bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time-of-day defines the efficacy of NAD+to treat diet-induced metabolic disease by adjusting oscillations of the hepatic circadian clock
Authors: Escalante-Covarrubias Q , Mendoza-Viveros L , González-Suárez M , Becerril-Pérez F , Pacheco-Bernal I , Carreño-Vázquez E , Mass-Sánchez P , Bustamante-Zepeda M , Orozco-Solís R , Aguilar-Arnal L 
Published: August 2022

SUMMARYThe circadian clock is a time-tracking endogenous system which anticipates and coordinates adaptation to daily environmental fluctuations. Circadian misalignment leads to obesity, which is accompanied by reduced levels of the clock-controlled metabolite NAD+. Concomitantly, increasing NAD+levels is emerging as a therapy for diet-induced obesity and type 2 diabetes; however, the impact of daily fluctuations of NAD+on these therapies remains unknown. Here, we demonstrate that time-of-day determines the efficacy of NAD+as a therapy for diet-induced metabolic disease in mice. Restoring regular NAD+oscillations at the onset of the active phase ameliorates metabolic markers of disease such as body weight and glucose and insulin tolerance, and restores hepatic gene expression related to inflammatory response and lipid metabolism. However, the same treatment designed to increase NAD+at the onset of the rest phase severely compromises these beneficial responses. Notably, hepatic nutrient-sensing mTOR, AMPK or AKT signaling, became rhythmic specifically in obese mice treated just before the active phase. Remarkably, NAD+at the onset of the rest phase was accompanied by uncoupled oscillations between the SCN and the hepatic clock, which were phase inverted in the liver, while keeping behavioral rhythms largely intact. These findings demonstrate that the time of day determines the beneficial effects of NAD+-based therapies and pave the way for the basic strategy of a chronobiology-based therapeutic approach.
The spatiotemporal neural dynamics of object recognition for natural images and line drawings
Authors: Singer Johannes J.D. , Cichy Radoslaw M. , Hebart Martin N. 
Published: August 2022

1.AbstractDrawings offer a simple and efficient way to communicate meaning. While line drawings capture only coarsely how objects look in reality, we still perceive them as resembling real-world objects. Previous work has shown that this perceived similarity is mirrored by shared neural representations for drawings and natural images, which suggests that similar mechanisms underlie the recognition of both. However, other work has proposed that representations of drawings and natural images become similar only after substantial processing has taken place, suggesting distinct mechanisms. To arbitrate between those alternatives, we measured brain responses resolved in space and time using fMRI and MEG, respectively, while human participants (female and male) viewed images of objects depicted as photographs, line drawings, or sketch-like drawings. Using multivariate decoding, we demonstrate that object category information emerged similarly fast and across overlapping regions in occipital, ventral-temporal and posterior parietal cortex for all types of depiction, yet with smaller effects at higher levels of visual abstraction. In addition, cross-decoding between depiction types revealed strong generalization of object category information from early processing stages on. Finally, by combining fMRI and MEG data using representational similarity analysis, we found that visual information traversed similar processing stages for all types of depiction, yet with an overall stronger representation for photographs. Together our results demonstrate broad commonalities in the neural dynamics of object recognition across types of depiction, thus providing clear evidence for shared neural mechanisms underlying recognition of natural object images and abstract drawings.2.Significance StatementWhen we see a line drawing, we effortlessly recognize it as an object in the world despite its simple and abstract style. Here we asked to what extent this correspondence in perception is reflected in the brain. To answer this question, we measured how neural processing of objects depicted as photographs and line drawings with varying levels of detail (from natural images to abstract line drawings) evolves over space and time. We find broad commonalities in the spatiotemporal dynamics and the neural representations underlying the perception of photographs and even abstract drawings. These results indicate a shared basic mechanism supporting recognition of drawings and natural images.
SIC50: Determination of IC50 by an optimized Sobel operator and a vision transformer
Authors: Wang Yongheng , Zhang Weidi , Yip Hoyin , Qu Chuyuan , Hu Hongru , Chen Xiaotie , Lee Teresa , Yang Xi , Yang Bingjun , Kumar Priyadarsini , Lee Su Yeon , Casimiro Javier J. , Zhang Jiawei , Lam Kit S. , Wang Aijun 
Published: August 2022

