bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positive feedback of SuFu negating protein 1 on Hedgehog signaling promotes colorectal tumor growth
Authors: Yan Zhengwei , Cheng Minzhang , Hu Guohui , Wang Yao , Zeng Shaopeng , Huang Aidi , Xu Linlin , Liu Yuan , Shi Chao , Deng Libin , Lu Quqin , Rao Hai , Lu Hua , Chen Ye-Guang , Luo Shiwen 
Published: February 2021

AbstractHedgehog (Hh) signaling plays a critical role in embryogenesis and tissue homeostasis, and its deregulation has been associated with tumor growth. The tumor suppressor SuFu inhibits Hh signaling by preventing the nuclear translocation of Gli and suppressing cell proliferation. Regulation of SuFu activity and stability is key to controlling Hh signaling. Here, we unveil SuFu Negating Protein 1 (SNEP1) as a novel Hh target, that enhances the ubiquitination and proteasomal degradation of SuFu and thus promotes Hh signaling. We further show that the E3 ubiquitin ligase LNX1 plays a critical role in the SNEP1-mediated degradation of SuFu. Accordingly, SNEP1 promotes colorectal cancer (CRC) cell proliferation and tumor growth. High levels of SNEP1 are detected in CRC tissues and are well correlated with poor prognosis in CRC patients. Moreover, SNEP1 overexpression reduces sensitivity to anti-Hh inhibitor in CRC cells. Altogether, our findings demonstrate that SNEP1 acts as a novel feedback regulator of Hh signaling by destabilizing SuFu and promoting tumor growth and anti-Hh resistance.
ERBB4 exonic deletions on chromosome 2q34 in patients with intellectual disability or epilepsy
Authors: Hyder Zerin , Van Paesschen Wim , Sabir Ataf , Sansbury Francis H. , Burke Katherine B. , Khan Naz , Chandler Kate E. , Cooper Nicola S. , Wright Ronnie , McHale Edward , Van Esch Hilde , Banka Siddharth 
Published: February 2021

AbstractERBB4 encodes the tyrosine kinase receptor HER4, a critical regulator of normal cell function and neurodevelopmental processes in the brain. One of the key ligands of HER4 is neureglin-1 (NRG1), and the HER4-NRG1 signalling pathway is essential in neural crest cell migration, and neuronal differentiation. Pharmacological inactivation of HER4 has been shown to hasten the progression of epileptogenesis in rodent models, and heterozygous ERBB4 null mice are shown to have cognitive deficits and delayed motor development. Thus far there is only a single case report in the literature of a heterozygous ERBB4 deletion in a patient with intellectual disability (ID). We identified nine subjects from five unrelated families with chromosome 2q34 deletions, resulting in heterozygous intragenic loss of multiple exons of ERBB4, associated with either non-syndromic ID or generalised epilepsy. In one family, the deletion segregated with ID in five affected relatives. Overall, this case series further supports that haploinsufficiency of ERBB4 leads to non-syndromic intellectual disability or epilepsy.
Evolutionary history and genetic connectivity across highly fragmented populations of an endangered daisy
Authors: Rodger Yael S. , Pavlova Alexandra , Sinclair Steve , Pickup Melinda , Sunnucks Paul 
Published: February 2021

AbstractConservation management can be aided by knowledge of genetic diversity and evolutionary history, so that ecological and evolutionary processes can be preserved. The Button Wrinklewort daisy (Rutidosis leptorrhynchoides) was a common component of grassy ecosystems in south-eastern Australia. It is now endangered due to extensive habitat loss and the impacts of livestock grazing, and is currently restricted to a few small populations in two regions >500 km apart, one in Victoria, the other in the Australian Capital Territory and nearby New South Wales (ACT/NSW). Using a genome-wide SNP dataset, we assessed patterns of genetic structure and genetic differentiation of 12 natural diploid populations. We estimated intrapopulation genetic diversity to scope sources for genetic management. Bayesian clustering and principal coordinate analyses showed strong population genetic differentiation between the two regions, and substantial substructure within ACT/NSW. A coalescent tree-building approach implemented in SNAPP indicated evolutionary divergence between the two distant regions. Among the populations screened, the last two known remaining Victorian populations had the highest genetic diversity, despite having among the lowest recent census sizes. A maximum likelihood population tree method implemented in TreeMix suggested little or no recent gene flow except potentially between very close neighbours. Populations that were more genetically distinctive had lower genetic diversity, suggesting that drift in isolation is likely driving population differentiation though loss of diversity, hence re-establishing gene flow among them is desirable. These results provide background knowledge for evidence-based conservation and support genetic rescue within and between regions to elevate genetic diversity and alleviate inbreeding.
Epigenetic responses of hare barley (Hordeum murinum subsp. leporinum) to climate change: an experimental, trait-based approach
Authors: Chano Víctor , Domínguez-Flores Tania , Hidalgo-Galvez Maria Dolores , Rodríguez-Calcerrada Jesús , Pérez-Ramos Ignacio Manuel 
Published: February 2021

