bluuebunny/crossref_metadata_2025_split huggingface dataset:
ParticleChromo3D: A Particle Swarm Optimization Algorithm for Chromosome and Genome 3D Structure Prediction from Hi-C Data
Authors: Vadnais David , Middleton Michael , Oluwadare Oluwatosin 
Published: February 2021

AbstractThe three-dimensional (3D) structure of chromatin has a massive effect on its function. Because of this, it is desirable to have an understanding of the 3D structural organization of chromatin. To gain greater insight into the spatial organization of chromosomes and genomes and the functions they perform, chromosome conformation capture techniques, particularly Hi-C, have been developed. The Hi-C technology is widely used and well-known because of its ability to profile interactions for all read pairs in an entire genome. The advent of Hi-C has greatly expanded our understanding of the 3D genome, genome folding, gene regulation and has enabled the development of many 3D chromosome structure reconstruction methods. Here, we propose a novel approach for 3D chromosome and genome structure reconstruction from Hi-C data using Particle Swarm Optimization approach called ParticleChromo3D. This algorithm begins with a grouping of candidate solution locations for each chromosome bin, according to the particle swarm algorithm, and then iterates its position towards a global best candidate solution. While moving towards the optimal global solution, each candidate solution or particle uses its own local best information and a randomizer to choose its path. Using several metrics to validate our results, we show that ParticleChromo3D produces a robust and rigorous representation of the 3D structure for input Hi-C data. We evaluated our algorithm on simulated and real Hi-C data in this work. Our results show that ParticleChromo3D is more accurate than most of the existing algorithms for 3D structure reconstruction. Our results also show that constructed ParticleChromo3D structures are very consistent, hence indicating that it will always arrive at the global solution at every iteration. The source code for ParticleChromo3D, the simulated and real Hi-C datasets, and the models generated for these datasets are available here:https://github.com/OluwadareLab/ParticleChromo3D
Rheb-mTOR Activation Rescues Amyloid Beta-Induced Cognitive Impairment and Memory Function by Restoring miR-146 Activity in Glial Cells
Authors: De Dipayan , Mukherjee Ishita , Guha Subhalakshmi , Paidi Ramesh Kumar , Chakrabarti Saikat , Biswas Subhas C. , Bhattacharyya Suvendra N. 
Published: February 2021

AbstractDeposition of amyloid beta plaques in adult rat or human brain is associated with increased production of proinflammatory cytokines by associated glial cells that are responsible for degeneration of the diseased tissue. The expression of these cytokines is usually under check and is controlled at post-transcriptional level via several microRNAs. Computational analysis of gene expression profiles of cortical regions of Alzheimer’s disease patients brain suggests ineffective target cytokine mRNA suppression by existing microRNPs in diseased brain. Exploring the mechanism of amyloid beta induced cytokine expression, we have identified how the inactivation of the repressive miR-146 microRNPs causes increased production of cytokines in amyloid beta exposed glial cells. In exploration of the cause of miRNP inactivation, we have noted amyloid beta oligomer induced sequestration of mTORC1 complex to early endosomes that results in decreased Ago2 phosphorylation, limited Ago2-miRNA uncoupling and retarded Ago2-cytokine mRNA interaction in rat astrocyte cells. Interestingly, constitutive activation of mTORC1 by Rheb activator restricts proinflammatory cytokine production by reactivating miR-146 microRNPs in amyloid beta exposed glial cells to rescue the disease phenotype in thein vivorat model of Alzheimer’s disease.
Charting the human amygdala development across childhood and adolescence: Manual and automatic segmentation
Authors: Zhou Quan , Liu Siman , Jiang Chao , He Ye , Zuo Xi-Nian 
Published: February 2021

