bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Effects of HDAC6 Inhibition Versus Knockout During Hepatic Ischemia–Reperfusion Injury Highlight Importance of HDAC6 C-terminal Zinc-finger Ubiquitin-binding Domain
Authors: Concors Seth J. , Hernandez Paul T. , O’Brien Ciaran , DePaolo John , Murken Douglas R. , Aufhauser David D. , Wang Zhonglin , Xiong Yan , Krumeich Lauren , Ge Guanghui , Beier Ulf H. , Bhatti Tricia R. , Kozikowski Alan P. , Avelar Leandro A. Alves , Kurz Thomas , Hancock Wayne W. , Levine Matthew H. 
Published: April 2024

Background.
Ischemia–reperfusion injury (IRI) causes significant morbidity in liver transplantation among other medical conditions. IRI following liver transplantation contributes to poor outcomes and early graft loss. Histone/protein deacetylases (HDACs) regulate diverse cellular processes, play a role in mediating tissue responses to IRI, and may represent a novel therapeutic target in preventing IRI in liver transplantation.

Methods.
Using a previously described standardized model of murine liver warm IRI, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were assessed at 24 and 48 h after reperfusion to determine the effect of different HDAC inhibitors.

Results.
Broad HDAC inhibition with trichostatin-A (TSA) was protective against hepatocellular damage (P < 0.01 for AST and P < 0.05 for ALT). Although HDAC class I inhibition with MS-275 provided statistically insignificant benefit, tubastatin-A (TubA), an HDAC6 inhibitor with additional activity against HDAC10, provided significant protection against liver IRI (P < 0.01 for AST and P < 0.001 for ALT). Surprisingly genetic deletion of HDAC6 or -10 did not replicate the protective effects of HDAC6 inhibition with TubA, whereas treatment with an HDAC6 BUZ-domain inhibitor, LakZnFD, eliminated the protective effect of TubA treatment in liver ischemia (P < 0.01 for AST and P < 0.01 for ALT).

Conclusions.
Our findings suggest TubA, a class IIb HDAC inhibitor, can mitigate hepatic IRI in a manner distinct from previously described class I HDAC inhibition and requires the HDAC6 BUZ-domain activity. Our data corroborate previous findings that HDAC targets for therapeutic intervention of IRI may be tissue-specific, and identify HDAC6 inhibition as a possible target in the treatment of liver IRI.
Stochastic epidemic models and their link with methods from survival analysis
Authors: Putter Hein , Goeman Jelle , Wallinga Jacco 
Published: April 2024

AbstractCompartmental models based on ordinary differential equations (ODE’s) quantifying the interactions between susceptible, infectious, and recovered individuals within a population have played an important role in infectious disease modeling. The aim of the present paper is to explain the link between stochastic epidemic models based on the susceptible-infectious-recovered (SIR) model, and methods from survival analysis. We illustrate how standard software for survival analysis in the statistical language R can be used to estimate pivotal parameters in the stochastic SIR model in the very much idealized situation where the epidemic is completely observed. Extensions incorporating interventions, age structure and heterogeneity are explored and illustrated.
Complementary methods for the study of interactions between eosinophils and cancer cells
Authors: Antonucci Caterina , Gambardella Adriana Rosa , Tirelli Valentina , Mattei Fabrizio , Schiavoni Giovanna 
Published: April 2024

