bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioinformatics analyses of significant genes, related pathways and candidate prognostic biomarkers in Alzheimer’s disease
Authors: Vastrad Basavaraj , Vastrad Chanabasayya 
Published: May 2021

AbstractAlzheimer’s disease (AD) is one of the most common causes of dementia and frailty. This study aimed to use bioinformatics analysis to identify differentially expressed genes (DEGs) in AD. The Expression profiling by high throughput sequencing dataset GSE125583 was downloaded from the Gene Expression Omnibus (GEO) database and DEGs were identified. After assessment of Gene Ontology (GO) terms and pathway enrichment for DEGs, a protein–protein interaction (PPI) network, module analysis, miRNA-hub gene regulatory network construction and TF-hub gene regulatory network were conducted via comprehensive target prediction and network analyses. Finally, we validated hub genes by receiver operating characteristic curve (ROC). In total, 956 DEGs were identified in the AD samples, including 479 up regulated genes and 477 down regulated genes. Functional enrichment analysis showed that these DEGs are mainly involved in the neuronal system, GPCR ligand binding, regulation of biological quality and cell communication. The hub genes of PAK1, ELAVL2, NSF, HTR2C, TERT, UBD, MKI67, HSPB1, PYHIN1 and TES might be associated with AD. The diagnostic value and expression levels of these hub genes in AD were further confirmed by ROC analysis. In conclusion, we identified pathways and crucial candidate genes that affect the outcomes of patients with AD, and these genes might serve as potential therapeutic targets.
Eusociality and the evolution of aging in superorganisms
Authors: Kramer Boris H. , van Doorn G. Sander , Arani Babak M. S. , Pen Ido 
Published: May 2021

AbstractEusocial insects – ants, bees, wasps and termites – are being recognized as model organisms to unravel the evolutionary paradox of aging for two reasons: (1) queens (and kings, in termites) of social insects outlive similar sized solitary insects by up to several orders of magnitude; (2) all eusocial taxa show a divergence of long queen and shorter worker lifespans, despite their shared genomes and even under risk-free laboratory environments. Traditionally, these observations have been explained by invoking classical evolutionary aging theory: well-protected inside their nests, queens are much less exposed to external hazards than foraging workers, and this provides natural selection the opportunity to favor queens that perform well at advanced ages. Although quite plausible, these verbal arguments have not been backed up by mathematical analysis. Here, for the first time, we provide quantitative models for the evolution of caste-specific aging patterns. We show that caste-specific mortality risks are in general neither sufficient nor necessary to explain the evolutionary divergence in lifespan between queens and workers and the extraordinary queen lifespans. Reproductive monopolization and the delayed production of sexual offspring in highly social colonies lead natural selection to inherently favor queens that live much longer than workers, even when exposed to the same external hazards. Factors that reduce a colony’s reproductive skew, such as polygyny and worker reproduction, tend to reduce the evolutionary divergence in lifespan between queens and workers. Caste-specific extrinsic hazards also affect lifespan divergence but to a much smaller extent than reproductive monopolization.
Towards Novel Herbicide Modes of Action by Inhibiting Lysine Biosynthesis in Plants
Authors: Soares da Costa Tatiana P. , Hall Cody J. , Panjikar Santosh , Wyllie Jessica A. , Christoff Rebecca M. , Bayat Saadi , Hulett Mark D. , Abbott Belinda M. , Gendall Anthony R. , Perugini Matthew A. 
Published: May 2021

AbstractWeeds are becoming increasingly resistant to our current herbicides, posing a significant threat to agricultural production. Therefore, new herbicides are urgently needed. In this study, we exploited a novel herbicide target, dihydrodipicolinate synthase (DHDPS), which catalyses the first and rate-limiting step in lysine biosynthesis. Using a high throughput chemical screen, we identified the first class of plant DHDPS inhibitors that have micromolar potency againstArabidopsis thalianaDHDPS isoforms. Employing X-ray crystallography, we determined that this class of inhibitors binds to a novel and unexplored pocket within DHDPS, which is highly conserved across plant species. We also demonstrated that the inhibitors attenuated the germination and growth ofA. thalianaseedlings and confirmed their pre-emergence herbicidal activity in soil-grown plants. These results provide proof-of-concept that lysine biosynthesis represents a promising target for the development of herbicides with a novel mode of action to tackle the global rise of herbicide resistant weeds.
SPT6 loss Permits the Transdifferentiation of Keratinocytes into an Intestinal Fate that Recapitulates Barrett’s Metaplasia
Authors: Vo Daniella T. , Fuller MacKenzie R. , Tindle Courtney , Anandachar Mahitha Shree , Das Soumita , Sahoo Debashis , Ghosh Pradipta 
Published: May 2021