AbstractThe developmental pattern of the amygdala throughout childhood and adolescence has been inconsistently reported in previous neuroimaging studies. Given the relatively small size of the amygdala on full brain MRI scans, discrepancies may be partly due to methodological differences in amygdalar segmentation. To investigate the impact of volume extraction methods on amygdala volume, we comparedFreeSurfer, FSLandvolBrainsegmentation measurements with those obtained by manual tracing. The manual tracing method, which we used as the ‘gold standard’, exhibited almost perfect intra- and inter-rater reliability. We observed systematic differences in amygdala volumes between automatic (FreeSurferandvolBrain) and manual methods. Specifically, compared with the manual tracing,FreeSurferestimated larger amygdalae, andvolBrainproduced smaller amygdalae whileFSLdemonstrated a mixed pattern. The tracing bias was not uniform, but higher for smaller amygdalae. We further modeled amygdalar growth curves using accelerated longitudinal cohort data from the Chinese Color Nest Project. Trajectory modeling and statistical assessments of the manually traced amygdalae revealed linearly increasing and parallel developmental patterns for both girls and boys, although the amygdalae of boys were larger than those of girls. Compared to these trajectories, the shapes of developmental curves were similar when using thevolBrainderived volumes.FreeSurferderived trajectories had more nonlinearities and appeared flatter.FSLderived trajectories demonstrated an inverted U shape and were significantly different from those derived from manual tracing method. The use of amygdala volumes adjusted for total gray-matter volumes, but not intracranial volumes, resolved the shape discrepancies and led to reproducible growth curves curves between manual tracing and the automatic methods (exceptFSL). Our findings revealed steady growth of the human amygdala, mirroring its functional development across the school age. Methodological improvements are warranted for current automatic tools to achieve more accurate tracing of the amygdala at school age, calling for next generation tools.
COVID-19-related symptoms 6 months after the infection - Update on a prospective cohort study in Germany
Authors: Rauch Barbara , Kern-Matschilles Stefanie , Haschka Stefanie J. , Sacco Vanessa , Potzel Anne L. , Banning Friederike , Benz Irina , Meisel Mandy , Seissler Jochen , Gar Christina , Lechner Andreas 
Published: February 2021

AbstractObjectiveMany anecdotal reports indicate the presence of ‘long COVID’ – COVID-19-related symptoms weeks to months after the acute illness. However, frequency and symptom-pattern of ‘long COVID’ in relation to acute disease severity are uncertain. As part of an ongoing, prospective cohort study we therefore conducted an online survey among adults 6 months after acute COVID-19.MethodsThe prospective online study Life&Covid is ongoing in Germany since May 2020. Participants were recruited 0 to 4 months after their SARS-CoV-2 infection und followed up by subsequent surveys. The survey 6 months after the infection was completed by 127 out of 148 individuals invited by email (86%). All grades of acute disease severity were included and 91% of the participants had been treated as outpatients during their acute illness.ResultsSix months after the infection, 67% of the study participants reported at least one symptom as a consequence of COVID-19. Exertional dyspnea (30% of participants), fatigue (25%) and diminished sense of taste/smell (19%) were the most common individual symptoms. At least one symptom, exertional dyspnea, and fatigue were reported more often after a severe acute illness, but diminished sense of taste/smell was unrelated to acute severity. Age group and sex did not associate with the frequency of symptoms at 6 months.ConclusionsBased on this study, the prevalence of COVID-19-related symptoms 6 months after the infection is high. Some bias for overestimation may have affected this result. Nevertheless, ‘long COVID’ requires attention in medical care and a better scientific understanding.
An alternative approach for bioanalytical assay development for wastewater-based epidemiology of SARS-CoV-2
Authors: Tim Boogaerts , Jacobs Lotte , De Roeck Naomi , Van den Bogaert Siel , Aertgeerts Bert , Lahousse Lies , van Nuijs Alexander L.N. , Delputte Peter 
Published: February 2021

