bluuebunny/crossref_metadata_2025_split huggingface dataset:
TransDFL: Identification of Disordered Flexible Linkers in Proteins by Transfer Learning
Authors: Pang Yihe , Liu Bin 
Published: June 2022

AbstractDisordered flexible linkers (DFLs) are the functional disordered regions in proteins, which are the sub-regions of intrinsically disordered regions (IDRs) and play important roles in connecting domains and maintaining inter-domain interactions. Trained with the limited available DFLs, the existing DFL predictors based on the machine learning techniques tend to predict the ordered residues as DFLs leading to a high false-positive rate (FPR) and low prediction accuracy. Previous studies have shown that DFLs are the extremely flexible disordered regions, which are usually predicted as disordered residues with high confidence [P(D) > 0.9] by an IDR predictor. Therefore, transferring an IDR predictor to an accurate DFL predictor is of great significance for understanding the functions of IDRs. In this study, we proposed a new predictor called TransDFL for identifying DFLs by transferring the RFPR-IDP predictor for IDR identification to the DFL prediction. The RFPR-IDP was pre-trained with IDR sequences to learn the general features between IDRs and DFLs, which is helpful to reduce the false positives in the ordered regions. RFPR-IDP was fine-tuned with the DFL sequences to capture the specific features of DFLs so as to be transferred into the TransDFL. Experimental results of two application scenarios (prediction of DFLs only in the IDRs or prediction of DFLs in the entire proteins) showed that TransDFL consistently outperforms the other exiting DFL predictors with higher accuracy. The corresponding web server of TransDFL can be freely accessed from http://bliulab.net/TransDFL/.
Natural gradient enables fast sampling in spiking neural networks
Authors: Masset Paul , Zavatone-Veth Jacob A. , Connor J. Patrick , Murthy Venkatesh N. , Pehlevan Cengiz 
Published: June 2022

AbstractFor animals to navigate an uncertain world, their brains need to estimate uncertainty at the timescales of sensations and actions. Sampling-based algorithms afford a theoretically-grounded framework for probabilistic inference in neural circuits, but it remains unknown how one can implement fast sampling algorithms in biologically-plausible spiking networks. Here, we propose to leverage the population geometry, controlled by the neural code and the neural dynamics, to implement fast samplers in spiking neural networks. We first show that two classes of spiking samplers—efficient balanced spiking networks that simulate Langevin sampling, and networks with probabilistic spike rules that implement Metropolis-Hastings sampling—can be unified within a common framework. We then show that careful choice of population geometry, corresponding to the natural space of parameters, enables rapid inference of parameters drawn from strongly-correlated high-dimensional distributions in both networks. Our results suggest design prin-ciples for algorithms for sampling-based probabilistic inference in spiking neural networks, yielding potential inspiration for neuromorphic computing and testable predictions for neurobiology.
Efficient Pangenome Construction through Alignment-Free Residue Pangenome Analysis (ARPA)
Authors: Lal Arnav , Moustafa Ahmed , Planet Paul J. 
Published: June 2022

AbstractProtein sequences can be transformed into vectors composed of counts for each amino acid (vector of Residue Counts; vRC) that are mathematically tractable and retain information about homology. We use vRCs to perform alignment-free, residue-based, pangenome analysis (ARPA; https://github.com/Arnavlal/ARPA). ARPA is 70-90 times faster at identifying homologous gene clusters compared to standard techniques, and offers rapid calculation, visualization, and novel phylogenetic approaches for pangenomes.
Mothers’ experiences of using Facebook groups for local breastfeeding support: results of an online survey exploring midwife moderation
Authors: Morse H. , Brown A. 
Published: June 2022