SUMMARYTransient depletion of the transcription elongation factor SPT6 in the keratinocyte has been recently shown to inhibit epidermal differentiation and stratification; instead, they transdifferentiate into a gut-like lineage. We show here that this phenomenon oftransdifferentiationrecapitulates Barrett’s metaplasia, the only human pathophysiologic condition in which a stratified squamous epithelium that is injured due to chronic acid reflux is trans-committed into an intestinal fate. The evidence we present here not only lend support to the notion that the keratinocytes are the cell of origin of Barrett’s metaplasia, but also provide mechanistic insights linking transient acid exposure, downregulation of SPT6, stalled transcription of the master regulator of epidermal fate TP63, loss of epidermal fate and metaplastic progression. Because Barrett’s metaplasia in the esophagus (BE) is a pre-neoplastic condition with no preclinical human models, these findings have a profound impact on the modeling Barrett’s metaplasia-in-a-dish.GRAPHIC ABSTRACTHIGHLIGHTSKeratinocytes transdifferentiate into the gut lineage upon depletion of SPT6Such transdifferentiation recapitulates Barrett’s metaplasia, not the healthy gutAcid downregulates SPT6, which derails the expression and functions of TP63Such downregulation precedes the metaplasia-dysplasia-neoplasia cascade
massNet: integrated processing and classification of spatially resolved mass spectrometry data using deep learning for rapid tumor delineation
Authors: Abdelmoula Walid M. , Stopka Sylwia , Randall Elizabeth C. , Regan Michael , Agar Jeffrey N. , Sarkaria Jann N. , Wells William M. , Kapur Tina , Agar Nathalie Y.R. 
Published: May 2021

AbstractMotivationMass spectrometry imaging (MSI) provides rich biochemical information in a label-free manner and therefore holds promise to substantially impact current practice in disease diagnosis. However, the complex nature of MSI data poses computational challenges in its analysis. The complexity of the data arises from its large size, high dimensionality, and spectral non-linearity. Preprocessing, including peak picking, has been used to reduce raw data complexity, however peak picking is sensitive to parameter selection that, perhaps prematurely, shapes the downstream analysis for tissue classification and ensuing biological interpretation.ResultsWe propose a deep learning model, massNet, that provides the desired qualities of scalability, non-linearity, and speed in MSI data analysis. This deep learning model was used, without prior preprocessing and peak picking, to classify MSI data from a mouse brain harboring a patient-derived tumor. The massNet architecture established automatically learning of predictive features, and automated methods were incorporated to identify peaks with potential for tumor delineation. The model’s performance was assessed using cross-validation, and the results demonstrate higher accuracy and a 174-fold gain in speed compared to the established classical machine learning method, support vector machine.Availability and ImplementationThe code is publicly available on GitHub.
Photonic chip-based multimodal super-resolution microscopy for histopathological assessment of cryopreserved tissue sections
Authors: Villegas-Hernández Luis E. , Dubey Vishesh , Nystad Mona , Tinguely Jean-Claude , Coucheron David A. , Dullo Firehun T. , Priyadarshi Anish , Acuña Sebastian , Mateos Jose M. , Barmettler Gery , Ziegler Urs , Hovd Aud-Malin Karlsson , Fenton Kristin Andreassen , Acharya Ganesh , Agarwal Krishna , Ahluwalia Balpreet Singh 
Published: May 2021

