bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two-stage Linked Component Analysis for Joint Decomposition of Multiple Biologically Related Data Sets
Authors: Chen Huan , Caffo Brian , Stein-O’Brien Genevieve , Liu Jinrui , Langmead Ben , Colantuoni Carlo , Xiao Luo 
Published: March 2021

SummaryIntegrative analysis of multiple data sets has the potential of fully leveraging the vast amount of high throughput biological data being generated. In particular such analysis will be powerful in making inference from publicly available collections of genetic, transcriptomic and epigenetic data sets which are designed to study shared biological processes, but which vary in their target measurements, biological variation, unwanted noise, and batch variation. Thus, methods that enable the joint analysis of multiple data sets are needed to gain insights into shared biological processes that would otherwise be hidden by unwanted intra-data set variation. Here, we propose a method called two-stage linked component analysis (2s-LCA) to jointly decompose multiple biologically related experimental data sets with biological and technological relationships that can be structured into the decomposition. The consistency of the proposed method is established and its empirical performance is evaluated via simulation studies. We apply 2s-LCA to jointly analyze four data sets focused on human brain development and identify meaningful patterns of gene expression in human neurogenesis that have shared structure across these data sets.
CVnCoV protects human ACE2 transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2
Authors: Hoffmann Donata , Corleis Björn , Rauch Susanne , Roth Nicole , Mühe Janine , Halwe Nico Joel , Ulrich Lorenz , Fricke Charlie , Schön Jacob , Kraft Anna , Breithaupt Angele , Wernike Kerstin , Michelitsch Anna , Sick Franziska , Wylezich Claudia , Müller Stefan O. , Mettenleiter Thomas C. , Petsch Benjamin , Dorhoi Anca , Beer Martin 
Published: March 2021

AbstractThe ongoing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic necessitates the fast development of vaccines as the primary control option. Recently, viral mutants termed “variants of concern” (VOC) have emerged with the potential to escape host immunity. VOC B.1.351 was first discovered in South Africa in late 2020, and causes global concern due to poor neutralization with propensity to evade preexisting immunity from ancestral strains. We tested the efficacy of a spike encoding mRNA vaccine (CVnCoV) against the ancestral strain BavPat1 and the novel VOC B.1.351 in a K18-hACE2 transgenic mouse model. Naive mice and mice immunized with formalin-inactivated SARS-CoV-2 preparation were used as controls. mRNA-immunized mice developed elevated SARS-CoV-2 RBD-specific antibody as well as neutralization titers against the ancestral strain BavPat1. Neutralization titers against VOC B.1.351 were readily detectable but significantly reduced compared to BavPat1. VOC B.1.351-infected control animals experienced a delayed course of disease, yet nearly all SARS-CoV-2 challenged naïve mice succumbed with virus dissemination and high viral loads. CVnCoV vaccine completely protected the animals from disease and mortality caused by either viral strain. Moreover, SARS-CoV-2 was not detected in oral swabs, lung, or brain in these groups. Only partial protection was observed in mice receiving the formalin-inactivated virus preparation. Despite lower neutralizing antibody titers compared to the ancestral strain BavPat1, CVnCoV shows complete disease protection against the novel VOC B.1.351 in our studies.
Naked mole-rats (Heterocephalus glaber) do not specialise on cooperative tasks
Authors: Siegmann Susanne , Feitsch Romana , Hart Daniel W. , Bennett Nigel C. , Penn Dustin J. , Zöttl Markus 
Published: March 2021

