julilili42/papers huggingface dataset:
Inhibition of altered Orai1 channels in Müller cells protects photoreceptors in retinal degeneration
2023-08-03

Abstract The expressions of ion channels by Müller glial cells (MGCs) may change in response to various retinal pathophysiological conditions. There remains a gap in our understanding of MGCs' responses to photoreceptor degeneration towards finding therapies. The study explores how an inhibition of store‐operated Ca 2+ entry (SOCE) and its major component, Orai1 channel, in MGCs protects photoreceptors from degeneration. The study revealed increased Orai1 expression in the MGCs of retinal degeneration 10 ( rd10 ) mice. Enhanced expression of oxidative stress markers was confirmed as a crucial pathological mechanism in rd10 retina. Inducing oxidative stress in rat MGCs resulted in increasing SOCE and Ca 2+ release‐activated Ca 2+ (CRAC) currents. SOCE inhibition by 2‐Aminoethoxydiphenyl borate (2‐APB) protected photoreceptors in degenerated retinas. Finally, molecular simulations proved the structural and dynamical features of 2‐APB to the target structure Orai1. Our results provide new insights into the physiology of MGCs regarding retinal degeneration and shed a light on SOCE and Orai1 as new therapeutic targets.
Aging Associates with Cilium Elongation and Dysfunction in Kidney and Pancreas
2023-08-03

Abstract Cilia are best known and most studied for their manifold functions enabling proper embryonic development. Loss of cilia or dysfunction thereof results in a great variety of congenital malformations and syndromes. However, there are also cilia‐driven conditions, which manifest only later in life, such as polycystic kidney disease. Even degenerative diseases in the central nervous system have recently been linked to alterations in cilia biology. Surprisingly though, there is very little knowledge regarding cilia in normally aged organisms absent any disease. Here, it is provided evidence that cilia in naturally aged mice are considerably elongated in the kidney and pancreas, respectively. Moreover, such altered cilia appear to have become dysfunctional as indicated by changes in cellular signaling.
Hydroclimate reconstructions in the Suguta Valley, northern Kenya, during the Early-Middle Pleistocene Transition
2023-08-03

The Early-Middle Pleistocene Transition (EMPT) between 1200 and 700 ka represents a major global climate transition from dominantly 41,000- to 100,000-year glacial cycles. The forces and mechanisms behind this transition and the response of African environments are not well understood. The active volcanism and tectonics of the East African Rift System add complexity to local environmental systems and can erase important proxy records, inhibiting studies of lacustrine dynamics. As a result, there is minimal understanding of how this transition impacted the region's lake systems. At Paleolake Suguta, in the northern Kenya Rift, however, flood basalts cap lacustrine EMPT-age deposits, preserving these strata and their valuable paleoenvironmental record. This research presents a high-resolution reconstruction of hydrological change from approximately 931 to 831 ka within the Suguta-Turkana Basin in the northern Kenya Rift. Paleolake dynamics are reconstructed from a 41 m sedimentary section using diatom morphology, sedimentology, and X-Ray Fluorescence elemental analysis. Results show that lake levels varied greatly during this part of the EMPT with two wetter phases and two drier phases developing over about 100 kyr. From ∼885–831 ka, especially, the Suguta-Turkana Basin exhibits rapid changes in paleohydrology, ranging between deep stratified lakes; shallow, well-mixed lakes; and complete desiccation, with some of these changes occurring on an order of hundreds of years. This EMPT Suguta-Turkana-Baringo record therefore provides valuable insight into hydroclimate variability at an overall resolution of several thousand years, allowing reconstruction of past environments during a period of poorly understood terrestrial environmental change.
A Taxonomically-informed Mass Spectrometry Search Tool for Microbial Metabolomics Data
2023-08-03

Abstract MicrobeMASST, a taxonomically-informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of &gt;60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbial-derived metabolites and relative producers, without a priori knowledge, will vastly enhance the understanding of microorganisms' role in ecology and human health.
Insulin Can Delay Neutrophil Extracellular Trap Formation In Vitro—Implication for Diabetic Wound Care?
2023-08-03

