proliferative disorders or amyloidosis. In asymptomatic (smouldering) myeloma the M-protein is greater than or equal to 30 g/l and/or bone marrow clonal cells greater than or equal to 10% but no related organ or tissue impairment (ROTI)(end-organ damage), which is typically manifested by increased calcium, renal insufficiency, anaemia, or bone lesions (CRAB) attributed to the plasma cell proliferative process. Symptomatic myeloma requires evidence of ROTI. Non-secretory myeloma is characterized by the absence of an M-protein in the serum and urine, bone marrow plasmacytosis and ROTI. Solitary plasmacytoma of bone, extramedullary plasmacytoma and multiple solitary plasmacytomas (+/- recurrent) are also defined as distinct entities. The use of these criteria will facilitate comparison of therapeutic trial data. Evaluation of currently available prognostic factors may allow better definition of prognosis in multiple myeloma.
2,066 citations
TL;DR: Small worked examples and one real data set are used to help end-users appreciate the essence of the GEE method and allow nonstatisticians to imagine the calculations involved when the Gee method is applied to more complex multivariate data.
Abstract: The method of generalized estimating equations (GEE) is often used to analyze longitudinal and other correlated response data, particularly if responses are binary. However, few descriptions of the method are accessible to epidemiologists. In this paper, the authors use small worked examples and one real data set, involving both binary and quantitative response data, to help end-users appreciate the essence of the method. The examples are simple enough to see the behind-the-scenes calculations and the essential role of weighted observations, and they allow nonstatisticians to imagine the calculations involved when the GEE method is applied to more complex multivariate data.
1,999 citations
TL;DR: Results from four studies involving more than 900 participants from different populations supported the proposed conceptualization of two types of passion: obsessive and harmonious.
Abstract: Passion is defined as a strong inclination toward an activity that people like, that they find important, and in which they invest time and energy Two types of passion are proposed: obsessive and harmonious Obsessive passion (OP) refers to a controlled internalization of an activity in one's identity that creates an internal pressure to engage in the activity that the person likes Harmonious passion (HP) refers to an autonomous internalization that leads individuals to choose to engage in the activity that they like HP promotes healthy adaptation whereas OP thwarts it by causing negative affect and rigid persistence Results from four studies involving more than 900 participants from different populations supported the proposed conceptualization
1,726 citations
TL;DR: The diversity of responses to environmental change among species contributing to the same ecosystem function, which is called response diversity, is critical to resilience and is particularly important for ecosystem renewal and reorganization following change.
Abstract: Biological diversity appears to enhance the resilience of desirable ecosystem states, which is required to secure the production of essential ecosystem services. The diversity of responses to environmental change among species contributing to the same ecosystem function, which we call response diversity, is critical to resilience. Response diversity is particularly important for ecosystem renewal and reorganization following change. Here we present examples of response diversity from both terrestrial and aquatic ecosystems and across temporal and spatial scales. Response diversity provides adaptive capacity in a world of complex systems, uncertainty, and human-dominated environments. We should pay special attention to response diversity when planning ecosystem management and restoration, since it may contribute considerably to the resilience of desired ecosystem states against disturbance, mismanagement, and degradation.
1,720 citations
TL;DR: It is reported here that the IκB kinase (IKK)–related kinases IKKϵ and TANK-binding kinase 1 are components of the virus-activated kinase that phosphorylate IRf-3 and IRF-7.
Abstract: Rapid induction of type I interferon expression, a central event in establishing the innate antiviral response, requires cooperative activation of numerous transcription factors. Although signaling pathways that activate the transcription factors nuclear factor kappaB and ATF-2/c-Jun have been well characterized, activation of the interferon regulatory factors IRF-3 and IRF-7 has remained a critical missing link in understanding interferon signaling. We report here that the IkappaB kinase (IKK)-related kinases IKKepsilon and TANK-binding kinase 1 are components of the virus-activated kinase that phosphorylate IRF-3 and IRF-7. These studies illustrate an essential role for an IKK-related kinase pathway in triggering the host antiviral response to viral infection.
