bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histopathological Landscape of Molecular Genetics and Clinical Determinants in MDS Patients
Authors: Brück Oscar , Lallukka-Brück Susanna , Hohtari Helena , Ianevski Aleksandr , Ebeling Freja , Kovanen Panu , Kytölä Soili , Aittokallio Tero , Ramos Pedro Marques , Porkka Kimmo , Mustjoki Satu 
Published: May 2020

AbstractIn myelodysplastic syndrome (MDS), bone marrow (BM) histopathology is visually assessed to identify dysplastic cellular morphology, cellularity, and blast excess. Yet, many morphological findings elude the human eye. Here, we extracted visual features of 236 MDS, 87 MDS/MPN, and 10 control BM biopsies with convolutional neural networks. Unsupervised analysis distinguished underlying correlations between tissue composition, leukocyte metrics, and clinical characteristics. We applied morphological features in elastic net-regularized regression models to predict genetic and cytogenetic aberrations, prognosis, and clinical variables. By parallelizing tile, pixel, and leukocyte-level image analysis, we deconvoluted each model to texture and cellular composition to dissect their pathobiological context. Model-based mutation predictions correlated with variant allele frequency and number of affected genes per pathway, demonstrating the models’ ability to identify relevant visual patterns. In summary, this study highlights the potential of deep histopathology in hematology by unveiling the fundamental association of BM morphology with genetic and clinical determinants.
Acute effects of passive listening to Indian musical scale on blood pressure and heart rate variability among healthy young individuals – a randomized controlled trial
Authors: Ubrangala Kirthana Kunikullaya , Vijayadas  , Kunnavil Radhika , Goturu Jaisri , Prakash Vadagenahalli S , Murthy Nandagudi Srinivasa 
Published: May 2020

AbstractBackgroundListening to music is entertaining but also has different health benefits. Music medicine involves passive listening to music, while music therapy involves active music making. Indian music is broadly classified into Hindustani and Carnatic music, each having their own system of musical scales (ragas). Scientific studies of Indian music as an intervention is meagre. Current study determines the effect of passive listening to one melodic scale of Indian music on cardiovascular electrophysiological parameters.MethodsAfter informed consent, healthy individuals aged 18 – 30 years, of either gender were recruited and randomly divided into 2 groups (n=34 each). Group A was exposed to passive listening to the music intervention [Hindustani melodic scale elaboration (Bhimpalas raga alaap)], while group B received no intervention except for few natural sounds (played once in every 2 minutes). Blood pressure (BP, systolic – SBP; diastolic – DBP) and Electrocardiogram in lead II were recorded with each condition lasting for 10 minutes (pre, during, post). Heart rate variability (HRV) analysis was done. Data was analysed using SPSS 20.0 version and p<0.05 was considered significant.ResultsPassive listening to the musical scale employed had a unique effect. In group A, the SBP did not change during the intervention but increased insignificantly after the intervention was stopped (P=0.054). The DBP increased in both the groups during intervention and was significant among subjects in group A (P=0.009), with an increase of 1.676 mm Hg (P=0.012) from pre-during and 1.824 mm Hg (P=0.026) from pre-post intervention. On HRV analysis mean NN interval increased and HR reduced in both the groups, but was significant only in group B (P=0.041 and 0.025 respectively). In group A, most of HRV parameters reduced during music intervention, and tended to return towards baseline after intervention, but was statistically significant for Total Power (P=0.031) and Low Frequency (P=0.013) change; while in group B a consistent significant rise in parasympathetic indicators [SDNN, RMSSD, Total power and HF (ms2)] over 30 minutes was observed.ConclusionUnique cardiovascular effects were recorded on passive listening to a particular Indian music melodic scale,raga Bhimpalas, wherein, a mild arousal response, was observed. This could be due to attention being paid to the melodic scale as it was an unfamiliar tune or due to certain notes of this melodic scale, that particularly caused an arousal or excitation response. In contrast, the control group had only relaxation response. Exploring electrophysiological effects of different genres, melodic scales and its properties after familiarizing with the music may be illustrative.
Brain activity during facial processing in autism spectrum disorder: an activation likelihood estimation (ALE) meta-analysis of neuroimaging studies
Authors: Costa Cristiano , Cristea Ioana Alina , Bò Elisa Dal , Melloni Caterina , Gentili Claudio 
Published: May 2020

