bluuebunny/crossref_metadata_2025_split huggingface dataset:
T-Rex: sTandalone Recorder of EXperiments; An easy and versatile neural recording platform
Authors: Amigó-Vega Joaquín , Ottenhoff Maarten C. , Verwoert Maxime , Kubben Pieter , Herff Christian 
Published: October 2022

AbstractRecording time in invasive neuroscientific empirical research is short and must be used as efficiently as possible. Time is often lost due to long setup times and errors by the researcher. Minimizing the number of manual actions reduces both and can be achieved by automating as much as possible. Importantly, automation should not reduce the flexibility of the system. Currently, recording setups are either custom-made by the researchers or provided as a module in comprehensive neuroscientific toolboxes, and no platforms exist focused explicitly on recording. Therefore, we developed a lightweight, flexible, platform- and measurement-independent recording system that can start and record experiments with a single press of a button. Data synchronization and recording are based on Lab Streaming Layer to ensure that all major programming languages and toolboxes can be used to develop and execute experiments. We have minimized the user restrictions as much as possible and imposed only two requirements on the experiment: The experiment should include a Lab Streaming Layer stream, and it should be able to run from a command line call. Further, we provided an easy-to-use interface that can be adjusted to specific measurement modalities, amplifiers, and participants. The presented system provides a new way of setting up and recording experiments for researchers and participants. Because of the automation and easy-to-use interface, the participant could even start and stop experiments by themselves, thus potentially providing data without the experimenter’s presence.
DLPFC-PPC-cTBS Effects on Metacognitive Awareness
Authors: Martin Antonio , Lane Timothy J. , Hsu Tzu-Yu 
Published: October 2022

AbstractBackgroundNeuroimaging and lesion studies suggested that the dorsolateral prefrontal and posterior parietal cortices mediate visual metacognitive awareness. The causal evidence provided by non-invasive brain stimulation, however, is inconsistent.Objective/HypothesisHere we revisit a major figure discrimination experiment adding a new Kanizsa figure task trying to resolve whether bilateral continuous theta-burst transcranial magnetic stimulation (cTBS) over these regions affects perceptual metacognition. Specifically, we tested whether subjective visibility ratings and/or metacognitive efficiency are lower when cTBS is applied to these two regions in comparison to an active control region.MethodsA within-subjects design including three sessions spaced by one-week intervals was implemented. In each session, every participant was administered bilateral cTBS to either prefrontal, control or parietal cortices. Two concurrent tasks were performed, a real and an illusory figure task, stabilising objective performance with use of an adaptive staircase procedure.ResultsWhen performing the replicated task, cTBS was found insufficient to disrupt neither visibility ratings nor metacognitive efficiency. However, with use of Kanizsa style illusory figures, cTBS over the dorsolateral prefrontal, but not over the posterior parietal cortex, was observed to significantly diminish metacognitive efficiency.Conclusion(s)Real and illusory figure tasks demonstrated different cTBS effects. A possible explanation is the involvement of the prefrontal cortex in the creation of expectations, which is necessary for efficient metacognition. Failure to replicate previous findings for the real figure task, however, cannot be said to support, conclusively, the notion that these brain regions have a causal role in metacognitive awareness. This inconsistent finding may result from certain limitations of our study, thereby suggesting the need for yet further investigation.
Propofol Reverses Surgery-Induced Neuroinflammation and Cognitive Impairment in Aged Mice via α5-GABAAReceptors
Authors: Nagarajan Rajasekar , Lyu Jinrui , Kambali Maltesh , Wang Muxiao , Pearce Robert A. , Rudolph Uwe 
Published: October 2022

AbstractSurgery may lead to long-lasting cognitive deficits that are referred to as perioperative neurocognitive disorder (NCD), particularly in elderly patients. Currently, no interventions are routinely employed in clinical practice to prevent perioperative NCD. Here we show that perioperative chronic intermittent administration of propofol to aged mice undergoing laparotomy under isoflurane anesthesia effectively blocks the surgery-induced increase in nitrosative stress, increased expression of proapoptotic proteins, microglial activation, and cognitive deficits. By contrast, in the absence of surgery and anesthesia, propofol had little effect on biochemical parameters and led to cognitive improvement only in a subset of behavioral paradigms. The actions of propofol were largely absent in mice lacking the GABAAreceptor α5-subunit, indicating that they are mediated by α5-containing GABAAreceptors. These results demonstrate that propofol – via α5-containing GABAAreceptors that are redistributed to the cell surface membranes in a sustained manner – can attenuate surgery-induced neuroinflammation and postsurgical cognitive deficits.
KDM6A/UTX promotes spermatogenic gene expression across generations but is dispensable for male fertility
Authors: Walters Benjamin William , Rainsford Shannon R , Dias Nicolas , Huang Xiaofang , de Rooij Dirk G , Lesch Bluma J 
Published: October 2022