AbstractAs a measure of cytotoxic potency, half-maximal inhibitory concentration (IC50) is the concentration at which a drug exerts half of its maximal inhibitory effect against target cells. It can be determined by various methods that require applying additional reagents or lysing the cells. Here, we describe a label-free Sobel-edge-based method, which we name SIC50, for the evaluation of IC50. SIC50 classifies pre-processed phase-contrast images with a state-of-art vision transformer and allows for the continuous assessment of IC50 in a faster and more cost-efficient manner. We have validated this method using four drugs and 1536-well plates, as well as built a first-of-its-kind web application. We anticipate this method will assist in the high-throughput screening of chemical libraries (e.g., small molecule drugs, siRNA, and microRNA and drug discovery.
Deep generative modeling of transcriptional dynamics for RNA velocity analysis in single cells
Authors: Gayoso Adam , Weiler Philipp , Lotfollahi Mohammad , Klein Dominik , Hong Justin , Streets Aaron , Theis Fabian J. , Yosef Nir 
Published: August 2022

AbstractRNA velocity has been rapidly adopted to guide the interpretation of transcriptional dynamics in snapshot single-cell transcriptomics data. Current approaches for estimating and analyzing RNA velocity can empirically reveal complex dynamics but lack effective strategies for quantifying the uncertainty of the estimate and its overall applicability to the system of interest. Here, we present veloVI (velocity variational inference), a deep generative modeling framework for estimating RNA velocity. veloVI learns a gene-specific dynamical model of RNA metabolism and provides a transcriptome-wide quantification of velocity uncertainty. We show in a series of examples that veloVI compares favorably to previous approaches for inferring RNA velocity with improvements in fit to the data, consistency across transcriptionally similar cells, and stability across preprocessing pipelines for quantifying RNA abundance. Further, we demonstrate that properties unique to veloVI, such as posterior velocity uncertainty, can be used to assess the appropriateness of analysis with velocity to the data at hand. Finally, we highlight veloVI as a flexible framework for modeling transcriptional dynamics by adapting the underlying dynamical model to use time-dependent transcription rates.
Reprogramming of lactate metabolism is linked to the oncogenesis of the virus-induced leukemia
Authors: Toyoda Kosuke , Yasunaga Jun-ichirou , Arima Yuichiro , Tsujita Kenichi , Tanaka Azusa , Hussein Osama , Sonoda Miyu , Watanabe Miho , Shichijo Takafumi , Kurita Daisuke , Nakashima Kazutaka , Yamada Kyohei , Miyoshi Hiroaki , Ohshima Koichi , Matsuoka Masao 
Published: August 2022

SummaryAcceleration of glycolysis is a common trait of cancer. A key metabolite, lactate, is properly secreted from cancer cells, since its accumulation is toxic. Here, we report that a viral oncogene, HTLV-1 bZIP factor (HBZ), bimodally upregulates TAp73 to promote lactate excretion from adult T-cell leukemia-lymphoma (ATL) cells. HBZ protein binds to EZH2 and reduces its occupancy of the TAp73 promoter. Meanwhile, HBZ RNA activates TAp73 transcription via the BATF3-IRF4 machinery. TAp73 upregulates the lactate transporters MCT1 and MCT4. Inactivation of TAp73 leads to intracellular accumulation of lactate, inducing cell death in ATL cells. Furthermore, TAp73 knockout diminished development of inflammation in HBZ-transgenic mice. An MCT1/4 inhibitor, syrosingopine, decreased the growth of ATL cells in vitro and in vivo. MCT1/4 expression was positively correlated with TAp73 in many cancers, and their upregulations were associated with dismal prognosis. Activation of the TAp73-MCT1/4 pathway could be a common mechanism contributing to oncogenesis.
Neutrophils in the brain are sources of neuroprotective molecules and demonstrate functional heterogeneity during chronicToxoplasma gondiiinfection
Authors: Bergersen Kristina V. , Kavvathas Bill , David Clement , Ford Byron D. , Wilson Emma H. 
Published: August 2022