AbstractWastewater-based epidemiology could be applied to track down SARS-CoV-2 outbreaks at high spatio-temporal resolution and could potentially be used as an early-warning for emergence of SARS-CoV-2 circulation in the general population. Epidemiological surveillance of SARS-CoV-2 could play a role in monitoring the spread of the virus in the population and controlling possible outbreaks. However, sensitive sample preparation and detection methods are necessary to detect trace levels of SARS-CoV-2 RNA in influent wastewater (IWW).Unlike predecessors, method development of a SARS-CoV-2 RNA concentration and detection procedure was performed with IWW samples with high viral SARS-CoV-2 loads (in combination with seeding IWW with a surrogate coronavirus). This is of importance since the SARS-CoV-2 genome in IWW might have already been subject to in-sewer degradation into smaller genome fragments or might be present in a different form (e.g. cell debris,…). Centricon Plus-70 (100 kDa) centrifugal filter devices resulted in the lowest and most reproducible Ct-values for SARS-CoV-2 RNA. Lowering pore sizes did not improve our limit of detection and quantification. Real-time polymerase chain reaction (qPCR) was employed for the amplification of the N1, N2, N3 and E_Sarbeco-gene.This is one of the first studies to apply digital polymerase chain reaction (dPCR) for the detection of SARS-CoV-2 RNA in IWW. Interestingly, qPCR results were comparable with dPCR results suggesting that qPCR is a valid method. In this study, dPCR was also used as a proxy to assess the precision of qPCR. In this light, dPCR showed high variability at low concentration levels (100 copies/µL), indicating that variability in bioanalytical assays for SARS-CoV-2 RNA might be substantial.On average, the N2-gene showed high in-sample stability in IWW for 10 days of storage at 4 °C. Between-sample variability was substantial due to the low native concentrations in IWW. Additionally, the E-gene proved to be less stable compared to the N2-gene and showed higher variability. Freezing the IWW samples resulted in a 10-fold decay of loads of the N2- and E-gene in IWW.Although WBE can already aid in filling some knowledge gaps in the epidemiological surveillance of SARS-CoV-2, future WBE studies should aim to further validate and standardize bioanalytical assays, especially with regards to methodological limitations.HighlightsDevelopment of an analytical procedure for detection of SARS-CoV-2 RNA in wastewaterExtraction recovery was evaluated in influent wastewaterPrecision measured with dPCR used as a proxy for qPCRqPCR of the N2 gene fragment showed high in-sample stability of SARS-CoV-2 on average
Emergence in late 2020 of multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 677
Authors: Hodcroft Emma B. , Domman Daryl B. , Snyder Daniel J. , Oguntuyo Kasopefoluwa Y. , Van Diest Maarten , Densmore Kenneth H. , Schwalm Kurt C. , Femling Jon , Carroll Jennifer L. , Scott Rona S. , Whyte Martha M. , Edwards Michael W. , Hull Noah C. , Kevil Christopher G. , Vanchiere John A. , Lee Benhur , Dinwiddie Darrell L. , Cooper Vaughn S. , Kamil Jeremy P. 
Published: February 2021

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) plays critical roles in host cell entry. Non-synonymous substitutions affecting S are not uncommon and have become fixed in a number of SARS-CoV-2 lineages. A subset of such mutations enable escape from neutralizing antibodies or are thought to enhance transmission through mechanisms such as increased affinity for the cell entry receptor, angiotensin-converting enzyme 2 (ACE2). Independent genomic surveillance programs based in New Mexico and Louisiana contemporaneously detected the rapid rise of numerous clade 20G (lineage B.1.2) infections carrying a Q677P substitution in S. The variant was first detected in the US on October 23, yet between 01 Dec 2020 and 19 Jan 2021 it rose to represent 27.8% and 11.3% of all SARS-CoV-2 genomes sequenced from Louisiana and New Mexico, respectively. Q677P cases have been detected predominantly in the south central and southwest United States; as of 03 Feb 2021, GISAID data show 499 viral sequences of this variant from the USA. Phylogenetic analyses revealed the independent evolution and spread of at least six distinct Q677H sub-lineages, with first collection dates ranging from mid-August to late November 2020. Four 677H clades from clade 20G (B.1.2), 20A (B.1.234), and 20B (B.1.1.220, and B.1.1.222) each contain roughly 100 or fewer sequenced cases, while a distinct pair of clade 20G clusters are represented by 754 and 298 cases, respectively. Although sampling bias and founder effects may have contributed to the rise of S:677 polymorphic variants, the proximity of this position to the polybasic cleavage site at the S1/S2 boundary are consistent with its potential functional relevance during cell entry, suggesting parallel evolution of a trait that may confer an advantage in spread or transmission. Taken together, our findings demonstrate simultaneous convergent evolution, thus providing an impetus to further evaluate S:677 polymorphisms for effects on proteolytic processing, cell tropism, and transmissibility.
Anaerobic oxidation of methane in sediments of a nitrate-rich, oligo-mesotrophic boreal lake
Authors: Rissanen Antti J , Jilbert Tom , Simojoki Asko , Mangayil Rahul , Aalto Sanni L , Peura Sari , Jäntti Helena 
Published: February 2021

