bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential evolutionary body size reduction in a Malagasy primate (Propithecus verreauxi) in response to human size-selective hunting pressure
Authors: Sullivan Alexis P. , Godfrey Laurie R. , Lawler Richard R. , Randrianatoandro Heritiana , Eccles Laurie , Culleton Brendan , Ryan Timothy M. , Perry George H. 
Published: March 2020

ABSTRACTThe Holocene arrival of humans on Madagascar precipitated major changes to the island’s biodiversity. The now-extinct, endemic “subfossil” megafauna of Madagascar were likely hunted by the island’s early human inhabitants. Perhaps in part due to preferential hunting of larger prey, no surviving species on Madagascar is larger than 10 kg. Outside of Madagascar, size-selective hunting pressure has resulted in the phyletic dwarfism of many still-living species across a diversity of phyla. On Madagascar, some subfossil bones of extant lemurs are considerably larger than those of the modern members of their species, but relatively large distances between the subfossil localities and modern samples that have been compared to date makes it impossible to reject the possibility that these size differences more simply reflect pre-existing ecogeographic variation. Here, we used high-resolution 3D scan data to conduct comparative morphological analyses of subfossil and modern skeletal remains of one of the larger extant lemurs, Verreaux’s sifakas (Propithecus verreauxi) from subfossil and modern sites ∼10 km adjacent: Taolambiby (bones dated to 725-560 – 1075-955 cal. years before present) and Beza Mahafaly Special Reserve, respectively. We found that the average subfossil sifaka bone (n=12) is 9% and significantly larger than that of modern sifakas (n=31 individuals; permutation test; p=0.037). When restricting the analysis to the single element and side with the largest representation in the subfossil sample (n=4 right distal femora), the average subfossil bone is 10% larger (p=0.046). While we cannot yet conclude whether this size difference reflects evolutionary change or an archaeological aggregation/taphonomic process, if this is a case of phyletic dwarfism in response to human size-selective harvesting pressures then the estimated rate of evolutionary change is slightly higher than that previously calculated for other archaeological cases of this phenomenon.
SerraNA: a program to determine nucleic acids elasticity from simulation data
Authors: Velasco-Berrelleza Victor , Burman Matthew , Shepherd Jack W. , Leake Mark C. , Golestanian Ramin , Noy Agnes 
Published: March 2020

AbstractThe resistance of DNA to stretch, twist and bend is broadly well estimated by experiments and is important for gene regulation and chromosome packing. However, their sequence-dependence and how bulk elastic constants emerge from local fluctuations is less understood. Here, we presentSerraNA, which is an open software that calculates elastic parameters of double-stranded nucleic acids from dinucleotide length up to the whole molecule using ensembles from numerical simulations. The program reveals that global bendability emerge from local periodic bending angles in phase with the DNA helicoidal shape. We also applySerraNAto the whole set of 136 tetra-bp combinations and we observe a high degree of sequence-dependence for all elastic parameters with differences over 200%. Tetramers with TA and CA base-pair steps are especially flexible, while tetramers containing AA and AT tend to be the most rigid. Our results thus suggest AT-rich motifs generate extreme mechanical properties depending of the exact sequence ordering, which seems critical for creating strong global bendability on longer sequences when phased properly.SerraNAis a tool to be applied in the next generation of interdisciplinary investigations to further understand what determines the elasticity of DNA.Graphical TOC Entry
Event-related potentials reflect prediction errors and pop-out during comprehension of degraded speech
Authors: Banellis Leah , Sokoliuk Rodika , Wild Conor J , Bowman Howard , Cruse Damian 
Published: March 2020