1,626 citations
TL;DR: In this article, the average soil carbon density of mangrove swamps (0.055 ± 0.004 g cm−3) is significantly higher than the salt marsh average ( 0.039 − 0.003 g cm −3) due to increased decay rates at higher temperatures.
Abstract: [1] Wetlands represent the largest component of the terrestrial biological carbon pool and thus play an important role in global carbon cycles. Most global carbon budgets, however, have focused on dry land ecosystems that extend over large areas and have not accounted for the many small, scattered carbon-storing ecosystems such as tidal saline wetlands. We compiled data for 154 sites in mangroves and salt marshes from the western and eastern Atlantic and Pacific coasts, as well as the Indian Ocean, Mediterranean Ocean, and Gulf of Mexico. The set of sites spans a latitudinal range from 22.4°S in the Indian Ocean to 55.5°N in the northeastern Atlantic. The average soil carbon density of mangrove swamps (0.055 ± 0.004 g cm−3) is significantly higher than the salt marsh average (0.039 ± 0.003 g cm−3). Soil carbon density in mangrove swamps and Spartina patens marshes declines with increasing average annual temperature, probably due to increased decay rates at higher temperatures. In contrast, carbon sequestration rates were not significantly different between mangrove swamps and salt marshes. Variability in sediment accumulation rates within marshes is a major control of carbon sequestration rates masking any relationship with climatic parameters. Globally, these combined wetlands store at least 44.6 Tg C yr−1 and probably more, as detailed areal inventories are not available for salt marshes in China and South America. Much attention has been given to the role of freshwater wetlands, particularly northern peatlands, as carbon sinks. In contrast to peatlands, salt marshes and mangroves release negligible amounts of greenhouse gases and store more carbon per unit area.
1,371 citations
TL;DR: Bereavement, sleep disturbance, disability, prior depression, and female gender appear to be important risk factors for depression among elderly community subjects despite the methodologic limitations of the studies and this meta-analysis.
Abstract: OBJECTIVE: The goal of this study was to determine risk factors for depression among elderly community subjects. METHOD: MEDLINE and PsycINFO were searched for potentially relevant articles published from January 1966 to June 2001 and from January 1967 to June 2001, respectively. The bibliographies of relevant articles were searched for additional references. Twenty studies met the following six inclusion criteria: original research reported in an English or French publication, study group of community residents, age of subjects 50 years or more, prospective study design, examination of at least one risk factor, and use of an acceptable definition of depression. The validity of studies was assessed according to the four primary criteria for risk factor studies described by the Evidence-Based Medicine Working Group. Information about group size at baseline and follow-up, age, proportion of men, depression criteria, exclusion criteria at baseline, length of follow-up, number of incident cases of depression,...
1,248 citations
International Agency for Research on Cancer1, German Cancer Research Center2, Curie Institute3, Queen's University Belfast4, University of Madras5, Kidwai Memorial Institute of Oncology6, Royal Prince Alfred Hospital7, McGill University8, University of Seville9, Mario Negri Institute for Pharmacological Research10, Johns Hopkins University11
TL;DR: HPV appears to play an etiologic role in many cancers of the oropharynx and possibly a small subgroup of cancers of The most common HPV type in genital cancers (HPV16) was also the most common in these tumors.
Abstract: = 1.5, 95% CI = 1.1 to 2.1) and the oropharynx (OR = 3.5, 95% CI = 2.1 to 5.9). Antibodies against HPV16 E6 or E7 were also associated with risk for cancers of the oral cavity (OR = 2.9, 95% CI = 1.7 to 4.8) and the oropharynx (OR = 9.2, 95% CI = 4.8 to 17.7). CONCLUSIONS: HPV appears to play an etiologic role in many cancers of the oropharynx and possibly a small subgroup of cancers of the oral cavity. The most common HPV type in genital cancers (HPV16) was also the most common in these tumors. The mechanism of transmission of HPV to the oral cavity warrants further investigation.