AbstractThe impact of reduced rainfall and increased temperatures forecasted by climate change models on plant communities will depend on the capacity of plant species to acclimate and adapt to new environmental conditions. The acclimation process is mainly driven by epigenetic regulation, including structural and chemical modifications on the genome that do not affect the nucleotide sequence. In plants, one of the best-known epigenetic mechanisms is cytosine-methylation. We evaluated the impact of 30% reduced rainfall (hereafter “drought” treatment; D), 3 °C increased air temperature (“warming”; W), and the combination of D and W (WD) on the phenotypic and epigenetic variability ofHordeum murinumsubsp.leporinumL., a grass species of high relevance in Mediterranean agroforestry systems. A full factorial experiment was set up in a savannah-like ecosystem located in southwestern Spain.H. murinumexhibited a large phenotypic plasticity in response to climatic conditions. Plants subjected to warmer conditions (i.e., W and WD treatments) flowered earlier, and those subjected to combined stress (WD) showed a higher investment in leaf area per unit of leaf mass (i.e., higher SLA) and produced heavier seeds. Our results also indicated that both the level and patterns of methylation varied substantially with the climatic treatments, with the combination of D and W inducing a clearly different epigenetic response compared to that promoted by D and W separately. The main conclusion achieved in this work suggests a potential role of epigenetic regulation of gene expression for the maintenance of homoeostasis and functional stability under future climate change scenarios.
Erectile dysfunction in patients with anxiety disorders: a systematic review
Authors: Velurajah Rajalaxmi , Brunckhorst Oliver , Waqar Muhammad , McMullen Isabel , Ahmed Kamran 
Published: February 2021

AbstractMen with anxiety disorders have been identified as high risk of developing erectile dysfunction (ED). The aim of this review is to define the prevalence and severity of ED in the male anxiety disorder population. A literature search of three electronic databases (PubMed, Embase and PsychINFO) and a grey literature registry was conducted. Inclusion criteria were studies that investigated adult males, documented diagnosis of anxiety disorders made by a qualified psychiatrist and use of a validated tool to diagnose ED such as International Index of Erectile Function or ICD-10/DSM-IV. The search yielded 1220 articles and 12 studies were selected. The anxiety disorders investigated were post-traumatic stress disorder, obsessive–compulsive disorder, social phobia/social anxiety disorder and panic disorder. We found that the median [IQR] prevalence of ED was 20.0 [5.1–41.2]% and the median [IQR] International Index of Erectile Function-5 scores were 17.62 [13.88–20.88], indicating a mild to moderate severity. Our review suggests a high prevalence of ED in the anxiety disorder population and ED may be more severe in this cohort, therefore advocating this is an important clinical topic. However, the evidence is limited due to the high heterogeneity between the studies and more research is required in this field.
Social networks predict the life and death of honey bees
Authors: Wild Benjamin , Dormagen David M. , Zachariae Adrian , Smith Michael L. , Traynor Kirsten S. , Brockmann Dirk , Couzin Iain D. , Landgraf Tim 
Published: February 2021

AbstractIn complex societies, individuals’ roles are reflected by interactions with other conspecifics. Honey bees (Apis mellifera) generally change tasks as they age, but developmental trajectories of individuals can vary drastically due to physiological and environmental factors. We introduce a succinct descriptor of an individual’s social network that can be obtained without interfering with the colony. This ‘network age’ accurately predicts task allocation, survival, activity patterns, and future behavior. We analyze developmental trajectories of multiple cohorts of individuals in a natural setting and identify distinct developmental pathways and critical life changes. Our findings suggest a high stability in task allocation on an individual level. We show that our method is versatile and can extract different properties from social networks, opening up a broad range of future studies. Our approach highlights the relationship of social interactions and individual traits, and provides a scalable technique for understanding how complex social systems function.
Dysregulated transcriptional responses to SARS-CoV-2 in the periphery
Authors: McClain Micah T. , Constantine Florica J. , Henao Ricardo , Liu Yiling , Tsalik Ephraim L. , Burke Thomas W. , Steinbrink Julie M. , Petzold Elizabeth , Nicholson Bradly P. , Rolfe Robert , Kraft Bryan D. , Kelly Matthew S. , Saban Daniel R. , Yu Chen , Shen Xiling , Ko Emily M. , Sempowski Gregory D. , Denny Thomas N. , Ginsburg Geoffrey S. , Woods Christopher W. 
Published: February 2021

