bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional profiles of functionally distinct HLADR+CD38+ CD8 T cells subsets from acute febrile dengue patients
Authors: Singh Prabhat , Bajpai Prashant , Maheshwari Deepti , Chawla Yadya M , Gottimukkala Kamalvishnu , Reddy Elluri Seetharami , Saini Keshav , Nayak Kaustuv , Gunisetty Sivaram , Aggarwal Charu , Jain Shweta , Chaitanya  , Singla Paras , Soneja Manish , Wig Naveet , Murali-Krishna Kaja , Chandele Anmol 
Published: September 2022

AbstractPrevious studies showed that a discrete population of the CD8 T cells with HLADR+CD38+ phenotype expand massively during the acute febrile phase of dengue natural infection. Although about a third of these massively expanding HLADR+CD38+ CD8 T cells were of CD69high phenotype, only a small fraction of them produced IFNγ upon in vitro peptide stimulation. What other cytokines/ chemokines do these peptides stimulated HLADR+CD38+ CD8 T cells express, what transcriptional profiles distinguish the CD69+IFNγ+, CD69+IFNγ-, and CD69-IFNγ- subsets, and whether the expansion of the total HLADR+CD38+ CD8 T cells or the IFNγ producing CD8 T cells differ depending on disease severity remained unclear. This study addresses these knowledge gaps. We find that the CD69+IFNγ+ subset uniquely expressed key genes involved in protein translation, cellular metabolism, proliferation and dendritic cell cross talk. Both the CD69+IFNγ+ and CD69+IFNγ- subsets had an antigen responsive gene signature with genes involved in cytotoxic effector functions, regulation of T cell receptor signaling, signaling by MAPK, chemotaxis and T cell trafficking to inflamed tissues with the expression being more robust in the IFNγ+ CD69+ subset. On the other hand, the CD69- IFNγ- subset was biased towards expression of genes that both augment and dampen T cell responses. Lastly, the expansion of total HLADR+ CD38+ CD8 T cells and also the IFNγ producing HLADR+ CD38+ CD8 T cells was similar in patients with different grades of disease. Taken together, this study provides valuable insights into the inherent diversity of the effector CD8 T cell response during dengue.
Low precipitation due to climate change consistently reduces multifunctionality of urban grasslands in mesocosms
Authors: Rojas-Botero Sandra , Teixeira Leonardo H. , Kollmann Johannes 
Published: September 2022

AbstractUrban grasslands are crucial for biodiversity and ecosystem services in cities, while little is known about their multifunctionality under climate change. Thus, we investigated the effects of simulated climate change, i.e., increased [CO2] and temperature, and reduced precipitation, on individual functions and overall multifunctionality in mesocosm grasslands sown with forbs and grasses in four different proportions aiming at mimicking road verge grassland patches. Climate change scenarios RCP 2.6 (control) and RCP 8.5 (worst-case) were simulated in walk-in climate chambers (ca. 7.7 m2), and watering was manipulated for normal vs. reduced precipitation. We measured eight indicator variables of ecosystem functions based on below- and above-ground characteristics. Recently established grassland communities responded to higher [CO2] and warmer conditions with increased vegetation cover, height, flower production, and soil respiration. Lower precipitation affected carbon cycling in the ecosystem by reducing biomass production and soil respiration. In turn, the water regulation capacity of the grasslands depended on precipitation interacting with climate change scenario, given the enhanced water efficiency resulting from increased [CO2] under RCP 8.5. Multifunctionality was negatively affected by reduced precipitation, especially under RCP 2.6. Trade-offs arose among single functions that performed best in either grass- or forb-dominated grasslands. Grasslands with an even ratio of plant functional types coped better with climate change and thus are good options for increasing the benefits of urban green infrastructure. Overall, we provide experimental evidence on the effects of climate change on the functionality of urban ecosystems. Designing the composition of urban grasslands based on ecological theory may increase their resilience to global change.
Time-scaled phylogenetic analysis of extant Lamiinae (Coleoptera, Cerambycidae) species of East of Marmara Basin, Türkiye, and their evolutionary similarity with the Eurasian congeners
Authors: Soydabaş-Ayoub Havva Kübra , Uçkan Fevzi 
Published: September 2022

