The diagnosis of autism spectrum disorder (ASD) at the earliest age possible is important for initiating optimally effective intervention. In the United States the average age of diagnosis is 4 ...years. Identifying metabolic biomarker signatures of ASD from blood samples offers an opportunity for development of diagnostic tests for detection of ASD at an early age.
To discover metabolic features present in plasma samples that can discriminate children with ASD from typically developing (TD) children. The ultimate goal is to identify and develop blood-based ASD biomarkers that can be validated in larger clinical trials and deployed to guide individualized therapy and treatment.
Blood plasma was obtained from children aged 4 to 6, 52 with ASD and 30 age-matched TD children. Samples were analyzed using 5 mass spectrometry-based methods designed to orthogonally measure a broad range of metabolites. Univariate, multivariate and machine learning methods were used to develop models to rank the importance of features that could distinguish ASD from TD.
A set of 179 statistically significant features resulting from univariate analysis were used for multivariate modeling. Subsets of these features properly classified the ASD and TD samples in the 61-sample training set with average accuracies of 84% and 86%, and with a maximum accuracy of 81% in an independent 21-sample validation set.
This analysis of blood plasma metabolites resulted in the discovery of biomarkers that may be valuable in the diagnosis of young children with ASD. The results will form the basis for additional discovery and validation research for 1) determining biomarkers to develop diagnostic tests to detect ASD earlier and improve patient outcomes, 2) gaining new insight into the biochemical mechanisms of various subtypes of ASD 3) identifying biomolecular targets for new modes of therapy, and 4) providing the basis for individualized treatment recommendations.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent studies report widespread usage or exposure to a variety of chemicals with structural or functional similarity to bisphenol A (BPA), referred to as BPA analogues or derivatives. These have ...been detected in foodstuffs, house dust, environmental samples, human urine or blood, and consumer products. Compared to BPA, relatively little is known about potential toxicity of these compounds. This scoping review aimed to summarize the human, animal, and mechanistic toxicity data for 24 BPA analogues of emerging interest to research and regulatory communities. PubMed was searched from March 1, 2015 to January 5, 2019 and combined with the results obtained from literature searches conducted through March 23, 2015, in The National Toxicology Program’s Research Report 4 (NTP RR-04), “Biological Activity of Bisphenol A (BPA) Structural Analogues and Functional Alternatives”. Study details are presented in interactive displays using Tableau Public. In total, 5748 records were screened for inclusion. One hundred sixty seven studies were included from NTP RR-04 and 175 studies were included from the updated literature search through January 2019. In total, there are 22, 117, and 221 human epidemiological, experimental animal, or in vitro studies included. The most frequently studied BPA analogues are bisphenol S (BPS), bisphenol F (4,4-BPF), and bisphenol AF (BPAF). Notable changes in the literature since 2015 include the growing body of human epidemiological studies and in vivo studies conducted in zebrafish. Numerous new endpoints were also evaluated across all three evidence streams including diabetes, obesity, and oxidative stress. However, few studies have addressed endpoints such as neurodevelopmental outcomes or impacts on the developing mammary or prostate glands, which are known to be susceptible to disruption by BPA. Further, there remains a critical need for better exposure information in order to prioritize experimental studies. Moving forward, researchers should also ensure that full dose responses are performed for all main effects in order to support hazard and risk characterization efforts. The evidence gathered here suggests that hazard and risk characterizations should expand beyond BPA in order to consider BPA structural and functional analogues.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We report a prozone effect in measurement of SARS-CoV-2 spike protein antibody levels from an antibody surveillance program. Briefly, the prozone effect occurs in immunoassays when excessively high ...antibody concentration disrupts the immune complex formation, resulting in a spuriously low reported result. Following participant inquiries, we observed anomalously low measurement of SARS-CoV-2 spike protein antibody levels using the Roche Elecsys® Anti-SARS-CoV-2 S immunoassay from participants in the Texas Coronavirus Antibody Research survey (Texas CARES), an ongoing prospective, longitudinal antibody surveillance program. In July, 2022, samples were collected from ten participants with anomalously low results for serial dilution studies, and a prozone effect was confirmed. From October, 2022 to March, 2023, serial dilution of samples detected 74 additional cases of prozone out of 1,720 participants' samples. Prozone effect may affect clinical management of at-risk populations repeatedly exposed to SARS-CoV-2 spike protein through multiple immunizations or serial infections, making awareness and mitigation of this issue paramount.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