AbstractInfection with the protozoan parasiteToxoplasma gondiileads to the formation of lifelong cysts in neurons of the brain that can have devastating consequences in the immunocompromised. However, despite the establishment of a chronic inflammatory state and infection-induced neurological changes, there are limited signs of clinical neuropathology resulting in an asymptomatic infection in the immunocompetent. This suggests the work of neuroprotective mechanisms to prevent clinical manifestations of disease. However, such sources of neuroprotection during infection remain largely unknown. This study identifies a population of neutrophils chronically present in the brain during Toxoplasma infection that express the neuroprotective molecules NRG-1, ErbB4, and MSR1. Further phenotyping of this population via flow cytometry and singe-cell RNA sequencing reveals two distinct subsets of neutrophils based on age that display functional heterogeneity. This includes cells transcriptionally prepared to function both as anti-parasitic effector cells and in a more alternative protective manner. Chronic depletion of neutrophils results in increased parasite burden and infection-induced vascular pathology. Lack of neutrophils during chronic infection also deleteriously affects neuronal regeneration and repair mechanisms. In conclusion, this work identifies and demonstrates a functionally diverse chronic neutrophil population that plays a dynamic role in controlling infection outcome in the CNS by balancing classical responses with neuroprotective functions.Author SummaryThe predominantly asymptomatic nature of chronicToxoplasma gondiiinfection despite the life-long infection of neurons suggests that there are neuroprotective mechanisms at work in the brain to maintain homeostasis and integrity. This study identifies neutrophils, normally considered a first-responding innate immune cell, as a prominent source of neuroprotective molecules duringToxoplasmainfection. Aged neutrophils in the brain exhibit an ability to be functionally flexible expressing signatures of classical proinflammatory responses; and neuroprotective, pro-angiogenic indicators. Lack of neutrophils during chronic infection leads to increased parasite burden, increased vascular damage, and decreased neuronal regeneration. We conclude that chronic brain neutrophils are a functionally dynamic population and a source of neuroprotection during infection and suggest that this is a potentially novel target to promote brain tissue repair without compromising anti-microbial activity.
Diversity of Ganglion Cell Responses to Saccade-like Image Shifts in the Primate Retina
Authors: Nitsche Steffen , Khani Mohammad H. , Karamanlis Dimokratis , Erol Yunus C. , Zapp Sören J. , Mietsch Matthias , Protti Dario A. , Rozenblit Fernando , Gollisch Tim 
Published: August 2022

AbstractSaccades are a fundamental part of natural vision. They interrupt fixations of the visual gaze and rapidly shift the image that falls onto the retina. These stimulus dynamics can cause activation or suppression of different retinal ganglion cells, but how they affect the encoding of visual information in different types of ganglion cells is largely unknown. Here, we recorded spiking responses to saccade-like shifts of luminance gratings from ganglion cells in isolated marmoset retinas and investigated how the activity depended on the combination of pre- and post-saccadic images. All identified cell types, On and Off parasol and midget cells as well as a type of Large Off cells, displayed distinct response patterns, including particular sensitivity to either the pre- or the post-saccadic image or combinations thereof. In addition, Off parasol and Large Off cells, but not On cells, showed pronounced sensitivity to whether the image changed across the transition. Stimulus sensitivity of On cells could be explained based on their responses to step changes in light intensity, whereas Off cells, in particular, parasol and the Large Off cells, seem to be affected by additional interactions that are not triggered during simple light-intensity flashes. Together, our data show that ganglion cells in the primate retina are sensitive to different combinations of pre- and post-saccadic visual stimuli. This contributes to the functional diversity of the retina’s output signals and to asymmetries between On and Off pathways and provides evidence of signal processing beyond what is triggered by isolated steps in light intensity.
Climate change, biotic yield gaps and disease pressure in cereal crops
Authors: Raza Muhammad Mohsin , Bebber Daniel P. 
Published: August 2022