1,207 citations
TL;DR: Block copolymer micelles are water-soluble biocompatible nanocontainers with great potential for delivering hydrophobic drugs but localization in several cytoplasmic organelles, including mitochondria, but not in the nucleus is revealed.
Abstract: Block copolymer micelles are water-soluble biocompatible nanocontainers with great potential for delivering hydrophobic drugs. An understanding of their cellular distribution is essential to achieving selective delivery of drugs at the subcellular level. Triple-labeling confocal microscopy in live cells revealed the localization of micelles in several cytoplasmic organelles, including mitochondria, but not in the nucleus. Moreover, micelles change the cellular distribution of and increase the amount of the agent delivered to the cells. These micelles may thus be worth exploring for their potential to selectively deliver drugs to specified subcellular targets.
TL;DR: An activation of pulvinar and superior colliculus by fearful expressions occurred specifically with low-frequency faces, suggesting that these subcortical pathways may provide coarse fear-related inputs to the amygdala.
Abstract: High and low spatial frequency information in visual images is processed by distinct neural channels. Using event-related functional magnetic resonance imaging (fMRI) in humans, we show dissociable roles of such visual channels for processing faces and emotional fearful expressions. Neural responses in fusiform cortex, and effects of repeating the same face identity upon fusiform activity, were greater with intact or high-spatial-frequency face stimuli than with low-frequency faces, regardless of emotional expression. In contrast, amygdala responses to fearful expressions were greater for intact or low-frequency faces than for high-frequency faces. An activation of pulvinar and superior colliculus by fearful expressions occurred specifically with low-frequency faces, suggesting that these subcortical pathways may provide coarse fear-related inputs to the amygdala.
TL;DR: Evidence is presented for a novel mechanism of disinhibition following peripheral nerve injury that involves a trans-synaptic reduction in the expression of the potassium–chloride exporter KCC2, and the consequent disruption of anion homeostasis in neurons of lamina I of the superficial dorsal horn, one of the main spinal nociceptive output pathways.
Abstract: Modern pain-control theory predicts that a loss of inhibition (disinhibition) in the dorsal horn of the spinal cord is a crucial substrate for chronic pain syndromes. However, the nature of the mechanisms that underlie such disinhibition has remained controversial. Here we present evidence for a novel mechanism of disinhibition following peripheral nerve injury. It involves a trans-synaptic reduction in the expression of the potassium-chloride exporter KCC2, and the consequent disruption of anion homeostasis in neurons of lamina I of the superficial dorsal horn, one of the main spinal nociceptive output pathways. In our experiments, the resulting shift in the transmembrane anion gradient caused normally inhibitory anionic synaptic currents to be excitatory, substantially driving up the net excitability of lamina I neurons. Local blockade or knock-down of the spinal KCC2 exporter in intact rats markedly reduced the nociceptive threshold, confirming that the reported disruption of anion homeostasis in lamina I neurons was sufficient to cause neuropathic pain.
TL;DR: In this article, the authors show that contemporary evolution is associated with the same factors that are driving the current extinction crisis: habitat loss and degradation, overharvesting and exotic species.
