bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV viral protein R induces loss of DCT1-type renal tubules
Authors: Latt Khun Zaw , Yoshida Teruhiko , Shrivastav Shashi , Abedini Amin , Reece Jeff M. , Sun Zeguo , Lee Hewang , Okamoto Koji , Dagur Pradeep , Heymann Jurgen , Zhao Yongmei , Chung Joon-Yong , Hewitt Stephen , Jose Pedro A. , Lee Kyung , He John Cijiang , Winkler Cheryl A. , Knepper Mark A. , Kino Tomoshige , Rosenberg Avi Z. , Susztak Katalin , Kopp Jeffrey B. 
Published: February 2023

AbstractHyponatremia and salt wasting is a common occurance in patients with HIV/AIDS, however, the understanding of its contributing factors is limited. HIV viral protein R (Vpr) contributes to HIV-associated nephropathy. To investigate the effects of Vpr on the expression level of theSlc12a3gene, encoding the Na-Cl cotransporter, which is responsible for sodium reabsorption in distal nephron segments, we performed single-nucleus RNA sequencing of kidney cortices from three wild-type (WT) and three Vpr-transgenic (Vpr Tg) mice. The results showed that the percentage of distal convoluted tubule (DCT) cells was significantly lower in Vpr Tg mice compared with WT mice (P < 0.05), and that in Vpr Tg mice,Slc12a3expression was not different in DCT cell cluster. ThePvalb+DCT1 subcluster had fewer cells in Vpr Tg mice compared with WT (P < 0.01). Immunohistochemistry demonstrated fewerSlc12a3+Pvalb+DCT1 segments in Vpr Tg mice. Differential gene expression analysis comparing Vpr Tg and WT in the DCT cluster showedIer3, an inhibitor of apoptosis, to be the most downregulated gene. These observations demonstrate that the salt-wasting effect of Vpr in Vpr Tg mice is mediated by loss ofSlc12a3+Pvalb+DCT1 segments via apoptosis dysregulation.
Effects of combined use of alcohol and delta-9-tetrahydrocannibinol on working memory in Long Evans rats
Authors: Carrica Lauren K. , Choi Chan Young , Walter Francis A. , Noonan Brynn L. , Shi Linyuan , Johnson Clare T. , Bradshaw Heather B. , Liang Nu-Chu , Gulley Joshua M. 
Published: February 2023

AbstractThe increase in social acceptance and legalization of cannabis over the last several years is likely to increase the prevalence of its co-use with alcohol. In spite of this, the potential for effects unique to co-use of these drugs, especially in moderate doses, has been studied relatively infrequently. We addressed this in the current study using a laboratory rat model of voluntary drug intake. Periadolescent male and female Long-Evans rats were allowed to orally self-administer ethanol, Δ9-tetrahydrocannibinol (THC), both drugs, or their vehicle controls from postnatal day (P) 30 to P47. They were subsequently trained and tested on an instrumental behavior task that assesses attention, working memory and behavioral flexibility. Similar to previous work, consumption of THC reduced both ethanol and saccharin intake in both sexes. Blood samples taken 14h following the final self-administration session revealed that females had higher levels of the THC metabolite THC-COOH. There were modest effects of THC on our delayed matching to position (DMTP) task, with females exhibiting reduced performance compared to their control group or male, drug using counterparts. However, there were no significant effects of co-use of ethanol or THC on DMTP performance, and drug effects were also not apparent in the reversal learning phase of the task when non-matching to position was required as the correct response. These findings are consistent with other published studies in rodent models showing that use of these drugs in low to moderate doses does not significantly impact memory or behavioral flexibility following a protracted abstinence period.
A Novel MHC-Independent Mechanism of Tumor Cell Killing by CD8+T Cells
Authors: Lerner Emily , Woroniecka Karolina , D’Anniballe Vincent , Wilkinson Daniel , Lorrey Selena , Waibl-Polania Jessica , Wachsmuth Lucas , Miggelbrink Alexandra , Raj Jude , Mohan Aditya , Cook Sarah , Tomaszewski William , Cui Xiuyu , Khasraw Mustafa , Gunn Michael D. , Fecci Peter E. 
Published: February 2023

