bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel methodology for localizing and studying the insect dorsal rim area morphology in 2D and 3D
Authors: Jie Vun Wen , Miettinen Arttu , Baird Emily 
Published: February 2022

1.AbstractPolarized light-based navigation in insects is facilitated by a specialised polarisation-sensitive part of the eye known as the dorsal rim area (DRA). Existing methods to study the anatomy of the DRA are in most cases destructive and very time consuming. Here, we present a novel method that allows for DRA localization using 3D volumetric images acquired through micro-computed tomography in combination with 2D photographs. We used the method on size polymorphic buff-tailed bumblebees,Bombus terrestris. We found that the size of the DRA can be easily acquired from photographs of the dorsal part of the eye. An allometric analysis of the size of the DRA in relation to body size inB. terrestrisshowed that the DRA region increases with body size but not at the same rate. Using our method, we localised the DRA in a 3D volume rendering of the eye using 2D photos localization of an individual’s DRA onto the volumetric image stack of the head allowed for individual-level descriptions of the ommatidial structures (lens, crystalline cones, rhabdoms) to be performed on three different eye regions (DRA, non-DRA, proximate to DRA). The only feature distinctly unique to the DRA ommatidia was the smaller dimension of crystalline cones in comparison to other regions. Using our novel methodology we provide the first individual-level description of DRA ommatidial features and a comparison of how the DRA area varies with body size in bumblebees.
A transcription factor and a phosphatase regulate temperature-dependent morphogenesis in a fungal plant pathogen
Authors: Francisco Carolina Sardinha , McDonald Bruce A. , Palma-Guerrero Javier 
Published: February 2022

ABSTRACTNaturally fluctuating temperatures provide a constant environmental stress that requires adaptation. Some fungal pathogens respond to heat stress by producing new morphotypes that maximize their overall fitness. The fungal wheat pathogen Z. tritici responds to heat stress by switching from its yeast-like blastospore form to hyphae or chlamydospores. The regulatory mechanisms underlying this switch are unknown. Here, we demonstrate that a differential heat stress response is ubiquitous in Z. tritici populations around the world. We used QTL mapping to identify a single locus associated with the temperature-dependent morphogenesis and we found two genes, the transcription factor ZtMsr1 and the protein phosphatase ZtYvh1, regulating this mechanism. We find that ZtMsr1 regulates repression of hyphal growth and induces chlamydospore formation whereas ZtYvh1 is required for hyphal growth. We next pinpointed that chlamydospore formation is a response to the intracellular osmotic stress generated by the heat stress. This intracellular stress stimulates the CWI and HOG MAPK pathways resulting in hyphal growth. If cell wall integrity is however compromised, ZtMsr1 represses the hyphal development program and might induce the chlamydospore-inducing genes as a stress-response survival strategy. Taken together, these results suggest a novel mechanism through which morphological transitions are orchestrated in Z. tritici – a mechanism possibly also present in other pleomorphic fungi.IMPORTANCETemperature is an environmental signal constantly monitored by pleomorphic fungi. Our experiments showed that yeast-to-hyphal or yeast-to-chlamydospore transitions are ubiquitous heat stress responses in Z. tritici. QTL mapping allowed us to identify a transcription factor and a protein phosphatase contributing to temperature-dependent morphogenesis. We showed that intracellular osmolarity is the pivotal signal inducing these transitions. We propose a regulatory network controlling Z. tritici morphogenesis, which may have broad implications for temperature sensing of fungal pathogens.
Anatomical connectivity profile development constrains medial-lateral topography in the dorsal prefrontal cortex
Authors: Li Wen , Shi Weiyang , Wang Haiyan , Li Jin , Cui Yue , Li Kaixin , Cheng Luqi , Lu Yuheng , Ma Liang , Chu Congying , Song Ming , Yang Zhengyi , Banaschewski Tobias , Bokde Arun L.W. , Desrivières Sylvane , Flor Herta , Grigis Antoine , Garavan Hugh , Gowland Penny , Walter Henrik , Brühl Rüdiger , Martinot Jean-Luc , Martinot Marie-Laure Paillère , Artiges Eric , Nees Frauke , Orfanos Dimitri Papadopoulos , Lemaitre Herve , Paus Tomáš , Poustka Luise , Hohmann Sarah , Millenet Sabina , Fröhner Juliane H. , Robinson Lauren , Smolka Michael N. , Winterer Jeanne , Whelan Robert , Schumann Gunter , Fan Lingzhong , Jiang Tianzi ,   IMAGEN Consortium
Published: February 2022