Abstract: Recent research has revealed that evolution often occurs on contemporary timescales, often within decades. Contemporary evolution is associated with the same factors that are driving the current extinction crisis: habitat loss and degradation, overharvesting and exotic species. Thus, it is relevant to many conservation situations. First, habitat fragmentation might influence the potential of a population to adapt in response environmental degradation. Second, certain harvesting strategies can result in the evolution of life-history traits, ultimately resulting in negative impacts on harvestable yield. Third, the establishment of exotic species can be influenced by their adaptive potential and our ability to limit that potential. Furthermore, contemporary evolution is of concern for intensively managed species, because it might reduce their fitness in native habitats. Ultimately, contemporary evolution is influenced by complex interactions among population size, genetic variation, the strength of selection, and gene flow, making most management scenarios unique. In a world filled with contemporary evolution, conservation efforts that ignore its implications will be less efficient and perhaps even risk prone. Humans have become an evolutionary force of extraordinary influence [1], evidenced most obviously by an unprecedented extinction rate that is attributable to their activities [2]. Human activities are also associated with evolutionary changes that can occur within a few hundred years, otherwise known as CONTEMPORARY EVOLUTION (see Glossary) [3‐5].
TL;DR: The PyMT mouse model is demonstrated to be an excellent one to understand the biology of tumor progression in humans, and its comparison to human breast tumors is compared.
Abstract: Animal models are powerful tools to analyze the mechanism of the induction of human breast cancer. Here we report a detailed analysis of mammary tumor progression in one mouse model of breast cancer caused by expression of the polyoma middle T oncoprotein (PyMT) in the mammary epithelium, and its comparison to human breast tumors. In PyMT mice, four distinctly identifiable stages of tumor progression from premalignant to malignant stages occur in a single primary tumor focus and this malignant transition is followed by a high frequency of distant metastasis. These stages are comparable to human breast diseases classified as benign or in situ proliferative lesions to invasive carcinomas. In addition to the morphological similarities with human breast cancer, the expression of biomarkers in PyMT-induced tumors is also consistent with those associated with poor outcome in humans. These include a loss of estrogen and progesterone receptors as well as integrin-beta1 expression and the persistent expression of ErbB2/Neu and cyclinD1 in PyMT-induced tumors as they progress to the malignant stage. An increased leukocytic infiltration was also closely associated with the malignant transition. This study demonstrates that the PyMT mouse model is an excellent one to understand the biology of tumor progression in humans.
TL;DR: The extremely low concentrations of several essential metals are both the cause and the result of ultraefficient uptake systems in the plankton and of widespread replacement of metals by one another for various biochemical functions.
Abstract: Planktonic uptake of some essential metals results in extraordinarily low concentrations in surface seawater. To sequester or take up these micronutrients, various microorganisms apparently release strong complexing agents and catalyze redox reactions that modify the bioavailability of trace metals and promote their rapid cycling in the upper water column. In turn, the low availability of some metals controls the rate of photosynthesis in parts of the oceans and the transformation and uptake of major nutrients such as nitrogen. The extremely low concentrations of several essential metals are both the cause and the result of ultraefficient uptake systems in the plankton and of widespread replacement of metals by one another for various biochemical functions.
TL;DR: Findings indicate considerable, normal variations in licking/grooming in the rat that are a stable, individual characteristic of rat dams.
TL;DR: It is shown that Cnp1, which encodes 2′,3′-cyclic nucleotide phosphodiesterase in oligodendrocytes, is essential for axonal survival but not for myelin assembly, and the chief function of glia in supporting axonal integrity can thus be completely uncoupled from its function in maintaining compact myelin.
Abstract: Myelination of axons by oligodendrocytes enables rapid impulse propagation in the central nervous system. But long-term interactions between axons and their myelin sheaths are poorly understood. Here we show that Cnp1, which encodes 2',3'-cyclic nucleotide phosphodiesterase in oligodendrocytes, is essential for axonal survival but not for myelin assembly. In the absence of glial cyclic nucleotide phosphodiesterase, mice developed axonal swellings and neurodegeneration throughout the brain, leading to hydrocephalus and premature death. But, in contrast to previously studied myelin mutants, the ultrastructure, periodicity and physical stability of myelin were not altered in these mice. Genetically, the chief function of glia in supporting axonal integrity can thus be completely uncoupled from its function in maintaining compact myelin. Oligodendrocyte dysfunction, such as that in multiple sclerosis lesions, may suffice to cause secondary axonal loss.