AbstractSARS-CoV-2 infection has been shown to trigger a wide spectrum of immune responses and clinical manifestations in human hosts. Here, we sought to elucidate novel aspects of the host response to SARS-CoV-2 infection through RNA sequencing of peripheral blood samples from 46 subjects with COVID-19 and directly comparing them to subjects with seasonal coronavirus, influenza, bacterial pneumonia, and healthy controls. Early SARS-CoV-2 infection triggers a powerful transcriptomic response in peripheral blood with conserved components that are heavily interferon-driven but also marked by indicators of early B-cell activation and antibody production. Interferon responses during SARS-CoV-2 infection demonstrate unique patterns of dysregulated expression compared to other infectious and healthy states. Heterogeneous activation of coagulation and fibrinolytic pathways are present in early COVID-19, as are IL1 and JAK/STAT signaling pathways, which persist into late disease. Classifiers based on differentially expressed genes accurately distinguished SARS-CoV-2 infection from other acute illnesses (auROC 0.95 [95% CI 0.92–0.98]). The transcriptome in peripheral blood reveals both diverse and conserved components of the immune response in COVID-19 and provides for potential biomarker-based approaches to diagnosis.
Ingredients for microbial life preserved in 3.5 billion-year-old fluid inclusions
Authors: Mißbach Helge , Duda Jan-Peter , van den Kerkhof Alfons M. , Lüders Volker , Pack Andreas , Reitner Joachim , Thiel Volker 
Published: February 2021

AbstractIt is widely hypothesised that primeval life utilised small organic molecules as sources of carbon and energy. However, the presence of such primordial ingredients in early Earth habitats has not yet been demonstrated. Here we report the existence of indigenous organic molecules and gases in primary fluid inclusions in c. 3.5-billion-year-old barites (Dresser Formation, Pilbara Craton, Western Australia). The compounds identified (e.g., H2S, COS, CS2, CH4, acetic acid, organic (poly-)sulfanes, thiols) may have formed important substrates for purported ancestral sulfur and methanogenic metabolisms. They also include stable building blocks of methyl thioacetate (methanethiol, acetic acid) – a putative key agent in primordial energy metabolism and thus the emergence of life. Delivered by hydrothermal fluids, some of these compounds may have fuelled microbial communities associated with the barite deposits. Our findings demonstrate that early Archaean hydrothermal fluids contained essential primordial ingredients that provided fertile substrates for earliest life on our planet.
Single-cell transcriptional profiling of human thymic stroma uncovers novel cellular heterogeneity in the thymic medulla
Authors: Bautista Jhoanne L. , Cramer Nathan T. , Miller Corey N. , Chavez Jessica , Berrios David I. , Byrnes Lauren E. , Germino Joe , Ntranos Vasilis , Sneddon Julie B. , Burt Trevor D. , Gardner James M. , Ye Chun J. , Anderson Mark S. , Parent Audrey V. 
Published: February 2021

AbstractThe thymus’ key function in the immune system is to provide the necessary environment for the development of diverse and self-tolerant T lymphocytes. While recent evidence suggests that the thymic stroma is comprised of more functionally distinct subpopulations than previously appreciated, the extent of this cellular heterogeneity in the human thymus is not well understood. Here we use single-cell RNA sequencing to comprehensively profile the human thymic stroma across multiple stages of life. Mesenchyme, pericytes and endothelial cells are identified as potential key regulators of thymic epithelial cell differentiation and thymocyte migration. In-depth analyses of epithelial cells reveal the presence of ionocytes as a medullary population, while the expression of tissue-specific antigens is mapped to different subsets of epithelial cells. This work thus provides important insight on how the diversity of thymic cells is established, and how this heterogeneity contributes to the induction of immune tolerance in humans.
Notch2-mediated plasticity between marginal zone and follicular B cells
Authors: Lechner Markus , Engleitner Thomas , Babushku Tea , Schmidt-Supprian Marc , Rad Roland , Strobl Lothar J. , Zimber-Strobl Ursula 
Published: February 2021