AbstractThe prefrontal cortex (PFC) is a highly variable, evolutionarily expanded brain region that is engaged in multiple cognitive processes. The subregions of the PFC mature relatively late compared with other brain regions, and the maturation times vary between these subregions. Among these, the dorsomedial and dorsolateral prefrontal cortex (dmPFC and dlPFC) share a parallel topographic pattern of functional connectivity, while participating in different types of complex behaviors. However, the developmental trajectories of the two areas remain obscure. In this study, we uncovered differences in the developmental trends of the dmPFC and dlPFC. These differences were mainly caused by structural and functional changes in the medial area of the superior frontal gyrus (SFG). The developmentally different arealization patterns were verified using multiple parcellation approaches with multimodal data, including structural magnetic resonance imaging (sMRI), diffusion MRI (dMRI), resting state functional MRI (rfMRI), and a publicly available transcriptomic dataset. Human brain gene expression data was also used to perform downstream analyses, which could inform us about the potential biological mechanisms underlying the developmentally different arealizations. Furthermore, behavioral analyses hinted at the effects of regionalization on ontogeny. In brief, this study revealed a tendency toward a medial-lateral prefrontal division and can provide a fuller understanding of the potential underlying genetic underpinnings as well as of the potential effects on developmental behavior.
Functional substitutability of native herbivores by livestock for soil carbon depends on microbial decomposers
Authors: Roy Shamik , Naidu Dilip GT , Bagchi Sumanta 
Published: February 2022

AbstractGrazing by large mammalian herbivores impacts climate as it can favor the size and stability of a large carbon (C) pool in soil. As native herbivores in the world’s grasslands, steppes, and savannas are progressively being displaced by livestock, it is important to ask whether livestock can emulate the functional roles of their native counterparts. While livestock and native herbivores can have remarkable similarity in their traits, they can differ greatly in their impacts on vegetation composition which can affect soil-C. It is uncertain how their similarities and differences impact soil-C via their influence on microbial decomposers. We test competing alternative hypotheses with a replicated, long-term, landscape-level, grazing-exclusion experiment to ask whether livestock in the Trans-Himalayan ecosystem of northern India can match decadal-scale (2005-2016) soil-C stocks under native herbivores. We evaluate multiple lines of evidence from 17 variables that influence soil-C (quantity and quality of C-input from plants, microbial biomass and metabolism, microbial community composition, veterinary antibiotics in soil), and asses their inter-relationships. Livestock and native herbivores differed in their effects on several soil microbial processes. Microbial carbon use efficiency (CUE) was 19% lower in soils under livestock. Compared to native herbivores, areas used by livestock contained 1.5 kg C m−2less soil-C. Structural equation models showed that alongside effects arising from plants, livestock alter soil microbial communities which is detrimental for CUE, and ultimately also for soil-C. Supporting evidence pointed toward a link between veterinary antibiotics used on livestock, microbial communities, and soil-C. Overcoming the challenges of sequestrating antibiotics to minimize their potential impacts on climate, alongside microbial rewilding under livestock, may reconcile the conflicting demands from food-security and ecosystem services. Conservation of native herbivores and better management of livestock is crucial for soil-C stewardship to envision and achieve natural climate solutions.
Pitfalls of machine learning models for protein-protein interactions
Authors: Lannelongue Loïc , Inouye Michael 
Published: February 2022