AbstractThe subfamily Lamiinae (Cerambycidae, Coleoptera) is striking due to its morphological diversity and species richness with intricate phylogenetic relationships. We inferred the phylogeny and evolutionary history of extant species of East of Marmara Basin, Türkiye, from the tribes Acanthocinini, Acanthoderini, Agapanthiini, Batocerini, Dorcadionini, Lamiini, Mesosini, Monochamini, Phytoeciini, Phrynetini, Pogonocherini (including Exocentrini) and Saperdini using partial mitochondrial cytochromecoxidase-I (COI) and16S rRNAand nuclear28S rRNAgene regions (2257 base pair alignment length). The most recent common ancestor (MRCA) of Lamiinae members included in the analyses was dated ∼127 million years ago (Mya) in the Cretaceous. The MRCA of Dorcadionini, Lamiini and Monochamini was younger than the common ancestors of the other close tribes. There was a concurrence between resolutions of Maximum Likelihood (ML) and Bayesian analyses on the affiliations of Dorcadionini and Monochamini to Lamiini and the proximity of Batocerini to Lamiini, Acanthocinini to Acanthoderini, Phrynetini to Pogonocherini, and Phytoeciini to Saperdini. TheCOI-based Neighbor-Joining and ML gene trees suggest that the closest relatives of the extant Lamiinae species of East of Marmara Basin were the European conspecifics or congeners. Moreover,ParaleproderaandLamia(Lamiini) were sisters toImantocera(Gnomini),Oberea(Obereini) toPhytoeciaPhytoeciini), andHippopsis(Agapanthiini) toOmosarotes singularisPascoe, 1860 (Acanthomerosternoplini). Our results support Dorcadionini, Gnomini and Monochamini as synonyms of Lamiini; and Obereini and Phytoeciini of Saperdini and suggest that the emergence of the living tribes included in this study was during Paleogene, and their intrageneric diversifications occurred during Cenozoic, mostly Neogene.
Genome-wide association studies of polygenic risk score-derived phenotypes may lead to inflated false positive rates
Authors: Uffelmann Emil , Posthuma Danielle , Peyrot Wouter J. 
Published: September 2022

AbstractIn a recent study, a polygenic risk score (PRS) for Alzheimer’s disease was used to construct a new phenotype for a subsequent genome-wide association study (GWAS). Here we show that the applied method, in which the same genetic variants are used to construct the PRS-derived phenotype as well as to assess their effect in a GWAS of the same phenotype, leads to inflated false positive rates. We illustrate this bias by simulation. We first simulate an initial discovery cohort, and run a GWAS of a disorder like Alzheimer’s disease. We then simulate a target cohort, in which we construct a PRS based on the initial GWAS results. Following the published study, we select the bottom and top 5% of individuals in the PRS distribution and define them as controls and cases. Lastly, we run a GWAS on the new PRS-derived phenotype using all genetic variants. We show that at a significance threshold of 5 × 10−8, false positive rates are inflated up to 0.004 (an 80,000-fold increase compared to 5 × 10−8). We also show that such inflation can be prevented by excluding all variants that were used to construct the PRS (as well as all variants in linkage disequilibrium), when a GWAS on a PRS-derived phenotype is conducted.
The glutathione S-transferase Gstt1 is a robust driver of survival and dissemination in metastases
Authors: Ferrer Christina M. , Boon Ruben , Cho Hyo Min , Bernasocchi Tiziano , Wong Lai Ping , Cetinbas Murat , Haggerty Elizabeth R. , Mitsiades Irene , Wojtkiewicz Gregory R. , McLoughlin Daniel E. , Kugel Sita , Rheinbay Esther , Sadreyev Ruslan , Juric Dejan , Mostoslavsky Raul 
Published: September 2022