AbstractEosinophils are a rare immune cell subset with important roles in Th2 immunity and, recently, in cancer. Interleukin IL-33 (IL-33) is well recognized for its important roles in the activation of eosinophils in Th2 immunity. On the other hand, IL-33 has been recently discovered to play central roles in cancer, in particular by activating eosinophils and increase their degranulation consequent to an intrinsic tumor cell killing function. We propose a dual approach methodology to extrapolate functional interactions of eosinophils with tumor cells, as a result of eosinophil stimulation. Human eosinophils (Eos) isolated from the blood of healthy donors by dextran sedimentation followed by magnetic sorting are exposed to IL-33 (Eos33) or IL-5 (Eos5, control) for 18 h. These pre-conditioned cells are then co-cultured with A375P melanoma cells to monitor cell-cell interactions. Acoustic focusing flow cytometry analysis is employed to evaluate the presence of Eos-tumor cell conjugates after 1h incubation of human eosinophils and A375P melanoma cells. Moreover, a 24 h time-lapse video recording approach is employed to obtain single cell tracking Eos profiles. This allows to quantitatively determine the interaction extent of Eos33, as opposed to Eos5 (control condition), with tumor cells. In conclusion, our protocols easily and quickly allow the extrapolation of relevant kinematic and biologically relevant parameters for tumor reactive eosinophils. Furthermore, these methods are adaptable to various models with other types of immune cell subsets and cancer cells and can be implemented on different video microscopy platforms and advanced flow cytometry systems.
Ubiquitin-specific protease 8 controls B-cell proteostasis and survival representing a target in multiple myeloma
Authors: Dufner Almut , Thery Fabien , Monaco Gianni , Lazarevic Jelena , Gorka Oliver , Chevalier Nina , Frosch Maximilian , van der Heden van Noort Gerbrand J. , Allmeroth Kira , Prinz Marco , Groß Olaf , Ovaa Huib , Geurink Paul P. , Schamel Wolfgang W. , Heissmeyer Vigo , Denzel Martin S. , Bruns Heiko , Schemionek Mirle , Impens Francis , Knobeloch Klaus-Peter 
Published: April 2024

AbstractUbiquitin-specific protease 8 is involved in endosomal/lysosomal trafficking, exerts multiple cellular functions, and was identified as a vulnerability gene for multiple myeloma, a disease characterized by clonal expansion of malignant plasma cells in the bone marrow. Here we characterized USP8 function in B cells and multiple myeloma, and analyzed its impact on the global and ubiquitin-modified proteome.Usp8depletion inUsp8f/fCd19-Cre mice affected B-cell survival and development favoring immature and innate-like B cells, as well as germinal center and plasma cells. This effect was accompanied by elevated immune-responses and Roquin depletion. Moreover, low USP8 expression at diagnosis correlated with decreased survival of multiple myeloma patients. B cells expressing catalytically inactive USP8 accumulated proteins modified with mixed ubiquitin/NEDD8 chains as hallmarks of proteotoxic stress, which we identified as favored USP8 substrates. Efficient USP8 knockdown reduced survival of multiple myeloma cells resistant to proteasome inhibition by bortezomib in a lysosomal dysfunction-dependent manner. Of note, the inhibitor DUB-IN-2 even more potently resensitized bortezomib-resistant multiple myeloma cells in an ER stress response-synergistic manner, and we confirmed applicability of DUB-IN-2/bortezomib combination treatment in a mouse transplantation model. Our analyses uncovered the potential of USP8 inhibition and of DUB-IN-2/bortezomib combination treatment in multiple myeloma.
Vocal and musical emotion perception, voice cue discrimination, and quality of life in cochlear implant users with and without acoustic hearing
Authors: Harding Eleanor E. , Gaudrain Etienne , Tillmann Barbara , Maat Bert , Harris Robert L. , Free Rolien H. , Başkent Deniz 
Published: April 2024

AbstractThis study aims to provide a comprehensive picture of auditory emotion perception in cochlear implant (CI) users by (1) investigating emotion categorization in both vocal (pseudo-speech) and musical domains and (2) how individual differences in residual acoustic hearing, sensitivity to voice cues (voice pitch, vocal tract length), and quality of life (QoL) might be associated with vocal emotion perception and, going a step further, also with musical emotion perception. In 28 adult CI users, with or without self-reported acoustic hearing, we showed that sensitivity (d’) scores for emotion categorization varied largely across the participants, in line with previous research. However, within participants, the d’ scores for vocal and musical emotion categorization were significantly correlated, indicating similar processing of auditory emotional cues across the pseudo-speech and music domains and robustness of the tests. Only for musical emotion perception, emotion d’ scores were higher in implant users with residual acoustic hearing compared to no acoustic hearing. The voice pitch perception did not significantly correlate with emotion categorization in either domain, while the vocal tract length significantly correlated in both domains. For QoL, only the subdomain of Speech production ability, but not the overall QoL scores, correlated with vocal emotion categorization, partially supporting previous findings. Taken together, results indicate that auditory emotion perception is challenging for some CI users, possibly a consequence of how available the emotion-related cues are via electric hearing. Improving these cues, either via rehabilitation or training, may also help auditory emotion perception in CI users.
How weedyArabidopsis thalianadominated the world: ancestral variation and polygenic adaptation
Authors: Lo Cheng-Yu , Chien Chih-Cheng , Lin Ya-Ping , Yeh Pei-Min , Lee Cheng-Ruei 
Published: April 2024

