bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atypical chemoreceptor arrays accommodate high membrane curvature
Authors: Muok Alise R. , Ortega Davi R. , Kurniyati Kurni , Yang Wen , Mabrouk Adam Sidi , Li Chunhao , Crane Brian R. , Briegel Ariane 
Published: March 2020

Abstract/SummaryThe prokaryotic chemotaxis system is arguably the best-understood signaling pathway in biology, but most insights have been obtained from only a few model organisms and many studies have relied on artificial systems that alter membrane curvature1–3. In all previously described species, chemoreceptors organize with the histidine kinase (CheA) and coupling protein (CheW) into a hexagonal (P6 symmetry) extended array that is considered universal among archaea and bacteria4,5. Here, for the first time, we report an alternative symmetry (P2) of the chemotaxis apparatus that emerges from a strict linear organization of CheA inTreponema denticolacells, which possesses arrays with the highest native curvature investigated thus far. Using cryo-ET, we reveal that theTdchemoreceptor arrays assume a truly unusual arrangement of the supra-molecular protein assembly that has likely evolved to accommodate the high membrane curvature. The arrays have several additional atypical features, such as an extended dimerization domain of CheA and a variant CheW-CheR-like fusion protein that is critical for maintaining an ordered chemosensory apparatus in an extremely curved cell. Furthermore, the previously characterizedTdoxygen sensor ODP influences array integrity and its loss substantially orders CheA. These results suggest a greater diversity of the chemotaxis signaling system than previously thought and demonstrate the importance of examining transmembrane systemsin vivoto retain native membrane curvature.
NormiRazor – Tool Applying GPU-accelerated Computing for Determination of Internal References in MicroRNA Transcription Studies
Authors: Grabia Szymon , Smyczynska Ula , Pagacz Konrad , Fendler Wojciech 
Published: March 2020

AbstractMotivationMulti-gene expression assays are an attractive tool in revealing complex regulatory mechanisms in living organisms. Normalization is an indispensable step of data analysis in all those studies, since it removes unwanted, non-biological variability from data. In targeted qPCR assays the normalization is typically performed with respect to prespecified reference genes, but the lack of robust strategy of their selection is reported in literature, especially in studies concerning circulating microRNAs (miRNA).ResultsPrevious studies concluded that averaged expressions of multi-miRNA combinations are more stable references than single genes. However, due to the number of such combinations the computational load is considerable and may be hindering for objective reference selection in large datasets. Existing implementations of normalization algorithms (geNorm, NormFinder and BestKeeper) have poor performance as every combination is evaluated sequentially. Thus, we designed an integrative tool which implemented those methods in a parallel manner on a graphics processing unit (GPU) using CUDA platform. We tested our approach on publicly available microRNA expression datasets. As a result the times of executions decreased 19-, 105- and 77-fold respectively for geNorm, BestKeeper and NormFinder.AvailabilityNormiRazor is available as web application at norm.btm.umed.pl.ContactWojciech Fendler,wojciech_fendler@dfci.harvard.edu.
Long-read transcriptome data of bee fungal parasite,Nosema ceranae
Authors: Chen Huazhi , Du Yu , Fan Yuanchan , Jiang Haibin , Xiong Cuiling , Zheng Yanzhen , Chen Dafu , Guo Rui 
Published: March 2020

ABSTRACTNosema ceranae, a widespread fungal parasite that infects honeybee and many other bee species, can seriously affect bee health and colony productivity. In this article,N. ceranaespores were purified followed by third-generation sequencing using Nanopore PromethION platform. Totally, 6988795 raw reads were yielded from purified spores, with a length distribution among 1 kb~10 kb and a quality (Q) score distribution among Q6~Q12. A total of 6953469 clean reads were obtained, and among them 73.98% were identified as being full-length. The length of redundant reads-removed full-length transcripts was ranged from 1 kb to 5 kb, with the most abundant length of 1 kb. These data will improve transcriptome quality ofN. ceranaesignificantly.
Early-life microbial intervention reduces colitis risk promoted by antibiotic-induced gut dysbiosis
Authors: Miyoshi Jun , Miyoshi Sawako , Delmont Tom O. , Cham Candace , Lee Sonny T.M. , Sakatani Aki , Yang Karen , Shan Yue , Kiefl Evan , Yousef Mahmoud , Crosson Sean , Sogin Mitchell , Antonopoulos Dionysios A. , Eren A. Murat , Leone Vanessa , Chang Eugene B. 
Published: March 2020