No large group of recently extinct placental mammals remains as evolutionarily cryptic as the approximately 280 genera grouped as 'South American native ungulates'. To Charles Darwin, who first ...collected their remains, they included perhaps the 'strangest animals ever discovered'. Today, much like 180 years ago, it is no clearer whether they had one origin or several, arose before or after the Cretaceous/Palaeogene transition 66.2 million years ago, or are more likely to belong with the elephants and sirenians of superorder Afrotheria than with the euungulates (cattle, horses, and allies) of superorder Laurasiatheria. Morphology-based analyses have proved unconvincing because convergences are pervasive among unrelated ungulate-like placentals. Approaches using ancient DNA have also been unsuccessful, probably because of rapid DNA degradation in semitropical and temperate deposits. Here we apply proteomic analysis to screen bone samples of the Late Quaternary South American native ungulate taxa Toxodon (Notoungulata) and Macrauchenia (Litopterna) for phylogenetically informative protein sequences. For each ungulate, we obtain approximately 90% direct sequence coverage of type I collagen α1- and α2-chains, representing approximately 900 of 1,140 amino-acid residues for each subunit. A phylogeny is estimated from an alignment of these fossil sequences with collagen (I) gene transcripts from available mammalian genomes or mass spectrometrically derived sequence data obtained for this study. The resulting consensus tree agrees well with recent higher-level mammalian phylogenies. Toxodon and Macrauchenia form a monophyletic group whose sister taxon is not Afrotheria or any of its constituent clades as recently claimed, but instead crown Perissodactyla (horses, tapirs, and rhinoceroses). These results are consistent with the origin of at least some South American native ungulates from 'condylarths', a paraphyletic assembly of archaic placentals. With ongoing improvements in instrumentation and analytical procedures, proteomics may produce a revolution in systematics such as that achieved by genomics, but with the possibility of reaching much further back in time.
Full text
Available for:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
HNF4α, a member of the nuclear receptor superfamily, regulates the genes involved in lipid and glucose metabolism. The expression of the
gene in the liver of HNF4α knock-out mice was higher versus ...wildtype controls, whereas oppositely,
promoter activity was 50% reduced by the overexpression of HNF4α in HepG2 cells, and treatment with retinoic acid (RA), a major metabolite of vitamin A, increased
promoter activity 15-fold. The human
promoter contains two DR5 and one DR8 binding motifs, as RA response elements (RARE) proximal to the transcription start site. While DR5 RARE1 was previously reported to be responsive to RARs but not to other nuclear receptors, we show here that mutation in DR5 RARE2 suppresses the promoter response to HNF4α and RARα/RXRα. Mutational analysis of ligand-binding pocket amino acids shown to be critical for fatty acid (FA) binding indicated that RA may interfere with interactions of FA carboxylic acid headgroups with side chains of S190 and R235, and the aliphatic group with I355. These results could explain the partial suppression of HNF4α transcriptional activation toward gene promoters that lack RARE, including
and
while conversely, HNF4α may bind to RARE sequences in the promoter of the genes such as
and
, activating these genes in the presence of RA. Thus, RA could act as either an antagonist towards HNF4α in genes lacking RAREs, or as an agonist for RARE-containing genes. Overall, RA may interfere with the function of HNF4α and deregulate HNF4α targets genes, including the genes important for lipid and glucose metabolism.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
ABSTRACTSchoenfeld, BJ, Pope, ZK, Benik, FM, Hester, GM, Sellers, J, Nooner, JL, Schnaiter, JA, Bond-Williams, KE, Carter, AS, Ross, CL, Just, BL, Henselmans, M, and Krieger, JW. Longer interset rest ...periods enhance muscle strength and hypertrophy in resistance-trained men. J Strength Cond Res 30(7)1805–1812, 2016—The purpose of this study was to investigate the effects of short rest intervals normally associated with hypertrophy-type training versus long rest intervals traditionally used in strength-type training on muscular adaptations in a cohort of young, experienced lifters. Twenty-one young resistance-trained men were randomly assigned to either a group that performed a resistance training (RT) program with 1-minute rest intervals (SHORT) or a group that employed 3-minute rest intervals (LONG). All other RT variables were held constant. The study period lasted 8 weeks with subjects performing 3 total body workouts a week comprised 3 sets of 8–12 repetition maximum (RM) of 7 different exercises per session. Testing was performed prestudy and poststudy for muscle strength (1RM bench press and back squat), muscle endurance (50% 1RM bench press to failure), and muscle thickness of the elbow flexors, triceps brachii, and quadriceps femoris by ultrasound imaging. Maximal strength was significantly greater for both 1RM squat and bench press for LONG compared to SHORT. Muscle thickness was significantly greater for LONG compared to SHORT in the anterior thigh, and a trend for greater increases was noted in the triceps brachii (p = 0.06) as well. Both groups saw significant increases in local upper body muscle endurance with no significant differences noted between groups. This study provides evidence that longer rest periods promote greater increases in muscle strength and hypertrophy in young resistance-trained men.
