bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case-control vs. case-only estimates of gene-environment interactions with common and misclassified clinical diagosis
Authors: Lobach Iryna , Sheng Ying , Lobach Siarhei , Zablotska Lydia , Huang Chiung-Yu 
Published: September 2019

ABSTRACTGenetic studies provide valuable information to assess if the effect of genetic variants varies by the non-genetic (“environmental”) variables, what is traditionally defined to be gene-environment interaction. A common complication is that multiple disease states present with the same set of symptoms, and hence share the clinical diagnosis. Because 1) disease states might have distinct genetic bases; and 2) frequencies of the disease states within the clinical diagnosis vary by the environmental variables, analyses of association with the clinical diagnosis as an outcome variable might result in false positive or false negative findings. We develop estimates for assessment of GxE in a case-only study and compare the case-control and case-only estimates. We report extensive simulation studies that evaluate empirical properties of the estimates and show the application to a study of Alzheimer’s disease.
Changes in ambient temperature are the prevailing cue in determiningBrachypodium distachyondiurnal gene regulation
Authors: MacKinnon Kirk J-M. , Cole Benjamin J. , Yu Chang , Coomey Joshua H. , Hartwick Nolan T. , Remigereau Marie-Stanislas , Duffy Tomás , Michael Todd P. , Kay Steve A. , Hazen Samuel P. 
Published: September 2019

SUMMARYPlants are continuously exposed to diurnal fluctuations in light and temperature, and spontaneous changes in their physical or biotic environment. The circadian clock coordinates regulation of gene expression with a 24-hour period, enabling the anticipation of these events.We used RNA sequencing to characterize theBrachypodium distachyontranscriptome under light and temperature cycles, as well as under constant conditions.Approximately 3% of the transcriptome was regulated by the circadian clock, a smaller proportion reported in most other species. For most transcripts that were rhythmic under all conditions, including many known clock genes, the period of gene expression lengthened from 24 to 27 h in the absence of external cues. To functionally characterize the cyclic transcriptome inB. distachyon, we used Gene Ontology enrichment analysis, and found several terms significantly associated with peak expression at particular times of the day. Furthermore we identified sequence motifs enriched in the promoters of similarly-phased genes, some potentially associated with transcription factors.When considering the overlap in rhythmic gene expression and specific pathway behavior, thermocycles was the prevailing cue that controlled diurnal gene regulation. Taken together, our characterization of the rhythmicB. distachyontranscriptome represents a foundational resource with implications in other grass species.
Draft genome sequence of a popular Indian tea genotype TV-1 [Camellia assamica L. (O). Kunze]
Authors: Mondal Tapan Kumar , Rawal Hukam Chand , Bera Biswajit , Kumar P. Mohan , Choubey Mrityunjay , Saha Gargi , Das Budhadeb , Bandyopadhyay Tanoy , Ilango R. Victor J. , Sharma Tilak Raj , Barua Anup , Radhakrishnan B. , Singh Nagendra Kumar 
Published: September 2019

ABSTRACTCamellia assamica L. (O). Kuntze. var. TV-1 from Assam, India is one of the most important tea cultivar of Indian Tea Industry which botanically belongs to Assam type and has distinct morphological as well as chemical constituent in leaf than China type of tea. We here present the first draft genome sequence of TV-1, assembled in 2.93 Gb size comprising of 14,824 scaffolds and covering 97.66% of the predicted genome size (3.0 Gb) as determined by flow cytometry. The N50 value, longest and average contig size for this draft genome was found to be as 538.96 Kb, 3.64 Mb and 197.99 Kb, respectively. There were 495,747 SSRs (Di- to Hexa-mers) in the genome and the repeat contents accounted for 71.87% of the genome. About 94.40% genome completeness was predicted with BUSCO, maximum among the published and reported tea genomes. The clustering of the assembled genome with Hi-C data resulted in 15 clusters ranging from the size of 631.46 Mb to 14.39 Mb and accounting 99.32% of assembled genome. This data will act as the starting point for unravelling the important genes and differentiating Indian tea from other commercially available tea varieties.
Long-term metabolic consequences of acute dioxin exposure differ between male and female mice
Authors: Hoyeck Myriam P , Blair Hannah , Ibrahim Muna , Solanki Shivani , Elsawy Mariam , Prakash Arina , Rick Kayleigh RC , Matteo Geronimo , O’Dwyer Shannon , Bruin Jennifer E 
Published: September 2019