Diabetes is a worldwide evolving disease with many associated complications, one of which is delayed or impaired wound healing. Appropriate wound healing strongly relies on the inflammatory reaction directly after injury, which is often altered in diabetic wound healing. After an injury, neutrophils are the first cells to enter the wound site. They have a special defense mechanism, neutrophil extracellular traps (NETs), consisting of released DNA coated with antimicrobial proteins and histones. Despite being a powerful weapon against pathogens, NETs were shown to contribute to impaired wound healing in diabetic mice and are associated with amputations in diabetic foot ulcer patients. The anti-diabetic drugs metformin and liraglutide have already been shown to regulate NET formation. In this study, the effect of insulin was investigated. NET formation after stimulation with PMA (phorbol myristate acetate), LPS (lipopolysaccharide), or calcium ionophore (CI) in the presence/absence of insulin was analyzed. Insulin led to a robust delay of LPS- and PMA-induced NET formation but had no effect on CI-induced NET formation. Mechanistically, insulin induced reactive oxygen species, phosphorylated p38, and ERK, but reduced citrullination of histone H3. Instead, bacterial killing was induced. Insulin might therefore be a new tool for the regulation of NET formation during diabetic wound healing, either in a systemic or topical application.
Energy-dependent periodicities of LS I +61°303 in the GeV band
2023-08-03

ABSTRACT LS I +61°303 is a rare representative of the gamma-ray binaries with a compact object known to be a pulsar. We report on the periodicity and spectral analysis of this source performed with more than 14 yr of Fermi/LAT data. The periodicity of LS I +61°303 is strongly energy dependent. Two periods P1 = 26.932 ± 0.004(stat) ± 0.008(syst) and P2 = 26.485 ± 0.004(stat) ± 0.007(syst) are detected only at E &amp;gt; 1 GeV and at E &amp;lt; 0.3 GeV correspondingly. Within 1σ (stat + syst) the periods are consistent with orbital (P2) and beat orbital/superorbital (P1) periods. We present the orbital light curves of the system in several energy bands and the results of the spectral analysis. We discuss the possible origin of the change in the variability pattern between 0.1 and 1 GeV energy.
Am I Crossing a Border? Spatial Regionalization and Route Choice Depends on Perceived Landmark Categorization
2023-08-03

ABSTRACTWe investigated the role of semantic similarities of place names in forming larger regions. The environment ́s place names allowed two alternative semantic categorizations corresponding to two equally valid regionalizations. In a priming phase, participants were biased to one or the other categorization scheme. Region perception was assessed by having participants choose between two equidistant routes crossing different numbers of region boundaries. Participants selected routes with a lower number of region crossings according to the primed categorization in 61% of all cases. The results show that perceived semantic similarity of place names affects route choice and the formation of spatial regions.KEYWORDS: Regionsroute choicecognitive mapspatial languagevirtual environments AcknowledgmentsWe are grateful to Svenja Zehender, Leonie Mödl and Jule Wildt for their contributions to the development of this experiment.Disclosure statementNo potential conflict of interest was reported by the authors.Author contributionAll authors contributed to the study conception and design. L.L. performed the experiments and analyzed the data. All authors jointly prepared the manuscript. All authors read and approved the final manuscript.Data availability statementData is available at https://osf.io/d75xu/.Data depositionhttps://doi.org/10.1101/2022.11.10.515979Informed consentInformed written consent was obtained from all individual participants included in the study.Research involving human participants and/or animalsThe manuscript does not contain data from clinical studies, patients, or non-human animal data.Additional informationFundingThe research reported in this paper was carried out at the Department of Biology of the University of Tübingen. Additional support was provided by the Deutsche Forschungsgemeinschaft (DFG – German Research Foundation) under Grant no. 381713393, within the Research Unit FOR2718: Modal and Amodal Cognition.
Disentangling periodic and aperiodic resting EEG correlates of personality
2023-08-03