AbstractPaternal chromatin undergoes extensive structural and epigenetic changes during mammalian spermatogenesis, producing sperm that contain an epigenome optimal for the transition to embryogenesis. Histone modifiers play an important role in this process by encoding specialized regulatory information in the sperm epigenome. Lysine demethylase 6a (KDM6A) promotes gene activation via demethylation of H3K27me3, a developmentally important repressive modification abundant throughout the epigenome of sperm and embryonic stem cells. Despite its developmental importance in pluripotent cells and germ cell progenitors, the function of KDM6A during spermatogenesis has not been described. Here, we show thatKdm6ais transiently expressed in the male germline in late spermatogonia and during the early stages of meiotic entry. Deletion ofKdm6ain the male mouse germline (Kdm6acKO) yielded a modest increase in sperm head defects but did not affect fertility or the overall progression of spermatogenesis. However, hundreds of genes were deregulated upon loss ofKdm6ain spermatogenic cells and in an immortalized spermatogonia cell line (GC-1 spg) with a strong bias towards downregulation. Single cell RNA-seq revealed that most of these genes were deregulated in spermatogenic cells at the same stage whenKdm6ais expressed and encode epigenetic factors involved in chromatin organization and modification. A subset of these genes was persistently deregulated in the male germ line across two generations of offspring ofKdm6acKO males. Our findings highlight KDM6A as a transcriptional activator in the mammalian male germline that is dispensable for spermatogenesis but important for safeguarding gene regulatory state intergenerationally.Author summaryOffspring viability and fitness relies upon the development of functional sperm and the integrity of information that they carry. Chromatin is modified and remodeled extensively throughout spermatogenesis to facilitate meiosis, DNA compaction, and to encode gene regulatory information for the next generation. In mice, a paternal germline lacking KDM6A, a histone modifier, yields offspring with reduced lifespans and increased cancer risk. How KDM6A functions in the paternal germline to support offspring health is unknown. Here, we show thatKdm6aexpression is limited to a distinct developmental interval when differentiated spermatogonia transition from mitosis to meiosis. During this timepoint, KDM6A acts as a transcriptional activator for hundreds of genes, many of which encode meiotic factors and epigenetic modifiers. Nevertheless, this activity is dispensable for overall spermatogenesis and fertility. Surprisingly, we find a significant overlap in germline transcriptomes ofKdm6acKO mice and wildtype offspring. We propose that KDM6A encodes gene regulatory information in the male germline that is retained across generations.
Characterization of undocumented CO2hydrothermal vent’s system in the Mediterranean Sea: implications for ocean acidification forecasting
Authors: D’Alessandro Michela , Gambi Maria Cristina , Caruso Cinzia , Di Bella Marcella , Esposito Valentina , Gattuso Alessandro , Giacobbe Salvatore , Kralj Martina , Italiano Francesco , Lazzaro Gianluca , Sabatino Giuseppe , Bazzarro Matteo , Urbini Lidia , De Vittor Cinzia 
Published: October 2022

AbstractA previously undocumented shallow water hydrothermal field from Sicily (Southern Tyrrhenian Sea, Italy), is here described based on a multidisciplinary investigation. The field, covering an area of nearly 8000 m2and ranging in depth from surface to −5 m, was explored in June 2021, to characterise the main physico-chemical features of the water column, describe bottom topography and features, and identify the main megabenthic and nektonic species. Twenty sites were investigated to characterize the carbonate system. Values of pH ranged between 7.84 and 8.04, ΩCa between 3.68 and 5.24 and ΩAr from 2.41 to 3.44. Geochemical analyses of hydrothermal fluids gases revealed a dominance of CO2(98.1%) along with minor amounts of oxygen and reactive gases. Helium isotope ratios (R/Ra =2.51) and δ13CCO2(3) support an inorganic origin of hydrothermal degassing of CO2and the ascent of heat and deep-seated magmatic fluids to the surface. Visual census of fishes and megabenthos (mainly sessile organisms) allowed identification of 62 species, of which four are protected by the SPA/BIO Protocol and two by the International Union for Conservation of Nature. The macroalgaeHalopteris scopariaandJania rubensand the spongeSarcotragussp. were the dominant taxa in the area, while among fishesCoris julisandChromis chromiswere predominant. The preliminary description of this venting field indicates this site as an area of considerable interest and suitable for future experimental studies on ocean acidification.
A new class of polymorphic T6SS effectors and tethers
Authors: Kanarek Katarzyna , Fridman Chaya Mushka , Bosis Eran , Salomon Dor 
Published: October 2022