AbstractProblemThe use of Breastfeeding Support Facebook (BSF) groups that are aimed at supporting women in specific local areas, with links to face to face support, is under researched. The role that midwives play in offering support to local mothers through these groups has not been examined.BackgroundAccess to ongoing support from professionals assists mothers in meeting their breastfeeding goals. Social media is increasingly being used to offer this support, improving maternal knowledge, self-efficacy and breastfeeding duration.AimTo examine impacts of moderator type on mothers’ perceptions of online breastfeeding support, including when midwives play an active role in moderation.MethodsAn online mixed methods survey was conducted in January 2020. Quantitative data was analysed descriptively and for associations using SPSSv26. Qualitative data was analysed thematically.FindingsTwo thousand and twenty-eight mothers who used local BSF groups completed the survey. The experiences of those participating in groups moderated by midwives versus other moderators such as peer supporters, were compared. Moderation was an important factor in mothers’ experiences, with trained support associated with greater engagement and more frequent visits, impacting on perceptions of group ethos, reliability and inclusivity. Midwife moderation was uncommon but valued, and associated with viewing local face to face midwifery support for breastfeeding more positively.ConclusionMidwife moderated or supported Facebook groups have the potential to add value to local face to face services and improve breastfeeding experiences in communities. The findings have important implications to support the development of integrated online interventions to improve public health.Statement of SignificanceProblemLow breastfeeding rates are connected to inconsistent access to quality local support. Mothers are frequently turning to social media groups for support but little is known about who runs and moderates them.What is Already KnownMothers have concerns about trustworthiness and reliability, despite finding Facebook groups useful for shared experience. There is insufficient evidence on moderation to recommend online models within maternity services.What this Paper AddsEvidence that Facebook groups linked to local face to face support are valued, and that trained moderators improves experiences. Access to local midwife support within Facebook groups improves perceptions of local midwifery support overall.
Personality traits are consistently associated with blood mitochondrial DNA copy number estimated from genome sequences in two genetic cohort studies
Authors: Oppong Richard F. , Terracciano Antonio , Picard Martin , Qian Yong , Butler Thomas J. , Tanaka Toshiko , Moore Ann Zenobia , Simonsick Eleanor M. , Opsahl-Ong Krista , Coletta Christopher , Sutin Angelina R. , Gorospe Myriam , Resnick Susan M. , Cucca Francesco , Scholz Sonja W. , Traynor Bryan J. , Schlessinger David , Ferrucci Luigi , Ding Jun 
Published: June 2022

AbstractBackgroundMitochondrial DNA copy number (mtDNAcn) in tissues and blood can be altered in conditions like diabetes and major depression and may play a role in aging and longevity. However, little is known about the association between mtDNAcn and personality traits linked to emotional states, metabolic health, and longevity. This study tests the hypothesis that blood mtDNAcn is related to personality traits and mediates the association between personality and mortality.MethodsWe assessed the big five personality domains and facets using the Revised NEO Personality Inventory (NEO-PI-R), assessed depressive symptoms with the Center for Epidemiologic Studies Depression Scale (CES-D), estimated mtDNAcn levels from whole-genome sequencing, and tracked mortality in participants from the Baltimore Longitudinal Study of Aging. Results were replicated in the SardiNIA Project.ResultsWe found that mtDNAcn was negatively associated with the Neuroticism domain and its facets and positively associated with facets from the other four domains. The direction and size of the effects were replicated in the SardiNIA cohort and were robust to adjustment for potential confounders in both samples. Consistent with the Neuroticism finding, higher depressive symptoms were associated with lower mtDNAcn. Finally, mtDNAcn mediated the association between personality and mortality risk.ConclusionsTo our knowledge, this is the first study to show a replicable association between mtDNAcn and personality. Furthermore, the results support our hypothesis that mtDNAcn is a biomarker of the biological process that explains part of the association between personality and mortality.
Progression of prostate cancer reprograms MYC-mediated lipid metabolism via lysine methyltransferase 2A
Authors: Whitlock Nichelle C. , White Margaret E. , Capaldo Brian J. , Ku Anson T. , Agarwal Supreet , Fang Lei , Wilkinson Scott , Trostel Shana Y. , Shi Zhen-Dan , Basuli Falguni , Wong Karen , Jagoda Elaine M. , Kelly Kathleen , Choyke Peter L. , Sowalsky Adam G. 
Published: June 2022

