bluuebunny/crossref_metadata_2025_split huggingface dataset:
A unique subset of pericystic endothelium associates with aberrant microvascular remodelling and impaired blood perfusion early in polycystic kidney disease
Authors: Jafree Daniyal J , Perera Charith , Ball Mary , Tolomeo Daniele , Pomeranz Gideon , Wilson Laura , Davis Benjamin , Mason William J , Funk Eva Maria , Kolatsi-Joannou Maria , Polschi Radu , Malik Saif , Stewart Benjamin J , Price Karen L , Mitchell Hannah , Motallebzadeh Reza , Muto Yoshiharu , Lees Robert , Needham Sarah , Moulding Dale , Chandler Jennie C , Walsh Claire L , Woolf Adrian S , Winyard Paul J D , Scambler Peter J , Hägerling René , Clatworthy Menna R , Humphreys Benjamin D , Lythgoe Mark F , Walker-Samuel Simon , Long David A 
Published: March 2024

ABSTRACTHallmarks of autosomal dominant polycystic kidney disease (ADPKD), the most common hereditary kidney anomaly, include expanding fluid-filled epithelial cysts, inflammation, and fibrosis. Despite previous work showing the potential of vascular-based therapies, renal microvascular alterations in ADPKD, and their timing, are poorly understood. Using single-cell transcriptomics of human kidney microvasculature, we identify a population of endothelial cells adjacent to cysts in ADPKD. This pericystic endothelium, distinguishable by its expression of osteopontin (SPP1), has a distinct molecular profile compared to the common endothelial cell injury signature in other kidney diseases. SPP1+pericystic endothelium was also present in an orthologous mouse model of ADPKD before overt kidney functional decline. By interrogating geometric, topological and fractal properties from three-dimensional imaging of early ADPKD mouse kidneys, we show that pericystic endothelium associates with disorganisation and non-uniformity of the renal cortical microvasculature. Concurrently, we detected region-specific reductions in cortical blood flow within ADPKD murine kidneys using arterial spin labelling. We conclude that ADPKD kidneys contain a unique subset of endothelium manifesting with aberrant remodelling and impaired blood perfusion. Its detection, prior to renal functional decline, advocates the vasculature as a therapeutic target to modulate or preserve renal function in early ADPKD.
Maternal cannabis use alters excitatory inputs to corticostriatal efferent neurons in rat offspring
Authors: Ginder Darren E. , Weimar Halle V. , Lindberg Jonathan E.M. , Fisher Zachary D.G. , Lim Miranda M. , Peters James H. , McLaughlin Ryan J. 
Published: March 2024

ABSTRACTWith the recent surge in cannabis legalization across North America, there is legitimate concern that rates of cannabis use during pregnancy will dramatically increase in the coming years. However, the long-term impacts of prenatal cannabis exposure (PCE) on the brain and behavior remain poorly understood. Using a model of passive cannabis vapor exposure, we have previously shown that PCE impairs behavioral flexibility in an attentional set-shifting task in adult offspring, which is orchestrated in part by excitatory inputs from the medial prefrontal cortex (mPFC) to the nucleus accumbens (NAc). Given the fundamental role of these corticostriatal inputs in coordinating flexible reward-seeking strategies, we used a combination of retrograde tracing andex vivoelectrophysiology to test the hypothesis that maternal cannabis use alters the synaptic and intrinsic membrane properties of corticostriatal efferent neurons in exposed male and female rat offspring. Specifically, pregnant rat dams were trained to self-administer vaporized cannabis (69.7% THC; 150 mg/ml) twice daily throughout mating and gestation and offspring were subsequently injected with fluorescent retrobeads into the NAc core prior to conducting whole-cellexvivo recordings of spontaneous excitatory and inhibitory post-synaptic currents (EPSC and IPSC, respectively) in retrolabeled mPFC neurons in adulthood. Our results indicate that PCE increases the frequency of spontaneous glutamatergic events (EPSCs) in NAc-projecting mPFC neurons in a sex-specific manner, which drives changes in excitatory to inhibitory (EPSC/IPSC) ratio, particularly in females. Furthermore, the amplitude of phasic glutamatergic events was reduced in cannabis-exposed offspring of both sexes, suggesting changes in postsynaptic receptor function. Altogether, these data demonstrate that PCE shifts the balance of excitatory/inhibitory inputs onto NAc-projecting mPFC neurons with limited effects on membrane conductance in females, resulting in reduced sex differences following maternal cannabis self-administration. These results provide putative neurophysiological mechanisms mediating previously observed behavioral changes, and future studies will need to test if these cannabis-induced changes are causal to long-term deficits in behavioral flexibility that have been previously documented in exposed offspring.
Improved synthesis and application of an alkyne-functionalized isoprenoid analogue to study the prenylomes of motor neurons, astrocytes and their stem cell progenitors
Authors: Suazo Kiall F. , Mishra Vartika , Maity Sanjay , Auger Shelby A. , Justyna Katarzyna , Petre Alex , Ottoboni Linda , Ongaro Jessica , Corti Stefania P. , Lotti Francesco , Przedborski Serge , Distefano Mark D. 
Published: March 2024