AbstractProtein-protein interactions (PPIs) are essential to understanding biological pathways as well as their roles in development and disease. Computational tools, based on classic machine learning, have been successful at predicting PPIsin silico, but the lack of consistent and reliable frameworks for this task has led to network models that are difficult to compare and discrepancies between algorithms that remain unexplained. To better understand the underlying inference mechanisms that underpin these models, we designed an open-source framework for benchmarking that accounts for a range of biological and statistical pitfalls while facilitating reproducibility. We use it to shed light on the impact of network topology and how different algorithms deal with highly connected proteins. By studying functional genomics-based and sequence-based models on human PPIs, we show their complementarity as the former performs best on lone proteins while the latter specialises in interactions involving hubs. We also show that algorithm design has little impact on performance with functional genomic data. We replicate our results between both human andS. cerevisiaedata and demonstrate that models using functional genomics are better suited to PPI prediction across species. With rapidly increasing amounts of sequence and functional genomics data, our study provides a principled foundation for future construction, comparison and application of PPI networks.
A paternal bias in germline mutation is widespread in amniotes and can arise independently of cell divisions
Authors: de Manuel Marc , Wu Felix L. , Przeworski Molly 
Published: February 2022

AbstractIn humans and other mammals, germline mutations are more likely to arise in fathers than in mothers. Although this sex bias has long been attributed to DNA replication errors in spermatogenesis, recent evidence from humans points to the importance of mutagenic processes that do not depend on cell division, calling into question our understanding of this basic phenomenon. Here, we infer the ratio of paternal-to-maternal mutations, α, in 42 species of amniotes, from putatively neutral substitution rates of sex chromosomes and autosomes. Despite marked differences in gametogenesis, physiologies and environments across species, fathers consistently contribute more mutations than mothers in all the species examined, including mammals, birds and reptiles. In mammals, α is as high as 4 and correlates with generation times; in birds and snakes, α appears more stable around 2. These observations are consistent with a simple model, in which mutations accrue at equal rates in both sexes during early development and at a higher rate in the male germline after sexual differentiation, with a conserved paternal-to-maternal ratio across species. Thus, α may reflect the relative contributions of two or more developmental phases to total germline mutations, and is expected to depend on generation time even if mutations do not track cell divisions.
Boosting with Omicron-matched or historical mRNA vaccines increases neutralizing antibody responses and protection against B.1.1.529 infection in mice
Authors: Ying Baoling , Scheaffer Suzanne M. , Whitener Bradley , Liang Chieh-Yu , Dmytrenko Oleksandr , Mackin Samantha , Wu Kai , Lee Diana , Avena Laura E. , Chong Zhenlu , Case James Brett , Ma LingZhi , Kim Thu , Sein Caralyn , Woods Angela , Berrueta Daniela Montes , Carfi Andrea , Elbashir Sayda M. , Edwards Darin K. , Thackray Larissa B. , Diamond Michael S. 
Published: February 2022

ABSTRACTThe B.1.1.529 Omicron variant jeopardizes vaccines designed with early pandemic spike antigens. Here, we evaluated in mice the protective activity of the Moderna mRNA-1273 vaccine against B.1.1.529 before or after boosting with preclinical mRNA-1273 or mRNA-1273.529, an Omicron-matched vaccine. Whereas two doses of mRNA-1273 vaccine induced high levels of serum neutralizing antibodies against historical WA1/2020 strains, levels were lower against B.1.1.529 and associated with infection and inflammation in the lung. A primary vaccination series with mRNA-1273.529 potently neutralized B.1.1.529 but showed limited inhibition of historical or other SARS-CoV-2 variants. However, boosting with mRNA-1273 or mRNA-1273.529 vaccines increased serum neutralizing titers and protection against B.1.1.529 infection. Nonetheless, the levels of inhibitory antibodies were higher, and viral burden and cytokines in the lung were slightly lower in mice given the Omicron-matched mRNA booster. Thus, in mice, boosting with mRNA-1273 or mRNA-1273.529 enhances protection against B.1.1.529 infection with limited differences in efficacy measured.
Spontaneous and ART-induced large offspring syndrome: similarities and differences in DNA methylome
Authors: Li Yahan , Lopes Jordana Sena , Fuster Pilar Coy , Rivera Rocío Melissa 
Published: February 2022

