Showing papers by "University of Missouri published in 2008"
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: This article reviews the recent progress in optical biosensors that use the label-free detection protocol, in which biomolecules are unlabeled or unmodified, and are detected in their natural forms, and focuses on the optical biosENSors that utilize the refractive index change as the sensing transduction signal.
2,060 citations
01 Sep 2008
TL;DR: It is shown why this is the case and offered a simple correction that makes the expected size of Cousineau confidence intervals the same as that of Loftus and Masson confidence intervals.
Abstract: Presenting confidence intervals around means is a common method of expressing uncertainty in data. Loftus and Masson (1994) describe confidence intervals for means in within‐subjects designs. These confidence intervals are based on the ANOVA mean squared error. Cousineau (2005) presents an alternative to the Loftus and Masson method, but his method produces confidence intervals that are smaller than those of Loftus and Masson. I show why this is the case and offer a simple correction that makes the expected size of Cousineau confidence intervals the same as that of Loftus and Masson confidence intervals.
1,630 citations
Colorado Department of Public Health and Environment1, University of Southern California2, Cincinnati Children's Hospital Medical Center3, Dartmouth College4, Cedars-Sinai Medical Center5, University of North Carolina at Chapel Hill6, Regions Hospital7, University of Missouri8, Icahn School of Medicine at Mount Sinai9, University of Michigan10, Georgia Regents University11, Arizona State University12, University of Texas Health Science Center at Houston13, University of Massachusetts Medical School14, University of California, San Francisco15
TL;DR: The USPSTF concludes that the evidence is insufficient to assess the benefits and harms of computed tomographic colonography and fecal DNA testing as screening modalities for colorectal cancer.
Abstract: DESCRIPTION Update of the 2002 U.S. Preventive Services Task Force (USPSTF) recommendation statement on screening for colorectal cancer. METHODS To update its recommendation, the USPSTF commissioned 2 studies: 1) a targeted systematic evidence review on 4 selected questions relating to test characteristics and benefits and harms of screening technologies, and 2) a decision analytic modeling analysis using population modeling techniques to compare the expected health outcomes and resource requirements of available screening modalities when used in a programmatic way over time. RECOMMENDATIONS The USPSTF recommends screening for colorectal cancer using fecal occult blood testing, sigmoidoscopy, or colonoscopy in adults, beginning at age 50 years and continuing until age 75 years. The risks and benefits of these screening methods vary. (A recommendation). The USPSTF recommends against routine screening for colorectal cancer in adults 76 to 85 years of age. There may be considerations that support colorectal cancer screening in an individual patient. (C recommendation). The USPSTF recommends against screening for colorectal cancer in adults older than age 85 years. (D recommendation). The USPSTF concludes that the evidence is insufficient to assess the benefits and harms of computed tomographic colonography and fecal DNA testing as screening modalities for colorectal cancer. (I statement).
1,347 citations
TL;DR: The results suggest that nitrifying bacteria are especially susceptible to inhibition byAg NPs, and the accumulation of Ag NPs could have detrimental effects on the microorganisms in wastewater treatment.
1,276 citations
TL;DR: It was observed that inhibition to nitrifying organisms correlated with the fraction of Ag nanoparticles less than 5 nm in the suspension, and it appeared that these size nanoparticles could be more toxic to bacteria than any other fractions of nanoparticles or their counterpart bulk species.
Abstract: The intrinsic slow growth of nitrifying bacteria and their high sensitivity to environmental perturbations often result in cell growth inhibition by toxicants. Nanoparticles are of great concern to the environment because of their small size and high catalytic properties. This work sought to determine size-dependent inhibition by Ag nanoparticles and evaluate the relationship between the inhibition and reactive oxygen species (ROS). Nanoparticles with an average size range of 9−21 nm were synthesized by varying the molar ratios of BH4− /Ag+in the solution. The resulting ROS generation was quantified in the presence and absence of the bacteria while the degree of inhibition was inferred from specific oxygen uptake rate measurements, determined by extant respirometry. By examining the correlation between nanoparticle size distribution, photocatalytic ROS generation, intracellular ROS accumulation, and nitrification inhibition, we observed that inhibition to nitrifying organisms correlated with the fraction ...
1,248 citations
TL;DR: This paper found that an increase in real oil price is associated with a significant increase in the short-term interest rate in the U.S. and eight out of 13 European countries within one or two months.
1,180 citations
TL;DR: This chapter strives to reduce that confusion and makes up-to-date assessments of these types of memory and evaluated and placed within a theoretical framework depicted in Fig. 1.