AbstractIt has been proposed that naked mole-rat (Heterocephalus glaber) societies resemble those of eusocial insects by showing a division of labour among non-breeding individuals. Earlier studies suggested that non-breeders belong to distinct castes that specialise permanently or temporarily on specific cooperative tasks. In contrast, recent research on naked mole-rats has shown that behavioural phenotypes are continuously distributed across non-breeders and that mole-rats exhibit considerable behavioural plasticity suggesting that individuals may not specialise permanently on work tasks. However, it is currently unclear whether individuals specialise temporarily and whether there is a sex bias in cooperative behaviour among non-breeders. Here we show that non-breeding individuals vary in overall cooperative investment, but do not specialise on specific work tasks. Within individuals, investment into specific cooperative tasks such as nest building, food carrying and burrowing are positively correlated, and there is no evidence that individuals show trade-offs between these cooperative behaviours. Non-breeding males and females do not differ in their investment in cooperative behaviours and show broadly similar age and body mass related differences in cooperative behaviours. Our results suggest that non-breeding naked mole-rats vary in their overall contribution to cooperative behaviours and that some of this variation may be explained by differences in age and body mass. Our data provide no evidence for temporary specialisation, as found among some eusocial insects, and suggests that the behavioural organisation of naked mole-rats resembles that of other cooperatively breeding vertebrates more than that of eusocial insect species.
Control of osteocyte dendrite formation by Sp7 and its target gene osteocrin
Authors: Wang Jialiang S. , Kamath Tushar , Mirzamohammadi Fatemeh , Rotter Daniel , Hojo Hironori , Castro Christian D. , Patel Rushi , Govea Nicolas , Enishi Tetsuya , Wu Yunshu , da Silva Martins Janaina , Bruce Michael , Brooks Daniel J. , Bouxsein Mary L. , Tokarz Danielle , Lin Charles P. , Abdul Abdul , Macosko Evan Z. , Fiscaletti Melissa , Munns Craig F. , Fujiwara Makoto , Kronenberg Henry M. , Wein Marc N. 
Published: March 2021

AbstractOsteocytes use an elaborate network of dendritic connections to control bone remodeling. Some osteoblasts embed within mineralized bone matrix, change shape, and become osteocytes. The molecular circuitry that drives dendrite formation during “osteocytogenesis” is poorly understood. Here we show that deletion ofSp7, a gene linked to rare and common skeletal disease, in mature osteoblasts and osteocytes causes severe defects in osteocyte dendrites. Unbiased profiling of Sp7 target genes and binding sites reveals unexpected repurposing of this transcription factor to drive dendrite formation.Osteocrinis a Sp7 target gene that promotes osteocyte dendrite formation and rescues phenotypic and molecular defects in Sp7-deficient mice. Single-cell RNA-sequencing demonstrates overt defects in osteocyte maturationin vivoin the absence of Sp7. Sp7-dependent gene networks enriched in developing osteocytes are associated with rare and common human skeletal traits. Moreover, humans homozygous for the osteogenesis imperfecta-causingSP7R316Cmutation show dramatic defects in osteocyte morphology. Genes that mark osteocytesin vivoand that are regulated by Sp7in vitroare highly enriched in neurons, highlighting shared features between osteocytic and neuronal connectivity. Taken together, these findings reveal a crucial role for Sp7 and its target geneOsteocrinin osteocytogenesis, demonstrating that pathways that control osteocyte development influence human bone diseases.
From temporal network data to the dynamics of social relationships
Authors: Gelardi Valeria , Barrat Alain , Claidiere Nicolas 
Published: March 2021

AbstractNetworks are well-established representations of social systems, and temporal networks are widely used to study their dynamics. Temporal network data often consist in a succession of static networks over consecutive time windows whose length, however, is arbitrary, not necessarily corresponding to any intrinsic timescale of the system. Moreover, the resulting view of social network evolution is unsatisfactory: short time windows contain little information, whereas aggregating over large time windows blurs the dynamics. Going from a temporal network to a meaningful evolving representation of a social network therefore remains a challenge. Here we introduce a framework to that purpose: transforming temporal network data into an evolving weighted network where the weights of the links between individuals are updated at every interaction. Most importantly, this transformation takes into account the interdependence of social relationships due to the finite attention capacities of individuals: each interaction between two individuals not only reinforces their mutual relationship but also weakens their relationships with others. We study a concrete example of such a transformation and apply it to several data sets of social interactions. Using temporal contact data collected in schools, we show how our framework highlights specificities in their structure and temporal organization. We then introduce a synthetic perturbation into a data set of interactions in a group of baboons to show that it is possible to detect a perturbation in a social group on a wide range of timescales and parameters. Our framework brings new perspectives to the analysis of temporal social networks.
α1-COP delivers sphingolipid modifiers and controls plasmodesmal callose deposition in Arabidopsis
Authors: Iswanto Arya Bagus Boedi , Vu Minh Huy , Kumar Ritesh , Shon Jong Cheol , Wu Shuwei , Kim Da-Ran , Sik Kwak Yeon , Hui Son Geon , Kang Hobin , Kim Woe Yoen , Kim Sang Hee , Liu Kwang Hyeon , Kim Jae-Yean 
Published: March 2021