AbstractPlant diseases are major causes of crop yield losses and exert a financial burden via expenditure on disease control. The magnitude of these burdens depends on biological, environmental and management factors, but this variation is poorly understood. Here we model the effects of weather on potential yield losses due to fungal plant pathogens (the biotic yield gap, Ygb) using experimental trials of fungicide-treated and untreated cereal crops in the UK, and project future Ygb under climate change. We find that Ygb varies between 10 and 20 % of fungicide-treated yields depending on crop, and increases under warmer winter and wetter spring conditions. Ygb will increase for winter wheat and winter barley under climate change, while declining for spring crops because drier summers offset the effects of warmer winters. Potential disease impacts are comparable in magnitude to the effects of suboptimal weather and crop varieties.
Top-down structuring of freshwater bacterial communities by mixotrophic and heterotrophic protists
Authors: Ivanković Marina , Ptacnik Robert , Bengtsson Mia Maria 
Published: August 2022

AbstractMixotrophic and heterotrophic protists hold a key position in aquatic microbial food webs. They account for the bulk of bacterivory in pelagic systems. However, the potential structuring effect of heterotrophic and especially mixotrophic protists on bacterial communities is far from clear. We conducted standardized short-term grazing experiments, to test for the overall impact on bacterial community structure and possible prey preferences of protist taxa with different phagotrophic nutritional modes. The used protist taxa covered a range from more phototrophic towards heterotrophic strategies, with obligate mixotrophic taxa employing phototrophy as the dominant strategy, towards facultative mixotrophic taxa relying more on phagotrophy, with the end of this gradient being covered by a phagoheterotroph lacking phototrophic capacity. Bacterioplankton from different lake systems was enriched and used to represent semi-natural bacterial assemblages that served as prey communities. Our study showed that similarities in protistan nutritional modes were reflected in similarities in their overall impact on bacterial communities. The impact intensity increased towards clear phagotrophic strategies, with mixotrophs in the phototrophic end of the gradient rather having a stabilizing impact on bacterial communities. Obligate mixotrophs grazed diverse prey in small amounts, while towards strict heterotrophic nutrition we observed an ingestion increase and selective depletion of bacteria with potential high growth rates. Future global change scenarios supporting the domination of obligate mixotrophic bacterivores might promote higher bacterial diversity in the illuminated zone of lakes.
Molecular characterization reveals subclasses of 1q gain in intermediate-risk Wilms tumors
Authors: van Belzen Ianthe A.E.M. , van Tuil Marc , Badloe Shashi , Strengman Eric , Janse Alex , Verwiel Eugène T.P. , van der Leest Douwe F.M. , de Vos Sam , Baker-Hernandez John , Groenendijk Alissa , de Krijger Ronald , Kerstens Hindrik H.D. , Drost Jarno , van den Heuvel-Eibrink Marry M. , Tops Bastiaan B.J. , Holstege Frank C.P. , Kemmeren Patrick , Hehir-Kwa Jayne Y. 
Published: August 2022

SummaryChromosomal alterations have recurrently been identified in Wilms tumors (WTs) and some are associated with poor prognosis. Gain of 1q (1q+) is of special interest given its high prevalence and is currently actively studied for its prognostic value. However, the underlying mutational mechanisms and functional effects remain unknown.For 30 primary WTs, we integrated somatic SNVs, CNs and SVs with expression data and distinguished four clusters characterized by affected biological processes: muscle differentiation, immune system, kidney development and proliferation. We identified 1q+ in eight tumors that differ in mutational mechanisms, subsequent rearrangements and genomic contexts. 1q+ tumors were present in all four expression clusters and individual tumors overexpress different genes on 1q. Through integrating CNs, SVs and gene expression, we identified subgroups of 1q+ tumors reflecting differences in the functional effect of 1q gain, indicating that expression data is likely needed for further risk stratification of 1q+ WTs.
In-vitro Analysis of Hemostatic Cotton Khadi Dressing with Kaolin/Chitosan-based Composition and Its Application as Prospective Wound Dressing
Authors: Raval Aayushi A , Patel Vishwa N , Pancholi Utkarsh V 
Published: August 2022