SummaryPerturbations in the early life gut microbiome are associated with increased risk to complex immune disorder like inflammatory bowel diseases. We previously showed maternal antibiotic-induced gut dysbiosis vertically passed to offspring increases experimental colitis risk in IL-10 gene deficient (IL-10−/−) mice. While this could arise from emergence of pathobionts or loss/lack of essential microbes needed for appropriate immunological education, our findings suggest the latter. A dominantBacteroidesstrain absent following antibiotic-induced perturbation was cultivated from murine fecal samples. Addition of this strain into mice with antibiotic-induced dysbiosis significantly promoted immune tolerance and reduced incidence of colitis in IL-10−/−mice, but only if engrafted early in life, and not during adulthood. Thus, key members of the gut microbiome are essential for development of immune tolerance to commensal microbes in early life and their addition in presence of gut dysbiosis during this period can reduce colitis risk in genetically prone hosts.HighlightsSpecific gut microbes promote early life immune tolerance to key commensal microbesLoss of early life keystone microbes increases colitis risk in genetically prone hostsEmergence of absent commensal microbes late in life worsened colitis outcomeEarly life exposure to a missing keystone Bacteroides strain reduced colitis risk
Perceived ambiguity of social interactions increases coupling between frontal and temporal nodes of the social brain
Authors: Ainsworth Matthew , Sallet Jérôme , Joly Olivier , Kyriazis Diana , Kriegeskorte Nikolaus , Duncan John , Schüffelgen Urs , Rushworth Matthew FS , Bell Andrew H 
Published: March 2020

ABSTRACTSocial behaviour is coordinated by a network of brain regions, including those involved in the perception of social stimuli and those involved in complex functions like inferring perceptual and mental states and controlling social interactions. The properties and function of many of these regions in isolation is relatively well understood but little is known about how these regions interact whilst processing dynamic social interactions. To investigate whether social network connectivity is modulated by social context we collected fMRI data from monkeys viewing “affiliative”, “aggressive”, or “ambiguous” social interactions. We show activation relating to the perception of social interactions along both banks of the superior temporal sulcus, parietal, medial and lateral PFC and caudate nucleus. Within this network we demonstrate that fronto-temporal connectivity are significantly modulated by social context. Crucially, we link the observation of specific behaviours to changes in connectivity within our network. Viewing aggressive or affiliative behaviour was associated with a limited increase in temporo-temporal and premotor-temporal connectivity respectively. By contrast, viewing ambiguous interactions was associated with a pronounced increase in cingulate-cingulate, temporo-temporal, and cingulate-temporal connectivity. We hypothesise that this widespread network synchronisation occurs when cingulate and temporal areas coordinate their activity when more difficult social inferences are made.
Testing the two-step model of plant root microbiome acquisition under multiple plant species and soil sources
Authors: Barajas Hugo R. , Martínez-Sánchez Shamayim , Romero Miguel F. , Hernández-Álvarez Cristóbal , Servín-González Luis , Peimbert Mariana , Cruz-Ortega Rocío , García-Oliva Felipe , Alcaraz Luis D. 
Published: March 2020

AbstractThe two-step model for plant root microbiomes considers soil as the primary microbial source. Active selection of the plant’s bacterial inhabitants results in a biodiversity decrease towards roots. We collectedin situruderal plant roots and their soils and used these soils as the main microbial input for single genotype tomatoes grown in a greenhouse. We massively sequenced the 16S rRNA and shotgun metagenomes of the soils,in situplants, and tomato roots. Tomato roots did follow the two-step model, while ruderal plants did not. Ruderal plants and their soils are closer than tomato and its soil, based on protein comparisons. We calculated a metagenomic tomato root core of 51 bacterial genera and 2,762 proteins, which could be the basis for microbiome-oriented plant breeding programs. The tomato and ruderal metagenomic differences are probably due to plant domestication trade-offs, impacting plant-microbe interactions.
Immune Digital Twin Blueprint: A Comprehensive Mechanistic Model of the Human Immune System
Authors: Amin Rada , Aghamiri Sara Sadat , Puniya Bhanwar Lal , Mayo Lauren , Startsev Dennis , Poore Kashish , Helikar Resa , Helikar Tomáš 
Published: March 2020

