bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strategies for vaccine design for corona virus using Immunoinformatics techniques
Authors: Basu Anamika , Sarkar Anasua , Maulik Ujjwal 
Published: March 2020

ABSTRACTThe cutting-edge technology vaccinomics is the combination of two topics immunogenetics and immunogenomics with the knowledge of systems biology and immune profiling for designing vaccine against infectious disease. In our present study, an epitope-based peptide vaccine against nonstructural protein 4 of beta coronavirus, using a combination of B cell and T cell epitope predictions, followed by molecular docking methods are performed. Here, protein sequences of homologous nonstructural protein 4 of beta coronavirus are collected and conserved regions present in them are investigated via phylogenetic study to determine the most immunogenic part of protein. From the identified region of the target protein, the peptide sequence IRNTTNPSAR from the region ranging from 38-47 and the sequence PTDTYTSVYLGKFRG from the positions of 76-90 are considered as the most potential B cell and T cell epitopes respectively. Furthermore, this predicted T cell epitopes PTDTYTSVY and PTDTYTSVYLGKFRG interacted with MHC allelic proteins HLA-A*01:01 and HLA-DRB5*01:01 respectively with the low IC50values. These epitopes are perfectly fitted into the epitope binding grooves of alpha helix of MHC I molecule and MHC II molecule with binding energy scores −725.0 Kcal/mole and −786.0 Kcal/mole respectively, showing stability in MHC molecules binding. This MHC restricted epitope PTDTYTSVY also showed a good conservancy of 50.16% in world population coverage. This MHC I HLA-A*01:01 allele is present among 58.87% of Chinese population also. Therefore, the epitopes IRNTTNPSAR and PTDTYTSVYLGKFRG may be considered as potential peptides for peptide-based vaccine for coronavirus after further experimental study.
Highly ACE2 Expression in Pancreas May Cause Pancreas Damage After SARS-CoV-2 Infection
Authors: Liu Furong , Long Xin , Zou Wenbin , Fang Minghao , Wu Wenjuan , Li Wei , Zhang Bixiang , Zhang Wanguang , Chen Xiaoping , Zhang Zhanguo 
Published: March 2020

AbstractThe ongoing outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in the end of 2019 in China has triggered a global public health crisis. Previous studies have shown that SARS-CoV-2 infects cells by binding angiotensin-converting enzyme 2 (ACE2), which is the same as SARS-CoV. The expression and distribution of ACE2 in the pancreas are unknown. At the same time, the injury of pancreas after SARS-CoV-2 infection has not been concerned. Here, we collected public datasets (bulk RNA-seq and single-cell RNA-seq) to indicate the expression and the distribution of ACE2 in pancreas (in both exocrine glands and islets). And further, clinical data including mild and severe patients with COVID-19 demonstrated there existed mild pancreatitis. In the 67 severe cases, 11 patients (16.41%) showed elevated levels of both amylase and lipase, and 5 patients (7.46%) showed imaging alterations. Only one patient (1.85%) showed elevated levels of both amylase and lipase in 54 mild cases, without imaging changes. Our study revealed the phenomenon and possible cause of mild pancreatic injury in patients with COVID-19. This suggests that pancreatitis after SARS-CoV-2 infection should also be paid attention in clinical work.
In Arabidopsis, low blue light enhances phototropism by releasing cryptochrome 1-mediated inhibition ofPIF4expression
Authors: Boccaccini Alessandra , Legris Martina , Krahmer Johanna , Allenbach-Petrolati Laure , Goyal Anupama , Galvan-Ampudia Carlos , Vernoux Teva , Karayekov Elisabeth , Casal Jorge , Fankhauser Christian 
Published: March 2020