AbstractThe current investigation illustrates the formulation of Kaolin/Chitosan-based composition by using a simple mechanochemical method that can produce a stabilized hemostatic composition. Chitosan is stabilized in sodium hydroxide solution with which kaolin solution is mixed under controlled conditions. When the formulated hemostatic composition was impregnated on cotton khadi dressing it showed drastically improved hemostatic efficiency as compared to standard cotton gauze. The tightly woven cotton khadi fabric has a larger surface area as compared to standard cotton gauze and so it retains more hemostatic composition. The hemostatic properties of the composition are characterized using various in-vitro testing techniques like bleeding time analysis, clotting time analysis, absorption strength study, and several other parameters. Investigation of the freshly drawn blood samples from humans was used for experimenting in order to obtain highly accurate results. The results demonstrate that Kaolin/Chitosan composite impregnated cotton khadi dressing can noticeably enhance the hemostasis other than being biocompatible as demonstrated through an animal model and fresh blood study.
Cytocipherdetermines significantly different populations of cells in single cell RNA-seq data
Authors: Balderson Brad , Piper Michael , Thor Stefan , Boden Mikael 
Published: August 2022

AbstractIdentification of cell types using single cell RNA-seq (scRNA-seq) is revolutionising the study of multicellular organisms. However, typical scRNA-seq analysis often involves post hoc manual curation to ensure clusters are transcriptionally distinct, which is time-consuming, error-prone, and irreproducible. To overcome these obstacles, we developedCytocipher, a bioinformatics method andscversecompatible software package that statistically determines significant clusters. Application ofCytocipherto normal tissue, development, disease, and large-scale atlas data reveals the broad applicability and power ofCytocipherto generate biological insights in numerous contexts. This included the identification of cell types not previously described in the datasets analyzed, such as CD8+ T cell subtypes in human peripheral blood mononuclear cells; cell lineage intermediate states during mouse pancreas development; and subpopulations of luminal epithelial cells over-represented in prostate cancer.Cytocipheralso scales to large datasets with high test performance, as shown by application to the Tabula Sapiens Atlas representing >480,000 cells.Cytocipheris a novel and generalisable method that statistically determines transcriptionally distinct and programmatically reproducible clusters from single cell data.Cytocipheris available athttps://github.com/BradBalderson/Cytocipher.
A role for the centrosome in regulating the rate of neuronal efferocytosis by microglia in vivo
Authors: Möller Katrin , Brambach Max , Villani Ambra , Gallo Elisa , Gilmour Darren , Peri Francesca 
Published: August 2022

AbstractDuring brain development, many newborn neurons undergo apoptosis and are engulfed by microglia, the tissue-resident phagocytes of the brain, in a process known as efferocytosis. A hallmark of microglia is their highly branched morphology characterised by the presence of numerous dynamic extensions that these cells use for scanning the brain parenchyma and engulfing unwanted material. The mechanisms driving branch formation and apoptotic cell engulfment in microglia are unclear. By taking a live imaging approach in zebrafish, we show that while microglia generate multiple microtubule-based branches, they only successfully engulf one apoptotic neuron at a time. Further investigation into the mechanism underlying this sequential engulfment revealed that targeted migration of the centrosome into one branch is predictive of phagosome formation and polarised vesicular trafficking. Moreover, experimentally doubling centrosomal numbers in microglia increases the rate of engulfment and even allows microglia to remove two neurons simultaneously, providing direct supporting evidence for a model where centrosomal migration is a rate-limiting step in branch-mediated efferocytosis. Conversely, light-mediated depolymerization of microtubules causes microglia to lose their typical branched morphology and switch to an alternative mode of engulfment, characterised by directed migration towards target neurons, revealing unexpected plasticity in their phagocytic ability. Finally, building on work focusing on the establishment of the immunological synapse, we identified a conserved signalling pathway underlying centrosomal movement in engulfing microglia.