AbstractProtein prenylation is one example of a broad class of post-translational modifications where proteins are covalently linked to various hydrophobic moieties. To globally identify and monitor levels of all prenylated proteins in a cell simultaneously, our laboratory and others have developed chemical proteomic approaches that rely on the metabolic incorporation of isoprenoid analogues bearing bio-orthogonal functionality followed by enrichment and subsequent quantitative proteomic analysis. Here, several improvements in the synthesis of the alkyne-containing isoprenoid analogue C15AlkOPP are reported to improve synthetic efficiency. Next, metabolic labeling with C15AlkOPP was optimized to obtain useful levels of metabolic incorporation of the probe in several types of primary cells. Those conditions were then used to study the prenylomes of motor neurons (ES-MNs), astrocytes (ES-As), and their embryonic stem cell progenitors (ESCs), which allowed for the identification of 54 prenylated proteins from ESCs, 50 from ES-MNs and 84 from ES-As, representing all types of prenylation. Bioinformatic analysis revealed specific enriched pathways, including nervous system development, chemokine signaling, Rho GTPase signaling, and adhesion. Hierarchical clustering showed that most enriched pathways in all three cell types are related to GTPase activity and vesicular transport. In contrast, STRING analysis showed significant interactions in two populations that appear to be cell type dependent. The data provided herein demonstrates that robust incorporation of C15AlkOPP can be obtained in ES-MNs and related primary cells purified via magnetic-activated cell sorting allowing the identification and quantification of numerous prenylated proteins. These results suggest that metabolic labeling with C15AlkOPP should be an effective approach for investigating the role of prenylated proteins in primary cells in both normal cells and disease pathologies, including ALS.Abstract Figure
EpicTope: narrating protein sequence features to identify non-disruptive epitope tagging sites
Authors: Zinski Joseph , Chung Henri , Joshi Parnal , Warrick Finn , Berg Brian D. , Glova Greg , McGrail Maura , Balciunas Darius , Friedberg Iddo , Mullins Mary 
Published: March 2024

AbstractEpitope tagging is an invaluable technique enabling the identification, tracking, and purification of proteins in vivo. We developed a tool, EpicTope, to facilitate this method by identifying amino acid positions suitable for epitope insertion. Our method uses a scoring function that considers multiple protein sequence and structural features to determine locations least disruptive to the protein’s function. We validated our approach on the zebrafish Smad5 protein, showing that multiple predicted internally tagged Smad5 proteins rescue zebrafishsmad5mutant embryos, while the N- and C-terminal tagged variants do not, also as predicted. We further show that the internally tagged Smad5 proteins are accessible to antibodies in wholemount zebrafish embryo immunohistochemistry and by western blot. Our work demonstrates that EpicTope is an accessible and effective tool for designing epitope tag insertion sites. EpicTope is available under a GPL-3 license from:https://github.com/FriedbergLab/Epictope
Stress vulnerability and resilience in children facing COVID-19-related discrimination: A quasi-experimental study using polygenic, brain, and sociodemographic data
Authors: Yi Jinwoo , Lee Eunji , Kim Bo-Gyeom , Kim Gakyung , Joo Yoonjung Yoonie , Cha Jiook 
Published: March 2024