AbstractBackgroundThough aberrant face processing is a hallmark of autistic spectrum disorder (ASD), findings on accompanying brain activity are divergent. Therefore, we conducted an activation likelihood estimation (ALE) meta-analysis of studies examining brain activity during face processing.MethodsWe searched PubMed and PsycINFO using combinations of terms as ‘fMRI’, ‘Autism Spectrum Disorder’, ‘Face Perception’. Eligible studies reported on DSM-diagnosed ASD patients, compared to controls (HC), using face stimuli presented in fMRI and reporting whole-brain analysis coordinates. We compared two approaches: “convergence of differences” (primary analysis) using study-level coordinates from ASD vs. HC contrasts, and “differences in convergence” (secondary) pooling coordinates within each group separately, and contrasting the resultant ALE-maps.ResultsThirty-five studies (655 ASD and 668 HC) were included. Primary analysis identified a cluster in amygdala/parahippocampus where HC showed greater convergence of activation. Secondary analysis yielded no significant results.ConclusionsResults suggest that ASD dysfunction in face processing relies on structures involved in emotional processing rather than perception. We also demonstrate that the two ALE methodologies lead to divergent results.
Evolution leads to emergence: An analysis of protein interactomes across the tree of life
Authors: Hoel Erik , Klein Brennan , Swain Anshuman , Grebenow Ross , Levin Michael 
Published: May 2020

AbstractThe internal workings of biological systems are notoriously difficult to understand. Due to the prevalence of noise and degeneracy in evolved systems, in many cases the workings of everything from gene regulatory networks to protein-protein interactome networks remain black boxes. One consequence of this black-box nature is that it is unclear at which scale to analyze biological systems to best understand their function. We analyzed the protein interactomes of over 1800 species, containing in total 8,782,166 protein-protein interactions, at different scales. We demonstrate the emergence of higher order ‘macroscales’ in these interactomes and that these biological macroscales are associated with lower noise and degeneracy and therefore lower uncertainty. Moreover, the nodes in the interactomes that make up the macroscale are more resilient compared to nodes that do not participate in the macroscale. These effects are more pronounced in interactomes of Eukaryota, as compared to Prokaryota. This points to plausible evolutionary adaptation for macroscales: biological networks evolve informative macroscales to gain benefits of both being uncertain at lower scales to boost their resilience, and also being ‘certain’ at higher scales to increase their effectiveness at information transmission. Our work explains some of the difficulty in understanding the workings of biological networks, since they are often most informative at a hidden higher scale, and demonstrates the tools to make these informative higher scales explicit.
Homology-directed repair involves multiple strand invasion cycles in fission yeast
Authors: Vines Amanda J. , Cox Kenneth , Leland Bryan A. , King Megan C. 
Published: May 2020

AbstractHomology-directed repair of DNA double-strand breaks (DSBs) can be a highly faithful pathway. Non-crossover repair dominates in mitotically growing cells, likely through a preference for synthesis-dependent strand annealing (SDSA). While genetic studies highlight a key role for the RecQ helicase BLM/Rqh1 (in human andS. pombecells, respectively) in promoting noncrossover repair, how homology-directed repair mechanism choice is orchestrated in time and space is not well understood. Here, we develop a microscopy-based assay in living fission yeast to determine the dynamics and kinetics of an engineered, site-specific interhomologue repair event. We observe highly efficient homology search and homology-directed repair in this system. Surprisingly, we find that the initial distance between the DSB and the donor sequence does not correlate with the duration of repair. Instead, we observe that repair is likely to involve multiple site-specific and Rad51-dependent co-localization events between the DSB and donor sequence, suggesting that efficient interhomologue repair in fission yeast often involves multiple strand invasion events. By contrast, we find that loss of Rqh1 leads to successful repair through a single strand invasion event, suggesting that multiple strand invasion cycles reflect ongoing SDSA. However, failure to repair is also more likely inrqh1Δcells, which could reflect increased strand invasion at non-homologous sites. This work has implications for the molecular etiology of Bloom syndrome, caused by mutations in BLM and characterized by aberrant sister chromatid crossovers and inefficient repair.
Regulated compartmentalization of enzymes in Golgi by GRASP55 controls cellular glycosphingolipid profile and function
Authors: Pothukuchi Prathyush , Agliarulo Ilenia , Pirozzi Marinella , Rizzo Riccardo , Russo Domenico , Turacchio Gabriele , Nüchel Julian , Yang Jia-Shu , Gehin Charlotte Julie Caroline , Capolupo Laura , Hernandez-Corbacho Maria Jose , Biswas Ansuman , Vanacore Giovanna , Dathan Nina , Nitta Takahiro , Henklein Petra , Thattai Mukund , Inokuchi Jin-Ichi , Hsu Victor W. , Plomann Markus , Obeid Lina M. , Hannun Yusuf A. , Luini Alberto , D’Angelo Giovanni , Parashuraman Seetharaman 
Published: May 2020