AbstractLarge/abnormal offspring syndrome (LOS/AOS) is a congenital overgrowth syndrome reported in ruminants produced by assisted reproduction (ART-LOS) which exhibit global disruption of the epigenome and transcriptome. LOS/AOS shares phenotypes and epigenotypes with the human congenital overgrowth condition Beckwith-Wiedemann syndrome. We have reported that LOS occurs spontaneously (SLOS), however, to date, no study has been conducted to determine if SLOS has the same methylome epimutations as ART-LOS. In this study, we performed whole genome bisulfite sequencing to examine global DNA methylation in SLOS and ART-LOS tissues. We observed unique patterns of global distribution of differentially methylated regions (DMRs) over different genomic contexts, such as promoters, CpG islands and surrounding regions, and repetitive sequences from different treatment groups. In addition, we identified hundreds of LOS-vulnerable DMRs across different cattle breeds when analyzing four idependent LOS experiments together. Specifically, there are 25 highly vulnerable DMRs that could potentially serve as molecular markers for the diagnosis of LOS, including at the promoters of DMRT2 and TBX18, at the imprinted gene bodies of IGF2R, PRDM8, and BLCAP/NNAT, and at multiple CpG islands. We also observed tissue-specific DNA methylation patterns between muscle and blood, and conservation of ART-induced DNA methylation changes between muscle and blood. We conclude that as in ART-LOS, alterations of the epigenome are involved in the etiology of SLOS. In addition, SLOS and ART-LOS share some similarities in methylome epimutations.
The evolution of novel biotic interactions at ecological margins in response to climate change involves alleles from across the geographical range of the UK Brown Argus butterfly
Authors: de Jong Maaike , van Rensburg Alexandra Jansen , Whiteford Samuel , Yung Carl J. , Beaumont Mark , Jiggins Chris , Bridle Jon 
Published: February 2022

AbstractUnderstanding the rate and extent to which populations can adapt to novel environments at their ecological margins is fundamental to predicting the persistence of biological communities during ongoing and rapid global change. Recent range expansion in response to climate change in the UK butterfly Aricia agestis is associated with the evolution of novel interactions with a larval food plant, and the loss of its ability to use its ancestral larval host species. Using ddRAD analysis of 61210 variable SNPs from 261 females from throughout the UK range of this species, we identify genomic regions at multiple chromosomes that are associated with these evolutionary responses, and their association with demographic history and ecological variation. Gene flow appears widespread throughout the range, despite the apparently fragmented nature of the habitats used by this species. Patterns of haplotype variation between selected and neutral genomic regions suggest that evolution associated with climate adaptation is polygenic, resulting from the independent spread of existing alleles throughout the established range of this species, rather than the colonisation of pre-adapted genotypes from coastal populations. These data suggest that rapid responses to climate change do not depend on the availability of pre-adapted genotypes. Instead, the evolution of novel forms of biotic interaction in Aricia agestis has occurred during range expansion, through the assembly of novel genotypes from alleles from multiple localities.
Olverembatinib inhibits SARS-CoV-2-Omicron variant-mediated cytokine release
Authors: Chan Marina , Holland Eric C. , Gujral Taranjit S 
Published: February 2022