AbstractComprehension of degraded speech requires higher-order expectations informed by prior-knowledge. Accurate top-down expectations of incoming degraded speech cause a subjective semantic “pop-out” or conscious breakthrough experience. Indeed, the same stimulus can be perceived as meaningless when no expectations are made in advance. We investigated the ERP correlates of these top-down expectations, their error signals, and the subjective pop-out experience in healthy participants. We manipulated expectations in a word-pair priming noise-vocoded speech task and investigated the role of top-down expectation with a between-groups attention manipulation. Consistent with the role of expectations in comprehension, repetition priming significantly enhanced perceptual intelligibility of the noise-vocoded degraded targets for attentive participants. An early ERP was larger for mismatched (i.e. unexpected) targets than matched targets, indicative of an initial error signal not reliant on top-down expectations. Subsequently, a P3a-like ERP was larger to matched targets than mismatched targets only for attending participants - i.e. a pop-out effect. Rather than relying on complex post hoc interactions between prediction error and precision to explain this apredictive pattern, we consider our data to be consistent with prediction error minimisation accounts for early stages of processing followed by Global Neuronal Workspace-like breakthrough and processing in service of task goals.
Non-random association of MHC-I alleles in favor of high diversity haplotypes in wild songbirds revealed by computer-assisted MHC haplotype inference using the R package MHCtools
Authors: Roved Jacob , Hansson Bengt , Stervander Martin , Hasselquist Dennis , Westerdahl Helena 
Published: March 2020

AbstractMajor histocompatibility complex (MHC) genes play a central role for pathogen recognition by the adaptive immune system. The MHC genes are often duplicated and tightly linked within a small genomic region. This structural organization suggests that natural selection acts on the combined property of multiple MHC gene copies in segregating haplotypes, rather than on single MHC genes. This may have important implications for analyses of patterns of selection on MHC genes. Here, we present a computer-assisted protocol to infer segregating MHC haplotypes from family data, based on functions in the R package MHCtools. We employed this method to identify 107 unique MHC class I (MHC-I) haplotypes in 116 families of wild great reed warblers (Acrocephalus arundinaceus). In our data, the MHC-I genes were tightly linked in haplotypes and inherited as single units, with only two observed recombination events among 334 offspring. We found substantial variation in the number of different MHC-I alleles per haplotype, and the divergence between alleles in MHC-I haplotypes was significantly higher than between randomly assigned alleles in simulated haplotypes. This suggests that selection has favored non-random associations of divergent MHC-I alleles in haplotypes to increase the range of pathogens that can be recognized by the adaptive immune system. Further studies of selection on MHC haplotypes in natural populations is an interesting avenue for future research. Moreover, inference and analysis of MHC haplotypes offers important insights into the structural organization of MHC genes, and may improve the accuracy of the MHC region inde novogenome assemblies.
Assessing anaerobic gut fungal (Neocalliamstigomycota) diversity using PacBio D1/D2 LSU rRNA amplicon sequencing and multi-year isolation
Authors: Hanafy Radwa A. , Johnson Britny , Youssef Noha H. , Elshahed Mostafa S. 
Published: March 2020

AbstractThe anaerobic gut fungi (AGF, Neocallimastigomycota) reside in the alimentary tracts of herbivores where they play a central role in the breakdown of ingested plant material. Accurate assessment of AGF diversity has been hampered by inherent deficiencies of the internal transcribed spacer1 (ITS1) region as a phylogenetic marker. Here, we report on the development and implementation of the D1/D2 region of the large ribosomal subunit (D1/D2 LSU) as a novel marker for assessing AGF diversity in culture-independent surveys. Sequencing a 1.4-1.5 Kbp amplicon encompassing the ITS1-5.8S rRNA-ITS2-D1/D2 LSU region in the ribosomal RNA locus from fungal strains and environmental samples generated a reference D1/D2 LSU database for all cultured AGF genera, as well as the majority of candidate genera encountered in prior ITS1-based diversity surveys. Subsequently, a D1/D2 LSU-based diversity survey using long read PacBio SMRT sequencing technology was conducted on fecal samples from 21 wild and domesticated herbivores. Twenty-eight genera and candidate genera were identified in the 17.7 K sequences obtained, including multiple novel lineages that were predominantly, but not exclusively, identified in wild herbivores. Association between certain AGF genera and animal lifestyles, or animal host family was observed. Finally, to address the current paucity of AGF isolates, concurrent isolation efforts utilizing multiple approaches to maximize recovery yielded 216 isolates belonging to twelve different genera, several of which have no prior cultured-representatives. Our results establish the utility of D1/D2 LSU and PacBio sequencing for AGF diversity surveys, and the culturability of a wide range of AGF taxa, and demonstrate that wild herbivores represent a yet-untapped reservoir of AGF diversity.
A Fully Automatic Deep Learning System for COVID-19 Diagnostic and Prognostic Analysis
Authors: Wang Shuo , Zha Yunfei , Li Weimin , Wu Qingxia , Li Xiaohu , Niu Meng , Wang Meiyun , Qiu Xiaoming , Li Hongjun , Yu He , Gong Wei , Bai Yan , Li Li , Zhu Yongbei , Wang Liusu , Tian Jie 
Published: March 2020