AbstractGlycans are important regulators of cell and organismal physiology. This requires that the glycan biosynthesis be controlled to achieve specific cellular glycan profiles. Glycans are assembled in the Golgi apparatus on secretory cargoes that traverse it. The mechanisms by which the Golgi apparatus ensures cell- and cargo-specific glycosylation remain obscure. We investigated how the Golgi apparatus regulates glycosylation by studying biosynthesis of glycosphingolipids, glycosylated lipids with critical roles in signalling and differentiation. We identified the Golgi matrix protein GRASP55 as a controller of sphingolipid glycosylation by regulating the compartmentalized localization of key sphingolipid biosynthetic enzymes in the Golgi. GRASP55 controls the localization of the enzymes by binding to them and regulating their entry into peri-Golgi vesicles. Impairing GRASP55-enzyme interaction decompartmentalizes these enzymes, changes the substrate flux across competing glycosylation pathways that results in alteration of the cellular glycosphingolipid profile. This GRASP55 regulated pathway of enzyme compartmentalization allows cells to make cell density-dependent adaptations in glycosphingolipid biosynthesis to suit cell growth needs. Thus, the Golgi apparatus controls the cellular glycan (glycosphingolipid) profile by governing competition between biosynthetic reactions through regulated changes in enzyme compartmentalization.
Biodiversity Research and Innovation in Antarctica and the Southern Ocean
Authors: Oldham Paul , Kindness Jasmine 
Published: May 2020

AbstractThis article examines biodiversity research and innovation in Antarctica and the Southern Ocean based on a review of 150,401 scientific articles and 29,690 patent families for Antarctic species. The paper exploits the growing availability of open access databases, such as the Lens and Microsoft Academic Graph, along with taxonomic data from the Global Biodiversity Information Facility (GBIF) to explore the scientific and patent literature for the Antarctic at scale. The paper identifies the main contours of scientific research in Antarctica before exploring commercially oriented biodiversity research and development in the scientific literature and patent publications. The paper argues that biodiversity is not a free good and must be paid for. Ways forward in debates on commercial research and development in Antarctica can be found through increasing attention to the valuation of ecosystem services, new approaches to natural capital accounting and payment for ecosystem services that would bring the Antarctic, and the Antarctic Treaty System, into the wider fold of work on the economics of biodiversity. Economics based approaches can be criticised for reducing biodiversity to monetary exchange values at the expense of recognition of the wider values of biodiversity and its services. However, approaches grounded in the economics of biodiversity provide a transparent framework for approaching commercial activity in the Antarctic and introducing requirements for investments in the conservation of Antarctic biodiversity by those who seek to profit from it.
Neutralizing Antibodies Isolated by a site-directed Screening have Potent Protection on SARS-CoV-2 Infection
Authors: Liu Xiaoyu , Gao Fang , Gou Liming , Chen Yin , Gu Yayun , Ao Lei , Shen Hongbing , Hu Zhibin , Guo Xiling , Gao Wei 
Published: May 2020

AbstractNeutralizing antibody is one of the most effective interventions for acute pathogenic infection. Currently, over three million people have been identified for SARS-CoV-2 infection but SARS-CoV-2-specific vaccines and neutralizing antibodies are still lacking. SARS-CoV-2 infects host cells by interacting with angiotensin converting enzyme-2 (ACE2) via the S1 receptor-binding domain (RBD) of its surface spike glycoprotein. Therefore, blocking the interaction of SARS-CoV-2-RBD and ACE2 by antibody would cause a directly neutralizing effect against virus. In the current study, we selected the ACE2 interface of SARS-CoV-2-RBD as the targeting epitope for neutralizing antibody screening. We performed site-directed screening by phage display and finally obtained one IgG antibody (4A3) and several domain antibodies. Among them, 4A3 and three domain antibodies (4A12, 4D5, and 4A10) were identified to act as neutralizing antibodies due to their capabilities to block the interaction between SARS-CoV-2-RBD and ACE2-positive cells. The domain antibody 4A12 was predicted to have the best accessibility to all three ACE2-interfaces on the spike homotrimer. Pseudovirus and authentic SARS-CoV-2 neutralization assays showed that all four antibodies could potently protect host cells from virus infection. Overall, we isolated multiple formats of SARS-CoV-2-neutralizing antibodies via site-directed antibody screening, which could be promising candidate drugs for the prevention and treatment of COVID-19.
Detection of pathogenicLeptospirain the environment and its association with antagonisticPseudomonasspp. and rainy season
Authors: Kumar K. Vinod , Lall Chandan , Raj R. Vimal , Vedhagiri K. , Maile Anwesh , Muruganandam N. , Sunish I. P. , Vijayachari Paluru 
Published: May 2020