Abstract: In the recent literature there has been considerable confusion about the three types of memory: long-term, short-term, and working memory. This chapter strives to reduce that confusion and makes up-to-date assessments of these types of memory. Long- and short-term memory could differ in two fundamental ways, with only short-term memory demonstrating (1) temporal decay and (2) chunk capacity limits. Both properties of short-term memory are still controversial but the current literature is rather encouraging regarding the existence of both decay and capacity limits. Working memory has been conceived and defined in three different, slightly discrepant ways: as short-term memory applied to cognitive tasks, as a multi-component system that holds and manipulates information in short-term memory, and as the use of attention to manage short-term memory. Regardless of the definition, there are some measures of memory in the short term that seem routine and do not correlate well with cognitive aptitudes and other measures (those usually identified with the term "working memory") that seem more attention demanding and do correlate well with these aptitudes. The evidence is evaluated and placed within a theoretical framework depicted in Fig. 1.
1,089 citations
TL;DR: Genomic data suggest that different gene classes tend to be retained after single-gene and whole-genome duplications, and in many cases the 'new' function of one copy is a secondary property that was always present, but that has been co-opted to a primary role after the duplication.
Abstract: Gene duplication provides raw material for functional innovation. Recent advances have shed light on two fundamental questions regarding gene duplication: which genes tend to undergo duplication? And how does natural selection subsequently act on them? Genomic data suggest that different gene classes tend to be retained after single-gene and whole-genome duplications. We also know that functional differences between duplicate genes can originate in several different ways, including mutations that directly impart new functions, subdivision of ancestral functions and selection for changes in gene dosage. Interestingly, in many cases the 'new' function of one copy is a secondary property that was always present, but that has been co-opted to a primary role after the duplication.
1,065 citations
TL;DR: The unusual structure of BST-2, which includes a transmembrane domain and a lumenal GPI anchor, may allow it to retain nascent enveloped virions on cellular membranes, providing a mechanism of viral restriction counteracted by a specific viral accessory protein.
1,018 citations
TL;DR: This paper improves upon best‐known guarantees for exact reconstruction of a sparse signal f from a small universal sample of Fourier measurements by showing that there exists a set of frequencies Ω such that one can exactly reconstruct every r‐sparse signal f of length n from its frequencies in Ω, using the convex relaxation.
Abstract: This paper improves upon best-known guarantees for exact reconstruction of a sparse signal f from a small universal sample of Fourier measurements. The method for reconstruction that has recently gained momentum in the sparse approximation theory is to relax this highly nonconvex problem to a convex problem and then solve it as a linear program. We show that there exists a set of frequencies Ω such that one can exactly reconstruct every r-sparse signal f of length n from its frequencies in Ω, using the convex relaxation, and Ω has size k(r, n) = O(r log(n)·log 2 (r) log(r logn)) = O(r log 4 n ). A random set Ω satisfies this with high probability. This estimate is optimal within the log log n and log 3 r factors. We also give a relatively short argument for a similar problem with k(r, n) ≈ r[12 + 8 log(n/r)] Gaussian measurements. We use methods of geometric functional analysis and probability theory in Banach spaces, which makes our arguments quite short.
TL;DR: In this article, the authors estimate that East Antarctica is close to a balanced mass budget, but large losses of ice occur in the narrow outlet channels of West Antarctic glaciers and at the northern tip of the Antarctic peninsula.
Abstract: Observed estimates of ice losses in Antarctica combined with regional modelling of ice accumulation in the interior suggest that East Antarctica is close to a balanced mass budget, but large losses of ice occur in the narrow outlet channels of West Antarctic glaciers and at the northern tip of the Antarctic peninsula.
TL;DR: A rigorous definition for the detection limit of resonant RI sensors is set forth that accounts for all parameters that affect the detection performance and will lead to design strategies for performance improvement of RI sensors.
Abstract: Refractive index (RI) sensors based on optical resonance techniques are receiving a high degree of attention because of the need to develop simple, low-cost, high-throughput detection technologies for a number of applications. While the sensing mechanism of most of the reported RI sensors is similar, the construction is quite different from technique to technique. It is desirable to have a uniform mechanism for comparing the various RI sensing techniques, but to date there exists a degree of variation as to how the sensing performance is quantified. Here we set forth a rigorous definition for the detection limit of resonant RI sensors that accounts for all parameters that affect the detection performance. Our work will enable a standard approach for quantifying and comparing the performance of optical resonance-based RI sensors. Additionally, it will lead to design strategies for performance improvement of RI sensors.