01 Aug 2003
TL;DR: Present evidence is sufficient to promote use of sterols and stanols for lowering LDL cholesterol levels in persons at increased risk for coronary heart disease.
Abstract: Foods with plant stanol or sterol esters lower serum cholesterol levels. We summarize the deliberations of 32 experts on the efficacy and safety of sterols and stanols. A meta-analysis of 41 trials showed that intake of 2 g/d of stanols or sterols reduced low-density lipoprotein (LDL) by 10%; higher intakes added little. Efficacy is similar for sterols and stanols, but the food form may substantially affect LDL reduction. Effects are additive with diet or drug interventions: eating foods low in saturated fat and cholesterol and high in stanols or sterols can reduce LDL by 20%; adding sterols or stanols to statin medication is more effective than doubling the statin dose. A meta-analysis of 10 to 15 trials per vitamin showed that plasma levels of vitamins A and D are not affected by stanols or sterols. Alpha carotene, lycopene, and vitamin E levels remained stable relative to their carrier molecule, LDL. Beta carotene levels declined, but adverse health outcomes were not expected. Sterol-enriched foods increased plasma sterol levels, and workshop participants discussed whether this would increase risk, in view of the marked increase of atherosclerosis in patients with homozygous phytosterolemia. This risk is believed to be largely hypothetical, and any increase due to the small increase in plasma plant sterols may be more than offset by the decrease in plasma LDL. There are insufficient data to suggest that plant stanols or sterols either prevent or promote colon carcinogenesis. Safety of sterols and stanols is being monitored by follow-up of samples from the general population; however, the power of such studies to pick up infrequent increases in common diseases, if any exist, is limited. A trial with clinical outcomes probably would not answer remaining questions about infrequent adverse effects. Trials with surrogate end points such as intima-media thickness might corroborate the expected efficacy in reducing atherosclerosis. However, present evidence is sufficient to promote use of sterols and stanols for lowering LDL cholesterol levels in persons at increased risk for coronary heart disease.
TL;DR: Interactions between microtubules and actin are a basic phenomenon that underlies many fundamental processes in which dynamic cellular asymmetries need to be established and maintained.
Abstract: Interactions between microtubules and actin are a basic phenomenon that underlies many fundamental processes in which dynamic cellular asymmetries need to be established and maintained. These are processes as diverse as cell motility, neuronal pathfinding, cellular wound healing, cell division and cortical flow. Microtubules and actin exhibit two mechanistic classes of interactions--regulatory and structural. These interactions comprise at least three conserved 'mechanochemical activity modules' that perform similar roles in these diverse cell functions.
TL;DR: Evidence is presented that the attenuated vesicular stomatitis strains, AV1 and AV2, embody all of the traits of an oncolytic virus, which will replicate preferentially in malignant cells, have the ability to treat disseminated metastases, and ultimately be cleared by the patient.
TL;DR: The results provide the first evidence for spontaneous variability and shift in neural mechanisms during navigation in humans.
Abstract: The human brain activity related to strategies for navigating in space and how it changes with practice was investigated with functional magnetic resonance imaging. Subjects used two different strategies to solve a place-learning task in a computer-generated virtual environment. One-half of the subjects used spatial landmarks to navigate in the early phase of training, and these subjects showed increased activation of the right hippocampus. The other half used a nonspatial strategy and showed, with practice, sustained increased activity within the caudate nucleus during navigation. Activation common to both groups was observed in the posterior parietal and frontal cortex. These results provide the first evidence for spontaneous variability and shift in neural mechanisms during navigation in humans.
TL;DR: The potential underlying mechanisms involved in the regulation of the mitochondrial checkpoint are reviewed and pathways for ER–mitochondrial crosstalk pertinent to a number of cell death stimuli are discussed.