SUMMARYExposure to environmental pollutants is consistently associated with increased diabetes risk in humans. In male mice, acute dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD) exposure supresses insulin secretion. This study investigated the long-term effects of a single TCDD injection (20 µg/kg) on glucose metabolism and beta cell function in male and female mice. TCDD-exposed males displayed modest fasting hypoglycemia for ∼4 weeks post-injection, reduced fasting insulin levels for up to 6 weeks, increased insulin sensitivity, and decreased beta cell area. TCDD-exposed females also had long-term suppressed basal plasma insulin levels, and abnormal insulin secretion for up to 6 weeks. Unlike males, TCDD did not impact insulin sensitivity or beta cell area in females, but did cause transient glucose intolerance 4 weeks post-exposure. Our results show that a single exposure to dioxin can supress basal insulin levels long-term in both sexes, but effects on metabolism are sex-dependent.
Road traffic delays and musculoskeletal health complaints among full-time bank employees: A cross-sectional study in Dhaka city
Authors: Ali Mohammad , Ahsan Gias U. , Uddin Zakir , Hossain Ahmed 
Published: September 2019

AbstractBackgroundThe factors of road traffic delays (RTDs) have significant consequences for both commuters’ health and the country’s economy as a whole. Addressing the musculoskeletal health complaints (MHCs) among full-time employees has not been fully explored. The current study investigates the association between RTDs-related factors and MHCs among bank employees.MethodsWe conducted a cross-sectional study among full-time employees from 32 banks in Dhaka city. Descriptive statistics summarized the gaps in the socio-demographic and RTDs-related factors on the one-month prevalence of MHCs. Random intercept logistic regression models were used to identify the associate factors of the MHCs.ResultsOut of 628 full-time bank employees, the one-month prevalence of MHCs was 57.7%. The MHCs are more prevalent among adults of age group 40-60 years (68%) than the age group 20-40 years (54%). The one-month prevalence of lower back pain (LBP) was highest (36.6%), followed by neck pain (22.9%) and upper back pain (21.2%). Multilevel logistic regression analysis of employees showed that the odds of MHCs were lower among male employees (AOR=0.42, 95% CI= 0.27, 0.64), car commuters (AOR = 0.38, 95% CI=0.19-0.76, reference: bus commuters) and rickshaw commuters (AOR=. = 0.39, 95% CI=0.22-0.69, reference: bus commuters). The MHCs were significantly higher among employees with following factors: obesity (AOR= 1.50, 95% CI= 1.02-2.21), prolonged commute time to the office (AOR = 7.48, 95% CI =3.64-15.38) and working extended-time in a day (AOR= 1.50, 95% CI= 1.02-2.21).ConclusionsThe study indicates a high burden of musculoskeletal health complaints among the employees in Dhaka city, and the most prevalent complaint was low back pain. Our study suggests that factors related to road traffic delays might act synergistically on developing musculoskeletal problems in full-time employees.
Temporal tuning of repetition suppression across the visual cortex
Authors: Fritsche Matthias , Lawrence Samuel J. D. , de Lange Floris P. 
Published: September 2019

AbstractThe visual system adapts to its recent history. A phenomenon related to this is repetition suppression (RS) - a reduction in neural responses to repeated compared to non-repeated visual input. An intriguing hypothesis is that the timescale over which RS occurs across the visual hierarchy is tuned to the temporal statistics of visual input features, which change rapidly in low-level areas but are more stable in higher-level areas. Here, we tested this hypothesis by studying the influence of the temporal lag between successive visual stimuli on RS throughout the visual system using fMRI. Twelve human volunteers engaged in four fMRI sessions in which we characterized the BOLD response to pairs of repeated and non-repeated natural images with inter-stimulus intervals (ISI) ranging from 50 to 1000 milliseconds to quantify the temporal tuning of RS along the posterior-anterior axis of the visual system. As expected, RS was maximal for short ISIs and decayed with increasing ISI. Furthermore, the overall magnitude of RS gradually increased from posterior to anterior visual areas. Crucially, however, and against our hypothesis, RS decayed at a similar rate in early and late visual areas. This finding challenges the prevailing view that the timescale of RS increases along the posterior-anterior axis of the visual system and suggests that RS is not tuned to temporal input regularities.
Microtubules deform the nucleus and force chromatin reorganization during early differentiation of human hematopoietic stem cells
Authors: Biedzinski S. , Faivre L. , Vianay B. , Delord M. , Blanchoin L. , Larghero J. , Théry M. , Brunet S. 
Published: September 2019