1.AbstractHistopathological assessment involves the identification of anatomical variations in tissues that are associated with diseases. While diffraction-limited optical microscopes assist in the diagnosis of a wide variety of pathologies, their resolving capabilities are insufficient to visualize some anomalies at subcellular level. Although a novel set of super-resolution optical microscopy techniques can fulfill the resolution demands in such cases, the system complexity, high operating cost, lack of multimodality, and low-throughput imaging of these methods limit their wide adoption in clinical settings. In this study, we interrogate the photonic chip as an attractive high-throughput super-resolution microscopy platform for histopathology. Using cryopreserved ultrathin tissue sections of human placenta, mouse kidney, and zebrafish eye retina prepared by the Tokuyasu method, we validate the photonic chip as a multi-modal imaging tool for histo-anatomical analysis. We demonstrate that photonic-chip platform can deliver multi-modal imaging capabilities such as total internal reflection fluorescence microscopy, intensity fluctuation-based optical nanoscopy, single-molecule localization microscopy, and correlative light-electron microscopy. Our results demonstrate that the photonic chip-based super-resolution microscopy platform has the potential to deliver high-throughput multimodal histopathological analysis of cryopreserved tissue samples.
Axons-on-a-Chip for Mimicking Non-Disruptive Diffuse Axonal Injury underlying Traumatic Brain Injury
Authors: Li Wei , Wang Haofei , Pan Xiaorong , Gagoski Dejan , Durisic Nela , Li Zhiyong , Zhao Chun-Xia , Wang Tong 
Published: May 2021

AbstractDiffuse axonal injury (DAI) is the most severe pathological feature of traumatic brain injury. However, how primary axonal injury is induced by mechanical stress and whether it could be mitigated remain unknown, largely due to the resolution limits of medical imaging approaches. Here we established an Axon-on-a-Chip (AoC) model for mimicking DAI and investigating its early cellular responses. By integrating computational fluid dynamics and microfluidic techniques, DAI was observed for the first time during mechanical stress, and a clear correlation between stress intensity and severity of DAI was elucidated. This AoC was further used to investigate the dynamic intracellular changes occurring simultaneously with stress, and identified delayed local Ca2+surges escorted rapid disruption of periodic axonal cytoskeleton during the early stage of DAI. Compatible with high-resolution live-microscopy, this model hereby provides a versatile system to identify early mechanisms underlying DAI, offering a platform for screening effective treatments to alleviate brain injuries.
Phenotyping stomatal closure by thermal imaging for GWAS and TWAS of water use efficiency-related genes
Authors: Pignon Charles P. , Fernandes Samuel B. , Valluru Ravi , Bandillo Nonoy , Lozano Roberto , Buckler Edward , Gore Michael A. , Long Stephen P. , Brown Patrick J. , Leakey Andrew D. B. 
Published: May 2021

AbstractStomata allow CO2uptake by leaves for photosynthetic assimilation at the cost of water vapor loss to the atmosphere. The opening and closing of stomata in response to fluctuations in light intensity regulate CO2and water fluxes and are essential to maintenance of water-use efficiency (WUE). However, little is known about the genetic basis for natural variation in stomatal movement, especially in C4crops. This is partly because the stomatal response to a change in light intensity is difficult to measure at the scale required for association studies. High-throughput thermal imaging was used to bypass the phenotyping bottleneck and assess 10 traits describing stomatal conductance (gs) before, during and after a stepwise decrease in light intensity for a diversity panel of 659 sorghum accessions. Results from thermal imaging significantly correlated with photosynthetic gas-exchange measurements.gstraits varied substantially across the population and were moderately heritable (h2up to 0.72). An integrated genome-wide and transcriptome-wide association study (GWAS/TWAS) identified candidate genes putatively driving variation in stomatal conductance traits. Of the 239 unique candidate genes identified with greatest confidence, 77 were orthologs of Arabidopsis genes related to functions implicated in WUE, including stomatal opening/closing (24 genes), stomatal/epidermal cell development (35 genes), leaf/vasculature development (12 genes), or chlorophyll metabolism/photosynthesis (8 genes). These findings demonstrate an approach to finding genotype-to-phenotype relationships for a challenging trait as well as candidate genes for further investigation of the genetic basis of WUE in a model C4grass for bioenergy, food, and forage production.One sentence summaryRapid phenotyping of 659 accessions ofSorghum bicolorrevealed heritable stomatal responses to a decrease in light. GWAS/TWAS was used to identify candidate genes influencing traits important to WUE.
A metagenomic view of novel microbial and metabolic diversity found within the deep terrestrial biosphere
Authors: Momper Lily , Casar Caitlin P. , Osburn Magdalena R. 
Published: May 2021