Abstract: Apoptotic programmed cell death pathways are activated by a diverse array of cell extrinsic and intrinsic signals, most of which are ultimately coupled to the activation of effector caspases. In many instances, this involves an obligate propagation through mitochondria, causing egress of critical proapoptotic regulators to the cytosol. Central to the regulation of the mitochondrial checkpoint is a complex three-way interplay between members of the BCL-2 family, which are comprised of an antiapoptotic subgroup including BCL-2 itself, and the proapoptotic BAX,BAK and BH3-domain-only subgroups. Constituents of all three of these BCL-2 classes, however, also converge on the endoplasmic reticulum (ER), an organelle whose critical contributions to apoptosis is only now becoming apparent. In addition to propagating death-inducing stress signals itself, the ER also contributes in a fundamental way to Fas-mediated apoptosis and to p53-dependent pathways resulting from DNA damage and oncogene expression. Mobilization of ER calcium stores can initiate the activation of cytoplasmic death pathways as well as sensitize mitochondria to direct proapoptotic stimuli. Additionally, the existence of BCL-2-regulated initiator procaspase activation complexes at the ER membrane has also been described. Here, we review the potential underlying mechanisms involved in these events and discuss pathways for ER-mitochondrial crosstalk pertinent to a number of cell death stimuli.
TL;DR: The findings of a survey that found a rate of 34 per 10000 for autism spectrum disorders (ASDs) among 3to 10-year-old children in metropolitan Atlanta suggest that these differences might reflect new diagnostic criteria for autism and increased availability of developmental disability services for children with autism in the 1990s.
Abstract: THE NUMBER OF EPIDEMIOLOGICAL STUDIES OF AUtism has increased in recent years, including in the United States, where investigators are now catching up in what has traditionally been a weak area of child psychiatric research in North America. In this issue of THE JOURNAL, Yeargin-Allsopp et al report the findings of a survey, which was funded by the Centers for Disease Control and Prevention, that found a rate of 34 per 10000 for autism spectrum disorders (ASDs) among 3to 10-year-old children in metropolitan Atlanta. The strengths of the survey include use of multiple ascertainment sources and large sample size (ie, 987 confirmed ASD cases compared with a median sample size of 50 in 32 previous studies), thereby allowing the authors to have good precision in the estimates and to conduct meaningful subgroup analyses. In addition, this study is the first to derive a robust population-based estimate for the rate of ASD in black children, which is comparable to other racial groups. Other findings are typical of those found in previous surveys with ASD cases, with a strong overrepresentation of boys, cognitive impairments in more than two thirds of cases, and a relatively high rate (8%) of epilepsy. Approximately 18% of the sample did not have a previous diagnosis or were not suspected of having ASD, and children from black, younger, or less educated mothers were more often identified through schools as the only source of case finding. These findings highlight the need to rely on multiple ascertainment sources in epidemiological studies of ASD and caution against findings that are based on single service provider databases. The prevalence rate of 34 per 10000 is, however, likely to be an underestimate. First, as the authors point out, children with milder or high-functioning (ie, normal IQ) ASD subtypes are likely to have been missed. Second, the lower prevalence in 3and 4-year-olds may reflect lower sensitivity of case identification among younger children for developmental disorders that often are diagnosed later. Third, there was an unexpected decrease in prevalence among 9and 10-year-olds. Although it would be tempting to interpret this age trend as indicative of a secular increase in the rate of ASD (ie, the younger the birth cohort, the higher the prevalence), such an explanation is both unlikely and biologically implausible because rates plateaued for birth cohorts aged 5 through 8. Rather, the authors suggest that these differences might reflect new diagnostic criteria for autism and increased availability of developmental disability services for children with autism in the 1990s. What this means, however, is that the