AbstractShade-avoiding plants includingArabidopsis thalianadisplay a number of growth responses elicited by shade cues including elongation of stem-like structures and repositioning of leaves. Shade also promotes phototropism of de-etiolated seedlings through repression of phytochrome B (phyB) presumably to enhance capture of unfiltered sunlight. Light cues indicative of shade include a reduction in the blue and red portions of the solar spectrum and a low red to far-red ratio. Here we show that in Arabidopsis seedlings both low blue and a low red to far-red ratio are required to rapidly enhance phototropism. However, prolonged low blue treatments through reduced cryptochrome 1 (cry1) activation are sufficient to promote phototropism. The enhanced phototropic response ofcry1mutants in the lab and in response to natural canopies depends onPHYTOCHROME INTERACTING FACTORs(PIFs). In favorable light conditions, cry1 limits the expression ofPIF4while in low blue light PIF4 expression increases, which contributes to phototropic enhancement. The analysis of a quantitative DII auxin reporter indicates that low blue light leads to enhanced auxin levels in the hypocotyl and, upon phototropic stimulation, a steeper auxin gradient across the hypocotyl. We conclude that phototropic enhancement by canopy shade results from the combined activities of phytochrome B and cry1 that converge on PIF regulation.ONE SENTENCE SUMMARYThe persistent depletion of blue light in natural canopy shade relieves the inhibitory effect of cryptochrome 1 on PIF4, enhancing phototropism in de-etiolated Arabidopsis seedlings.Financial supportThis work was supported by the University of Lausanne and a grant from the Swiss National Science foundation (n° 310030B_179558 to C.F.); Human Frontier Science Program organization (HFSP) Grant RPG0054-2013, ANR-12-BSV6-0005 grant (AuxiFlo) to T.V.; The University of Buenos Aires (Grant 20020100100437 to J. J. C.), andAgencia Nacional de Promoción Científica y Tecnológica of Argentina(Grant PICT-2018-01695 to J. J. C.). Alessandra Boccaccini and Martina Legris are funded by Marie Curie fellowships H2020-MSCA-IF-2017 grants CRoSh 796283 and Flat-Leaf 796443 respectively.
SCRAPP: A tool to assess the diversity of microbial samples from phylogenetic placements
Authors: Barbera Pierre , Czech Lucas , Lutterop Sarah , Stamatakis Alexandros 
Published: March 2020

AbstractMicrobial ecology research is currently driven by the continuously decreasing cost of DNA sequencing and the improving accuracy of data analysis methods. One such analysis method is phylogenetic placement, which establishes the phylogenetic identity of the anonymous environmental sequences in a sample by means of a given phylogenetic reference tree. However, assessing the diversity of a sample remains challenging, as traditional methods do not scale well with the increasing data volumes and/or do not leverage the phylogenetic placement information.Here, we presentSCRAPP, a highly parallel and scalable tool that uses a molecular species delimitation algorithm to quantify the diversity distribution over the reference phylogeny for a given phylogenetic placement of the sample.SCRAPPemploys a novel approach to cluster phylogenetic placements, called placement space clustering, to efficiently perform dimensionality reduction, so as to scale on large data volumes. Furthermore, it utilizes the phylogeny-aware molecular species delimitation methodmPTPto quantify diversity.We evaluatedSCRAPPusing both, simulated and empirical datasets. We use simulated data to verify our approach. Tests on an empirical dataset show that SCRAPP-derived metrics can classify samples by their diversity-correlated features equally well or better than existing, commonly used approaches.SCRAPPis available athttps://github.com/pbdas/scrapp
Persistence and stability of interacting species in response to climate warming: The role of trophic structure
Authors: Kaur Taranjot , Dutta Partha Sharathi 
Published: March 2020