AbstractThe accepted paradigm for both cellular and antitumor immunity relies upon tumor cell kill by CD8+T cells recognizing cognate antigens presented in the context of target cell major histocompatibility complex class I (MHC I) molecules. Likewise, a classically described mechanism of tumor immune escape is tumor MHC-I downregulation. Here, we report that CD8+T cells maintain the capacity to kill tumor cells that are entirely devoid of MHC-I expression. This capacity proves to be dependent on interactions between T cell NKG2D and tumor NKG2D ligands (NKG2DL). Necessarily, tumor cell kill in these instances is antigen-independent, although prior T cell antigen-specific activation is required and can be furnished by myeloid cells or even neighboring MHC-replete tumors cells. These mechanisms are activein vivoin mice, as well asin vitroin human tumor systems, and are obviated by NKG2D knockout or blockade. Tumor cell killing following T cell NKG2D engagement is Fas-independent and appears to involve granzyme. These studies potentially obviate the long-advanced notion that downregulation of MHC-I is a viable means of tumor immune escape, and instead identify the NKG2D/NKG2DL axis as a novel therapeutic target for enhancing T cell-dependent anti-tumor immunity against MHC loss variants.
Endothelial cell derived microvesicles modulate cerebrovascular and brain aging via miR-17-5p and serve as potential biomarkers for vascular aging
Authors: Zhang Huiting , Xie Zi , Zhao Yuhui , Chen Yanyu , Xu Xiaobing , Ye Ye , Yang Yuping , Zhong Wangtao , Zhao Bin , Ma Xiaotang 
Published: February 2023

AbstractVascular aging, characterized by brain endothelial cells (ECs) senescence and dysfunction, has been known to lead to various age-related cerebrovascular and neurodegenerative diseases. However, its underlying mechanisms remain elusive. ECs derived microvesicles (EMVs) and exosomes (EEXs) carry the characteristics of parent cells and transfer their contents to modulate the functions of recipient cells, holding the potential to evaluate or regulate vascular aging. Here, we found that young or aged ECs released EMVs were more effective than their released EEXs on alleviating or aggravating mice cerebrovascular and brain aging as indicated by SA-β-gal staining, cerebral blood flow, blood brain barrier function, aging related markers and cognitive ability test. We further identified that these EMVs regulated cerebrovascular and brain aging by transferring miR-17-5p and could modulate ECs senescence and functions via miR-17-5p/PI3K/Akt pathway. Plasma EMVs and their contained miR-17-5p (EMV-miR-17-5p) were significantly increased or decreased in the elderly, and were closely correlated with vascular aging. Receiver Operating Characteristic (ROC) analysis showed that the area under the curve was 0.724 for EMVs, 0.77 for EMV-miR-17-5p and 0.815 for their combination for distinguishing vascular aging. Our results revealed the novel roles for EMVs that could more effectively modulate vascular and brain aging than EEXs by regulating ECs functions through miR-17-5p/PI3K/Akt pathway, and also suggested that EMVs and EMV-miR-17-5p represent promising biomarkers and therapeutic targets for vascular aging.
Population dynamics hide phenotypic changes driven by subtle chemical exposures: implications for risk assessments
Authors: del Arco Ana , Becks Lutz , de Vicente Inmaculada 
Published: February 2023