AbstractDuring the pandemic, perceived COVID-19-related discrimination aggravated children’s stress levels. The remaining question is to evaluate the individual variability in these effects and to identify vulnerable or resilient populations and why. Using the Adolescent Brain and Cognitive Development dataset (N= 1,116) and causal machine learning approach – Generalized Random Forest, we examined the average and individual treatment effects of perceived discrimination on stress levels immediately and six months later. Their variability and key factors were also assessed. We observed significant variability in the acute effects of perceived discrimination across children and pinpointed the frontotemporal cortical volume and white matter connectivity (streamline counts) as key factors of stress resilience and vulnerability. The variability of these neurostructural factors partially originated from the environmental and genetic attributes. The finding was replicated in held-out samples (N= 2,503). Our study has the potential for personalized prescriptive modeling to prevent children’s future psychopathology after the pandemic.
High Resolution Multi-delay Arterial Spin Labeling with Transformer based Denoising for Pediatric Perfusion MRI
Authors: Shou Qinyang , Zhao Chenyang , Shao Xingfeng , Herting Megan M , Wang Danny JJ 
Published: March 2024

AbstractMulti-delay arterial spin labeling (MDASL) can quantitatively measure cerebral blood flow (CBF) and arterial transit time (ATT), which is particularly suitable for pediatric perfusion imaging. Here we present a high resolution (iso-2mm) MDASL protocol and performed test-retest scans on 21 typically developing children aged 8 to 17 years. We further proposed a Transformer-based deep learning (DL) model with k-space weighted image average (KWIA) denoised images as reference for training the model. The performance of the model was evaluated by the SNR of perfusion images, as well as the SNR, bias and repeatability of the fitted CBF and ATT maps. The proposed method was compared to several benchmark methods including KWIA, joint denoising and reconstruction with total generalized variation (TGV) regularization, as well as directly applying a pretrained Transformer model on a larger dataset. The results show that the proposed Transformer model with KWIA reference can effectively denoise multi-delay ASL images, not only improving the SNR for perfusion images of each delay, but also improving the SNR for the fitted CBF and ATT maps. The proposed method also improved test-retest repeatability of whole-brain perfusion measurements. This may facilitate the use of MDASL in neurodevelopmental studies to characterize typical and aberrant brain development.
An experimental evaluation of the relationship between the induced radiofrequency heating near an implanted conductive medical device during MRI, scanner reported B1+rms, and scanner reported average transmit power
Authors: Gultekin David H. , Vaughan J. Thomas , Shrivastava Devashish 
Published: March 2024

AbstractBackgroundTime-varying radiofrequency (RF) fields necessary to perform magnetic resonance imaging (MRI) may induce excessive heating near implanted conductive medical devices during MRI. Both time and space-averaged root mean square of the effective magnetic field (B1+rms) and whole-body average specific absorption rate (SAR) (average RF power per unit body weight) have been proposed as metrics to control the induced heating and avoid unintended thermal injury.PurposeTo evaluate the relationship between the induced RF heating near an implanted conductive medical device, scanner-reported B1+rms, and scanner-reported RF power.MethodsRF heating was measured near the electrodes of deep brain stimulation (DBS) lead placed in a gel phantom using fluoroptic temperature probes in a commercial 3T scanner during MRI. Four transmit and receive RF coil combinations were used, a circularly polarized head transmit and receive coil, a 20-channel head and neck, a 32-channel head, or a 64-channel head and neck receive-only coil with a whole-body transmit coil. RF heating was induced by running a 2D GRE sequence with two RF pulse types (fast and normal) with varying flip angles of 30°, 60°, and 90° and by turning the receive-only coils off and on. The scanner-reported B1+rms and RF power were recorded.ResultsMeasurements show that the induced temperature change correlated linearly with both the scanner-reported B1+rms and RF power for each coil combination. However, the variation in the induced heating for various RF coil combinations appeared to be much larger for the scanner-reported B1+rms compared to the scanner-reported RF power.ConclusionAdditional studies across other MR scanners are needed to better understand the full extent of the variation in the induced heating near implanted conductive devices as a function of the scanner-reported B1+rms and RF power to develop conservative and reliable patient labeling.
The Global Impact of COVID-19 on Tuberculosis: A Thematic Scoping Review, 2020-2023
Authors: Marco Michael H. , Ahmedov Sevim , Castro Kenneth G. 
Published: March 2024