AbstractCallose is a plant cell wall polymer in the form of β-1,3-glucan, which regulates symplasmic channel size at plasmodesmata (PD). It plays a crucial role in a variety of processes in plants through the regulation of intercelluar symplasmic continuity. However, how to maintain callose homeostasis at PD in the molecular levels is poorly understood. To further elucidate the mechanism of PD callose homeostasis, we screened and identified an Arabidopsis mutant plant that exhibited excessive callose deposition at PD. Based on the Next-generation sequencing (NGS)-based mapping, other mutant allele analysis, and complementation assay, the mutated gene was shown to beα1-COP, which encodes a member of the COPI coatomer complex comprised of α, β, β′, γ, δ, ε, and ζ subunits. Since there is no report on the link between COPI and callose/PD, it was extremely curious to know the roles ofα1-COPor COPI in PD regulation through callose deposition. Here, we report that loss-of-function ofα1-COPdirectly elevates the callose accumulation at PD by affecting subcellular protein localization of callose degradation enzyme PdBG2. This process is linked to ERH1, an inositol phosphoryl ceramide synthase (IPCS), and glucosylceramide synthase (GCS) functions through physical interactions with the α1-COP protein. In addition, the loss-of-function ofα1-COPalso alters the subcellular localization of ERH1 and GCS proteins, results in a reduction of GlcCers and GlcHCers molecules, which are the key SL species for lipid raft formation. According to our findings, we propose that α1-COP protein, together with the SL modifiers controlling lipid raft compositions, regulates the function of GPI-anchored PD proteins and hence the callose turnover at PD and symplastic movement of biomolecules. Our findings provide the first key clue to link the COPI-mediated intracellular trafficking pathway to the callose-mediated intercellular signaling pathway through PD.One-sentence summaryPlant-specific coatomer protein functions as a negative regulator of callose accumulation by regulating the translocation of sphingolipid enzymes.
Genome-wide screen identifies curli amyloid fibril as a bacterial component promoting host neurodegeneration
Authors: Wang Chenyin , Lau Chun Yin , Ma Fuqiang , Zheng Chaogu 
Published: March 2021

AbstractGrowing evidence indicate that gut microbiota play a critical role in regulating the progression of neurodegenerative diseases, such as Parkinson’s disease (PD). The molecular mechanism underlying such microbe-host interaction is unclear. In this study, by feedingC. elegansexpressing human α-syn withE. coliknockout mutants, we conducted a genome-wide screen to identify bacterial genes that promote host neurodegeneration. The screen yielded 38 genes that fall into several genetic pathways, including curli formation, lipopolysaccharide assembly, adenosylcobalamin biosynthesis among others. We then focused on the curli amyloid fibril and found that genetically deleting or pharmacologically inhibiting the curli major subunit CsgA inE. colireduced α-syn-induced neuronal death, restored mitochondrial health, and improved neuronal functions. CsgA secreted by the bacteria colocalized with α-syn inside neurons and promoted α-syn aggregation through cross-seeding. Similarly, curli also promoted neurodegeneration inC. elegansmodels of AD, ALS, and HD and in human neuroblastoma cells.
Mutations in a β-group of solute carrier gene are responsible for egg and eye coloration of thebrown egg 4(b-4) mutant in the silkworm,Bombyx mori
Authors: Tomihara Kenta , Satta Katsuya , Matsuzaki Shohei , Yoshitake Kazutoshi , Yamamoto Kimiko , Uchiyama Hironobu , Yajima Shunsuke , Futahashi Ryo , Katsuma Susumu , Osanai-Futahashi Mizuko , Kiuchi Takashi 
Published: March 2021