ABSTRACTBackgroundThe activities of MYC, the androgen receptor, and its associated pioneer factors demonstrate substantial reprogramming between early and advanced prostate cancer. Although previous studies have shown a shift in cellular metabolic requirements associated with prostate cancer progression, the epigenetic regulation of these processes is incompletely described. Here, we have integrated chromatin immunoprecipitation sequencing (ChIP-seq) and whole-transcriptome sequencing to identify novel regulators of metabolism in advanced prostate tumors characterized by elevated MYC activity.ResultsUsing ChIP-seq against MYC, HOXB13, and AR in LNCaP cells, we observed redistribution of co-bound sites suggestive of differential KMT2A activity as a function of MYC expression. In a cohort of 177 laser-capture microdissected foci of prostate tumors, KMT2A expression was positively correlated with MYC activity, AR activity, and HOXB13 expression, but decreased with tumor grade severity. However, KMT2A expression was negatively correlated with these factors in 25 LuCaP patient-derived xenograft models of advanced prostate cancer and 99 laser-capture microdissected foci of metastatic castration-resistant prostate cancer. Stratified by KMT2A expression, ChIP-seq against AR and HOXB13 in 15 LuCaP patient-derived xenografts showed an inverse association with sites involving genes implicated in lipid metabolism, including the arachidonic acid metabolic enzyme PLA2G4F. LuCaP patient-derived xenograft models grown as organoids recapitulated the inverse association between KMT2A expression and fluorine-18 labeled arachidonic acid uptake in vitro.ConclusionsOur study demonstrates that the epigenetic activity of transcription factor oncogenes exhibits a shift during prostate cancer progression with distinctive phenotypic effects on metabolism. These epigenetically driven changes in lipid metabolism may serve as novel targets for the development of novel imaging agents and therapeutics.
Functional connectivity fingerprints of the frontal eye fields and inferior frontal junction in the dorsal vs. ventral prefrontal cortex
Authors: Soyuhos Orhan , Baldauf Daniel 
Published: June 2022

AbstractNeuroimaging evidence suggests that the frontal eye field (FEF) and inferior frontal junction (IFJ) govern the encoding of spatial and non-spatial (such as feature- or object-based) representations, respectively, both during visual attention and working memory tasks. However, it is still unclear whether such contrasting functional segregation is also reflected in their underlying functional connectivity patterns. Here, we hypothesized that FEF has predominant functional coupling with spatiotopically organized regions in the dorsal (‘where’) visual stream, whereas IFJ has predominant functional connectivity with the ventral (‘what’) visual stream. We applied seed-based functional connectivity analyses to temporally high-resolving resting-state magnetoencephalography (MEG) recordings. We parcellated the brain according to the multimodal Glasser atlas and tested, for various frequency bands, whether the spontaneous activity of each parcel in the ventral and dorsal visual pathway has predominant functional connectivity with FEF or IFJ. The results show that FEF has a robust power correlation with the dorsal visual pathway in beta and gamma bands. In contrast, anterior IFJ (IFJa) has a strong power coupling with the ventral visual stream in delta, beta, and gamma oscillations. Moreover, while FEF is directly phase-coupled with the superior parietal lobe in the beta band, IFJa is directly phase-coupled with the middle and inferior temporal cortex in delta and gamma oscillations. We argue that these intrinsic connectivity fingerprints are congruent with each brain region’s function. Therefore, we conclude that FEF and IFJ have dissociable connectivity patterns that fit their respective functional roles in spatial vs. non-spatial top-down attention and working memory control.
Long-term label-free assessments of individual bacteria using three-dimensional quantitative phase imaging and hydrogel-based immobilization
Authors: Shin Jeongwon , Park Jinho , Kim Geon , Lee Moosung , Park Yongkeun 
Published: June 2022

AbstractThree-dimensional (3D) quantitative phase imaging (QPI) enables long-term label-free tomographic imaging and quantitative analysis of live individual bacteria. However, the Brownian motion or motility of bacteria in a liquid medium produces motion artifacts during 3D measurements and hinders precise cell imaging and analysis. Meanwhile, existing cell immobilization methods produce noisy backgrounds and even alter cellular physiology. Here, we introduce a protocol that utilizes hydrogels for high-quality 3D QPI of live bacteria maintaining bacterial physiology. We demonstrate long-term high-resolution quantitative imaging and analysis of individual bacteria, including measuring the biophysical parameters of bacteria and responses to antibiotic treatments.Abstract Figure
Macroevolutionary constraints on global microbial diversity
Authors: Fishman FJ , Lennon JT 
Published: June 2022