Previous studies of the resting electroencephalography (EEG) correlates of personality traits have conflated periodic and aperiodic sources of EEG signals. As each type of activity is associated with different underlying neural dynamics, disentangling these can avoid measurement confounds and clarify interpretation of key findings. Using a large sample (N=300), we investigated how disentangling these activities impacts findings related to two research programs within personality neuroscience. In Study 1 we tested for associations between Extraversion and two putative markers of reward sensitivity—Left Frontal Alpha asymmetry (LFA) and Frontal-Posterior Theta (FPT). In Study 2 we used machine learning to predict personality trait scores from resting EEG. In both studies, power within each EEG frequency bin was quantified as both total power and separate contributions of periodic and aperiodic activity. In Study 1, total power LFA and FPT correlated negatively with Extraversion (r ~ -.14), but this effect disappeared when LFA and FPT were derived only from periodic activity. In Study 2, all Big Five traits could be decoded from periodic power (r ~ .20), and agreeableness could also be decoded from total power and from aperiodic indices. Taken together, these results show how separation of periodic and aperiodic activity in resting EEG recordings allow us to re-evaluate findings in personality neuroscience. Disentangling these signals allows for more reliable findings relating to periodic EEG markers of personality and also provides novel aperiodic measures to be explored in this field.
The need for hemispheric separation in pairwise structural disconnection studies
2023-08-04

Abstract The development of new approaches indirectly measuring the structural disconnectome has recently led to an increase in studies investigating pairwise structural disconnections following brain damage. Previous studies jointly analyzed patients with left hemispheric and patients with right hemispheric lesions when investigating a behavior of interest. An alternative approach would be to perform analyses separated by hemisphere, which has been applied in only a minority of studies to date. The present simulation study investigated whether joint or separate analyses (or both equally) are appropriate to reveal the ground truth disconnections. In fact, both approaches resulted in very different patterns of disconnection. In contrast to analyses separated by hemisphere, joint analyses introduced a bias to the disadvantage of intra‐hemispheric disconnections. Intra‐hemispheric disconnections were statistically underpowered in the joint analysis and thus surpassed the significance threshold with more difficulty compared to inter‐hemispheric disconnections. This statistical imbalance was also shown by a greater number of significant inter‐hemispheric than significant intra‐hemispheric disconnections. This bias from joint analyses is based on mechanisms similar to those underlying the “partial injury problem.” We therefore conclude that pairwise structural disconnections in patients with unilateral left hemispheric and with unilateral right hemispheric lesions exhibiting a specific behavior (or disorder) of interest should be studied separately by hemisphere rather than in a joint analysis.
Hard rock dark biosphere and habitability
2023-08-04

The discovery that most of the prokaryotic diversity and biomass on Earth resides in the deep subsurface, calls for an improved definition of habitability, which should consider the existence of dark biospheres in other planets and moons of the Solar System and beyond. The discovery of “interior liquid water worlds” on some ice moons with waterless surfaces has piqued wide astrobiological interest, but the sporadic mentions of the possibility of life in the deep subsurface of rocky planets in recent habitability reviews calls for a methodical effort to develop sufficient knowledge, both scientific and technological, to include the dark biospheres in our habitability assessments. In this review we analyze recent developments and the methodologies employed to characterize Earth’s continental hard rock deep subsurface to both prepare the future exploration of the putative dark biosphere of Mars and to highlight its importance when evaluating planetary habitability.
The role of epigenetic changes in the pathology and treatment of inherited retinal diseases
2023-08-04

Elucidation of the cellular changes that occur in degenerating photoreceptors of people with inherited retinal diseases (IRDs) has been a focus for many research teams, leading to numerous theories on how these changes affect the cell death process. What is clearly emerging from these studies is that there are common denominators across multiple models of IRD, regardless of the underlying genetic mutation. These common markers could open avenues for broad neuroprotective therapeutics to prevent photoreceptor loss and preserve functional vision. In recent years, the role of epigenetic modifications contributing to the pathology of IRDs has been a particular point of interest, due to many studies noting changes in these epigenetic modifications, which coincide with photoreceptor cell death. This review will discuss the two broad categories of epigenetic changes, DNA methylation and histone modifications, that have received particular attention in IRD models. We will review the altered epigenetic regulatory events that are believed to contribute to cell death in IRDs and discuss the therapeutic potential of targeting these alterations.
Why Central Asia’s Mushiston is not a source for the Late Bronze Age tin ingots from the Uluburun shipwreck
2023-08-04