AbstractBacteria use the type VI secretion system (T6SS) to deliver toxic effectors into bacterial or eukaryotic cells during interbacterial competition, host colonization, or when resisting predation. The identity of many effectors remains unknown. Here, we identify RIX, a new domain that defines a class of polymorphic T6SS cargo effectors. RIX, which is widespread in theVibrionaceaefamily, is located at N-termini of proteins containing diverse antibacterial and anti-eukaryotic toxin domains. We demonstrate that RIX-containing proteins are delivered via T6SS into neighboring cells, and that RIX is necessary and sufficient for secretion. We show that RIX-containing proteins can also act as tethers, enabling the T6SS-mediated delivery of other cargo effectors by a previously undescribed mechanism. RIX-containing proteins significantly enlarge the repertoire of known T6SS effectors, especially those with anti-eukaryotic activities. Our findings also suggest that T6SSs may play a major, currently underappreciated, role in interactions between vibrios and eukaryotes.
Vitamin D deficiency and SARS‑CoV‑2 infection: Big-data analysis from March 2020 to March 2021. D-COVID study
Authors: Neira Álvarez M , Navarro Jiménez G , Anguita Sánchez N , Bermejo Olano M.M , Queipó R , Benavent Nuñez M , Parralejo Jimenez A , López Yepes G , Sáez Nieto C 
Published: October 2022

ABSTRACTBackgroundVitamin D has been proposed to have immunomodulatory functions and therefore play a role in coronavirus infection (COVID-19). However, there is no conclusive evidence on its impact on COVID-19 infection and evolution.ObjectiveTo study the association between COVID-19 infection and vitamin D deficiency in patients of a terciary university hospital. To investigate the clinical evolution and prognosis of patients with COVID-19 and vitamin D deficiency.MethodsUsing big-data analytics and artificial intelligence through the SAVANA Manager clinical platform, we analysed clinical data from patients with COVID-19 atended in a terciary university hospital from March 2020 to March 2021.ResultsOf the 143.157 analysed patients, 36.261 subjects had COVID-19 infection (25.33%); during this period; of these 2588 had vitamin D deficiency (7.14%). Among subjects with COVID-19 and vitamin D deficiency, there was a higher proportion of women OR 1.45 [95% CI 1.33-1.57], adults older than 80 years OR 2.63 [95%CI 2.38-2.91], people living in nursing homes OR 2.88 [95%CI 2.95-3.45] and walking dependence OR 3.45 [95%CI 2.85-4.26]. Regarding clinical course, a higher number of subjects with COVID-19 and vitamin D deficiency required hospitalitation OR 2.41 [95%CI 2.22-2-61], intensive unit care (ICU) OR 2.22 [95% CI 1.64-3.02], had a longer mean hospital stay 3.94 (2.29) p=0.02 and higher mortality OR 1.82 [95%CI 1.66-2.01].)ConclusionLow serum 25 (OH) Vitamin-D level was significantly associated with a worse clinical evolution and prognosis of COVID-19 infection. We found a higher proportion of institutionalised and dependent people over 80 years of age among patients with COVID-19 and vitamin D deficiency.
Two new species ofCrocusseriesScardicifrom the Western Balkans
Authors: Shuka Donald , Kerndorff Helmut , Waminal Nomar , Ranđelovič Vladimir , Harpke Doerte 
Published: October 2022