AbstractCoronavirus disease 2019 (COVID-19) has spread globally, and medical resources become insufficient in many regions. Fast diagnosis of COVID-19, and finding high-risk patients with worse prognosis for early prevention and medical resources optimization is important. Here, we proposed a fully automatic deep learning system for COVID-19 diagnostic and prognostic analysis by routinely used computed tomography.We retrospectively collected 5372 patients with computed tomography images from 7 cities or provinces. Firstly, 4106 patients with computed tomography images and gene information were used to pre-train the DL system, making it learn lung features. Afterwards, 1266 patients (924 with COVID-19, and 471 had follow-up for 5+ days; 342 with other pneumonia) from 6 cities or provinces were enrolled to train and externally validate the performance of the deep learning system.In the 4 external validation sets, the deep learning system achieved good performance in identifying COVID-19 from other pneumonia (AUC=0.87 and 0.88) and viral pneumonia (AUC=0.86). Moreover, the deep learning system succeeded to stratify patients into high-risk and low-risk groups whose hospital-stay time have significant difference (p=0.013 and 0.014). Without human-assistance, the deep learning system automatically focused on abnormal areas that showed consistent characteristics with reported radiological findings.Deep learning provides a convenient tool for fast screening COVID-19 and finding potential high-risk patients, which may be helpful for medical resource optimization and early prevention before patients show severe symptoms.Take-home messageFully automatic deep learning system provides a convenient method for COVID-19 diagnostic and prognostic analysis, which can help COVID-19 screening and finding potential high-risk patients with worse prognosis.
COVID-19 infection induces readily detectable morphological and inflammation-related phenotypic changes in peripheral blood monocytes, the severity of which correlate with patient outcome
Authors: Zhang Dan , Guo Rui , Lei Lei , Liu Hongjuan , Wang Yawen , Wang Yili , Qian Hongbo , Dai Tongxin , Zhang Tianxiao , Lai Yanjun , Wang Jingya , Liu Zhiqiang , Chen Tianyan , He Aili , O’Dwyer Michael , Hu Jinsong 
Published: March 2020

AbstractBackgroundExcessive monocyte/macrophage activation with the development of a cytokine storm and subsequent acute lung injury, leading to acute respiratory distress syndrome (ARDS) is a feared consequence of infection with COVID-19. The ability to recognize and potentially intervene early in those patients at greatest risk of developing this complication could be of great clinical utility.MethodsWe performed detailed flow cytometric analysis of peripheral blood samples from 28 COVID-19 patients treated at Xian No.8 Hospital and the First Affiliated Hospital of Xian Jiaotong University in early 2020 in an attempt to identify factors that could help predict severity of disease and patient outcome.FindingsWhile we did not detect significant differences in the number of monocytes between patients with COVID-19 and normal healthy individuals,we did identify significant morphological and functional differences, which are more pronounced in patients requiring prolonged hospitalization and ICU admission. Patients with COVID-19 have larger than normal monocytes, easily identified on forward scatter, side scatter analysis by routine flow cytometry,with the presence of a distinct population of monocytes with high forward scatter (FSC-high). On more detailed analysis, these FSC-high monocytes are CD11b+, CD14+, CD16+, CD68+, CD80+, CD163+, CD206+and secrete IL-6, IL-10 and TNF-alpha, consistent with an inflammatory phenotype.ConclusionsThe detection and serial monitoring of this subset of inflammatory monocytes using flow cytometry could be of great help in guiding the prognostication and treatment of patients with COVID-19 and merits further evaluation.
DDX5 targets tissue-specific RNAs to promote intestine tumorigenesis
Authors: Abbasi Nazia , Long Tianyun , Li Yuxin , Ma Evelyn , Yee Brian A. , Patel Parth R. , Sayed Ibrahim M , Varki Nissi , Das Soumita , Ghosh Pradipta , Yeo Gene W. , Huang Wendy J.M. 
Published: March 2020