AbstractThe identity of electron acceptors in promoting anaerobic oxidation of methane (AOM) in the sediments of boreal lakes is currently unknown. Here, we studied the AOM rate of sediment slurries collected from three profundal stations of a nitrate-rich, oligo-mesotrophic, boreal lake (Lake Pääjärvi, Finland), under varying nitrate concentrations using13C-labelling. Furthermore, vertical profiles of the sediment and porewater geochemistry, and the microbial communities (16S rRNA gene and shotgun metagenomic sequencing) were analyzed. Despite geochemical data indicating that simultaneous consumption of nitrate and methane took place at the sediment layers chosen for incubations, AOM rate was not enhanced by nitrate amendments at either of the stations. AOM rate was much higher at the shallow Station 1 (0.9-6.8 nmol C cm-3d-1) with high contents of labile phytoplankton-derived organic matter, than at the deeper stations, Station 2 (0-0.3 nmol C cm-3d-1) and 3 (0-0.2 nmol C cm-3d-1). Accordingly, a higher relative abundance of methanotrophic archaea (CandidatusMethanoperedens) and bacteria (Methylococcales) were observed in the layers chosen for incubations at Station 1 than at the other stations. Besides nitrate, the geochemical profiles indicated that AOM was potentially coupled with iron or sulfate reduction at all stations. Furthermore, putative nitrite-reducing methanotrophs (Ca. Methylomirabilis) were the most abundant methanotrophs above the incubation layer at Station 2 and 3, which suggests that nitrite reduction also plays a role in driving AOM in the study lake. We conclude that AOM is not uniquely coupled to nitrate reduction in sediments of nitrate-rich, oligo-mesotrophic, boreal lakes.
Evaluating Sleep Disturbances in Children with Rare Genetic Neurodevelopmental Syndromes
Authors: Veatch Olivia J. , Malow Beth A. , Lee Hye-Seung , Knight Aryn , Barrish Judy O. , Neul Jeffrey L. , Lane Jane B. , Skinner Steven A. , Kaufmann Walter E. , Miller Jennifer L. , Driscoll Daniel J. , Bird Lynne M. , Butler Merlin G. , Dykens Elisabeth M. , Gold June-Anne , Kimonis Virginia , Bacino Carlos A. , Tan Wen-Hann , Kothare Sanjeev V. , Peters Sarika U. , Percy Alan K. , Glaze Daniel G. 
Published: February 2021

AbstractBackgroundAdequate sleep is important for proper neurodevelopment and positive health outcomes. Sleep disturbances are more prevalent in children with genetically determined neurodevelopmental syndromes compared to typically developing counterparts. We characterize sleep behavior in Rett (RTT), Angelman (AS) and Prader-Willi (PWS) syndromes in order to identify effective approaches for treating sleep problems in these populations. We compared sleep-related symptoms across individuals with these different syndromes to each other, and to typically developing controls.MethodsChildren were recruited from the Rare Diseases Clinical Research Network (RDCRN) consortium registries; unaffected siblings were enrolled as related controls. For each participant, a parent completed multiple sleep questionnaires including: Pediatric Sleep Questionnaire (Sleep-Disordered Breathing [SDB]); Children’s Sleep Habits Questionnaire; Pediatric Daytime Sleepiness Scale.ResultsSleep data were analyzed from 714 participants, ages 2-18 years. Young children with AS had more reported sleep problems than children with RTT or PWS. Older children with RTT had more reported daytime sleepiness than those with AS or PWS. Finally, all individuals with RTT had more evidence of sleep-disordered breathing when compared to individuals with PWS. Notably, typically developing siblings were also reported to have sleep problems, except for sleep-related breathing disturbances which were associated with each of the genetic syndromes.ConclusionsIndividuals with RTT, AS and PWS frequently experience sleep problems, including sleep-disordered breathing. Screening for sleep problems in individuals with these and other neurogenetic disorders should be included in clinical assessment and managements. These data may also be useful in developing treatment strategies and in clinical trials.
Epigenetic changes with age primes mammary luminal epithelia for cancer initiation
Authors: Sayaman Rosalyn W. , Miyano Masaru , Senapati Parijat , Shalabi Sundus , Zirbes Arrianna , Todhunter Michael E. , Seewaldt Victoria , Neuhausen Susan L. , Stampfer Martha R. , Schones Dustin E. , LaBarge Mark A. 
Published: February 2021