TL;DR: For centers and countries, a target threshold TTR exists (estimated between 58% and 65%) below which there appears to be little benefit of OAC over antiplatelet therapy, and a wide variation exists in international normalized ratio control, as measured by TTR, between clinical centers and between countries.
Abstract: Background— Oral anticoagulation (OAC) therapy is effective in atrial fibrillation but requires vigilance to maintain the international normalized ratio in the therapeutic range. This report examines how differences in time in therapeutic range (TTR) between centers and between countries affect the outcomes of OAC therapy. Methods and Results— In a posthoc analysis, the TTRs of patients on OAC in a randomized trial of OAC versus clopidogrel plus aspirin (Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events [ACTIVE W]) were used to calculate the mean TTR for each of 526 centers and 15 countries. Proportional-hazards analysis, with and without adjustment for baseline variables, was performed, with patients stratified by TTR quartile and country. A wide variation in TTRs was found between centers, with mean TTRs for centers in the 4 quartiles of 44%, 60%, 69%, and 78%. For patients at centers below the median TTR (65%), no treatment benefit was demonstrated as measured by r...
TL;DR: Observations suggest that mitochondrial dysfunction may be a central cause of insulin resistance and associated complications, and interventions that improve mitochondrial function also improve insulin resistance.
Abstract: Insulin resistance is characteristic of obesity, type 2 diabetes, and components of the cardiometabolic syndrome, including hypertension and dyslipidemia, that collectively contribute to a substantial risk for cardiovascular disease. Metabolic actions of insulin in classic insulin target tissues (eg, skeletal muscle, fat, and liver), as well as actions in nonclassic targets (eg, cardiovascular tissue), help to explain why insulin resistance and metabolic dysregulation are central in the pathogenesis of the cardiometabolic syndrome and cardiovascular disease. Glucose and lipid metabolism are largely dependent on mitochondria to generate energy in cells. Thereby, when nutrient oxidation is inefficient, the ratio of ATP production/oxygen consumption is low, leading to an increased production of superoxide anions. Reactive oxygen species formation may have maladaptive consequences that increase the rate of mutagenesis and stimulate proinflammatory processes. In addition to reactive oxygen species formation, genetic factors, aging, and reduced mitochondrial biogenesis all contribute to mitochondrial dysfunction. These factors also contribute to insulin resistance in classic and nonclassic insulin target tissues. Insulin resistance emanating from mitochondrial dysfunction may contribute to metabolic and cardiovascular abnormalities and subsequent increases in cardiovascular disease. Furthermore, interventions that improve mitochondrial function also improve insulin resistance. Collectively, these observations suggest that mitochondrial dysfunction may be a central cause of insulin resistance and associated complications. In this review, we discuss mechanisms of mitochondrial dysfunction related to the pathophysiology of insulin resistance in classic insulin-responsive tissue, as well as cardiovascular tissue.
TL;DR: It is time to consider excessive sitting a serious health hazard, with the potential for ultimately giving consideration to the inclusion of too much sitting (or too few breaks from sitting) in physical activity and health guidelines.
Abstract: Moderate-to vigorous-intensity physical activity has an established preventive role in cardiovascular disease, type 2 diabetes, obesity, and some cancers. However, recent epidemiologic evidence suggests that sitting time has deleterious cardiovascular and metabolic effects that are independent of whether adults meet physical activity guidelines. Evidence from “inactivity physiology” laboratory studies has identified unique mechanisms that are distinct from the biologic bases of exercising. Opportunities for sedentary behaviors are ubiquitous and are likely to increase with further innovations in technologies. We present a compelling selection of emerging evidence on the deleterious effects of sedentary behavior, as it is underpinned by the unique physiology of inactivity. It is time to consider excessive sitting a serious health hazard, with the potential for ultimately giving consideration to the inclusion of too much sitting (or too few breaks from sitting) in physical activity and health guidelines.
TL;DR: In this paper, the authors outline the problems and costs of distinguishing between two types of happiness, and provide detailed recommendations for a research program on well-being with greater scientific precision.