AbstractTumorigenesis in different segments of the intestinal tract involves tissue-specific oncogenic drivers. In the colon, complement component 3 (C3) activation is a major contributor to inflammation and malignancies. By contrast, tumorigenesis in the small intestine involves fatty acid-binding protein 1 (FABP1). However, little is known of the upstream mechanisms driving their expressions in different segments of the intestinal tract. Here, we report that an RNA binding protein DDX5 augments C3 and FABP1 expressions post-transcriptionally to promote tumorigenesis in the colon and small intestine, respectively. Mice with epithelial-specific knockout of DDX5 are protected from intestine tumorigenesis. The identification of DDX5 as the common upstream regulator of tissue-specific oncogenic molecules provides a new therapeutic target for intestine cancers.
Dually localized proteins found in both the apicoplast and mitochondrion utilize the Golgi-dependent pathway for apicoplast targeting inToxoplasma gondii
Authors: Prasad Aparna , Mastud Pragati , Patankar Swati 
Published: March 2020

ABSTRACTLike other apicomplexan parasites,Toxoplasma gondiiharbours a four-membraned endosymbiotic organelle - the apicoplast. Apicoplast proteins are nuclear-encoded and trafficked to the organelle through the endoplasmic reticulum (ER). From the ER to the apicoplast, two distinct protein trafficking pathways can be used. One such pathway is the cell’s secretory pathway involving the Golgi, while the other is a unique Golgi-independent pathway. Using different experimental approaches, many apicoplast proteins have been shown to utilize the Golgi-independent pathway, while a handful of reports show that a few proteins use the Golgi-dependent pathway. This has led to an emphasis towards the unique Golgi-independent pathway when apicoplast protein trafficking is discussed in the literature. Additionally, the molecular features that drive proteins to each pathway are not known. In this report, we systematically test eight apicoplast proteins, using a C-terminal HDEL sequence to assess the role of the Golgi in their transport. We demonstrate that dually localised proteins of the apicoplast and mitochondrion (TgSOD2,TgTPx1/2 andTgACN) are trafficked through the Golgi while proteins localised exclusively to the apicoplast are trafficked independent of the Golgi. Mutants of the dually localised proteins that localised exclusively to the apicoplast also showed trafficking through the Golgi. Phylogenetic analysis ofTgSOD2,TgTPx1/2 andTgACN suggested that the evolutionary origins ofTgSOD2,TgTPx1/2 lie in the mitochondrion whileTgACN appears to have originated from the apicoplast. Collectively, with these results, for the first time, we establish that the driver of the Golgi-dependent trafficking route to the apicoplast is the dual localisation of the protein to the apicoplast and the mitochondrion.
Persistent Epigenetic Reprogramming of Sweet Taste by Diet
Authors: Vaziri Anoumid , Khabiri Morteza , Genaw Brendan T. , May Christina E. , Freddolino Peter L. , Dus Monica 
Published: March 2020

AbstractDiets rich in sugar, salt, and fat alter taste perception and food intake, leading to obesity and metabolic disorders, but the molecular mechanisms through which this occurs are unknown. Here we show that in response to a high sugar diet, the epigenetic regulator Polycomb Repressive Complex 2.1 (PRC2.1) persistently reprograms the sensory neurons ofD. melanogasterflies to reduce sweet sensation and promote obesity. In animals fed high sugar, the binding of PRC2.1 to the chromatin of the sweet gustatory neurons is redistributed to repress a developmental transcriptional network that modulates the responsiveness of these cells to sweet stimuli, reducing sweet sensation. Importantly, half of these transcriptional changes persist despite returning the animals to a control diet, causing a permanent decrease in sweet taste. Our results uncover a new epigenetic mechanism that, in response to the dietary environment, regulates neural plasticity and feeding behavior to promote obesity.
Androgen signaling connects short isoform production to breakpoint formation at Ewing sarcoma breakpoint region 1 via an R-loop-dependent mechanism
Authors: Nicholas Taylor R. , Hollenhorst Peter C. 
Published: March 2020