ABSTRACTHematopoietic stem cells (HSC) can differentiate into all hematopoietic lineages to support hematopoiesis. Cells from the myeloid and lymphoid lineages fulfill distinct functions with specific shapes and intra-cellular architectures. The role of cytokines in the regulation of HSC differentiation has been intensively studied but our understanding of the potential contribution of inner cell architecture is relatively poor. Here we show that large invaginations are generated by microtubule constraints on the swelling nucleus of human HSCs during early commitment toward the myeloid lineage. These invaginations are associated with chromatin reorganization, local loss of H3K9 trimethylation and changes in expression of specific hematopoietic genes. This establishes the role of microtubules in defining the unique lobulated nuclear shape observed in myeloid progenitor cells and suggests that this shape is important to establish the gene expression profile specific to this hematopoietic lineage. It opens new perspectives on the implications of microtubule-generated forces, in the early specification of the myeloid lineage.
MicroRNAs Cause Accelerated Decay of Short-Tailed Target mRNAs
Authors: Eisen Timothy J. , Eichhorn Stephen W. , Subtelny Alexander O. , Bartel David P. 
Published: September 2019

SummaryMicroRNAs (miRNAs) specify recruitment of deadenylases to mRNA targets. Despite this recruitment, we find that miRNAs have almost no effect on steady-state poly(A)-tail lengths of their targets in mouse fibroblasts, which motivates acquisition of pre-steady-state measurements of the effects of miRNAs on tail lengths, mRNA levels, and translational efficiencies. Effects on translational efficiency are minimal compared to effects on mRNA levels—even for newly transcribed target mRNAs. Effects on target mRNA levels accumulate as the mRNA population approaches steady state, whereas effects on tail lengths peak for recently transcribed target mRNAs and then subside. Computational modeling of this phenomenon reveals that miRNAs cause not only accelerated deadenylation of their targets but also accelerated decay of short-tailed target molecules. This unanticipated effect of miRNAs largely prevents short-tailed target mRNAs from accumulating despite accelerated target deadenylation. The net result is a nearly imperceptible change to the steady-state tail-length distribution of targeted mRNAs.HighlightsmiRNAs cause accelerated decay of short-tailed target moleculesThis accelerated decay largely prevents accumulation of short-tailed target mRNAsmiRNAs are similarly effective on short-lived and long-lived target mRNAsIn 3T3 cells, miRNA effects on translation are negligible—even for nascent mRNA
Changes in life history and population size can explain relative neutral diversity levels on X and autosomes in extant human populations
Authors: Amster Guy , Murphy David A. , Milligan William M. , Sella Guy 
Published: September 2019

AbstractIn human populations, relative levels of neutral polymorphism on the X and autosomes differ markedly from each other and from the naive theoretical expectation of ¾. These differences have attracted considerable attention, with studies highlighting several potential causes, including male biased mutation and reproductive variance, historical changes in population size, and selection at linked loci. We revisit this question in light of our new theory about the effects of life history and given pedigree-based estimates of the dependence of human mutation rates on sex and age. We demonstrate that life history effects, particularly higher generation times in males than females, likely had multiple effects on human X-to-autosomes (X:A) polymorphism ratios, through the extent of male mutation bias, the equilibrium X:A ratios of effective population sizes, and differential responses to changes in population size. We also show that the standard approach of using divergence between species to correct for the male bias in mutation results in biased estimates of X:A effective population size ratios. We obtain alternative estimates using pedigree-based estimates of the male mutation bias, which reveal X:A ratios of effective population sizes to be considerably greater than previously appreciated. We then show that the joint effects of historical changes in life history and population size can explain X:A polymorphism ratios in extant human populations. Our results suggest that ancestral human populations were highly polygynous; that non-African populations experienced a substantial reduction in polygyny and/or increase in male-biased generation times around the out of Africa bottleneck; and that extant diversity levels were affected by fairly recent changes in sex-specific life history.Significance StatementAll else being equal, the ratio of diversity levels on X and autosomes at selectively neutral sites should mirror the ratio of their numbers in the population and thus equal ¾. In reality, the ratios observed across human populations differ markedly from ¾ and from each other. Because from a population perspective, autosomes spend an equal number of generations in both sexes while the X spends twice as many generations in females, these departures from the naïve expectations likely reflect differences between male and female life histories and their effects on mutation processes. Indeed, we show that the ratios observed across human populations can be explained by demographic history, assuming plausible, sex-specific mutation rates, generation times and reproductive variances.
An alternative mechanism of early nodal clustering and myelination onset in GABAergic neurons of the central nervous system
Authors: Thetiot Melina , Freeman Sean A. , Roux Thomas , Dubessy Anne-Laure , Aigrot Marie-Stéphane , Rappeneau Quentin , Lejeune François-Xavier , Tailleur Julien , Sol-Foulon Nathalie , Lubetzki Catherine , Desmazieres Anne 
Published: September 2019