AbstractOver the past century, the Earth has experienced roughly 0.4–0.8°C rise in the average temperature and which is projected to increase between 1.4–5.8°C by the year 2100. The increase in the Earth’s temperature directly influences physiological traits of individual species in ecosystems. However, the effect of these changes in community dynamics, so far, remains relatively unknown. Here we show that the consequences of warming (i.e., increase in the global mean temperature) on the interacting species persistence or extinction are correlated with their trophic complexity and community structure. In particular, we investigate different nonlinear bioenergetic tri-trophic food web modules, commonly observed in nature, in the order of increasing trophic complexity; a food chain, a diamond food web and an omnivorous interaction. We find that at low temperatures, warming can destabilize the species dynamics in the food chain as well as the diamond food web, but it has no such effect on the trophic structure that involves omnivory. In the diamond food web, our results indicate that warming does not support top-down control induced co-existence of intermediate species. However, in all the trophic structures warming can destabilize species up to a threshold temperature. Beyond the threshold temperature, warming stabilizes species dynamics at the cost of the extinction of higher trophic species. We demonstrate the robustness of our results when a few system parameters are varied together with the temperature. Overall, our study suggests that variations in the trophic complexity of simple food web modules can influence the effects of climate warming on species dynamics.
Charge-Altering Releasable Transporters Enable Specific Phenotypic Manipulation of Resting Primary Natural Killer Cells
Authors: Wilk Aaron J. , Benner Nancy L. , Vergara Rosemary , Haabeth Ole A.W. , Levy Ronald , Waymouth Robert M. , Wender Paul A. , Blish Catherine A. 
Published: March 2020

ABSTRACTNatural killer (NK) cells are capable of rapid and robust cytotoxicity, making them excellent tools for immunotherapy. However, their recalcitrance to standard transfection techniques has limited both mechanistic studies and clinical applications. Current approaches for NK cell manipulation rely on viral transduction or methods requiring NK cell activation, which can alter NK cell function. Here, we report that non-viral Charge-Altering Releasable Transporters (CARTs) efficiently transfect primary human NK cells with mRNA without relying on NK cell activation. Compared to electroporation, CARTs transfect NK cells two orders of magnitude more efficiently, better preserve cell viability, and cause minimal reconfiguration of NK cell phenotype and function. Finally, we use CARTs to generate highly cytotoxic primary human chimeric antigen receptor NK cells, indicating potential therapeutic utility of this technique. To our knowledge, CARTs represent the first efficacious transfection technique for resting primary NK cells that preserves NK cell phenotype, and can drive new biological discoveries and clinical applications of this understudied lymphocyte subset.
Drivers of large-scale spatial demographic variation in a perennial plant
Authors: Römer Gesa , Christiansen Ditte M. , de Buhr Hendrik , Hylander Kristoffer , Jones Owen R. , Merinero Sonia , Reitzel Kasper , Ehrlén Johan , Dahlgren Johan P. 
Published: March 2020

AbstractTo understand how the environment drives spatial variation in population dynamics, we need to assess the effects of a large number of potential drivers on the vital rates (survival, growth and reproduction), and explore these relationships over large geographical areas and long environmental gradients. In this study, we examined the effects of a broad variety of abiotic and biotic environmental factors, including intraspecific density, on the demography of the forest understory herbActaea spicatabetween 2017 and 2019 at 40 sites across Sweden, including the northern range margin of its distribution. We assessed the effect of potential environmental drivers on vital rates using generalized linear mixed models (GLMMs), and then quantified the impact of each important driver on population growth rate (λ) using integral projection models (IPMs). Population dynamics ofA. spicatawere mostly driven by environmental factors affecting survival and growth, such as air humidity, soil depth and forest tree species composition, and thus those drivers jointly determined the realized niche of the species. Soil pH had a strong effect on the flowering probability, while the effect on population growth rate was relatively small. In addition to identifying specific drivers forA. spicata’spopulation dynamics, our study illustrates the impact that spatial variation in environmental conditions can have on λ. Assessing the effects of a broad range of potential drivers, as done in this study, is important not only to quantify the relative importance of different drivers for population dynamics but also to understand species distributions and abundance patterns.
The immune system fails to mount a protective response to Gram-positive or Gram-negative bacterial prostatitis
Authors: Lupo Federico , Rousseau Matthieu , Canton Tracy , Ingersoll Molly A. 
Published: March 2020