AbstractCrocusseriesScardicihas only two members,C. scardicusandC. pelistericusdistributed at higher elevations in the Balkan Peninsula. In the course of our research, we discovered two new species growing on alpine meadows and pastures in the serpentine massifs in Albania and limestones in North Macedonia, respectively. The morphology and phylogenetic analyses (two nuclear single-copy markers, nrITS, two chloroplast markers) place the new species within seriesScardici. Both new species are closely related toC. scardicus, but morphologically and ecologically clearly differentiated. We also measured genome sizes for all seriesScardicispecies and report here the largest genomes found up to now in crocuses. The impact of different habitat types and isolation on separate mountain ranges in this alpine group of plants is discussed, too.
Mitochondrial dysfunction rapidly modulates the abundance and thermal stability of cellular proteins
Authors: Groh Carina , Haberkant Per , Stein Frank , Filbeck Sebastian , Pfeffer Stefan , Savitski Mikhail M. , Boos Felix , Herrmann Johannes M. 
Published: October 2022

AbstractCellular functionality relies on a well-balanced, but highly dynamic proteome. Dysfunction of mitochondrial protein import leads to the cytosolic accumulation of mitochondrial precursor proteins which compromise cellular proteostasis and trigger the mitoprotein-induced stress response. To dissect the effects of mitochondrial dysfunction on the cellular proteome as a whole, we developed pre-post thermal proteome profiling (ppTPP). This multiplexed time-resolved proteome-wide thermal stability profiling approach with isobaric peptide tags in combination with a pulsed SILAC labeling elucidated dynamic proteostasis changes in several dimensions: In addition to adaptations in protein abundance, we observed rapid modulations of the thermal stability of individual cellular proteins. Strikingly, different functional groups of proteins showed characteristic response patterns and reacted with group-specific kinetics, allowing the identification of the functional modules that are relevant for mitoprotein-induced stress. Thus, our new ppTPP approach uncovered a complex response network that orchestrates proteome homeostasis in eukaryotic cells by time-controlled adaptations of protein abundance and protein stability.
Daily Artificial Gravity is Associated with Greater Neural Efficiency during Sensorimotor Adaptation
Authors: Tays G.D. , Hupfeld K.E. , McGregor H.R. , Gadd N.E. , Kofman I. S. , De Dios Y. E. , Mulder E.R. , Bloomberg J.J. , Mulavara A.P. , Wood S.J. , Seidler R. D. 
Published: October 2022

AbstractAltered vestibular signaling and body unloading in microgravity results in sensory reweighting and adaptation. Microgravity effects are well-replicated in head-down tilt bed rest (HDBR). Artificial gravity (AG) is a potential countermeasure to mitigate effects of microgravity. We examined the effectiveness of daily AG for mitigating brain and/or behavioral changes in 60 days of HDBR. One group received AG for 30 minutes daily (AG; n=16) and a control group spent the same time in HDBR but received no AG (CTRL; n=8). All participants performed a sensorimotor adaptation task 5 times during fMRI scanning: twice prior to HDBR twice during HDBR, and once following HDBR. The AG group showed similar behavioral adaptation effects compared with the CTRLs. We identified decreased brain activation in the AG group from pre to late HDBR in the cerebellum for the task baseline portion and in the thalamus, calcarine, cuneus, premotor cortices, and superior frontal gyrus in the AG group during the early adaptation phase. The two groups also exhibited differential brain-behavior correlations. Together, these results suggest that AG may result in a reduced recruitment of brain activity for basic motor processes and sensorimotor adaptation. These effects may stem from somatosensory and vestibular stimulation from AG.
An inducible explant model for dissecting osteoclast-osteoblast coordination in health and disease
Authors: Whitlock Jarred M. , de Castro Luis F. , Collins Michael T. , Chernomordik Leonid V. , Boyce Alison M. 
Published: October 2022