ABSTRACTThe deep terrestrial subsurface is a large and diverse microbial habitat and a vast repository of biomass. However, in relation to its size and physical heterogeneity we have limited understanding of taxonomic and metabolic diversity in this realm. Here we present a detailed metagenomic analysis of samples from the Deep Mine Microbial Observatory (DeMMO) spanning depths from the surface to 1.5 km deep in the crust. From these eight geochemically and spatially distinct fluid samples we reconstructed ∼600 metagenome assembled genomes (MAGs), representing 50 distinct phyla and including 18 candidate phyla. These novel clades include many members of the Patescibacteria superphylum and two new MAGs from candidate phylum OLB16, a phylum originally identified in DeMMO fluids and for which only one other MAG is currently available. We find that microbes spanning this expansive phylogenetic diversity and physical space are often capable of numerous dissimilatory energy metabolisms and are poised to take advantage of nutrients as they become available in relatively isolated fracture fluids. This metagenomic dataset is contextualized within a four-year geochemical and 16S rRNA time series, adding another invaluable piece to our knowledge of deep subsurface microbial ecology.
Theta phase mediates deliberate action switching in human Supplementary Motor Areas
Authors: Maffei Giovanni , Zucca Riccardo , Puigbò Jordi-Ysard , Santos-Pata Diogo , Galli Marco , Campo Adrià Tauste , Rocamora Rodrigo , Verschure Paul 
Published: May 2021

ABSTRACTThe ability to deliberately overwrite ongoing automatic actions is a necessary feature of adaptive behavior. It has been proposed that the supplementary motor areas (SMAs) operate as a controller that orchestrates the switching between automatic and deliberate processes by inhibiting ongoing behaviors and so facilitating the execution of alternative ones. In addition, previous studies support the involvement of SMAs theta waves (4-9 Hz) in cognitive control. However, the exact role of such oscillatory dynamics and their contribution to the control of action are not fully understood. To investigate the mechanisms by which the SMAs support direct control of deliberate behavior, we recorded intracranial electroencephalography (iEEG) activity in humans performing a motor sequence task. Subjects had to perform a “change of plans” motor task requiring habitual movements to be overwritten at unpredictable moments. We found that SMAs were exclusively active during trials that demand action reprogramming in response to the unexpected cue but were silent during automatic action execution. Importantly, SMAs activity was characterized by a distinct temporal pattern, expressed in a stereotypical phase alignment of theta oscillations. More specifically, single trial motor performance was correlated with the trial contribution to the global inter-trial phase coherence, with higher coherence associated with faster trials. In addition, theta phase modulated the amplitude of gamma oscillations, with higher cross-frequency coupling in faster trials. Our results suggest that within frontal cortical networks, theta oscillations could encode a control signal that promotes the execution of deliberate actions.
Robust IgM responses following vaccination are associated with prevention ofMycobacterium tuberculosisinfection in macaques
Authors: Irvine Edward B. , O’Neil Anthony , Darrah Patricia A. , Shin Sally , Choudhary Alok , Li Wenjun , Honnen William , Mehra Smriti , Kaushal Deepak , Gideon Hannah Priyadarshini , Flynn JoAnne L. , Roederer Mario , Seder Robert A. , Pinter Abraham , Fortune Sarah , Alter Galit 
Published: May 2021

AbstractDevelopment of an effective tuberculosis (TB) vaccine has suffered from an incomplete understanding of the correlates of protection againstMycobacterium tuberculosis(Mtb). However, recent work has shown that compared to standard intradermal Bacille Calmette-Guerin (BCG) vaccination, intravenous (IV) BCG vaccination provides nearly complete protection against TB in rhesus macaques. While studies have focused on cellular immunity in this setting, the antibody response elicited by IV BCG vaccination remains incompletely defined. Using an agnostic antibody profiling approach, here we show that IV BCG drives superior antibody responses in the plasma and the bronchoalveolar lavage fluid (BAL). While IV BCG immunization resulted in the broad expansion of antibody titers and effector functions, surprisingly, IgM titers were among the strongest markers of reduced bacterial burden in the plasma and BAL of BCG immunized animals. Moreover, IgM immunity was also enriched among animals receiving protective vaccination with an attenuatedMtbstrain. Finally, a LAM-specific IgM monoclonal antibody reducedMtbsurvivalin vitro. Collectively, these data highlight the potential importance of IgM responses as a marker and as a functional mediator of protection against TB.
Dendritic spine morphology regulates calcium-dependent synaptic weight change
Authors: Bell M. K. , Holst M. V. , Lee C. T. , Rangamani P. 
Published: May 2021