AbstractBacterial prostatitis affects 1% of men, with increased incidence in the elderly. It is defined by the frequency and urgency to urinate, localized pain, and positive bacterial cultures in expressed seminal fluids. Acute bacterial prostatitis frequently progresses to chronicity, which is marked by recurrent acute episodes interspersed with asymptomatic periods of variable duration. Up to 80% of bacterial prostatitis cases are caused by Gram-negative uropathogenicE. coli(UPEC) or Gram-positiveE. faecalis. Antibiotic treatment is standard of care, however, global dissemination of antimicrobial resistant uropathogens threatens efficacy of therapy. Thus, development of non-antibiotic-based approaches to treat bacterial prostatitis is a priority. One challenge is that the immune response to infection in the prostate is incompletely understood. We used a mouse model of transurethral bacterial instillation to study the immune response to UPEC orE. faecalisprostate infection. Both uropathogens exhibited tropism for the prostate over the bladder early post-infection. UPEC infection induced greater proinflammatory cytokine expression and neutrophil and monocyte infiltration compared toE. faecalisinfection. Following challenge infection, cytokine responses and myeloid cell infiltration were largely comparable to primary infection. Characteristic of memory responses, more lymphoid cells infiltrating the prostate in the second infection compared to the primary infection. Unexpectedly, however, bacterial burden in prostates challenged with either UPEC orE. faecaliswas equal or greater than in primary infection, despite that an adaptive response to UPEC infection was evident in the bladder of the same animals. Thus, an immune response to primary infection is initiated, however it does not protect against reinfection. Our findings support the idea that chronic or recurrent prostatitis develops in the absence of efficacious immunity to infection. A greater understanding of the mechanisms underlying this observation may point to actionable targets for immunotherapy.
Morphological pseudotime ordering and fate mapping reveals diversification of cerebellar inhibitory interneurons
Authors: Wang Wendy Xueyi , Lefebvre Julie L. 
Published: March 2020

AbstractUnderstanding how diverse neurons are assembled into circuits requires a framework for describing cell types and their developmental trajectories. Here, we combined genetic fate mapping and pseudo-temporal profiling to resolve the diversification of cerebellar inhibitory interneurons based on morphology. The molecular layer interneurons (MLIs) derive from a common progenitor but comprise a diverse population of dendritic-, somatic-, and axon initial segment-targeting interneurons. MLIs are classically divided into two types. However, their morphological heterogeneity suggests an alternate model of one continuously varying population. Through clustering and trajectory inference of 811 MLI reconstructions at maturity and during development, we show that MLIs divide into two discrete classes but also present significant within-class heterogeneity. Pseudotime trajectory mapping uncovered the emergence of distinct phenotypes during migration and axonogenesis, well before neurons reach their final positions. Our study illustrates the utility of quantitative single-cell methods to morphology for defining the diversification of neuronal subtypes.
An Inherent Structural Difference Between Serine and Threonine Phosphorylation: Phosphothreonine Prefers an Ordered, Compact, Cyclic Conformation
Authors: Pandey Anil K. , Ganguly Himal K. , Sinha Sudipta Kumar , Daniels Kelly E. , Yap Glenn P. A. , Patel Sandeep , Zondlo Neal J. 
Published: March 2020