SummaryEwing sarcoma breakpoint region 1 (EWSR1) encodes a multifunctional protein that can cooperate with the transcription factor ERG to promote prostate cancer. The EWSR1 gene is also commonly involved in oncogenic gene rearrangements in Ewing sarcoma. Despite the cancer relevance ofEWSR1, its regulation is poorly understood. Here we find that in prostate cancer, androgen signaling upregulates a 5’EWSR1isoform by promoting usage of an intronic polyadenylation site. This isoform encodes a cytoplasmic protein that can strongly promote cell migration and clonogenic growth. Deletion of an Androgen Receptor (AR) binding site near the 5’EWSR1polyadenylation site abolished androgen-dependent upregulation. This polyadenylation site is also near the Ewing sarcoma breakpoint hotspot, and androgen signaling promoted R-loop and breakpoint formation. RNase H overexpression reduced breakage and 5’EWSR1isoform expression suggesting an R-loop dependent mechanism. These data suggest that androgen signaling can promote R-loops internal to theEWSR1gene leading to early transcription termination and breakpoint formation.
Identification of sulfenylated cysteines inArabidopsis thalianaproteins using a disulfide-linked peptide reporter
Authors: Wei Bo , Willems Patrick , Huang Jingjing , Tian Caiping , Yang Jing , Messens Joris , Van Breusegem Frank 
Published: March 2020

ABSTRACTIn proteins, hydrogen peroxide (H2O2) reacts with redox-sensitive cysteines to form cysteine sulfenic acid, also known asS-sulfenylation. These cysteine oxidation events can steer diverse cellular processes by altering protein interactions, trafficking, conformation, and function. Previously, we had identifiedS-sulfenylated proteins by using a tagged proteinaceous probe based on the yeast AP-1–like (Yap1) transcription factor that specifically reacts with sulfenic acids and traps them through a mixed disulfide bond. However, the identity of theS-sulfenylated amino acid residues remained enigmatic. Here, we present a technological advancement to identifyin situsulfenylated cysteines directly by means of the transgenic Yap1 probe. InArabidopsis thalianacells, after an initial affinity purification and a tryptic digestion, we further enriched the mixed disulfide-linked peptides with an antibody targeting the YAP1C-derived peptide (C598SEIWDR) that entails the redox-active cysteine. Subsequent mass spectrometry analysis with pLink 2 identified 1,745 YAP1C cross-linked peptides, indicating sulfenylated cysteines in over 1,000 proteins. Approximately 55% of these YAP1C-linked cysteines had previously been reported as redox-sensitive cysteines (S-sulfenylation,S-nitrosylation, and reversibly oxidized cysteines). The presented methodology provides a noninvasive approach to identify sulfenylated cysteines in any species that can be genetically modified.
Emergence of a hybrid PKS‐NRPS secondary metabolite cluster in a clonal population of the rice blast fungus Magnaporthe oryzae
Authors: Zhong Zhenhui , Lin Lianyu , Zheng Huakun , Bao Jiandong , Chen Meilian , Zhang Limei , Tang Wei , Ebbole Daniel J. , Wang Zonghua 
Published: March 2020

SummarySecondary metabolites (SMs) are crucial for fungi and vary in function from beneficial antibiotics to pathogenicity factors. To generate diversified SMs that enable different functions, SM‐coding regions rapidly evolve in fungal genomes. However, the driving force and genetic mechanism of fungal SM diversification in the context of host‐pathogen interactions remain largely unknown. Previously, we grouped field populations of the rice blast fungus Magnaporthe oryzae (syn: Pyricularia oryzae) into three major globally distributed clades based on population genomic analyses. Here, we characterize a recent duplication of an avirulent gene‐containing SM cluster, ACE1, in a clonal M. oryzae population (Clade 2). We demonstrate that the ACE1 cluster is specifically duplicated in Clade 2, a dominant clade in indica rice‐growing areas. With long‐read sequencing, we obtained chromosome‐level genome sequences of four Clade 2 isolates, which displayed differences in genomic organization of the ACE1 duplication process. Comparative genomic analyses suggested that the original ACE1 cluster experienced frequent rearrangement in Clade 2 isolates and revealed that the new ACE1 cluster is located in a newly formed and transposable element‐rich region. Taken together, these results highlight the frequent mutation and expansion of an avirulent gene‐containing SM cluster through transposable element‐mediated whole‐cluster duplication in the context of host‐pathogen interactions.