AbstractThe immune system is a complex and dynamic network, crucial for combating infections and maintaining health. Developing a comprehensive digital twin of the immune system requires incorporating essential cellular components and their interactions. This study presents the first blueprint for an immune system digital twin, consisting of a comprehensive and simulatable mechanistic model. It integrates 51 innate and adaptive immune cells, 37 secretory factors, and 11 disease conditions, providing the foundation for developing a multi-scale model. The cellular-level model demonstrates its potential in characterizing immune responses to various single and combinatorial disease conditions. By making the model available in easy-to-use formats directly in the Cell Collective platform, the community can easily and further expand it. This blueprint represents a significant step towards developing general-purpose immune digital twins, with far-reaching implications for the future of digital twin technology in life sciences and healthcare, advancing patient care, and accelerating precision medicine.
Activation of Macrophages by CpG DNA and LPS: an FTIR Spectroscopic Study
Authors: Spahiu Emrulla , Dogan Senol , Schnauß Jörg , Gursel Mayda , Severcan Feride 
Published: March 2020

AbstractThe innate immune response triggered by CpG DNA can improve host survival following pathogen challenge. Whether CpG ODN-mediated immune activation leads to global molecular changes in cells that are detectable by FTIR spectroscopy is currently unknown. Here, we used Attenuated Total Reflectance (ATR) Fourier Transform Infrared (FTIR) spectroscopy to monitor the molecular changes in murine macrophage RAW 264.7 cells upon activation with CpG DNA and lipopolysaccharide (LPS). By PCA analysis, we identified the sources of variation to follow with detailed spectral analysis. CpG DNA and LPS treatment increase the total nucleic acid concentration from the early periods post-activation, and DNA synthesis follows RNA synthesis. RNA-specific peak shows the activation state of macrophages in early periods post-treatment. CpG DNA and LPS result in an initial rapid increase in the total protein concentration, leveling off two hours post-activation. Both activated groups increase the concentration of fatty acids, triglycerides, and cholesterol, pointing out to a shared synthesis pathway andde novolipogenesis. This study, for the first time, demonstrates the use of FTIR spectroscopy as an independent modality to monitor the activation dynamics of murine macrophages upon activation with CpG DNA and LPS.
The Glycosphingolipid GM3 Modulates Conformational Dynamics of the Glucagon Receptor
Authors: Ansell T. Bertie , Song Wanling , Sansom Mark S. P. 
Published: March 2020

AbstractThe extracellular domain (ECD) of Class B1 G-protein coupled receptors (GPCRs) plays a central role in signal transduction and is uniquely positioned to sense both the extracellular and membrane environments. Whilst recent studies suggest a role for membrane lipids in the modulation of Class A and Class F GPCR signalling properties, little is known about the effect of lipids on Class B1 receptors. In this study, we employed multiscale molecular dynamics (MD) simulations to access the dynamics of the glucagon receptor (GCGR) ECD in the presence of native-like membrane bilayers. Simulations showed that the ECD could move about a hinge region formed by residues Q122-E126 to adopt both closed and open conformations relative to the TMD. ECD movements were modulated by binding of the glycosphingolipid GM3. These large-scale fluctuations in ECD conformation that may affect the ligand binding and receptor activation properties. We also identify a unique PIP2interaction profile near ICL2/TM3 at the G-protein coupling interface, suggesting a mechanism of engaging G-proteins which may have a distinct dependence on PIP2compared to Class A GPCRs. Given the structural conservation of Class B1 GPCRs, the modulatory effects of GM3 and PIP2on GCGR may be conserved across these receptors, offering new insights into potential therapeutic targeting.Statement of SignificanceThe role of lipids in regulation of Class B GPCRs remains elusive, despite recent structural advances. In this study, multi-scale molecular dynamics simulations are used to evaluate lipid interactions with the glucagon receptor, a Class B1 GPCR. We find that the glycosphingolipid GM3 binds to the glucagon receptor extracellular domain (ECD), modulating the dynamics of the ECD and promoting movement away from the transmembrane domain. We also identify a unique PIP2interaction fingerprint in a region known to be important for bridging G-protein coupling in Class A GPCRs. Thus, this study provides molecular insight into the behaviour of the glucagon receptor in a complex lipid bilayer environment which may aid understanding of glucagon receptor signalling properties.
Poly(ADP-ribose) glycohydrolase promotes formation and homology-directed repair of meiotic DNA double-strand breaks independent of its catalytic activity
Authors: Janisiw Eva , Raices Marilina , Balmir Fabiola , Paz Luis Paulin , Baudrimont Antoine , von Haeseler Arndt , Yanowitz Judith L. , Jantsch Verena , Silva Nicola 
Published: March 2020