AbstractPhosphorylation and dephosphorylation of proteins by kinases and phosphatases are central to cellular responses and function. The structural effects of serine and threonine phosphorylation were examined in peptides and in proteins, by circular dichroism, NMR spectroscopy, bioinformatics analysis of the PDB, small-molecule X-ray crystallography, and computational investigations. Phosphorylation of both serine and threonine residues induces substantial conformational restriction in their physiologically more important dianionic forms. Threonine exhibits a particularly strong disorder-to-order transition upon phosphorylation, with dianionic phosphothreonine preferentially adopting a cyclic conformation with restrictedϕ(ϕ∼ –60°) stabilized by three noncovalent interactions: a strong intraresidue phosphate-amide hydrogen bond, an n→π* interaction between consecutive carbonyls, and an n→σ* interaction between the phosphate Oγ lone pair and the antibonding orbital of C–Hβ that restricts theχ2side chain conformation. Proline is unique among the canonical amino acids for its covalent cyclization on the backbone. Phosphothreonine can mimic proline’s backbone cyclization via noncovalent interactions. The preferred torsions of dianionic phosphothreonine areϕ,ψ= polyproline helix or α-helix (ϕ∼ –60°);χ1=g−;χ2= eclipsed C–H/O–P bonds. This structural signature is observed in diverse proteins, including the activation loops of protein kinases and protein-protein interactions. In total, these results suggest a structural basis for the differential use and evolution of threonine versus serine phosphorylation sites in proteins, with serine phosphorylation typically inducing smaller, rheostat-like changes, versus threonine phosphorylation promoting larger, step function-like switches, in proteins.
Identification, presence, and possible multifunctional regulatory role of invertebrate gonadotropin-releasing hormone/corazonin molecule in the great pond snail (Lymnaea stagnalis)
Authors: Fodor István , Zrinyi Zita , Urbán Péter , Herczeg Róbert , Büki Gergely , Koene Joris M. , Tsai Pei-San , Pirger Zsolt 
Published: March 2020

AbstractIn the last years, the interpretation of gonadotropin-releasing hormone (GnRH) neuropeptide superfamily has changed tremendously. One main driver is the investigation of functions and evolutionary lineage of previously identified molluscan GnRH molecules. Emerging evidence suggests not only reproductive, but also diverse biological effects of these molecules and proposes they should most likely be called corazonin (CRZ). Clearly, a more global understanding necessitates further exploration of species-specific functions and structure of invGnRH/CRZ peptides. Towards this goal, we have identified the full-length cDNA of invGnRH/CRZ peptide in an invertebrate model species, the great pond snailLymnaea stagnalis, termed ly-GnRH/CRZ, and characterized the transcript and peptide distribution in the central nervous system (CNS) and peripheral organs. Our results are consistent with previous data that molluscan GnRHs are more related to CRZs and serve diverse functions. For this, our findings support the notion that peptides originally termed molluscan GnRH are multifunctional modulators and that nomenclature change should be taken into consideration.
The genomic landscapes of individual melanocytes from human skin
Authors: Tang Jessica , Fewings Eleanor , Chang Darwin , Zeng Hanlin , Liu Shanshan , Jorapur Aparna , Belote Rachel L. , McNeal Andrew S. , Yeh Iwei , Arron Sarah T. , Judson-Torres Robert L. , Bastian Boris C. , Shain A. Hunter 
Published: March 2020

AbstractEvery cell in the human body has a unique set of somatic mutations, yet it remains difficult to comprehensively genotype an individual cell. Here, we developed solutions to overcome this obstacle in the context of normal human skin, thus offering the first glimpse into the genomic landscapes of individual melanocytes from human skin. We comprehensively genotyped 133 melanocytes from 19 sites across 6 donors. As expected, sun-shielded melanocytes had fewer mutations than sun-exposed melanocytes. However, within sun-exposed sites, melanocytes on chronically sun-exposed skin (e.g. the face) displayed a lower mutation burden than melanocytes on intermittently sun-exposed skin (e.g. the back). Melanocytes located adjacent to a skin cancer had higher mutation burdens than melanocytes from donors without skin cancer, implying that the mutation burden of normal skin can be harnessed to measure cumulative sun damage and skin cancer risk. Moreover, melanocytes from healthy skin commonly harbor pathogenic mutations, likely explaining the origins of the melanomas that arise in the absence of a pre-existing nevus. Phylogenetic analyses identified groups of related melanocytes, suggesting that melanocytes spread throughout skin as fields of clonally related cells, invisible to the naked eye. Overall, our study offers an unprecedented view into the genomic landscapes of individual melanocytes, revealing key insights into the causes and origins of melanoma.