AbstractTypically, humans contract leptospirosis through exposure to soil or water contaminated with the urine of infected animals. Specifically, people working in inundated fields, engaged in aquatic sports, or exposed to contaminated floodwater after periods of heavy rainfall bear the risk of contracting leptospirosis. There is a critical gap in the knowledge of the environmental cycle, transmission, and interaction ofLeptospiraspecies with its environment. A few studies establish the presence of higher concentration of leptospires during the rainy season when compared to the dry season. Therefore, we assessed the abundance of leptospires during the dry and wet months and their interaction with other microbes. The overall detection rate of leptospires in paddy field for the test period was 52 (49.5%). Leptospiral concentration positively correlated with the amount of rainfall (mm) during the sampling when compared to months that received comparatively less rainfall (60% vs. 28.5%, respectively). When observed for the microbial interaction,Leptospirashowed significant negative correlation withPseudomonasand rainfall in the paddy field. Moreover, Pseudomonas negatively correlated with the amount of rainfall. Corroborative results ofin-vitrostudies suggest the antagonistic effect ofPseudomonasspp. on leptospires. The results indicate that seasonal changes influence the diversity of free-living well-adaptive aquatic antagonistic microbe populations and may in turn determine the survival ofLeptospirain the environment. Thus, microbial interaction can be the possible enigma for the fluctuation ofLeptospiracount in rainy and dry seasons in environmental surface water, which needs to be further confirmed. This will pave way for a better understanding of the survival of leptospires and the seasonal trend of exposure to humans.
Coupling metabolic addiction with negative autoregulation to improve strain stability and pathway yield
Authors: Lv Yongkun , Gu Yang , Xu Jingliang , Zhou Jingwen , Xu Peng 
Published: May 2020

AbstractMetabolic addiction, an organism that is metabolically addicted with a compound to maintain its growth fitness, is an underexplored area in metabolic engineering. Microbes with heavily engineered pathways or genetic circuits tend to experience metabolic burden leading to degenerated or abortive production phenotype during long-term cultivation or scale-up. A promising solution to combat metabolic instability is to tie up the end-product with an intermediary metabolite that is essential to the growth of the producing host. Here we present a simple strategy to improve both metabolic stability and pathway yield by coupling chemical addiction with negative autoregulatory genetic circuits. Naringenin and lipids compete for the same precursor with inversed pathway yield in oleaginous yeast. Negative autoregulation of the lipogenic pathways, enabled by CRISPRi and fatty acid-inducible promoters, repartitioned malonyl-CoA to favor flavonoid synthesis and increased naringenin production by 74.8%. With flavonoid-sensing hybrid promoters to control leucine synthesis, this flavonoid addiction phenotype confers a selective growth advantage to the naringenin-producing cell. The engineered yeast persisted 90.9% of naringenin titer up to 324 generations. Cells without flavonoid addiction regained growth fitness but lost 94.5% of the naringenin titer after cell passage beyond 300 generations. Metabolic addiction and negative autoregulation may be generalized as basic tools to eliminate metabolic heterogeneity, improve strain stability and pathway yield.
Optimizing mevalonate pathway for squalene production inYarrowia lipolytica
Authors: Liu Huan , Wang Fang , Deng Li , Xu Peng 
Published: May 2020