ABSTRACTBiologists have long sought to quantify the number of species on Earth. Often missing from these efforts is the contribution of microorganisms. Despite recent large-scale sampling efforts, estimates of global microbial diversity span many orders of magnitude. To reconcile this uncertainty, it is important to consider how speciation and extinction over the last four billion years constrain inventories of biodiversity. We parameterized macroevolutionary and mass-extinction event models to determine how diversification limits present-day microbial diversity. We find that while 106-107 taxa is most probable, much larger values (≥1012) are feasible. Allowing for mass extinction events does not greatly alter these conclusions. Along with empirical predictions, our models provide support for a massive global-scale microbiome while shedding light on the upper limits of life on Earth.
Fatty acid metabolism changes in association with neurobehavioral deficits in animal models of fetal alcohol spectrum disorders
Authors: Hwang Hye Mee , Kawasawa Yuka Imamura , Basha Aiesha , Mohammad Shahid , Hashimoto-Torii Kazue 
Published: June 2022

AbstractFetal alcohol spectrum disorders (FASD) show various behavioral problems due to prenatal alcohol exposure (PAE). Our previous study found significant changes in gene expressions linked to fatty acid metabolism in the brain of the PAE mouse model. Given the importance of fatty acids in normal brain functions and the contributions to neurodegenerative diseases, we hypothesized that the fatty acids changed by PAE contribute to neurobehavioral deficits in FASD. This study found an increase of palmitic acid and arachidonic acid in phospholipid compositions in the cerebral cortex of PAE at postnatal day 30. The increase of palmitic acid was consistent with the increase of the producing enzyme, fatty acid synthase (Fasn). The decrease of 26:6 fatty acid was also found in phospholipid. It is consistent with the increase of the Elongation of very long chain fatty acids protein 4 (ELOVL4) which uses 26:6 as a substrate for making very long chain fatty acids. However, there was no increase in the elongated products. Rather, we found an accumulation of the lipid droplets (LDs) in the PAE brain, suggesting changes in fatty acid metabolism that lead to the accumulation of excessive fatty acids. Although metabolic measurements, including plasma triglyceride level, were not affected by PAE, the abundance of fatty acid-related gut microbiota was altered. Interestingly, multi-omics association analysis revealed a potential contribution of the altered gut microbiota, primarily Ruminococcaceae that produces short chain fatty acid, to LD formation in the PAE brain and the behavioral problems, suggesting that the gut microbiome could serve as a tool to facilitate uncovering the brain pathophysiology of FASD and a potential target to mitigate neurobehavioral problems.
Development and application of an uncapped mRNA platform
Authors: Zheng Xiaodi , Liu Biao , Ni Peng , Cai Linkang , Shi Xiaotai , Ke Zonghuang , Zhang Siqi , Hu Bing , Yang Binfeng , Xu Yiyan , Long Wei , Fang Zhizheng , Wang Yang , Zhang Wen , Xu Yan. , Wang Zhong , Pan Kai , Zhou Kangping , Wang Hanming , Geng Hui , Hu Han , Liu Binlei 
Published: June 2022