ABSTRACTIdentifying adaptive mechanisms of metastatic cancer cells remains an elusive question in the treatment of metastatic disease, particularly in pancreatic cancer (PDA), where the majority of patients present with metastatic lesions at the time of diagnosis. A loss-of-function shRNA targeted screen in metastatic-derived cells identifiedGstt1, a member of the glutathione S-transferase superfamily, as uniquely required for metastasis and dissemination however dispensable for primary tumor growth.Gstt1is expressed in early disseminated tumor cells (DTCs), is retained within a subpopulation of slow-cycling cells within established metastases and its inhibition led to a regression of macrometastatic lesions. This distinct Gstt1highpopulation is highly metastatic and retains slow-cycling phenotypes, EMT features, and DTC characteristics compared to the Gstt1lowpopulation. Mechanistic studies indicate that in this subset of cells, Gstt1 maintains metastases by binding to and modifying intracellular fibronectin, regulating Fibronectin secretion from cancer cells and deposition into the metastatic microenvironment. We identified Gstt1 as a novel mediator of metastasis, highlighting the importance of metastatic heterogeneity and its influence on the metastatic tumor microenvironment.
Discovery of a novel monoclonal PD-L1 antibody H1A that promotes T-cell mediated tumor killing activity in renal cell carcinoma
Authors: An Zesheng , Hsu Michelle A. , Gicobi Joanina K. , Xu Tianxiao , Harrington Susan M. , Zhang Henan , Pavelko Kevin D. , Hirdler Jacob B. , Lohse Christine M. , Nabavizadeh Reza , Pessoa Rodriguo R. , Sharma Vidit , Thompson R. Houston , Leibovich Bradley C. , Dong Haidong , Lucien Fabrice 
Published: September 2022

AbstractIn the last decade, the therapeutic landscape of renal cell carcinoma has rapidly evolved with the addition of PD-1/PD-L1 immune checkpoint inhibitors in the armamentarium of oncologists. Despite clinical evidence of improved oncological outcomes, only a minority of patients experience long-lasting antitumor immune response and complete response. The intrinsic and acquired resistance to PD-1/PD-L1 immune checkpoint blockade is an important challenge for patients and clinicians as no reliable tool has been developed to predict individualized response to immunotherapy. In this study, we demonstrate the translational relevance of an ex-vivo functional assay that measure the tumor cell killing ability of patient-derived CD8 T cells isolated from peripheral blood. Cytotoxic activity of CD8 T cells was improved at 3-month post-radical nephrectomy compared to baseline and it was associated with higher circulating levels of tumor-reactive effector CD8 T cells (CD11ahighCX3CR1+GZMB+). Pretreatment of peripheral immune cells with FDA-approved PD-1/PD-L1 inhibitors enhanced tumor cell killing activity of CD8 T cells but differential response was observed at the individual patient level. Finally, we found a newly developed monoclonal antibody (H1A), which induces PD-L1 degradation, demonstrated superior efficacy in promoting T-cell mediated tumor killing activity compared to FDA-approved PD-1/PD-L1 inhibitors. PBMC immunophenotyping by mass cytometry revealed enrichment of effector CD8 T cells in H1A-treated PBMC. To conclude, our study lays the ground for future investigation of the therapeutic value of H1A as a next-generation immune checkpoint inhibitor. Furthermore, further work is needed to evaluate the potential of measuring T-cell cytotoxicity activity as a tool to predict individual response to immune checkpoint inhibitors in patients with advanced renal cell carcinoma.
Genetic deletion and pharmacologic inhibition of FcER1 reduces renal injury in mouse models of diabetic nephropathy
Authors: Rashmi Priyanka , Silva Andrea Alice , Sigdel Tara , Damm Izabella , Gouvêa Ana Luisa Figueira , Koliwad Suneil , Walavalkar Vighnesh , Hakroush Samy , Sarwal Minnie M. 
Published: September 2022