AbstractFollicular B (FoB) and marginal zone B (MZB) cells are functionally and spatially distinct mature B cell populations in the spleen, originating from a Notch2-dependent fate decision after splenic influx of immature transitional B cells. In the B cell follicle, a Notch2-signal is provided by DLL-1-expressing fibroblasts. However, it is unclear whether FoB cells, which are in close contact with these DLL-1 expressing fibroblasts, can also differentiate to MZB cells if they receive a Notch2-signal. Here, we show induced Notch2IC-expression in FoB cells re-programs mature FoB cells into bona fide MZB cells as is evident from the surface phenotype, localization, immunological function and transcriptome of these cells. Furthermore, the lineage conversion from FoB to MZB cells occurs in immunocompetent wildtype mice. These findings demonstrate plasticity between mature FoB and MZB cells that can be driven by a singular signaling event, the activation of Notch2.
Genome sequences reveal global dispersal routes and suggest convergent genetic adaptations in seahorse evolution
Authors: Li Chunyan , Olave Melisa , Hou Yali , Qin Geng , Schneider Ralf F. , Gao Zexia , Tu Xiaolong , Wang Xin , Qi Furong , Nater Alexander , Kautt Andreas F. , Wan Shiming , Zhang Yanhong , Liu Yali , Zhang Huixian , Zhang Bo , Zhang Hao , Qu Meng , Liu Shuaishuai , Chen Zeyu , Zhong Jia , Zhang He , Meng Lingfeng , Wang Kai , Yin Jianping , Huang Liangmin , Venkatesh Byrappa , Meyer Axel , Lu Xuemei , Lin Qiang 
Published: February 2021

AbstractSeahorses have a circum-global distribution in tropical to temperate coastal waters. Yet, seahorses show many adaptations for a sedentary, cryptic lifestyle: they require specific habitats, such as seagrass, kelp or coral reefs, lack pelvic and caudal fins, and give birth to directly developed offspring without pronounced pelagic larval stage, rendering long-range dispersal by conventional means inefficient. Here we investigate seahorses’ worldwide dispersal and biogeographic patterns based on a de novo genome assembly ofHippocampus erectusas well as 358 re-sequenced genomes from 21 species. Seahorses evolved in the late Oligocene and subsequent circum-global colonization routes are identified and linked to changing dynamics in ocean currents and paleo-temporal seaway openings. Furthermore, the genetic basis of the recurring “bony spines” adaptive phenotype is linked to independent substitutions in a key developmental gene. Analyses thus suggest that rafting via ocean currents compensates for poor dispersal and rapid adaptation facilitates colonizing new habitats.
Aquila enables reference-assisted diploid personal genome assembly and comprehensive variant detection based on linked reads
Authors: Zhou Xin , Zhang Lu , Weng Ziming , Dill David L. , Sidow Arend 
Published: February 2021

AbstractWe introduce Aquila, a new approach to variant discovery in personal genomes, which is critical for uncovering the genetic contributions to health and disease. Aquila uses a reference sequence and linked-read data to generate a high quality diploid genome assembly, from which it then comprehensively detects and phases personal genetic variation. The contigs of the assemblies from our libraries cover >95% of the human reference genome, with over 98% of that in a diploid state. Thus, the assemblies support detection and accurate genotyping of the most prevalent types of human genetic variation, including single nucleotide polymorphisms (SNPs), small insertions and deletions (small indels), and structural variants (SVs), in all but the most difficult regions. All heterozygous variants are phased in blocks that can approach arm-level length. The final output of Aquila is a diploid and phased personal genome sequence, and a phased Variant Call Format (VCF) file that also contains homozygous and a few unphased heterozygous variants. Aquila represents a cost-effective approach that can be applied to cohorts for variation discovery or association studies, or to single individuals with rare phenotypes that could be caused by SVs or compound heterozygosity.
Crystal structure of a photosynthetic LH1-RC in complex with its electron donor HiPIP
Authors: Kawakami Tomoaki , Yu Long-Jiang , Liang Tai , Okazaki Koudai , Madigan Michael T. , Kimura Yukihiro , Wang-Otomo Zheng-Yu 
Published: February 2021