rate of 41 to 45 in 10000 obtained for the 5to 8-year-olds might be more accurate. This rate also is more in line with those of 3 recent surveys that yielded prevalence estimates in the range of 60 per 10000. High prevalence rates from more recent epidemiological surveys have fueled the debate about a possible epidemic of autism. However, 4 separate issues need to be addressed. The first issue concerns the best current estimate for the prevalence of autism and related disorders. Increasing and consistent evidence from recent surveys shows that the prevalence rate for ASDs (including not only autism disorder but also Asperger disorder and pervasive developmental disorder–not otherwise specified) is approximately 60 per 10000; the study results from Yeargin-Allsopp et al concur with this conclusion. This estimate translates to approximately 425000 children younger than age 18 years with ASDs in the United States, including 114000 children younger than 5 years. The second issue is whether the prevalence of ASD has increased over time. Surveys conducted in the 1960s and 1970s only dealt with autism disorder (as opposed to ASD) and with a rather narrow definition of autism, as per Kanner’s descriptions, and not accounting for autism occurring in subjects who are not mentally retarded. Thus, comparisons of rates over time generally deal with studies that have used different case definitions, making interpretation of time trends difficult. The closest estimate of ASD prevalence available in the late 1970s was 20 per 10000 in a survey from the United Kingdom that was limited to the severely impaired children with ASD. Comparing rates for subtypes of ASD provide another avenue for estimation over time especially for autism disorder, but as shown by Yeargin-Allsopp et al and other surveys, the breakdown in ASD subtypes is not always reli-
TL;DR: Skin biopsies from AD and psoriasis patients were analyzed and decreased expression of a constellation of antimicrobial genes occurs as the result of local up-regulation of Th2 cytokines and the lack of elevated amounts of TNF-α and IFN-γ under inflammatory conditions in AD skin.
Abstract: Atopic dermatitis (AD) and psoriasis are the two most common chronic skin diseases. However patients with AD, but not psoriasis, suffer from frequent skin infections. To understand the molecular basis for this phenomenon, skin biopsies from AD and psoriasis patients were analyzed using GeneChip microarrays. The expression of innate immune response genes, human beta defensin (HBD)-2, IL-8, and inducible NO synthetase (iNOS) was found to be decreased in AD, as compared with psoriasis, skin (HBD-2, p = 0.00021; IL-8, p = 0.044; iNOS, p = 0.016). Decreased expression of the novel antimicrobial peptide, HBD-3, was demonstrated at the mRNA level by real-time PCR (p = 0.0002) and at the protein level by immunohistochemistry (p = 0.0005). By real-time PCR, our data confirmed that AD, as compared with psoriasis, is associated with elevated skin production of Th2 cytokines and low levels of proinflammatory cytokines such as TNF-alpha, IFN-gamma, and IL-1beta. Because HBD-2, IL-8, and iNOS are known to be inhibited by Th2 cytokines, we examined the effects of IL-4 and IL-13 on HBD-3 expression in keratinocyte culture in vitro. We found that IL-13 and IL-4 inhibited TNF-alpha- and IFN-gamma-induced HBD-3 production. These studies indicate that decreased expression of a constellation of antimicrobial genes occurs as the result of local up-regulation of Th2 cytokines and the lack of elevated amounts of TNF-alpha and IFN-gamma under inflammatory conditions in AD skin. These observations could explain the increased susceptibility of AD skin to microorganisms, and suggest a new fundamental rule that may explain the mechanism for frequent infection in other Th2 cytokine-mediated diseases.
TL;DR: In this paper, a simple model is proposed to explain the development of a homogeneous microstructure in high pressure torsion (HPT) processing of pure nickel samples, showing that the distributions of grain boundary misorientations are similar in the center and at the periphery of the samples.
TL;DR: The data indicate that NUDR is a repressor of the 5-HT1A receptor in raphe cells the function of which is abrogated by a promoter polymorphism, suggesting a novel transcriptional model in which the G(-1019) allele derepresses 5- HT1A autoreceptor expression to reduce serotonergic neurotransmission, predisposing to depression and suicide.