AbstractThe composition of a species could change with demographic turnovers, where dominant populations quickly expanded and replaced others. However, whether such events have a genetic basis remains to be investigated. Previous studies showed thatArabidopsis thalianaexperienced a significant demographic turnover, where “non-relicts” replaced “relicts” throughout Eurasia. Here, we showed that non-relicts have smaller seeds, more seeds per fruit, and a higher germination rate, making them more competitive over relicts. Using a unique population enriching relict alleles while minimizing population structure, we identified candidate loci and showed that such trait divergence was caused by the divergent sorting of multiple ancient haplotypes in a Mendelian gene and joint allele frequency change of polygenes affecting single-trait divergence and multi-trait covariance. This study is one of the few genetic investigations of species-wide demographic turnover, emphasizing the importance of processes different from the much-focused hard selective sweep.
Host range of naturally and artificially evolved symbiotic bacteria for a specific host insect
Authors: Sugiyama Ryuga , Moriyama Minoru , Koga Ryuichi , Fukatsu Takema 
Published: April 2024

ABSTRACTDiverse insects are intimately associated with specific symbiotic bacteria, where host and symbiont are integrated into an almost inseparable biological entity. These symbiotic bacteria usually exhibit host specificity, uncultivability, reduced genome size, and other peculiar traits relevant to their symbiotic lifestyle. How host-symbiont specificity is established at the very beginning of symbiosis is of interest but poorly understood. To gain insight into the evolutionary issue, we adopted an experimental approach using the recently developed evolutionary model of symbiosis between the stinkbugPlautia staliandEscherichia coli. Based on the laboratory evolution ofP. stali-E. colimutualism, we selected ΔcyaAmutant ofE. colias an artificial symbiont ofP. stalithat has established mutualism by a single mutation. In addition, we selected a natural cultivable symbiont ofP. staliof relatively recent evolutionary origin. These artificial and natural symbiotic bacteria ofP. staliwere experimentally inoculated to symbiont-deprived newborn nymphs of diverse stinkbug species. Strikingly, the mutualisticE. coliwas unable to establish infection and support growth and survival of all the stinkbug species except forP. stali, uncovering that host specificity can be established at a very early stage of symbiotic evolution. Meanwhile, the natural symbiont was able to establish infection and support growth and survival of several stinkbug species in addition toP. stali, unveiling that a broader host range of the symbiont has evolved in nature. Based on these findings, we discuss what factors are relevant to the establishment of host specificity in the evolution of symbiosis.IMPORTANCEHow does host-symbiont specificity emerge at the very beginning of symbiosis? This question is difficult to address, because it is generally difficult to directly observe the onset of symbiosis. However, recent development of experimental evolutionary approaches to symbiosis has brought about a breakthrough. Here we tackled this evolutionary issue using a symbioticEscherichia colicreated in laboratory and a naturalPantoeasymbiont, which are both mutualistic to the stinkbugPlautia stali. We experimentally replaced essential symbiotic bacteria of diverse stinkbugs by the artificial and natural symbionts ofP. stali, and evaluated whether the symbiotic bacteria evolved for a specific host can establish infection and support growth and survival of heterospecific hosts. Strikingly, the artificial symbiont showed strict host specificity toP. staliwhereas the natural symbiont was capable of symbiosis with diverse stinkbugs, which provide insight into how host-symbiont specificity can be established at early evolutionary stages of symbiosis.
Perceptions of children and young people in England on the smokefree generation policy: a focus group study
Authors: Davies Nathan P , Murray Rachael L , Langley Tessa , Morling Joanne R , Bains Manpreet 
Published: April 2024