AbstractDendritic spines act as biochemical computational units and must adapt their responses according to their activation history. Calcium influx acts as the first signaling step during post-synaptic activation and is a determinant of synaptic weight change. Dendritic spines also come in a variety of sizes and shapes. To probe the relationship between calcium dynamics and spine morphology, we used a stochastic reaction-diffusion model of calcium dynamics in idealized and realistic geometries. We show that despite the stochastic nature of the various calcium channels, receptors, and pumps, spine size and shape can modulate calcium dynamics and subsequently synaptic weight updates in a deterministic manner. Through a series of exhaustive simulations, we find that the calcium dynamics and synaptic weight change depend on the volume-to-surface area of the spine. The relationships between calcium dynamics and spine morphology identified in idealized geometries also hold in realistic geometries suggesting that there are geometrically determined deterministic relationships that may modulate synaptic weight change.
KAI2 regulates seedling development by mediating light-induced remodelling of auxin transport
Authors: Hamon-Josse Maxime , Villaecija-Aguilar Jose Antonio , Ljung Karin , Leyser Ottoline , Gutjahr Caroline , Bennett Tom 
Published: May 2021

SUMMARYThe photomorphogenic remodelling of seedling growth upon exposure to light is a key developmental transition in the plant life cycle. The α/β-hydrolase signalling protein KARRIKIN-INSENSITIVE2 (KAI2), a close homologue of the strigolactone receptor DWARF14 (D14), is involved in this process, andkai2mutants have strongly altered seedling growth as a result1. KAI2 and D14 both act through the MAX2 (MORE AXILLARY BRANCHING2) F-box protein to target proteins of the SMAX1-LIKE (SUPPRESSOR OF MAX2 1) (SMXL) family for degradation, but the signalling events downstream of this step are unclear in both pathways2. Here, we show thatkai2phenotypes arise because of a failure to downregulate auxin transport from the seedling shoot apex towards the root system, rather than a failure to respond to lightper se. We demonstrate that KAI2 controls the light-induced remodelling of the PIN-mediated auxin transport system in seedlings, promoting the reduction of PIN3, PIN4, and PIN7 abundance in older tissues, and the increase of PIN1, PIN2, PIN3, and PIN7 abundance in the root meristem, consistent with transition from elongation-mediated growth in the dark to meristematically-mediated growth in the light. We show that removing PIN3, PIN4 and PIN7 fromkai2mutants, or pharmacological inhibition of auxin transport and synthesis, is sufficient to suppress mostkai2seedling phenotypes. KAI2 is not required for the light-mediated changes in PIN gene expression but is required for the changes in PIN protein abundance at the plasma membrane; we thus propose that KAI2 acts to promote vesicle trafficking, consistent with previous suggestions about D14-mediated signalling in the shoot3.
Spatial control of cell division by GA-OsGRF7/8 module in a leaf explains the leaf length variation between cultivated and wild rice
Authors: Jathar Vikram , Saini Kumud , Chauhan Ashish , Rani Ruchi , Ichihashi Yasunori , Ranjan Aashish 
Published: May 2021

SummaryCellular and genetic understanding of rice leaf size regulation is limited, despite rice being the staple food of more than half of the global population. We investigated the mechanism controlling the rice leaf length using cultivated and wild rice accessions that remarkably differed for leaf size.Comparative transcriptomics, Gibberellic Acid (GA) quantification, and leaf kinematics of the contrasting accessions suggested the involvement of GA, cell cycle, and Growth-Regulating Factors (GRFs) in the rice leaf size regulation. Zone-specific expression analysis and VIGS established the functions of specific GRFs in the process.The leaf length of the selected accessions was strongly correlated with GA levels. Higher GA content in wild rice accessions with longer leaves and GA-induced increase in the leaf length via an increase in cell division confirmed a GA-mediated regulation of division zone in rice. Downstream to GA,OsGRF7andOsGRF8function for controlling cell division to determine the rice leaf length.Spatial control of cell division to determine the division zone size mediated by GA and downstream OsGRF7 and OsGRF8 explains the leaf length differences between the cultivated and wild rice. This mechanism to control rice leaf length might have contributed to optimizing leaf size during domestication.