Abstract: Inhibition of serotonergic raphe neurons is mediated by somatodendritic 5-HT1A autoreceptors, which may be increased in depressed patients. We report an association of the C(-1019)G 5-HT1A promoter polymorphism with major depression and suicide in separate cohorts. In depressed patients, the homozygous G(-1019) allele was enriched twofold versus controls (p = 0.0017 and 0.0006 for G/G genotype and G allele distribution, respectively), and in completed suicide cases the G(-1019) allele was enriched fourfold (p = 0.002 and 0.00008 for G/G genotype and G allele distribution, respectively). The C(-1019) allele was part of a 26 bp imperfect palindrome that bound transcription factors nuclear NUDR [nuclear deformed epidermal autoregulatory factor (DEAF-1)]/suppressin and Hairy/Enhancer-of-split-5 (Drosophila) (Hes5) to repress 5-HT1A or heterologous promoters, whereas the G(-1019) allele abolished repression by NUDR, but only partially impaired Hes5-mediated repression. Recombinant NUDR bound specifically to the 26 bp palindrome, and endogenous NUDR was present in the major protein-DNA complex from raphe nuclear extracts. Stable expression of NUDR in raphe cells reduced levels of endogenous 5-HT1A protein and binding. NUDR protein was colocalized with 5-HT1A receptors in serotonergic raphe cells, hippocampal and cortical neurons, and adult brain regions including raphe nuclei, indicating a role in regulating 5-HT1A autoreceptor expression. Our data indicate that NUDR is a repressor of the 5-HT1A receptor in raphe cells the function of which is abrogated by a promoter polymorphism. We suggest a novel transcriptional model in which the G(-1019) allele derepresses 5-HT1A autoreceptor expression to reduce serotonergic neurotransmission, predisposing to depression and suicide.
TL;DR: The hypothesis that reactivation of a consolidated memory can return it to a labile, sensitive state - in which it can be modified, strengthened, changed or even erased is revisited.
TL;DR: A specific etiology can be determined in the majority of children with global developmental delay and certain routine screening tests are indicated and depending on history and examination findings, additional specific testing may be performed.
Abstract: Objective: To make evidence-based recommendations concerning the evaluation of the child with a nonprogres- sive global developmental delay. Methods: Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a four-tiered scheme of evidence classification. Results: Global developmental delay is common and affects 1% to 3% of children. Given yields of about 1%, routine metabolic screening is not indicated in the initial evaluation of a child with global developmental delay. Because of the higher yield (3.5% to 10%), even in the absence of dysmorphic features or features suggestive of a specific syndrome, routine cytogenetic studies and molecular testing for the fragile X mutation are recommended. The diagnosis of Rett syndrome should be considered in girls with unexplained moderate to severe developmental delay. Additional genetic studies (e.g., subtelomeric chromosomal rearrangements) may also be considered in selected children. Evaluation of serum lead levels should be restricted to those children with identifiable risk factors for excessive lead exposure. Thyroid studies need not be undertaken (unless clinically indicated) if the child underwent newborn screening. An EEG is not recommended as part of the initial evaluation unless there are historical features suggestive of epilepsy or a specific epileptic syndrome. Routine neuroimaging, with MRI preferred to CT, is recommended particularly if abnormalities are found on physical examination. Because of the increased incidence of visual and auditory impairments, children with global developmental delay may undergo appropriate visual and audiometric assessment at the time of diagnosis. Conclusions: A specific etiology can be determined in the majority of children with global developmental delay. Certain routine screening tests are indicated and depending on history and examination findings, additional specific testing may be performed. NEUROLOGY 2003;60:367-380
TL;DR: The effects of foliar applied SA, acetyl salicylic acid (ASA) and gentisic acid (GTA) on photosynthetic rates and growth of soybean and corn under greenhouse conditions and in some cases treatment with these compounds resulted in increased leaf areas and plant dry mass, however, plant height and root length were not affected.