ABSTRACTBackgroundThis study investigates perceptions of young people towards the planned smokefree generation (SFG) policy in England, which will ban sale of tobacco products to those born in or after 2009. It focuses on SFG policy acceptability, design and implementation.MethodsWe conducted 7 semi-structured focus groups with 36 participants aged 12 - 21 (mean = 15) in England over video call and in person. 21 participants were female and 15 male. Participants were purposively sampled to include those from areas of greater deprivation and for use of tobacco or e-cigarettes. Data was analysed using the framework approach.ResultsParticipants expressed broadly negative perceptions towards tobacco and its manufacturers. Most participants supported SFG policy goals and its focus on freedom from addiction and harm. Many believed the law would benefit from stringent enforcement, inclusion of e-cigarette products, tobacco licensing, and input from young people. A minority raised concerns about the loss of freedom to purchase tobacco and believed it would have little effect on smoking rates.ConclusionCommunication of the freedom-giving nature of SFG is likely to resonate with many young people. Enforcement, communication, and involvement of young people in SFG should be considered carefully to maximise policy impact.What is already known on this topicObservational and modelling studies of raising the legal age of sale of tobacco show its effectiveness in reducing smoking rates in target populations. The UK is currently on track to be the first nation to introduce a generational ban on tobacco products, but little is known about young people’s perceptions on this policy.What this study addsThe overarching goal and preventative approach of SFG has the power to resonate with young people, including nicotine product users, but there is likely to be a small minority opposed to SFG on philosophical principles and perceptions of limited effectiveness. Young people may have mixed feelings about e-cigarettes being excluded from SFG due to misperceptions of equivalent harm between products.How this study might affect research, practice or policyOur study suggests involvement of young people in SFG’s design and accompanying communication is likely to strengthen its legitimacy and appeal. Our sample were largely supportive of well-resourced, consistent enforcement of SFG law with strong penalties for retailers who break the law.
Gastric modulation of food reward, olfaction and taste in obesity and bariatric surgery: an artificial intelligence assisted scoping review protocol
Authors: Ritsch Nina , Bourque Camille , Bergeron Frederic , Nazare Julie-Anne , Dougkas Anestis , Iceta Sylvain 
Published: April 2024

AbstractObjectiveTo understand the extent and nature of the available research on gastric modulation of food reward, olfaction, and taste in people with obesity or those who have undergone bariatric surgery.IntroductionBariatric surgery-induced weight loss is partially attributed to shifts in food preferences resulting from alterations in sensory perceptions and changes in reward system. The stomach’s innervation and mechanical function have been theorized to play a significant role in these modifications, as suggested by numerous preclinical studies. However, the extent and nature of these connections in clinical settings require further elucidation.Inclusion criteriaThis review will examine studies on the influence of gastric innervation and/or mechanical function on food reward, olfaction, and taste. Selected studies will include participants of all ages with obesity or bariatric surgery. Both observational studies and controlled experiments will be considered, while study protocols, opinion articles, letters to the editor, book chapters, oral communication or poster abstracts and systematic reviews will be excluded.MethodsThe search will be undertaken in MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, Google Scholar, and gray literature. No date parameters will be set, and all languages will be considered. Citations will be uploaded into EndNote 20.0 and duplicates removed using Covidence. The remaining studies will be analyzed by 3 reviewers using a two-stage procedure with the ASReview python package. The full-text screening and the data extraction will be conducted by 2 reviewers on Covidence. An additional reviewer will be consulted in the event of disagreement. Tabulated results will be accompanied by a narrative summary.
The RESIST Senior Individuals Cohort: Design, participant characteristics and aims
Authors: Roesner LM , Gupta KM , Kopfnagel V , van Unen N , Kemmling Y , Heise J , Castell S , Jiang X , Riemann L , Traidl S , Lange B , Sühs KW , Illig T , Strowig T , Li Y , Förster R , Huehn J , Schulz TF , Werfel T ,   the RESIST SI Cohort Investigators
Published: April 2024