AbstractSqualene is the gateway molecule for triterpene-based natural products and steroids-based pharmaceuticals. As a super lubricant, it has been used widely in health care industry due to its skin compatibility and thermostability. Squalene is traditionally sourced from shark-hunting or oil plant extraction, which is cost-prohibitive and not sustainable. Reconstitution of squalene biosynthetic pathway in microbial hosts is considered as a promising alternative for cost-efficient and scalable synthesis of squalene. In this work, we reported the engineering of the oleaginous yeast,Y. lipolytica, as a potential host for squalene production. We systematically identified the bottleneck of the pathway and discovered that the native HMG-CoA reductase led to the highest squalene improvement. With the recycling of NADPH from the mannitol cycle, the engineered strain produced about 180.3 mg/l and 188.2 mg/L squalene from glucose or acetate minimal media, respectively. By optimizing the C/N ratio, controlling the media pH and mitigating the acetyl-CoA flux competition from lipogenesis, the engineered strain produced about 502.7 mg/L squalene in shake flaks, a 28-fold increase compared to the parental strain (17.2 mg/L). We also profiled the metabolic byproducts citric acid and mannitol level and observed that they are reincorporated into cell metabolism at the late stage of fermentation. This work may serve as a baseline to harnessY. lipolyticaas an oleaginous cell factory for production of squalene or terpene-based chemicals.
Antagonistic Effects of Intraspecific Cooperation and Interspecific Competition on Thermal Performance
Authors: Tsai Hsiang-Yu , Rubenstein Dustin R. , Chen Bo-Fei , Liu Mark , Chan Shih-Fan , Chen De-Pei , Sun Syuan-Jyun , Yuan Tzu-Neng , Shen Sheng-Feng 
Published: May 2020

AbstractUnderstanding how climate-mediated biotic interactions shape thermal niche width is critical in an era of global change. Yet, most previous work on thermal niches has ignored detailed mechanistic information about the relationship between temperature and organismal performance, which can be described by a thermal performance curve. Here, we develop a model that predicts the width of thermal performance curves will be narrower in the presence of interspecific competitors, causing a species’ optimal breeding temperature to diverge from that of a competitor. We test this prediction in the Asian burying beetleNicrophorus nepalensis, confirming that the divergence in actual and optimal breeding temperatures is the result of competition with blowflies. However, we further show that intraspecific cooperation enables beetles to outcompete blowflies by recovering their optimal breeding temperature. Ultimately, linking direct (abiotic factors) and indirect effects (biotic interactions) on niche width will be critical for understanding species-specific responses to climate change.
Sensitivity assessment of SARS-CoV-2 PCR assays developed by WHO referral laboratories
Authors: Etievant Sibyle , Bal Antonin , Escuret Vanessa , Brengel–Pesce Karen , Bouscambert Maude , Cheynet Valérie , Generenaz Laurence , Oriol Guy , Destras Gregory , Billaud Geneviève , Josset Laurence , Frobert Emilie , Morfin Florence , Gaymard Alexandre 
Published: May 2020

AbstractThe sensitivity of SARS-CoV-2 RT-PCR tests developed by Charité (Germany), HKU (Hong-Kong), China CDC (China), US CDC (United-States), and Institut Pasteur, Paris (France) was assessed on SARS-CoV-2 cell culture supernatants and clinical samples. Although all RT-PCR assays performed well for SARS-CoV-2 detection, RdRp Institut Pasteur (IP2, IP4), N China CDC, and N1 US CDC were found to be the most sensitive.
Direct PA-binding by Chm7 is required for nuclear envelope surveillance at herniations
Authors: Thaller David J. , Tong Danqing , Marklew Christopher J. , Borah Sapan , Ciani Barbara , Lusk C. Patrick 
Published: May 2020

AbstractMechanisms that control nuclear membrane remodeling are essential to maintain the integrity of the nucleus but remain to be fully defined. Here, we identify a phosphatidic acid (PA)-binding activity in the nuclear envelope-specific ESCRT, Chm7, in budding yeast. PA-binding is mediated through a conserved hydrophobic stretch of amino acids, which confers specific binding to the inner nuclear membrane (INM). This INM-binding is independent but nonetheless required for interaction with the LAP2-emerin-MAN1 (LEM) domain protein, Heh1 (LEM2). Consistent with the functional importance of PA-binding, mutation of this region inhibits recruitment of Chm7 to the INM and abolishes Chm7 function in the context of nuclear envelope herniations or “blebs” that form during defective nuclear pore complex (NPC) biogenesis. In fact, we show that PA accumulates at nuclear envelope herniations. We suggest that local control of PA metabolism is important for ensuring productive nuclear envelope remodeling and that its dysregulation may contribute to pathologies associated with defective NPC assembly.