Abstract: In recent years, well-being researchers have distinguished between eudaimonic happiness (e.g., meaning and purpose; taking part in activities that allow for the actualization of one's skills, talents, and potential) and hedonic happiness (e.g., high frequencies of positive affect, low frequencies of negative affect, and evaluating life as satisfying). Unfortunately, this distinction (rooted in philosophy) does not necessarily translate well to science. Among the problems of drawing too sharp a line between ‘types of happiness’ is the fact that eudaimonia is not well-defined and lacks consistent measurement. Moreover, empirical evidence currently suggests that hedonic and eudaimonic well-being overlap conceptually, and may represent psychological mechanisms that operate together. In this article, we outline the problems and costs of distinguishing between two types of happiness, and provide detailed recommendations for a research program on well-being with greater scientific precision. The purpose of life ...
TL;DR: The LysM RLK1-mediated chitin signaling pathway is unique, but it may share a conserved downstream pathway with the FLS2/flagellin- and EFR/EF-Tu–mediated signaling pathways.
Abstract: Chitin, a polymer of N -acetyl-d-glucosamine, is found in fungal cell walls but not in plants. Plant cells can perceive chitin fragments (chitooligosaccharides) leading to gene induction and defense responses. We identified a LysM receptor-like protein (LysM RLK1) required for chitin signaling in Arabidopsis thaliana . The mutation in this gene blocked the induction of almost all chitooligosaccharide-responsive genes and led to more susceptibility to fungal pathogens but had no effect on infection by a bacterial pathogen. Additionally, exogenously applied chitooligosaccharides enhanced resistance against both fungal and bacterial pathogens in the wild-type plants but not in the mutant. Together, our data indicate that LysM RLK1 is essential for chitin signaling in plants (likely as part of the receptor complex) and is involved in chitin-mediated plant innate immunity. The LysM RLK1-mediated chitin signaling pathway is unique, but it may share a conserved downstream pathway with the FLS2/flagellin- and EFR/EF-Tu–mediated signaling pathways. Additionally, our work suggests a possible evolutionary relationship between the chitin and Nod factor perception mechanisms due to the similarities between their potential receptors and between the signal molecules perceived by them.
University of Miami1, Rosalind Franklin University of Medicine and Science2, Veterans Health Administration3, United States Department of Veterans Affairs4, University of Missouri–Kansas City5, American Association of Clinical Endocrinologists6, American Diabetes Association7, Texas A&M University8, University of Missouri9, University of Arizona10, Washington University in St. Louis11, Icahn School of Medicine at Mount Sinai12, University of Pittsburgh13
TL;DR: A task force was assembled by the ADA to address and concisely summarize recent literature in this area and then recommend what should be included in the comprehensive foot exam for adult patients with diabetes.
Abstract: It is now 10 years since the last technical review on preventative foot care was published (1), which was followed by an American Diabetes Association (ADA) position statement on preventive foot care in diabetes (2). Many studies have been published proposing a range of tests that might usefully identify patients at risk of foot ulceration, creating confusion among practitioners as to which screening tests should be adopted in clinical practice. A task force was therefore assembled by the ADA to address and concisely summarize recent literature in this area and then recommend what should be included in the comprehensive foot exam for adult patients with diabetes. The committee was cochaired by the immediate past and current chairs of the ADA Foot Care Interest Group (A.J.M.B. and D.G.A.), with other panel members representing primary care, orthopedic and vascular surgery, physical therapy, podiatric medicine and surgery, and the American Association of Clinical Endocrinologists.
The lifetime risk of a person with diabetes developing a foot ulcer may be as high as 25%, whereas the annual incidence of foot ulcers is ∼2% (3–7). Up to 50% of older patients with type 2 diabetes have one or more risk factors for foot ulceration (3,6). A number of component causes, most importantly peripheral neuropathy, interact to complete the causal pathway to foot ulceration (1,3–5). A list of the principal contributory factors that might result in foot ulcer development is provided in Table 1.
View this table:
Table 1—
Risk factors for foot ulcers
The most common triad of causes that interact and ultimately result in ulceration has been identified as neuropathy, deformity, and trauma (5). As identification of those patients at risk of foot problems is the first step in preventing such complications, this report will focus on key components of the …
TL;DR: The pig model may provide opportunities to address persistent questions about CF pathogenesis and accelerate discovery of strategies for prevention and treatment.
Abstract: Almost two decades after CFTR was identified as the gene responsible for cystic fibrosis (CF), we still lack answers to many questions about the pathogenesis of the disease, and it remains incurable. Mice with a disrupted CFTR gene have greatly facilitated CF studies, but the mutant mice do not develop the characteristic manifestations of human CF, including abnormalities of the pancreas, lung, intestine, liver, and other organs. Because pigs share many anatomical and physiological features with humans, we generated pigs with a targeted disruption of both CFTR alleles. Newborn pigs lacking CFTR exhibited defective chloride transport and developed meconium ileus, exocrine pancreatic destruction, and focal biliary cirrhosis, replicating abnormalities seen in newborn humans with CF. The pig model may provide opportunities to address persistent questions about CF pathogenesis and accelerate discovery of strategies for prevention and treatment.