SummaryPoly(ADP-ribosyl)ation is a reversible post-translational modification synthetized by ADP-ribose transferases and removed by poly(ADP-ribose) glycohydrolase (PARG), which plays important roles in DNA damage repair. While well-studied in somatic tissues, much less is known about poly(ADP-ribosyl)ation in the germline, where DNA double-strand breaks are introduced by a regulated program and repaired by crossover recombination to establish a tether between homologous chromosomes. The interaction between the parental chromosomes is facilitated by meiotic specific adaptation of the chromosome axes and cohesins, and reinforced by the synaptonemal complex. Here, we uncover an unexpected role for PARG in promoting the induction of meiotic DNA breaks and their homologous recombination-mediated repair inCaenorhabditis elegans. PARG-1/PARG interacts with both axial and central elements of the synaptonemal complex, REC-8/Rec8 and the MRN/X complex. PARG-1 shapes the recombination landscape and reinforces the tightly regulated control of crossover numbers without requiring its catalytic activity. We unravel roles in regulating meiosis, beyond its enzymatic activity in poly(ADP-ribose) catabolism.
Hippocampal inputs engage CCK+ interneurons to mediate endocannabinoid-modulated feed-forward inhibition in the prefrontal cortex
Authors: Liu Xingchen , Dimidschstein Jordane , Fishell Gordon , Carter Adam G. 
Published: March 2020

ABSTRACTConnections from the ventral hippocampus (vHPC) to the prefrontal cortex (PFC) regulate cognition, emotion and memory. These functions are also tightly regulated by inhibitory networks in the PFC, whose disruption is thought to contribute to mental health disorders. However, relatively little is known about how the vHPC engages different populations of interneurons in the PFC. Here we use slice physiology and optogenetics to study vHPC-evoked feed-forward inhibition in the mouse PFC. We first show that cholecystokinin (CCK+), parvalbumin (PV+), and somatostatin (SOM+) interneurons are prominent in layer 5 (L5) of infralimbic PFC. We then show that vHPC inputs primarily activate CCK+ and PV+ interneurons, with weaker connections onto SOM+ interneurons. CCK+ interneurons make stronger synapses onto pyramidal tract (PT) cells over nearby intratelencephalic (IT) cells. However, CCK+ inputs undergo depolarization-induced suppression of inhibition (DSI) and CB1 receptor modulation only at IT cells. Moreover, vHPC-evoked feed-forward inhibition undergoes DSI only at IT cells, confirming a central role for CCK+ interneurons. Together, our findings show how vHPC directly engages multiple populations of inhibitory cells in deep layers of the infralimbic PFC, highlighting unexpected roles for both CCK+ interneurons and endocannabinoid modulation in hippocampal-prefrontal communication.
The relationship between effective molarity and affinity governs rate enhancements in tethered kinase-substrate reactions
Authors: Speltz Elizabeth B. , Zalatan Jesse G. 
Published: March 2020

AbstractScaffold proteins are thought to accelerate protein phosphorylation reactions by tethering kinases and substrates together, but there is little quantitative data on their functional effects. To assess the contribution of tethering to kinase reactivity, we compared intramolecular and intermolecular kinase reactions in a minimal model system. We find that tethering can enhance reaction rates in a flexible tethered kinase system, and the magnitude of the effect is sensitive to the structure of the tether. The largest effective molarity we obtained was ∼0.08 µM, which is much lower than the effects observed in small molecule model systems and tethered protein-ligand interactions. We further demonstrate that the tethered, intramolecular reaction only makes a significant contribution to observed rates when the scaffolded complex assembles at concentrations below the effective molarity. These findings provide a quantitative framework that can be applied to understand endogenous protein scaffolds and to engineer synthetic networks.
Rho1 activation recapitulates early gastrulation events in the ventral, but not dorsal, epithelium ofDrosophilaembryos
Authors: Rich Ashley , Fehon Richard G. , Glotzer Michael 
Published: March 2020