AbstractPhotosynthetic electron transfers occur through multiple components ranging from small soluble proteins to large integral membrane protein complexes. Co-crystallization of a bacterial photosynthetic electron transfer complex that employs weak hydrophobic interactions was achieved by using high-molar-ratio mixtures of a soluble donor protein (high-potential iron-sulfur protein, HiPIP) with a membrane-embedded acceptor protein (reaction center, RC) at acidic pH. The structure of the co-complex offers a snapshot of a transient bioenergetic event and revealed a molecular basis for thermodynamically unfavorable interprotein electron tunneling. HiPIP binds to the surface of the tetraheme cytochrome subunit in the light-harvesting (LH1) complex-associated RC in close proximity to the low-potential heme-1 group. The binding interface between the two proteins is primarily formed by uncharged residues and is characterized by hydrophobic features. This co-crystal structure provides a model for the detailed study of long-range trans-protein electron tunneling pathways in biological systems.
Innate cell profiles during the acute and convalescent phase of SARS-CoV-2 infection in children
Authors: Neeland Melanie R. , Bannister Samantha , Clifford Vanessa , Dohle Kate , Mulholland Kim , Sutton Philip , Curtis Nigel , Steer Andrew C. , Burgner David P. , Crawford Nigel W. , Tosif Shidan , Saffery Richard 
Published: February 2021

AbstractChildren have mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confirmed disease (COVID-19) compared to adults and the immunological mechanisms underlying this difference remain unclear. Here, we report acute and convalescent innate immune responses in 48 children and 70 adults infected with, or exposed to, SARS-CoV-2. We find clinically mild SARS-CoV-2 infection in children is characterised by reduced circulating subsets of monocytes (classical, intermediate, non-classical), dendritic cells and natural killer cells during the acute phase. In contrast, SARS-CoV-2-infected adults show reduced proportions of non-classical monocytes only. We also observe increased proportions of CD63+ activated neutrophils during the acute phase to SARS-CoV-2 in infected children. Children and adults exposed to SARS-CoV-2 but negative on PCR testing display increased proportions of low-density neutrophils that we observe up to 7 weeks post exposure. This study characterises the innate immune response during SARS-CoV-2 infection and household exposure in children.
Short-lived metal-centered excited state initiates iron-methionine photodissociation in ferrous cytochrome c
Authors: Reinhard Marco E. , Mara Michael W. , Kroll Thomas , Lim Hyeongtaek , Hadt Ryan G. , Alonso-Mori Roberto , Chollet Matthieu , Glownia James M. , Nelson Silke , Sokaras Dimosthenis , Kunnus Kristjan , Driel Tim Brandt van , Hartsock Robert W. , Kjaer Kasper S. , Weninger Clemens , Biasin Elisa , Gee Leland B. , Hodgson Keith O. , Hedman Britt , Bergmann Uwe , Solomon Edward I. , Gaffney Kelly J. 
Published: February 2021

AbstractThe dynamics of photodissociation and recombination in heme proteins represent an archetypical photochemical reaction widely used to understand the interplay between chemical dynamics and reaction environment. We report a study of the photodissociation mechanism for the Fe(II)-S bond between the heme iron and methionine sulfur of ferrous cytochrome c. This bond dissociation is an essential step in the conversion of cytochrome c from an electron transfer protein to a peroxidase enzyme. We use ultrafast X-ray solution scattering to follow the dynamics of Fe(II)-S bond dissociation and 1s3p (Kβ) X-ray emission spectroscopy to follow the dynamics of the iron charge and spin multiplicity during bond dissociation. From these measurements, we conclude that the formation of a triplet metal-centered excited state with anti-bonding Fe(II)-S interactions triggers the bond dissociation and precedes the formation of the metastable Fe high-spin quintet state.
High performance Wannier interpolation of Berry curvature and related quantities with WannierBerri code
Authors: Tsirkin Stepan S. 
Published: February 2021

AbstractWannier interpolation is a powerful tool for performing Brillouin zone integrals over dense grids of k points, which are essential to evaluate such quantities as the intrinsic anomalous Hall conductivity or Boltzmann transport coefficients. However, more complex physical problems and materials create harder numerical challenges, and computations with the existing codes become very expensive, which often prevents reaching the desired accuracy. In this article, I present a series of methods that boost the speed of Wannier interpolation by several orders of magnitude. They include a combination of fast and slow Fourier transforms, explicit use of symmetries, and recursive adaptive grid refinement among others. The proposed methodology has been implemented in the python code WannierBerri, which also aims to serve as a convenient platform for the future development of interpolation schemes for other phenomena.