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: Results of 90 studies of episodic memory for both item and associative information provided support for the age-related associative/binding deficit suggestion, indicating a larger effect of age on memory for Associative information than for item information.
Abstract: In this meta-analysis, the authors evaluated recent suggestions that older adults' episodic memory impairments are partially due to a reduced ability to encode and retrieve associated/bound units of information. Results of 90 studies of episodic memory for both item and associative information in 3,197 young and 3,192 older adults provided support for the age-related associative/binding deficit suggestion, indicating a larger effect of age on memory for associative information than for item information. Moderators assessed included the type of associations, encoding instructions, materials, and test format. Results indicated an age-related associative deficit in memory for source, context, temporal order, spatial location, and item pairings, in both verbal and nonverbal material. An age-related associative deficit was quite pronounced under intentional learning instructions but was not clearly evident under incidental learning instructions. Finally, test format was also found to moderate the associative deficit, with older adults showing an associative/binding deficit when item memory was evaluated via recognition tests but not when item memory was evaluated via recall tests, in which case the age-related deficits were similar for item and associative information.
TL;DR: In this paper, the association of a country's investor protection regime with the quality of reported earnings is examined for a large sample of firms from 42 countries, and three attributes of earnings are evaluated: the magnitude of abnormal accruals, the likelihood of reporting losses, and earnings conservatism (timely loss recognition).
Abstract: The association of a country's investor protection regime with the quality of reported earnings is examined for a large sample of firms from 42 countries. Three attributes of earnings are evaluated: the magnitude of abnormal accruals, the likelihood of reporting losses, and earnings conservatism (timely loss recognition). We find that earnings quality increases for firms with Big 4 auditors when a country's investor protection regime gives stronger protection to investors; specifically, abnormal accruals are smaller, there is a greater likelihood of reporting losses, and earnings conservatism is greater. In contrast, earnings of firms with non-Big 4 auditors are largely unaffected by different investor protection regimes. The study adds to a growing body of research showing that accounting practices are influenced by a country's institutions. However, our results differ from prior studies by demonstrating that country-level effects are mediated by audit enforcement, and in particular the incentives of Big 4 auditors to perform higher quality audits in countries with stricter investor protection regimes.
TL;DR: In this paper, the authors propose a theoretical framework that delineates the consequences of the construct and empirically tests the proposed framework using role-playing experiments, finding that when customers participate in the service recovery process in self-service technology contexts, they are more likely to report higher levels of role clarity, perceived value of future co-creation, satisfaction with service recovery, and intention to co-create value in the future.
Abstract: The benefits of customer co-creation of value in the service context are well recognized. However, little is known about service failures in a co-creation context and the consequent roles of both firms and customers in the advent of service recovery. In conceptualizing a new construct, “customer participation in service recovery,” this study proposes a theoretical framework that delineates the consequences of the construct and empirically tests the proposed framework using role-playing experiments. The results indicate that, when customers participate in the service recovery process in self-service technology contexts, they are more likely to report higher levels of role clarity, perceived value of future co-creation, satisfaction with the service recovery, and intention to co-create value in the future. Theoretical and managerial implications of the findings are discussed.
TL;DR: An economical, efficient, single-step method for SNP discovery, validation and characterization that uses deep sequencing of reduced representation libraries (RRLs) from specified target populations and may be applied to any species with at least a partially sequenced genome.
Abstract: High-density single-nucleotide polymorphism (SNP) arrays have revolutionized the ability of genome-wide association studies to detect genomic regions harboring sequence variants that affect complex traits. Extensive numbers of validated SNPs with known allele frequencies are essential to construct genotyping assays with broad utility. We describe an economical, efficient, single-step method for SNP discovery, validation and characterization that uses deep sequencing of reduced representation libraries (RRLs) from specified target populations. Using nearly 50 million sequences generated on an Illumina Genome Analyzer from DNA of 66 cattle representing three populations, we identified 62,042 putative SNPs and predicted their allele frequencies. Genotype data for these 66 individuals validated 92% of 23,357 selected genome-wide SNPs, with a genotypic and sequence allele frequency correlation of r = 0.67. This approach for simultaneous de novo discovery of high-quality SNPs and population characterization of allele frequencies may be applied to any species with at least a partially sequenced genome.