ABSTRACTMetabolic bone diseases are a collection of disorders resulting in diminished skeletal integrity and changes in bone mass due to perturbations in the life-long process of bone remodeling. Perturbations in the number, size and nuclear multiplicity of osteoclasts underpin the development of diverse metabolic bone diseases that impact >13% of adults over age 50 world-wide. Each metabolic bone disease (e.g., osteoporosis, Paget’s disease, fibrous dysplasia (FD), osteopetrosis) presents with unique phenotypes, rises from distinct etiologies and progresses with disparate severities, but all are underpinned by a breakdown in osteoclast formation/function. These perturbations of osteoclast formation/function either stem from or cause dysfunctional osteoclast-osteoblast coordination. Unfortunately, a mechanistic understanding of osteoclast-osteoblast coordination and communication is lacking and represents a major barrier to understanding the biology underpinning bone remodeling and the development of effective treatments targeting this process. Here we have developed an inducibleex vivoculture model that models osteoclast-osteoblast coordination in the bone remodeling compartment. Doxycycline addition to cultures activates GαsR201Cexpression and RANKL release from osteoprogenitors, which elicits the differentiation and fusion of neighboring preosteoclasts. In turn, multinucleated osteoclast formation promotes the proliferation of osteoprogenitors, accompanied by the robust release of RANK+extracellular vesicles, all within ∼4 days. This system recapitulates many aspects of the complex osteoclast-osteoblast coordination required for the function of the bone remodeling compartment in both health and diseases underpinned by excessive osteoclast formation. Moreover, based on the ease of isolation, culture, reproducibility and the general adaptability of these cultures to a variety of assays, we expect that this new model will expedite the investigation of osteoclast-osteoblast coordination and osteoclast fusion in bone remodeling and offer a powerful tool for evaluating signaling cascades and novel therapeutic interventions in osteoclast-linked skeletal disease.One-Sentence SummaryConditional, inducible,ex vivomarrow explants offer a novel tool for studying osteoclast formation and osteoclast-osteoblast coordination in a rapid convenient culture model.
Intranasal SARS-CoV-2 RBD decorated nanoparticle vaccine enhances viral clearance in the Syrian hamster model
Authors: Patel DR , Minns AM , Sim DG , Field CJ , Kerr AE , Heinly T , Luley EH , Rossi R.M. , Bator C. , Moustafa I.M. , Hafenstein SL , Lindner SE , Sutton TC 
Published: October 2022

ABSTRACTMultiple vaccines have been developed and licensed for SARS-CoV-2. While these vaccines reduce disease severity, they do not prevent infection, and SARS-CoV-2 continues to spread and evolve. To prevent infection and limit transmission, vaccines must be developed that induce immunity in the respiratory tract. Therefore, we performed proof-of-principle vaccination studies with an intranasal nanoparticle vaccine against SARS-CoV-2. The vaccine candidate consisted of the self-assembling 60-subunit I3-01 protein scaffold covalently decorated with the SARS-CoV-2 receptor binding domain (RBD) using the SpyCatcher-SpyTag system. We verified the intended antigen display features by reconstructing the I3-01 scaffold to 3.4A using cryo-EM, and then demonstrated that the scaffold was highly saturated when grafted with RBD. Using this RBD-grafted SpyCage scaffold (RBD+SpyCage), we performed two unadjuvanted intranasal vaccination studies in the “gold-standard” preclinical Syrian hamster model. Hamsters received two vaccinations 28 days apart, and were then challenged 28 days post-boost with SARS-CoV-2. The initial study focused on assessing the immunogenicity of RBD+SpyCage, which indicated that vaccination of hamsters induced a non-neutralizing antibody response that enhanced viral clearance but did not prevent infection. In an expanded study, we demonstrated that covalent bonding of RBD to the scaffold was required to induce an antibody response. Consistent with the initial study, animals vaccinated with RBD+SpyCage more rapidly cleared SARS-CoV-2 from both the upper and lower respiratory tract. These findings demonstrate the intranasal SpyCage vaccine platform can induce protection against SARS-CoV-2 and, with additional modifications to improve immunogenicity, is a versatile platform for the development of intranasal vaccines targeting respiratory pathogens.IMPORTANCEDespite the availability of efficacious COVID vaccines that reduce disease severity, SARS-CoV-2 continues to spread. To limit SARS-CoV-2 transmission, the next generation of vaccines must induce immunity in the mucosa of the upper respiratory tract. Therefore, we performed proof-of-principle, unadjuvanted intranasal vaccination studies with a recombinant protein nanoparticle scaffold, SpyCage, decorated with the receptor-binding domain (RBD) of the S protein (SpyCage+RBD). We show that SpyCage+RBD was immunogenic and enhanced SARS-CoV-2 clearance from the nose and lungs of Syrian hamsters. Moreover, covalent grafting of the RBD to the scaffold was required to induce an immune response when given via the intranasal route. These proof-of-concept findings indicate that with further enhancements to immunogenicity (e.g., adjuvant incorporation, antigen optimization), the SpyCage scaffold has potential as a versatile, intranasal vaccine platform for respiratory pathogens.