AbstractThebrown egg 4(b-4) is a recessive mutant in the silkworm (Bombyx mori), whose egg and adult compound eyes exhibit a reddish-brown color instead of normal purple and black, respectively. By double digest restriction-site associated DNA sequencing (ddRAD-seq) analysis, we narrowed down a region linked to theb-4phenotype to approximately 1.1 Mb that contains 69 predicted gene models. RNA-seq analysis in ab-4strain indicated that one of the candidate genes had a different transcription start site, which generates a short open reading frame. We also found that exon skipping was induced in the same gene due to an insertion of a transposable element in other twob-4mutant strains. This gene encoded a putative amino acid transporter that belongs to the β-group of solute carrier (SLC) family and is orthologous toDrosophilaeye color mutant gene,mahogany(mah). Accordingly, we named this geneBmmah. We performed CRISPR/Cas9-mediated gene knockout targetingBmmah. Several adult moths in generation 0 (G0) had totally or partially reddish-brown compound eyes. We also established threeBmmahknockout strains, all of which exhibit reddish-brown eggs and adult compound eyes. Furthermore, eggs from complementation crosses between theb-4mutants and theBmmahknockout mutants also exhibited reddish-brown color, which was similar to theb-4mutant eggs, indicating thatBmmahis responsible for theb-4phenotypes.HighlightResponsible region for thebrown egg 4(b-4) mutation was narrowed down by double digest restriction-site associated DNA sequencing (ddRAD-seq).The gene structure was disrupted in one of the candidate genes,Bombyx mori mahogany(Bmmah), in theb-4mutant strains.CRISPR/Cas9-mediated gene knockout and complementation test confirmed that theBmmahis responsible for theb-4phenotypes.TheBmmahencoded a putative amino acid transporter that belongs to the β-group of solute carrier family.TheBmmahgene is essential for normal colorization of eggs, compound eyes, and ganglions.Graphical abstract
Microglial refinement of A-fibre projections in the postnatal spinal cord dorsal horn is required for normal maturation of dynamic touch
Authors: Xu Yajing , Koch Stephanie C. , Chamessian Alexander , He Qianru , Sundukova Mayya , Heppenstall Paul , Ji RuRong , Fitzgerald Maria , Beggs Simon 
Published: March 2021

AbstractSensory systems are shaped in postnatal life by the refinement of synaptic connections. In the dorsal horn of the spinal cord, sensory circuits undergo postnatal activity dependent reorganisation, including the retraction of primary afferent A-fibres from superficial to deeper laminae which is accompanied by decreases in cutaneous sensitivity. Here we show that microglia, the resident immune cells in the CNS, phagocytose A-fibre terminals in superficial laminae in the first weeks of life. Genetic perturbation of microglial engulfment at that time prevents the normal process of A-fibre retraction, resulting in increased sensitivity of dorsal horn cells to dynamic tactile cutaneous stimulation, and behavioural hypersensitivity to dynamic touch. Thus, functional microglia are necessary for normal postnatal development of dorsal horn sensory circuits. In the absence of microglial engulfment, superfluous A-fibre projections remain in the dorsal horn and the balance of sensory connectivity is disrupted, leading to lifelong hypersensitivity to dynamic touch.Impact statementMicroglia phagocytose superfluous A-fibres in the superficial spinal dorsal horn during normal development, the disruption of which leads to long term aberrant dynamic touch processing and behaviour.
SAF-A promotes origin licensing and replication fork progression to ensure robust DNA replication
Authors: Connolly Caitlin , Takahashi Saori , Miura Hisashi , Hiratani Ichiro , Gilbert Nick , Donaldson Anne D. , Hiraga Shin-ichiro 
Published: March 2021

AbstractThe organisation of chromatin is closely intertwined with biological activities of chromosome domains, including transcription and DNA replication status. Scaffold attachment factor A (SAF-A), also known as Heteronuclear Ribonucleoprotein Protein U (HNRNPU), contributes to the formation of open chromatin structure. Here we demonstrate that SAF-A promotes the normal progression of DNA replication, and enables resumption of replication after inhibition. We report that cells depleted for SAF-A show reduced origin licensing in G1 phase, and consequently reduced origin activation frequency in S phase. Replication forks progress slowly in cells depleted for SAF-A, also contributing to reduced DNA synthesis rate. Single-cell replication timing analysis revealed that the boundaries between early- and late-replicating domains are blurred in cells depleted for SAF-A. Associated with these defects, SAF-A-depleted cells show elevated γH2A phosphorylation and tend to enter quiescence. Overall we find that SAF-A protein promotes robust DNA replication to ensure continuing cell proliferation.
Respiration, heartbeat, and conscious tactile perception
Authors: Grund Martin , Al Esra , Pabst Marc , Dabbagh Alice , Stephani Tilman , Nierhaus Till , Gaebler Michael , Villringer Arno 
Published: March 2021