AbstractBackgroundThis thematic scoping review of publications sought to understand the global impact of COVID-19 on tuberculosis (TB), interpret the scope of resonating themes, and offer policy recommendations to stimulate TB recovery and future pandemic preparedness.Data SourcesPublications were captured from three search engines, PubMed, EBSCO, and Google Scholar, and applicable websites written in English from January 1, 2020, to April 30, 2023.Study SelectionOur scoping review was limited to publications detailing the impact of COVID-19 on TB. Original research, reviews, letters, and editorials describing the deleterious and harmful––yet sometimes positive–– impact of COVID-19 (sole exposure) on TB (sole outcome) were included. The objective was to methodically categorize the impacts into themes through a comprehensive review of selected studies to provide significant health policy guidance.Data ExtractionTwo authors independently screened citations and full texts, while the third arbitrated when consensus was not met. All three performed data extraction.Data Synthesis/ResultsOf 1,755 screened publications, 176 (10%) covering 39 countries over 41 months met the inclusion criteria. Ten principal themes were established, which encompassed TB’s care cascade, patient-centered care, psychosocial issues, and health services: 1) case-finding and notification (n=45; 26%); 2) diagnosis and laboratory systems (n=19; 10.7%) 3) prevention, treatment, and care (n=22; 12.2%); 4) telemedicine/telehealth (n=12; 6.8%); 5) social determinants of health (n=14; 8%); 6) airborne infection prevention and control (n=8; 4.6%); 7) health system strengthening (n=22; 13%); 8) mental health (n=13; 7.4%); 9) stigma (n=11; 6.3%); and 10) health education (n=10; 5.7%).LimitationsHeterogeneity of publications within themes.ConclusionsWe identified ten globally generalizable themes of COVID-19’s impact on TB. These thematic areas will guide evidence-informed policies to strengthen comprehensive global responses, recovery for TB, and future airborne pandemic preparedness.Primary Funding SourceUnited States Agency for International Development
Changes of urinary proteome in rats after intragastric administration of zinc gluconate
Authors: Shen Ziyun , Yang Minhui , Wang Haitong , Gao Youhe 
Published: March 2024

AbstractZinc is an essential element for maintaining normal physiological function in living organisms. In this study, the urine proteome of rats before and after short-term intragastric administration of 82 mg/kg/d zinc gluconate (equivalent to 11.7 mg/kg/d zinc) was compared and analyzed. Many differential proteins have been reported to be zinc-related, such as mucin-2 (MUC-2) (14 times before compared with after gavage, p = 0.005) and transthyretin (3.9 times after gavage compared with before gavage, p = 0.0004). Biological processes enriched in differential proteins (e.g., regulation of apoptosis process, immune system process, etc.), molecular functions (e.g., calcium binding, copper binding, signaling receptor activity, etc.), KEGG pathways (e.g., complement and coagulation cascades, PI3K-Akt signaling pathway, etc.) showed correlation with zinc. In this study, we explore the overall effect of zinc on the body from the perspective of urine proteomics, which is helpful to deeply understand the biological function of zinc and broaden the application potential of urine proteomics.
Why is the Omicron main protease of SARS-CoV-2 less stable than its wild-type counterpart? A crystallographic, biophysical, and theoretical study of the free enzyme and its complex with inhibitor 13b-K
Authors: Ibrahim Mohamed , Sun Xinyuanyuan , de Oliveira Vinicius Martins , Liu Ruibin , Clayton Joseph , Kilani Haifa El , Shen Jana , Hilgenfeld Rolf 
Published: March 2024