AbstractVentral furrow formation, the first step inDrosophilagastrulation, is a well-studied example of tissue morphogenesis. Rho1 is highly active in a subset of ventral cells and is required for this morphogenetic event. However, it is unclear whether spatially patterned Rho1 activity alone is sufficient to recapitulate all aspects of this morphogenetic event, including anisotropic apical constriction and coordinated cell movements. Here, using an optogenetic probe that rapidly and robustly activates Rho1 inDrosophilatissues, we show that Rho1 activity induces ectopic deformations in the dorsal and ventral epithelia ofDrosophilaembryos. These perturbations reveal substantial differences in how ventral and dorsal cells, both within and outside the zone of Rho1 activation, respond to spatially and temporally identical patterns of Rho1 activation. Our results demonstrate that an asymmetric zone of Rho1 activity is not sufficient to recapitulate ventral furrow formation and indicate that additional, ventral-specific factors contribute to the cell- and tissue-level behaviors that emerge during ventral furrow formation.
Home buyouts: a tool for mitigation or recovery?
Authors: Binder Sherri Brokopp , Greer Alex , Zavar Elyse 
Published: March 2020

PurposeHome buyout programs are typically funded by the federal government and implemented by local agencies. How these agencies design and implement buyouts has considerable impacts on participating households and communities, making understanding the internal processes of implementing agencies a critical component of buyout research. This study addresses this issue by exploring the early design and implementation phases of a buyout program in Harris County, Texas, following Hurricane Harvey.Design/methodology/approachData were collected via semi-structured interviews with buyout staff and government stakeholders. Data were analyzed in two phases using grounded theory methodology and holistic coding.FindingsThere was considerable tension regarding the role of buyouts in mitigation and recovery. Participants conceptualized buyouts as mitigation programs, but recognized that residents, in contrast, viewed buyouts as a tool for household recovery.Research limitations/implicationsThis study adds to questions raised in the literature about the efficacy of buyouts and other relocation efforts implemented in response to disasters and global climate change. Future research should work to build systematic knowledge regarding design, implementation, and impacts of buyouts on affected households and communities.Practical implicationsTension in the purpose of buyouts may be the cause of consistent shortcomings in buyout implementation including attrition, checkerboarding, and transfer of risk. Funding, timing, and the scale of buyouts do not align with household recovery needs and priorities, limiting the mitigation potential of buyouts.Originality/valueThis study identifies a fundamental tension in the purpose of buyout programs that has yet to be discussed in the literature.
Can’t change my political disaffection! The role of political disaffection, trust, and resistance to change in internet voting
Authors: Sharma Shwadhin 
Published: March 2020

Purpose
This paper aims to put the focus on political disaffection that the voters may have and its impact on their resistance to the changes, thereby influencing intention to adopt Internet voting. This study also examines the impact of perceived risk and technological skills on the trust of the Internet technology and informal networks, such as social influence and media influence on the trust of the government.

Design/methodology/approach
To empirically test the model, an online survey is administered to 851 people who are eligible to vote.

Findings
The findings show that positive media influence and social influence also significantly impact trust in government but trust in government does not necessarily decrease resistance to change and positively impact intention to adopt eVoting. Also, the resistance to change was shown to significantly influence the intention to use Internet voting.

Research limitations/implications
A primary potential limitation of this study is the use of convenience sampling, which may lead to self-selection bias that limits the generalization of our research to all citizens.

Practical implications
Government institutions, as well as political parties, can use the findings of this research to understand how political dissatisfaction such as apathy and cynicism can increase trust in technology and lead to higher participation in online voting.

Originality/value
While the focus on previous literature has been heavily on security and system requirements, this study expands existing research by exploring voting habits, political disaffection, the resistance of change and informal influence on intention to use online voting.