AbstractEcological risk assessment of chemicals focuses on the response of different taxa in isolation not taking ecological and evolutionary interplay in communities into account. Its consideration would, however, allow for an improved assessment by testing for implications within and across trophic levels and changes in the phenotypic and genotypic diversity within populations. We present a simple experimental system that can be used to evaluate the ecological and evolutionary responses to chemical exposure at microbial community levels. We exposed a microbial model system of the ciliateTetrahymena thermophila(predator) and the bacteriumPseudomonas fluorescens(prey) to iron released from Magnetic Particles (MP-Fedis), which are Phosphorus (P) adsorbents used in lake restoration. Our results show that while the responses of predator single population size differed across concentrations of MP-Fedisand the responses of prey from communities differed also across concentration of MP-Fedis, the community responses (species ratio) were similar for the different MP-Fedisconcentrations. Looking further at an evolutionary change in the bacterial preys’ defence, we found that MP-Fedisdrove different patterns and dynamics of defence evolution. Overall, our study shows how similar community dynamics mask changes at evolutionary levels what would be overlooked in the design of current risk assessment protocols where evolutionary approaches are not considered.
Automated microarray for single-cell sorting and collection of lymphocytes following HIV reactivation
Authors: Cortés-Llanos Belén , Jain Vaibhav , Volkheimer Alicia , Browne Edward P. , Murdoch David M. , Allbritton Nancy L. 
Published: February 2023

AbstractA promising strategy to cure HIV infected individuals is to use latency reversing agents (LRAs) to reactivate latent viruses, followed by host clearance of infected reservoir cells. However, reactivation of latent proviruses within infected cells is heterogeneous and often incomplete. This fact limits strategies to cure HIV which may require complete elimination of viable virus from all cellular reservoirs. For this reason, understanding the mechanism(s) of reactivation of HIV within cellular reservoirs is critical to achieve therapeutic success. Methodologies enabling temporal tracking of single cells as they reactivate followed by sorting and molecular analysis of those cells are urgently needed. To this end, microraft arrays were adapted to image T-lymphocytes expressing mCherry under the control of the HIV long terminal repeat (LTR) promoter, in response to the application of various LRAs (prostratin, iBET151, and SAHA). In response to prostratin, iBET151, and SAHA, 30.5 %, 11.2 %, and 12.1 % percentage of cells respectively, reactivated similar to that observed in other experimental systems. The arrays enabled large numbers of single cells (>25,000) to be imaged over time. mCherry fluorescence quantification identified cell subpopulations with differing reactivation kinetics. Significant heterogeneity was observed at the single cell level between different LRAs in terms of time to reactivation, rate of mCherry fluorescence increase upon reactivation, and peak fluorescence attained. In response to prostratin, subpopulations of T lymphocytes with slow and fast reactivation kinetics were identified. Single T-lymphocytes that were either fast or slow reactivators were sorted, and single-cell RNA-sequencing was performed. Different genes associated with inflammation, immune activation, and cellular and viral transcription factors were found. These results advance our conceptual understanding of HIV reactivation dynamics at the single-cell level toward a cure for HIV.
Individual prediction tendencies do not generalise across modalities
Authors: Schubert Juliane , Suess Nina , Weisz Nathan 
Published: February 2023

ABSTRACTPredictive processing theories, which model the brain as a “prediction machine”, explain a wide range of cognitive functions, including learning, perception and action. Furthermore, it is increasingly accepted that aberrant prediction tendencies play a crucial role in psychiatric disorders. Given this explanatory value for clinical psychiatry, prediction tendencies are often implicitly conceptualised as individual traits or as tendencies that generalise across situations. As this has not yet explicitly been shown, in the current study, we quantify to what extent the individual tendency to anticipate sensory features of high probability generalises across modalities. Using magnetoencephalography (MEG), we recorded brain activity while participants were presented a sequence of four different (either visual or auditory) stimuli, which changed according to predefined transitional probabilities of two entropy levels: ordered vs. random. Our results show that, on a group-level, under conditions of low entropy, stimulus features of high probability are preactivated in the auditory but not in the visual modality. Crucially, the magnitude of the individual tendency to predict sensory events seems not to correlate between the two modalities. Furthermore, reliability statistics indicate poor internal consistency, suggesting that the measures from the different modalities are unlikely to reflect a single, common cognitive process. In sum, our findings suggest that quantification and interpretation of individual prediction tendencies cannot be generalised across modalities.
Identical Tau Filaments in Subacute Sclerosing Panencephalitis and Chronic Traumatic Encephalopathy
Authors: Qi Chao , Hasegawa Masato , Takao Masaki , Sakai Motoko , Sasaki Mayasuki , Mizutani Masashi , Akagi Akio , Iwasaki Yasushi , Miyahara Hiroaki , Yoshida Mari , Scheres Sjors H.W. , Goedert Michel 
Published: February 2023