SUMMARYIn vertebrates, fast saltatory conduction along myelinated axons relies on the node of Ranvier. How nodes assemble on CNS neurons is not yet fully understood. We recently highlighted that clusters similar to nodes can form prior to myelin deposition in hippocampal GABAergic neurons and are associated with increased conduction velocity. Here, we used a live imaging approach to characterize the intrinsic mechanisms underlying the assembly of these early clusters. We first demonstrated that their components can partially pre-assemble prior to membrane targeting and determined the molecular motors involved in their trafficking. We then demonstrated the key role of the protein β2Nav for clustering initiation. We further unraveled the fate of these early clusters, by showing that they participate in node formation, but also have an unexpected role in guiding oligodendrocyte processes prior to myelin deposition. Altogether our results shed light on an alternative mechanism of nodal clustering and myelination onset.
The Dynamics of Cytoplasmic mRNA Metabolism
Authors: Eisen Timothy J. , Eichhorn Stephen W. , Subtelny Alexander O. , Lin Kathy S. , McGeary Sean E. , Gupta Sumeet , Bartel David P. 
Published: September 2019

SummaryFor all but a few mRNAs, the dynamics of metabolism are unknown. Here, we developed an experimental and analytical framework for examining these dynamics for mRNAs from thousands of genes. mRNAs of mouse fibroblasts exit the nucleus with diverse intragenic and intergenic poly(A)-tail lengths. Once in the cytoplasm, they have a broad (1000-fold) range of deadenylation rate constants, which correspond to cytoplasmic lifetimes. Indeed, with few exceptions, degradation appears to occur primarily through deadenylation-linked mechanisms, with little contribution from either endonucleolytic cleavage or deadenylation-independent decapping. Most mRNA molecules degrade only after their tail lengths fall below 25 nt. Decay rate constants of short-tailed mRNAs vary broadly (1000-fold) and are more rapid for short-tailed mRNAs that had previously undergone more rapid deadenylation. This coupling helps clear rapidly deadenylated mRNAs, enabling the large range in deadenylation rate constants to impart a similarly large range in stabilities.HighlightsmRNAs enter the cytoplasm with diverse intra- and intergenic lengthsmRNA deadenylation rates span a 1000-fold range and correspond to mRNA half-livesAfter their tails become short, mRNAs decay at rates that span a 1000-fold rangeMore rapidly deadenylated mRNAs decay more rapidly upon reaching short tail lengths
Structural neural connectivity analysis in zebrafish with restricted anterograde transneuronal viral labeling and quantitative brain mapping
Authors: Ma Manxiu , Kler Stanislav , Pan Y. Albert 
Published: September 2019