ABSTRACTA novel uncapped mRNA platform was developed. Five lipid nanoparticle (LNP)-encapsulated mRNA constructs were made to evaluate several aspects of our platform, including transfection efficiency and durabilityin vitroandin vivoand the activation of humoral and cellular immunity in several animal models. The constructs were eGFP-mRNA-LNP (for enhanced green fluorescence mRNA), Fluc-mRNA-LNP (for firefly luciferase mRNA), SδT-mRNA-LNP (for Delta strain SARS-CoV-2 spike protein trimer mRNA), gDED-mRNA-LNP (for truncated glycoprotein D mRNA coding ectodomain from herpes simplex virus type 2 (HSV2)) and gDFR-mRNA-LNP (for truncated HSV2 glycoprotein D mRNA coding amino acids 1∼400). Quantifiable target protein expression was achievedin vitroandin vivowith eGFP-and Fluc-mRNA-LNP. SδT-mRNA-LNP, gDED-mRNA-LNP and gDFR-mRNA-LNP induced both humoral and cellular immune responses comparable to those obtained by previously reported capped mRNA-LNP constructs. Notably, SδT-mRNA-LNP elicited neutralizing antibodies in hamsters against the Omicron and Delta strains. Additionally, gDED-mRNA-LNP and gDFR-mRNA-LNP induced potent neutralizing antibodies in rabbits and mice. The mRNA constructs with uridine triphosphate (UTP) outperformed those with N1-methylpseudouridine triphosphate (N1mψTP) in the induction of antibodies via SδT-mRNA-LNP. Our uncapped, process-simplified, and economical mRNA platform may have broad utility in vaccines and protein replacement drugs.
Density-dependent selection at high food levels leads to the evolution of persistence but not constancy in Drosophila melanogaster populations
Authors: Pandey Neha , Joshi Amitabh 
Published: June 2022

ABSTRACTMechanisms through which population dynamics evolve to be stable have been a subject of considerable interest in population biology. One of the ways through which population stability is likely to evolve is via density-dependent selection with or without an r and K trade-off. In this paper, we test whether the specific combination of egg number and food amount under which density-dependent selection is implemented affects the evolution of population stability attributes in D. melanogaster populations that have evolved under density-dependent selection for 75 generations. Our findings show that these populations have evolved higher persistence stability than controls, although constancy stability did not evolve. Moreover, these populations did not show an r-K trade-off, and evolved persistence largely through a significant decrease in sensitivity of growth rate to population density, especially at densities ranging from medium to the equilibrium population size. Qualitative comparison of these findings with those from another set of crowding-adapted D. melanogaster populations that had evolved both constancy and persistence stability, suggests that the ecology of larval crowding influences the consequent evolution of stability attributes. We discuss previous findings on the evolution of life-history traits to argue that differences in the ecology of density-dependent selection experienced at the larval stage affects population stability differently by altering the sensitivity of population growth rate to population density.
Assessing combinatorial diversity of aureochrome bZIPs through genome-wide screening
Authors: Khamaru Madhurima , Nath Deep , Mitra Devrani , Roy Soumen 
Published: June 2022

AbstractAureochromes are unique blue light-responsive LOV (Light Oxygen Voltage) photoreceptors cum basic leucine zipper (bZIP) transcription factors (TFs), present exclusively in photosynthetic marine stramenopiles. Considering the availability of the complete genome sequence, this study focuses particularly on aureochromes from Ectocaupus siliculosus. Aureochromes mediate light-regulated developmental responses in this brown photosynthetic algae. Both the LOV sensor and the bZIP effector shows sequence-structure conservation. The LOV+bZIP modules of aureochrome homologs/ paralogs are not only structurally similar but also show an identical oligomeric state -- preferably dimeric. Aureochromes execute diverse cellular responses in different photosynthetic stramenopiles-- though their activities can vary even within a given algal species. Besides a heterogeneous linker connecting the sensor-effector and a flexible N-terminal region, the sequence composition of both the domains is vital. Therefore, it is important to understand whether aureochromes select dimerization partners from the same family or interact with other bZIPs as well. To regulate multifarious bio-logical activities, it is possible that aureochromes activate the global TF interaction network. Following homo/heterodimer modeling, we address the compatibility of dimerization partners by screening through heptad repeats. We evaluate the dimer interface area in terms of gain in solvation energy as well as the number of hydrogen bonds/salt bridge interactions. We further explore the relative stability of these structures from a graph-theoretic perspective through well-studied measures such as the energy of the graph and average participation coefficient. Furthermore, we also conduct an information-theoretic analysis using network information centrality and Kullback-Leibler divergence. We find that all our investigations into the relative stability of these dimers using diverse methods from bioinformatics, network science, and, information theory are in harmonious agreement. Our approach and findings should facilitate the design of experiments.