Social–ecological networks (SENs) represent the complex relationships between ecological and social systems and are a useful tool for analyzing and managing ecosystem services. However, mainstreaming ...the application of SENs in ecosystem service research has been hindered by a lack of clarity about how to match research questions to ecosystem service conceptualizations in SEN (i.e., as nodes, links, attributes, or emergent properties). Building from different disciplines, we propose a typology to represent ecosystem service in SENs and identify opportunities and challenges of using SENs in ecosystem service research. Our typology provides guidance for this growing field to improve research design and increase the breadth of questions that can be addressed with SEN to understand human–nature interdependencies in a changing world.
Social–ecological networks (SENs) provide a promising approach to represent the complex ecological, social, and social–ecological relationships that influence ecosystems service supply.Ecosystem services can be represented in SENs as nodes, links, attributes, or as emergent properties of the network, each bringing distinct aspects of ecosystem services into focus to address different questions.Applications of SENs in ecosystem service research can foster: (i) understanding of the social and ecological drivers of ecosystem services; (ii) forecasting of the impacts of stressors; (iii) investigation of trade-offs between ecosystem services; and (iv) assessment of the effects of alternative management options.Ecosystem service research would benefit from a typology to conceptualize particular ecosystem services in SEN analyses and from greater clarity of when ecosystem service research can benefit from a SEN approach.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BAF180, a subunit of the PBAF chromatin remodeling complex, is frequently mutated in cancer. Although PBAF regulates transcription, it remains unclear whether this is what drives tumorigenesis in ...cells lacking BAF180. Based on data from yeast, we hypothesized that BAF180 may prevent tumorigenesis by promoting cohesion. Here, we show BAF180 is required for centromeric cohesion in mouse and human cells. Mutations identified in tumor samples are unable to support this activity, and also compromise cohesion-dependent functions in yeast. We provide evidence of genome instability in line with loss of cohesion, and importantly, we find dynamic chromosome instability following DNA damage in cells lacking BAF180. These data demonstrate a function for BAF180 in promoting genome stability that is distinct from its well-characterized role in transcriptional regulation, uncovering a potent mechanism for its tumor-suppressor activity.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The mammalian evolutionary tree has lost several major clades through recent human-caused extinctions. This process of historical biodiversity loss has particularly affected tropical island regions ...such as the Caribbean, an area of great evolutionary diversification but poor molecular preservation. The most enigmatic of the recently extinct endemic Caribbean mammals are the Nesophontidae, a family of morphologically plesiomorphic lipotyphlan insectivores with no consensus on their evolutionary affinities, and which constitute the only major recent mammal clade to lack any molecular information on their phylogenetic placement. Here, we use a palaeogenomic approach to place Nesophontidae within the phylogeny of recent Lipotyphla. We recovered the near-complete mitochondrial genome and sequences for 17 nuclear genes from a ∼750-year-old Hispaniolan Nesophontes specimen, and identify a divergence from their closest living relatives, the Solenodontidae, more than 40 million years ago. Nesophontidae is thus an older distinct lineage than many extant mammalian orders, highlighting not only the role of island systems as "museums" of diversity that preserve ancient lineages, but also the major human-caused loss of evolutionary history.
PDF