SummaryAging causes molecular changes that manifest as stereotypical phenotypes yet aging-associated diseases progress only in certain individuals. At lineage-specific resolution, we show how stereotyped and variant responses are integrated in mammary epithelia. Age-dependent directional changes in gene expression and DNA methylation (DNAm) occurred almost exclusively in luminal cells and implicated genome organizersSATB1andCTCF. DNAm changes were robust indicators of aging luminal cells, and were either directly (anti-)correlated with expression changes or served as priming events for subsequent dysregulation, such as demethylation ofESR1-binding regions in DNAm-regulatoryCXXC5in older luminal cells and luminal-subtype cancers. Variance-driven changes in the transcriptome of both luminal and myoepithelial lineages further contributed to age-dependent loss of lineage fidelity. The pathways affected by transcriptomic and DNAm changes during aging are commonly linked with breast cancer, and together with the differential variability found across individuals, influence aging-associated cancer susceptibility in a subtype-specific manner.
Impaired clock gene expression and abnormal diurnal regulation of hippocampal inhibitory transmission and spatial memory in a mouse model of Alzheimer’s disease
Authors: Fusilier Allison R. , Davis Jennifer A. , Paul Jodi R. , Yates Stefani D. , McMeekin Laura J. , Goode Lacy K. , Mokashi Mugdha V. , van Groen Thomas , Cowell Rita M. , McMahon Lori L. , Roberson Erik D. , Gamble Karen L. 
Published: February 2021

ABSTRACTPatients with Alzheimer’s disease (AD) often have fragmentation of sleep/wake cycles and disrupted 24-h (circadian) activity. Despite this, little work has investigated the potential underlying day/night disruptions in cognition and neuronal physiology in the hippocampus. The molecular clock, an intrinsic transcription-translation feedback loop that regulates circadian behavior, may also regulate hippocampal neurophysiological activity. We hypothesized that disrupted diurnal variation in clock gene expression in the hippocampus corresponds with loss of normal day/night differences in membrane excitability, synaptic physiology, and cognition. We previously reported that the Tg-SwDI mouse model of AD has disrupted circadian locomotor rhythms and neurophysiological output of the suprachiasmatic nucleus (the primary circadian clock). Here, we report that Tg-SwDI mice failed to show day-night differences in a spatial working memory task, unlike wild-type controls that exhibited enhanced spatial working memory at night. Moreover, Tg-SwDI mice had lower levels of Per2, one of the core components of the molecular clock, at both mRNA and protein levels when compared to age-matched controls. Interestingly, we discovered neurophysiological impairments in area CA1 of the Tg-SwDI hippocampus. In controls, spontaneous inhibitory post-synaptic currents (sIPSCs) in pyramidal cells showed greater amplitude and lower inter-event interval during the day than the night. However, the normal day/night differences in sIPSCs were absent (amplitude) or reversed (inter-event interval) in pyramidal cells from Tg-SwDI mice. In control mice, current injection into CA1 pyramidal cells produced more firing during the night than during the day, but no day/night difference in excitability was observed in Tg-SwDI mice. The normal day/night difference in excitability in controls was blocked by GABA receptor inhibition. Together, these results demonstrate that the normal diurnal regulation of inhibitory transmission in the hippocampus is diminished in a mouse model of AD, leading to decreased daytime inhibition onto hippocampal CA1 pyramidal cells. Uncovering disrupted day/night differences in circadian gene regulation, hippocampal physiology, and memory in AD mouse models may provide insight into possible chronotherapeutic strategies to ameliorate Alzheimer’s disease symptoms or delay pathological onset.
The effect of resource depletion on the thermal response of mosquito population fitness
Authors: Huxley Paul J. , Murray Kris A. , Cator Lauren J. , Pawar Samraat 
Published: February 2021

ABSTRACTThe temperature-dependencies of life history traits are increasingly being used to predict how climatic warming will affect vector-borne disease dynamics, partially by affecting the abundance dynamics of the vector population. Such predictions generally arise from mathematical models that incorporate the temperature dependence of traits measured under laboratory conditions. These temperature-trait relationships are typically estimated from juvenile populations reared under optimal resource conditions, even though natural populations experience intermittent resource depletion. Using laboratory experiments on the mosquitoAedes aegypti, combined with a stage-structured population model, we show that resource depletion in the juvenile habitat can significantly depress the vector’s maximal population growth rate (rm) across the entire temperature range, cause it to peak at a lower temperature, and narrow its thermal niche width. Our results provide compelling evidence for future studies to consider resource depletion when predicting the effects of global change on vector-borne disease transmission, disease vectors and other arthropods.