ABSTRACTSubacute sclerosing panencephalitis (SSPE) occurs in some individuals after measles infection, following a symptom-free period of several years. It resembles chronic traumatic encephalopathy (CTE), which happens after repetitive head impacts or exposure to blast waves, following a symptom-free period. As in CTE, when present, the neurofibrillary changes of SSPE are concentrated in superficial cortical layers. Here we used electron cryo-microscopy of tau filaments from two cases of SSPE to show that the tau folds of SSPE and CTE are identical. Two types of filaments were each made of two identical protofilaments with an extra density in the β-helix region. Like in CTE, the vast majority of tau filaments were Type I, with a minority of Type II filaments. These findings suggest that the CTE tau fold can be caused by different environmental insults, which may be linked by inflammatory changes.
Monitoring plasma nucleosome concentrations to measure disease response and progression in dogs with hematopoietic malignancies
Authors: Wilson-Robles Heather , Warry Emma , Miller Tasha , Jarvis Jill , Matsushita Matthew , Miller Pamela , Herzog Marielle , Turatsinze Jean-Valery , Kelly Theresa K. , Butera S. Thomas , Michel Gaetan 
Published: February 2023

AbstractBackgroundHematopoietic malignancies are extremely common in pet dogs and represent nearly 30% of the malignancies diagnosed in this population each year. Clinicians commonly use existing tools such as physical exam findings, radiographs, ultrasound and baseline blood work to monitor these patients for treatment response and remission. Circulating biomarkers, such as prostate specific antigen or carcinoembryonic antigen, can be useful tools for monitoring treatment response and remission status in human cancer patients. To date, there has a been a lack of useful circulating biomarkers available to veterinary oncology patients.MethodsCirculating plasma nucleosome concentrations were evaluated at diagnosis, throughout treatment and during remission monitoring for 40 dogs with lymphoma, acute myelogenous leukemia and multiple myeloma. Additionally, C-reactive protein and thymidine kinase-1 levels were recorded.ResultsPlasma nucleosome concentrations were significantly higher at diagnosis and progressive disease than they were when dogs were in remission. All but two dogs had plasma nucleosome concentrations that returned to the low range during treatment. These two dogs had the shortest progression free and overall survival times. Dogs with the highest plasma nucleosome concentrations had a significantly shorter first progression free survival than dogs with lower plasma nucleosome concentrations at diagnosis. Plasma nucleosome concentrations correlated better with disease response and progression than either thymidine kinase or C reactive protein.ConclusionsPlasma nucleosome concentrations can be a useful tool for treatment monitoring and disease progression in dogs with hematopoietic malignancies.
sciCSR infers B cell state transition and predicts class-switch recombination dynamics using single-cell transcriptomic data
Authors: Ng Joseph CF , Garcia Guillem Montamat , Stewart Alexander T , Blair Paul , Dunn-Walters Deborah K , Mauri Claudia , Fraternali Franca 
Published: February 2023