AbstractThe number of older adults worldwide is growing exponentially. However, while living longer, older individuals are more susceptible to both non-infectious and infectious diseases, at least in part due to alterations of the immune system. Here, we report on a prospective cohort study investigating the influence of age on immune responses and susceptibility to infection. The RESIST Senior Individuals (SI) cohort was established as a general population cohort with a focus on the elderly, enrolling an age- and sex-stratified sample of 650 individuals (n=100 20-39y, n=550 61-94y, 2019-2023, Hannover, Germany). It includes clinical, demographic, and lifestyle data and also extensive biomaterial sampling. Initial insights indicate that the SI cohort exhibits characteristics of the aging immune system and the associated susceptibility to infection, thereby providing a suitable platform for the decoding of age-related alterations of the immune system and unraveling the molecular mechanisms underlying the impaired immune responsiveness in aging populations by exploring comprehensive, unbiased multi-omics datasets.
Spatial hepatocyte plasticity of gluconeogenesis during the metabolic transitions between fed, fasted and starvation states
Authors: Okada Junichi , Landgraf Austin , Xiaoli Alus M. , Liu Li , Horton Maxwell , Schuster Victor L. , Yang Fajun , Sidoli Simone , Qiu Yunping , Kurland Irwin J. , Eliscovich Carolina , Shinoda Kosaku , Pessin Jeffrey E. 
Published: April 2024

ABSTRACTThe liver acts as a master regulator of metabolic homeostasis in part by performing gluconeogenesis. This process is dysregulated in type 2 diabetes, leading to elevated hepatic glucose output. The parenchymal cells of the liver (hepatocytes) are heterogeneous, existing on an axis between the portal triad and the central vein, and perform distinct functions depending on location in the lobule. Here, using single cell analysis of hepatocytes across the liver lobule, we demonstrate that gluconeogenic gene expression (Pck1andG6pc) is relatively low in the fed state and gradually increases first in the periportal hepatocytes during the initial fasting period. As the time of fasting progresses, pericentral hepatocyte gluconeogenic gene expression increases, and following entry into the starvation state, the pericentral hepatocytes show similar gluconeogenic gene expression to the periportal hepatocytes. Similarly, pyruvate-dependent gluconeogenic activity is approximately 10-fold higher in the periportal hepatocytes during the initial fasting state but only 1.5-fold higher in the starvation state. In parallel, starvation suppresses canonical beta-catenin signaling and modulates expression of pericentral and periportal glutamine synthetase and glutaminase, resulting in an enhanced pericentral glutamine-dependent gluconeogenesis. These findings demonstrate that hepatocyte gluconeogenic gene expression and gluconeogenic activity are highly spatially and temporally plastic across the liver lobule, underscoring the critical importance of using well-defined feeding and fasting conditions to define the basis of hepatic insulin resistance and glucose production.
Molecular mechanism of the endothelin receptor type B interactions with Gs, Gi, and Gq
Authors: Ham Donghee , Shihoya Wataru , Nureki Osamu , Inoue Asuka , Chung Ka Young 
Published: April 2024

SUMMARYThe endothelin receptor type B (ETB) exhibits promiscuous coupling with various G protein subtypes including Gs, Gi/o, Gq/11, and G12/13, leading to multi-modal signal transduction. Recent fluorescence and structural studies have raised questions regarding the coupling efficiencies and determinants of these G protein subtypes. Herein, by utilizing an integrative approach, combining hydrogen/deuterium exchange mass spectrometry and NanoLuc Binary Technology-based cellular systems, we investigated conformational changes of Gs, Gi and Gq triggered by ETBactivation. ETBcoupled to Gi and Gq but not with Gs. We underscored the critical roles of specific regions, including the C-terminus of Gα and intracellular loop 2 (ICL2) of ETBin ETB-Gi1 or ETB-Gq coupling. Although The C-terminus of Gα is essential for ETB-Gi1 and ETB-Gq coupling, ETBICL2 influences Gq-coupling but not Gi1-coupling. Our results suggest a differential coupling efficiency of ETBwith Gs, Gi1, and Gq, accompanied by distinct conformational changes in G proteins upon ETB-induced activation.