AbstractFcER1 forms a high affinity multimeric cell-surface receptor for the Fc region of immunoglobulin E (IgE) and controls the activation of mast cells and basophils. Antigen binding and cross-linking of FcER1 associated IgE induces several downstream signaling pathways that result in diverse outcomes. Canonical signaling through IgE-FcER1 has been related to allergic responses, however, recent studies have identified that their function in mast cell and basophils contribute to other pathogenic conditions such as cancer and diabetes. Previous studies have demonstrated that FcER1 protein is upregulated in advanced diabetic kidney disease (DKD) making it a targetable molecule for the treatment of DKD. This study presents evidence that loss of FcER1 signaling reduces proteinuria and renal injury in two pre-clinical mouse models of diabetes. Mice deficient for fcer1 are protected from streptozotocin mediated induction of proteinuria and display reduced fibrosis and mast cell infiltration in kidney. Furthermore, inhibition of FcER1 signaling with an antibody directed against the γ-subunit reduces proteinuria in a spontaneous model of type II diabetes. Our results show significant reduction of proteinuria and tissue damage in pre-clinical DKD models demonstrating the potential of FcER1 inhibitory approaches for developing new therapies in DKD.
HiC4D: Forecasting spatiotemporal Hi-C data with residual ConvLSTM
Authors: Liu Tong , Wang Zheng 
Published: September 2022

AbstractMotivationThe Hi-C experiments have been extensively used for the studies of mammalian genomic structures. In the last few years, spatiotemporal Hi-C has significantly contributed to the study of genome dynamic reorganization. However, computationally forecasting spatiotemporal Hi-C data still has not been seen in the literature.ResultsWe present HiC4D for addressing the problem of forecasting spatiotemporal Hi-C data. We designed and tested a novel network, which is a combination of residual network and convolutional long short-term memory (ConvLSTM), and named it residual ConvLSTM (ResConvLSTM). We evaluated our new method and compared it with other four methods including three outstanding video-prediction methods from the literature: ConvLSTM, spatiotemporal LSTM (ST-LSTM), and simple video prediction (SimVP), and one self-designed naïve network (NaiveNet) as a baseline. We used four different spatiotemporal Hi-C datasets for the blind test, including two from mouse embryogenesis, one from somatic cell nuclear transfer (SCNT) embryos, and one from human embryogenesis. Our evaluation results indicate that ResConvLSTM almost always outperforms the other four methods on four blind-test datasets in terms of accurately reproducing spatiotemporal Hi-C contact matrices at future time steps. Our benchmarks also indicate that all five methods can successfully recover the boundaries of topologically associating domains (TADs) called on the experimental Hi-C contact matrices.AvailabilityHiC4D is publicly available athttp://dna.cs.miami.edu/HiC4D/.
Haloperidol-induced immediate early genes in striatopallidal neurons requires the converging action of cAMP/PKA/DARPP-32 and mTOR pathways
Authors: Onimus Oriane , Valjent Emmanuel , Fisone Gilberto , Gangarossa Giuseppe 
Published: September 2022

AbstractAntipsychotics share the common pharmacological feature of antagonizing the dopamine 2 receptor (D2R) which is abundant in the striatum and involved in both the therapeutic and side effects of this drugs class. Pharmacological blockade of striatal D2R, by disinhibiting the D2R-containing medium-size spiny neurons (MSNs), leads to a plethora of molecular, cellular and behavioral adaptations which are central in the action of antipsychotics. Here, we focused on the cell type-specific (D2R-MSNs) regulation of some striatal immediate early genes (IEGs), such as cFos, Arc and Zif268. Taking advantage of transgenic mouse models, pharmacological approaches and immunofluorescence analyses, we found that haloperidol-induced IEGs in the striatum required the synergistic activation of A2a (adenosine) and NMDA (glutamate) receptors. At the intracellular signaling level, we found that the PKA/DARPP-32 and mTOR pathways synergistically cooperate to control the induction of IEGs by haloperidol. By confirming and further expanding previous observations, our results provide novel insights into the regulatory mechanisms underlying the molecular/cellular action of antipsychotics in the striatum.
Subjective assessment and taste strips testing of gustatory function, at home, and in the lab
Authors: Green Tomer , Wolf Anne , Oleszkiewicz Anna , Aronis Anna , Hummel Thomas , Pepino Marta Y , Niv Masha Y 
Published: September 2022