TL;DR: It is concluded that altered puberty timing should be considered an adverse effect, although the magnitude of change considered adverse was not assessed and additional analyses of existing puberty-timing data are recommended to examine secular trends and trends in the temporal sequence of pubertal events.
Abstract: Whether children, especially girls, are entering and progressing through puberty earlier today than in the mid-1900s has been debated. Secular trend analysis, based on available data, is limited by data comparability among studies in different populations, in different periods of time, and using different methods. As a result, conclusions from data comparisons have not been consistent. An expert panel was asked to evaluate the weight of evidence for whether the data, collected from 1940 to 1994, are sufficient to suggest or establish a secular trend in the timing of puberty markers in US boys or girls. A majority of the panelists agreed that data are sufficient to suggest a trend toward an earlier breast development onset and menarche in girls but not for other female pubertal markers. A minority of panelists concluded that the current data on girls' puberty timing for any marker are insufficient. Almost all panelists concluded, on the basis of few studies and reliability issues of some male puberty markers, that current data for boys are insufficient to evaluate secular trends in male pubertal development. The panel agreed that altered puberty timing should be considered an adverse effect, although the magnitude of change considered adverse was not assessed. The panel recommended (1) additional analyses of existing puberty-timing data to examine secular trends and trends in the temporal sequence of pubertal events; (2) the development of biomarkers for pubertal timing and methods to discriminate fat versus breast tissue, and (3) establishment of cohorts to examine pubertal markers longitudinally within the same individuals.
TL;DR: Multiple levels of molecular interactions are suggested, each of which contribute specific functional features and together create a sophisticated signaling device in bacteria that mediate chemotaxis.
TL;DR: A number of rare sequence variants in the coding region, including two missense changes in conserved residues of the alpha-neurexin 1 leader sequence and of an epidermal growth factor (EGF)-like domain, suggest that even subtle changes in NRXN1 might contribute to susceptibility to ASD.
Abstract: Autism is a neurodevelopmental disorder of complex etiology in which genetic factors play a major role. We have implicated the neurexin 1 (NRXN1) gene in two independent subjects who display an autism spectrum disorder (ASD) in association with a balanced chromosomal abnormality involving 2p16.3. In the first, with karyotype 46,XX,ins(16;2)(q22.1;p16.1p16.3)pat, NRXN1 is directly disrupted within intron 5. Importantly, the father possesses the same chromosomal abnormality in the absence of ASD, indicating that the interruption of α-NRXN1 is not fully penetrant and must interact with other factors to produce ASD. The breakpoint in the second subject, with 46,XY,t(1;2)(q31.3;p16.3)dn, occurs ∼750 kb 5′ to NRXN1 within a 2.6 Mb genomic segment that harbors no currently annotated genes. A scan of the NRXN1 coding sequence in a cohort of ASD subjects, relative to non-ASD controls, revealed that amino acid alterations in neurexin 1 are not present at high frequency in ASD. However, a number of rare sequence variants in the coding region, including two missense changes in conserved residues of the α-neurexin 1 leader sequence and of an epidermal growth factor (EGF)-like domain, respectively, suggest that even subtle changes in NRXN1 might contribute to susceptibility to ASD.
TL;DR: Evidence linking alcohol abuse in late adolescence with neurologic damage and social impairments is described, and whether these are the bases for the association of adolescent drinking with increased risks of mental health, substance abuse, and social problems in adulthood is discussed.
Abstract: Late adolescence (ie, 16–20 years of age) is a period characterized by escalation of drinking and alcohol use problems for many and by the onset of an alcohol use disorder for some. This heightened period of vulnerability is a joint consequence of the continuity of risk from earlier developmental stages and the unique neurologic, cognitive, and social changes that occur in late adolescence. We review the normative neurologic, cognitive, and social changes that typically occur in late adolescence, and we discuss the evidence for the impact of these transitions on individual drinking trajectories. We also describe evidence linking alcohol abuse in late adolescence with neurologic damage and social impairments, and we discuss whether these are the bases for the association of adolescent drinking with increased risks of mental health, substance abuse, and social problems in adulthood. Finally, we discuss both the challenges and successes in the treatment and prevention of adolescent drinking problems.
TL;DR: These findings uncover a unique strategy of bacterial pathogenesis where virulence effectors block signal transmission through a key common component of multiple MAMP-receptor complexes.