AbstractDuring the continuing evolution of SARS-CoV-2, the Omicron variant of concern emerged in the second half of 2021 and has been dominant since November that year. Along with its sublineages, it has maintained a prominent role ever since. The Nsp5 main protease (Mpro) of the Omicron virus is characterized by a single dominant mutation, P132H. Here we determined the X-ray crystal structures of the P132H mutant (or O-Mpro) as free enzyme and in complex with the Mproinhibitor, the alpha-ketoamide13b-K, and we conducted enzymology, biophysical as well as theoretical studies to characterize the O-Mpro. We found that O-Mprohas a similar overall structure and binding with13b-K; however, it displays lower enzymatic activity and lower thermal stability compared to the WT-Mpro(with “WT” referring to the original Wuhan-1 strain). Intriguingly, the imidazole ring of His132 and the carboxylate plane of Glu240 are in a stacked configuration in the X-ray structures determined here. The empirical folding free energy calculations suggest that the O-Mprodimer is destabilized relative to the WT-Mprodue to the less favorable van der Waals interactions and backbone conformation in the individual protomers. The all-atom continuous constant pH molecular dynamics (MD) simulations reveal that His132 and Glu240 display coupled titration. At pH 7, His132 is predominantly neutral and in a stacked configuration with respect to Glu240 which is charged. In order to examine whether the Omicron mutation eases the emergence of further Mpromutations, we also determined crystal structures of the relatively frequent P132H+T169S double mutant but found little evidence for a correlation between the two sites.
Matrix game between full siblings in Mendelian populations
Authors: Garay József , Varga Tamás , Csiszár Villő , Móri Tamás F. , Szilágyi András 
Published: March 2024

AbstractWe demonstrate that static evolutionary stability implies the stability of the corresponding interior equilibrium point in genotype dynamics, while a certain form of monotonicity ensures the global stability of a homozygote state.We apply our findings to familial selection in a diploid, panmictic population, where the survival rates of siblings within monogamous and exogamous families are determined by a matrix game, and the behavior is uniquely determined by an autosomal recessive-dominant or intermediate allele pair. We provide conditions for the existence of each homozygote.In our numerical investigations of the Prisoner’s Dilemma between siblings, we distinguish two scenarios: cooperation (collaborating case) or defector-cooperator strategy pair (alternating case) that maximizes the siblings’ survival rates. Based on the stability of the pure cooperator and defector states, we provide a potential classification of genotype dynamics. We find that the pure cooperator population cannot fixate in the alternating case. However, in the collaborating case, fixation is possible but not necessary, since bistability, coexistence, moreover, the monostable fixation of pure defector state can also occur due to the interplay between the phenotypic payoff function and the genotype-phenotype mapping, which collectively determine the outcome of natural selection. In donation game, the classical Hamilton’s rule implies the fixation of the cooperation in all considered genotype-phenotype mappings.Author SummaryIn this article, we explore the dynamics among full siblings who can mutually aid each other for survival. The strategy (cooperator or defector) of each sibling is determined by Mendelian (dominant-recessive or intermediate) inheritance. The interaction between two siblings is modelled as a Prisoner’s Dilemma. We examine two scenarios: cooperation (collaborating case) and a defector-cooperator strategy pair (alternating case), aiming to maximize the combined survival rates of the interacting siblings. The endpoint of natural selection is determined by Mendelian inheritance and the two Prisoner’s dilemma scenarios. Our findings reveal the potential for the fixation of both cooperation and defection, as well as the stable coexistence of these strategies within the studied selection environment. Notably, in the alternating case, the fixation of a pure cooperating population is not achievable under the considered inheritance systems. Furthermore, when cooperation is recessive, its fixation is more likely but not guaranteed.