AbstractGustatory ability is an important marker of health status, including COVID-19 disease. We compare self-reporting with home and lab psychophysical “taste strips” tests in healthy subjects. The taste test consisted of paper strips impregnated with sweet, bitter, salty, or sour tastants, and with the trigeminal stimulus capsaicin, each in high and in low concentration. The test was carried out either in a controlled lab environment (74 participants, 47 women) with the strips being administered by the experimenter or self-administered by the participants at home (77 participants, 59 women). After self-reporting their subjective assessment of chemosensory ability, the participant identified the taste of each strip and rated intensity and pleasantness.Identification score, intensity, and pleasantness averaged over the 8 taste strips were similar between the lab and the home-administered tests. Self-rated taste ability did not correlate with any of these scores, but strongly correlated with self-rated smell ability in the lab group (r=0.73), and moderately correlated in the home group (r=0.51). Taste identification correlated with intensity ratings (r=0.63 lab, r=0.36 home) but not with the pleasantness ratings (r=-0.14 lab, r=0.1 home).The results of the taste strips test were similar in the lab and at home for healthy young participants and provide a baseline against which taste tests can be compared in future applications.
Design, synthesis and biological evaluation of novel quercetin derivatives as PPAR-γ partial agonists by modulating Epithelial-mesenchymal transition in lung cancer metastasis
Authors: Ballav Sangeeta , Bhosale Mrinalini , Lokhande Kiran Bharat , Paul Manash K. , Padhye Subhash , Swami K. Venkateswara , Ranjan Amit , Basu Soumya 
Published: September 2022

ABSTRACTEpithelial-to-mesenchymal transition (EMT) is responsible for driving metastasis of multiple cancer types including lung cancer. Peroxisome proliferator-activated receptor (PPAR)-γ, a ligand-activated transcription factor, controls expression of variety of genes involved in EMT, cellular differentiation, fatty acid metabolism, insulin sensitivity and adipogenesis. Several synthetic compounds act as potent full agonist for PPAR-γ. However, owing to their serious adverse effects, restricts their long-term application. Therefore, partial agonist has been greatly in demand which involves reduced and balanced PPAR-γ activity. Our previous study discerned the efficacy of quercetin and its derivatives to attain favourable stabilization with PPAR-γ. Here we extended this work by synthesizing five novel quercetin derivatives (QDs) namely thiosemicarbazone (QUETSC) and hydrazones (QUEINH, QUENH, QUE2FH and QUESH) and analysed their effects in modulating EMT of lung cancer cell lines via PPAR-γ partial activation. QDs-treated A549 cells exhibited cell death strongly in a dose and time dependent manner at nanomolar concentration along with anti-migratory effects compared to NCI-H460 cells. Of the five derivatives we screened, QUETSC, QUE2FH and QUESH exhibited the property of partial activation as compared to the over-expressive level of rosiglitazone (RSG). Consistently, with PPAR-γ partial activation, these QDs also suppressed EMT process by markedly down-regulating the levels of mesenchymal markers (Snail, Slug and Zeb-1) and concomitant up-regulation of epithelial marker (E-cadherin). In the light of these evidences; QUETSC, QUE2FH and QUESH could be used as a novel selective partial PPAR-γ modulators whose pharmacological properties is distinct from RSG and may be exploited as potential therapeutic anti-metastatic agent.
The perception of auditory motion in sighted and early blind individuals
Authors: Park Woon Ju , Fine Ione 
Published: September 2022

ABSTRACTMotion detection is a fundamental property of the visual system that plays an important role across many of the human senses. In vision, motion processing is classically described using a motion energy model which assumes spatiotemporally selective (i.e., non-separable) filters that capture the smooth continuous change in spatial position over time afforded by moving objects. However, in the case of audition, it is still not clear whether or not the primary mechanisms underlying motion sensitivity are spatiotemporally selective. We used a psychophysical reverse correlation paradigm, where participants discriminated the direction of a motion signal in the presence of spatiotemporal noise, to determine whether the filters underlying auditory motion discrimination were spatiotemporally separable or non-separable. We then examined whether these auditory motion filters were altered as a result of early blindness. We found that both sighted and early blind individuals have separable filters. However, early blind individuals show increased sensitivity to auditory motion, with reduced susceptibility to noise, with filters that were more accurate in detecting motion onsets/offsets. An ideal observer model suggested that the reliance on separable filters may be more optimal given the limited spatial resolution in auditory input.