AbstractClass-switch recombination (CSR) is an integral part of B cell maturation. Steady-state analyses of isotype distribution (e.g. B cell receptor [BCR] repertoire analysis of snapshots during an immune response) do not directly measure CSR dynamics, which is crucial in understanding how B cell maturation is regulated across time. We present sciCSR (pronounced ‘scissor’, single-cell inference of class switch recombination), a computational pipeline which analyses CSR events and dynamics of B cells from single-cell RNA-sequencing (scRNA-seq) experiments. sciCSR re-analyses transcriptomic sequence alignments to differentiate productive heavy-chain immunoglobulin transcripts from germline “sterile” transcripts. From a snapshot of B cell scRNA-seq data, a Markov state model is built by the pipeline to infer the dynamics and direction of CSR. Applying sciCSR on SARS-CoV-2 vaccination time-course scRNA-seq data, we observe that sciCSR predicts, using data from an earlier timepoint in the collected time-course, the isotype distribution of BCR repertoires of subsequent timepoints with high accuracy (cosine similarity ∼ 0.9). sciCSR also recapitulates CSR patterns in mouse models where B cell maturation was perturbed using gene knockouts. sciCSR infers cell state transitions using processes specific to B cells, identifies transitions which are often missed by conventional RNA velocity analyses, and can reveal insights into the regulation of CSR and the dynamics of B cell maturation during an immune response.
Manganese Enhanced Magnetic Resonance Imaging reveals light-induced brain asymmetry in embryo
Authors: Lorenzi Elena , Tambalo Stefano , Vallortigara Giorgio , Bifone Angelo 
Published: February 2023

AbstractThe idea that sensory stimulation to the embryo (in uteroorin ovo) may be crucial for brain development is widespread. Unfortunately, up to now evidence was only indirect because imaging of embryonic brain activityin vivowas not viable. Here we applied for the first time Manganese Enhanced Magnetic Resonance Imaging (MEMRI) to the eggs of domestic chicks. We revealed light-induced brain asymmetry by comparing embryonic brain activityin vivoof eggs that were stimulated by light or maintained in the darkness. Our protocol paves the way to investigation of the effects of a variety of sensory stimulations on brain activity in embryo.SignificanceSensory stimulation in embryo may be crucial for many aspects of brain and behavioral development (e.g., mother language in humans). However, direct evidence of this is lacking because imaging of embryonic brain activityin vivois not viable. Here we established a new protocol for measuring embryonic brain activityin vivoin domestic chick eggs. We were able to visualize in vivo the effect of light stimulation on the development of structural brain asymmetries of the embryo. The protocol established paves the way for collecting further evidence on the effects of sensory stimulation on embryonic brain activity.
Is environmental enrichment beneficial for laboratory animals? A systematic review of studies in zebrafish
Authors: Gallas-Lopes Matheus , Benvenutti Radharani , Donzelli Nayne I. Z. , Marcon Matheus 
Published: February 2023

ABSTRACTEnvironmental enrichment (EE) consists of a series of interventions that are carried out in the home environment to provide greater exposure to sensory stimuli with the objective of mimicking the natural habitat for the animals housed in the laboratory, offering a more complex environment like those found in nature. Some studies have shown the positive effects of EE on zebrafish housed in a laboratory environment. However, this evidence is still very recent and accompanied by contradictory results. Furthermore, there is great variability in the protocols applied, and in the conditions of the tests, tanks, and materials used for creating an EE environment. This substantial variability can bring many uncertainties to the development of future studies and hinder the reproducibility and replicability of research. In this context, the main objective of this study was to carry out a systematic review of the literature aiming to provide an overview of the EE protocols used in zebrafish. We conducted a systematic review following PRISMA recommendations. The literature search was performed in PubMed, Scopus, and Web of Science databases and the studies were selected based on inclusion/exclusion criteria. We performed data extraction and risk of bias analysis of the studies included. A total of 901 articles were identified in the databases and 27 of these studies were included in this review. Among these studies, the effect of EE was evaluated as two different proposals. (1) to improve animal welfare and (2) as an intervention for the prevention of some disorders. Although the zebrafish EE protocols presented a series of experimental differences, the results showed that the benefits of the EE for zebrafish were robust. According to the results described here, the use of EE in the zebrafish home tank provides better welfare and may reduce sources of bias in scientific experiments, such as high-stress levels and fighting events.