SUMMARYThe Omicron variant has become dominant in the U.S. and around the world. This variant is found to be 2-fold more infectious than the Delta variant, posing a significant threat of severe cases and death. We and others have recently reported that the N-terminus domain (NTD) of the SARS-CoV-2 of various variants is responsible for inducing cytokine release in human PBMCs. Here, we demonstrate that the NTD of the Omicron variant remains highly effective at inducing cytokine release in human PBMCs. Furthermore, we show that Ponatinib and a novel compound, Olverembatinib, are potent Omicron NTD-mediated cytokine release inhibitors. Target profiling revealed that Olverembatinib blocks most of the previously identified kinases responsible for cytokine release. Together, we propose that Ponatinib and Olverembatinib may represent an attractive therapeutic option for treating moderate to severe COVID-19 cases.HIGHLIGHTSThe N-terminus domain (NTD) of the SARS-CoV-2 Omicron variant strongly induces multiple inflammatory molecules in PBMCs, unaffected by the mutations observed in the NTD.The cytokine release mediated by the Omicron variant is comparable to the Delta variant.Olverembatinib, a clinical-stage multi-kinase inhibitor, potently inhibits Omicron NTD-mediated cytokine release.Olverembatinib could relieve severe symptoms associated with COVID-19 Omicron and Delta variants.
Distinct sensitivities to SARS-CoV-2 variants in vaccinated humans and mice
Authors: Walls Alexandra C. , VanBlargan Laura A. , Wu Kai , Choi Angela , Navarro Mary Jane , Lee Diana , Avena Laura , Berrueta Daniela Montes , Pham Minh N. , Elbashir Sayda , Miranda Marcos C. , Kepl Elizabeth , Johnson Max , Blackstone Alyssa , Sprouse Kaitlin , Fiala Brooke , O’Connor Megan A. , Brunette Natalie , Arunachalam Prabhu S. , Shirreff Lisa , Rogers Kenneth , Carter Lauren , Fuller Deborah H. , Villinger Francois , Pulendran Bali , Diamond Michael S. , Edwards Darin K. , King Neil P. , Veesler David 
Published: February 2022

AbstractThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has led to the development of a large number of vaccines, several of which are now approved for use in humans. Understanding vaccine-elicited antibody responses against emerging SARS-CoV-2 variants of concern (VOC) in real time is key to inform public health policies. Serum neutralizing antibody titers are the current best correlate of protection from SARS-CoV-2 challenge in non-human primates and a key metric to understand immune evasion of VOC. We report that vaccinated BALB/c mice do not recapitulate faithfully the breadth and potency of neutralizing antibody responses against VOC, as compared to non-human primates or humans, suggesting caution should be exercised when interpreting data for this animal model.
Azole resistance associated regulatory motifs within the promoter of cyp51A in Aspergillus fumigatus
Authors: Kühbacher Alexander , Peiffer Mandy , Hortschansky Peter , Merschak Petra , Bromley Michael J , Haas Hubertus , Brakhage Axel A , Gsaller Fabio 
Published: February 2022

AbstractAspergillus fumigatus is one of the deadliest fungal species causing hundreds of thousands of deaths each year. As azoles provide the preferred first-line option for treatment of Aspergillosis, the increase in rates of resistance and the poor therapeutic outcomes for those infected with a resistant isolate constitutes a serious global health threat. Azole resistance is frequently associated with specific tandem repeat duplications of a promoter element upstream of cyp51A, the gene which encodes the target for this drug class in A. fumigatus. This promoter element is recognized by the activating transcription factors SrbA and AtrR. This region also provides a docking platform for the CCAAT-binding-complex (CBC) and HapX that cooperate in the regulation of genes involved in iron-consuming pathways including cyp51A. Here, we studied the regulatory contribution of SrbA, AtrR, CBC and HapX binding sites on cyp51A expression and azole resistance during different iron availability employing promoter mutational analysis and protein/DNA interaction analysis. This strategy revealed iron status-dependent and -independent roles of these regulatory elements. We show that promoter occupation by both AtrR and SrbA is required for iron-independent steady-state transcriptional activation of cyp51A and its induction during short-term iron exposure relies on HapX binding. We further uncover the HapX binding site as repressor element the disruption of which elevates cyp51A expression and azole resistance regardless of iron availability.