AbstractPrevious studies have shown that timing of sensory stimulation during the cardiac cycle interacts with perception. Given the natural coupling of respiration and cardiac activity, we investigated here their joint effects on tactile perception. Forty-one healthy female and male human participants reported conscious perception of finger near-threshold electrical pulses (33% null trials) and decision confidence while electrocardiography, respiratory activity, and finger photoplethysmography were recorded. Participants adapted their respiratory cycle to expected stimulus onsets to preferentially occur during late inspiration / early expiration. This closely matched heart rate variation (sinus arrhythmia) across the respiratory cycle such that most frequent stimulation onsets occurred during the period of highest heart rate probably indicating highest alertness and cortical excitability. Tactile detection rate was highest during the first quadrant after expiration onset. Inter-individually, stronger respiratory phase-locking to the task was associated with higher detection rates. Regarding the cardiac cycle, we confirmed previous findings that tactile detection rate was higher during diastole than systole and newly specified its minimum at 250 - 300 ms after the R-peak corresponding to the pulse wave arrival in the finger. Expectation of stimulation induced a transient heart deceleration which was more pronounced for unconfident decision ratings. Inter-individually, stronger post-stimulus modulations of heart rate were linked to higher detection rates. In summary, we demonstrate how tuning to the respiratory cycle and integration of respiratory-cardiac signals are used to optimize performance of a tactile detection task.Significance statementMechanistic studies on perception and cognition tend to focus on the brain neglecting contributions of the body. Here, we investigated how respiration and heartbeat influence tactile perception: Respiration phase-locking to expected stimulus onsets corresponds to highest heart rate (and presumably alertness/cortical excitability) and correlates with detection performance. Tactile detection varies across the heart cycle with a minimum when the pulse reaches the finger and a maximum in diastole. Taken together with our previous finding of unchanged early ERPs across the cardiac cycle we conclude that these effects are not a peripheral physiological artifact but a result of cognitive processes that model our body’s internal state, make predictions to guide behavior, and might also tune respiration to serve the task.
Introduction bias: Imbalance in species introductions may obscure the identification of traits associated with invasiveness
Authors: Palma Estibaliz , Yen Jian , Vesk Peter A. , Vilà Monserrat , Catford Jane A. 
Published: March 2021

1AbstractThe introduction stage is usually overlooked in trait-based studies of invasiveness, implicitly assuming that species introductions are random. However, human activities promote the movement of specific types of species. Thus, species deliberately introduced for distinct purposes (e.g. gardening, forestry) or as contaminants of human commodities (e.g. stowaway) will likely show particular traits. If species with certain traits have been preferentially introduced (i.e. introduction bias), some traits may have been mistakenly linked to species’ invasion abilities due to their influence on introduction probability.In this work, we propose a theoretical framework with different scenarios of introduction bias. The introduction scenarios are: (1)Random introduction, independent from traits; (2)Biologically biased introduction, following the worldwide distribution of the trait; and (3)Human biased introduction, following a theoretical introduction pathway that favours the introduction of species with high values of the trait. We evaluate how the introduced trait distributions in these scenarios may affect trait distributions in naturalized and invasive species pools under different hypothesized associations between traits and the probabilities of naturalization and invasion. The aim of this work is to identify situations where ignoring introduction bias may lead to spurious correlations being found between species’ traits and species’ ability to become naturalized or invasive.Our framework strongly points to the need to evaluate the traits of species that have become naturalized or invasive along with the traits of species that have failed to do so in order to unravel any existing introduction bias that may confound the correlation between species’ traits and invasion success. Overlooking a possible introduction bias may lead to the overestimation of the correlation between the trait and the species’ invasion ability, especially in cases when the pool of introduced species shows extreme values of the trait distribution (as compared to a random introduction). Trait-based studies that deserve special attention to avoid undesired effects of introduction bias on their findings are: those that investigate naturalization using only the pool of naturalized species, and those studies that examine invasiveness by comparing invasive species with native species.