AbstractThe unique combination of small size, translucency, and powerful genetic tools makes larval zebrafish a uniquely useful vertebrate system to investigate normal and pathological brain structure and function. While functional connectivity can now be assessed (via fluorescent calcium or voltage reporters) at the whole-brain scale, it remains challenging to systematically determine structural connections and identify connectivity changes during development or disease. To address this, we developedTracer withRestrictedAnterogradeSpread (TRAS), a novel vesicular stomatitis virus (VSV)-based neural circuit labeling approach. TRAS makes use of replication-incompetent VSV (VSVΔG) and a helper virus (lentivirus) to enable anterograde transneuronal spread between efferent axons and their direct postsynaptic targets but restricts further spread to downstream areas. We integrated TRAS with the Z-Brain zebrafish 3D atlas for quantitative connectivity analysis and identified targets of the retinal and habenular efferent projections, in patterns consistent with previous reports. We compared retinofugal connectivity patterns between wild-type anddown syndrome cell adhesion molecule-like 1(dscaml1) mutant zebrafish and revealed differences in topographical distribution and potential changes in the retinofugal targeting of excitatory versus inhibitory retinorecipient cells. These results demonstrate the utility of TRAS for quantitative structural connectivity analysis that would be valuable for detecting novel efferent targets and mapping connectivity changes underlying neurological or behavioral deficits.
Metabolite therapy guided by liquid biopsy proteomics delays retinal neurodegeneration
Authors: Wert Katherine J. , Velez Gabriel , Vijayalakshmi Kanchustambham , Shankar Vishnu , Sengillo Jesse D. , Zare Richard N. , Bassuk Alexander G. , Tsang Stephen H. , Mahajan Vinit B. 
Published: September 2019

AbstractNeurodegenerative diseases are debilitating, incurable disorders caused by progressive neuronal cell death. Retinitis pigmentosa (RP) is a blinding neurodegenerative disease that results in retinal photoreceptor cell death and progresses to the loss of the entire neural retinal network. We previously found that proteomic analysis of the adjacent vitreous serves as way to indirectly biopsy the neural retina and identify changes in the retinal proteome. We therefore analyzed protein expression in liquid vitreous biopsies from autosomal recessive retinitis pigmentosa (arRP) patients withPDE6Amutations and arRP mice withPde6ɑ mutations.Proteomic analysis of retina and vitreous samples identified molecular pathways affected at the onset of photoreceptor cell death. Based on affected molecular pathways, arRP mice were treated with a ketogenic diet or metabolites involved in fatty-acid synthesis, oxidative phosphorylation, and the tricarboxylic acid (TCA) cycle. Dietary supplementation of a single metabolite, ɑ-ketoglutarate, increased docosahexaeonic acid (DHA) levels, provided neuroprotection, and enhanced visual function in arRP mice. A ketogenic diet delayed photoreceptor cell loss, while vitamin B supplementation had a limited effect. Finally, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) revealed restoration of key metabolites that correlated with our proteomic findings: pyrimidine and purine metabolism (uridine, dihydrouridine, and thymidine), glutamine and glutamate (glutamine/glutamate conversion), and succinic and aconitic acid (TCA cycle). This study demonstrates that replenishing TCA cycle metabolites via oral supplementation prolongs vision and provides a neuroprotective effect on the photoreceptor cells and inner retinal network.One Sentence SummaryThe study shows protein and metabolite pathways affected during neurodegeneration and that replenishing metabolites provides a neuroprotective effect on the retina.
Animal biosynthesis of complex polyketides in a photosynthetic partnership
Authors: Torres Joshua P. , Lin Zhenjian , Winter Jaclyn M. , Krug Patrick J. , Schmidt Eric W. 
Published: September 2019

ABSTRACTAnimals are rich sources of complex polyketides, including pharmaceuticals, cosmetics, and other products. Most polyketides are associated with microbial or plant metabolism1. For this reason, symbiotic bacteria or dietary organisms are often the true producers of compounds found in animals2,3. Although increasing evidence suggests that animals themselves make some compounds4–7, the origin of most polyketides in animals remains unknown. This problem makes it difficult to supply useful animal compounds as drugs and severely constrains our understanding of chemical diversity and the scope of biosynthesis in nature. Here, we demonstrate that animals produce microbe-like complex polyketides. We report a previously undocumented but widespread branch of fatty acid synthase- (FAS)-like proteins that have been retooled by evolution to synthesize complex products. One FAS-like protein uses only methylmalonyl-CoA as a substrate, otherwise unknown in animal lipid metabolism, and is involved in an intricate partnership between a sea slug and captured chloroplasts. The enzyme’s complex, methylated polyketide product results from a metabolic interplay between algal chloroplasts and animal host cells, and also likely facilitates the survival of both symbiotic partners, acting as a photoprotectant for plastids and an antioxidant for the slug8–12. Thus, we find that animals can unexpectedly synthesize a large and medically useful class of structurally complex polyketides previously ascribed solely to microbes, and can use them to promote symbiotic organelle maintenance. Because this represents an otherwise uncharacterized branch of polyketide and fatty acid metabolism, we anticipate a large diversity of animal polyketide products and enzymes awaiting discovery.