Tin was a crucial commodity in prehistory to produce bronze, and knowledge of the origins of this metal is important for understanding cultural relations and the complexity and extent of trade. However, many aspects of the provenance of tin are still not resolved. A recent study in Science Advances 8(48) examined the historically significant tin ingots from the Uluburun shipwreck, which are key to the economy and long-distance trade of tin in the Late Bronze Age Mediterranean and beyond. Isotopic and chemical data of the objects was collected, from which a tin origin from Central Asia, particularly Mushiston in Tajikistan, and Anatolia was reconstructed. The study thereby proposed a solution to the long-standing riddle of tin provenance via scientific reasoning and comparative data. While this avenue of investigation is intriguing, this article maintains that the authors’ arguments do not support their far-reaching conclusions. Instead, it emphasises the similarities with Late and Middle Bronze Age tin ingots from Israel and Britain, and alternatively suggests a common origin of part of the Uluburun cargo with these items. South-west England is considered a very likely source region, but other tin ingots of the Uluburun wreck could also originate from Afghanistan and perhaps somewhere else.
Children's study habits are predicted by their parents' learning strategy preferences
2023-08-04

Many studies have identified both cognitive and motivational factors influencing students' use of learning strategies but the roles of family and social factors have been overlooked. This study examines whether parents' beliefs about the effectiveness of learning strategies influence the learning strategies that their children use, with intergenerational longitudinal data. 200 pairs of parents and their adolescent children. Parents and children separately rated how effective they believed 21 different learning strategies to be, with children also rating the frequency of their strategy use. Ratings were repeated approximately 1 year later. We found that the pattern of parents' strategy effectiveness beliefs at the first time point predicted that of their children's use of the strategies one year later, even controlling for children's strategy use pattern at the first time point. This finding demonstrates the importance of considering familial factors when studying students' learning strategy use.
Mobile instrumental assessment of swallowing in residential aged care homes
2023-08-04

Abstract Purpose Adults living in residential-aged-care-homes (RACHs) with oropharyngeal dysphagia may not have timely access to instrumental swallowing assessment due to barriers, including the need to travel off-site for assessment. This study describes the feasibility, utility, and acceptability of mobile Flexible-Endoscopic-Swallowing-Assessment (mFEES) in Australian residential-aged-care-homes (RACHs). Method Residents with dysphagia living in RACHs were assessed using onsite mFEES. Feasibility, utility, and acceptability were measured at institutional, resident, and implementation levels. Result Healthcare professionals and medical decision makers reported that mFEES facilitated a better understanding of residents’ swallowing function/dysphagia management and was beneficial over off-site services. Self-rated discomfort during mFEES was low and most residents presented with no or minimal anxiety about the procedure. Costs of mobile assessments are documented. Conclusion mFEES was a safe, well tolerated, and practical service that offered opportunity to enhance person-centered clinical care in older adults living with dysphagia in RACHs.
Abstract P3026: Multimodal Imaging To Identify Pre-signals For Acute Aortic Dissection By Using Marfan Syndrome Model Mouse
2023-08-04

Background: Marfan syndrome (MFS) is a genetic disorder caused by mutations in the gene encoding theextracellular matrix Fibrillin-1 (FBN1), resulting in systemic connective tissue abnormalities. The mostcommon life-threatening conditions are aortic rupture and/or dissection. Aortic dissections show a highmortality rate, but the details of molecular triggers are unknown, particularly in acute aortic dissection(AAD). Raman spectroscopy is a technique for analyzing molecular structures from Raman spectra. It hasrecently attracted attention in the biology field because it can non-invasively distinguish between diseaseand non-disease areas. Objectives: This study aimed to identify the signals that induce changes in the aortic wall prior to acuteaortic dissection using genetic analysis and Raman spectroscopy with preservation of positional information. Methods: An acute aortic dissection model was created by using MFS model mice (Fbn1 mgR/mgR ) byadministration of angiotensin II (AngII) via osmotic pump (Fbn1 mgR/mgR -AAD). Aortas from wild-type(WT), Fbn1 mgR/mgR and Fbn1 mgR/mgR -AAD mice were harvested, and frozen sections were prepared. Thevascular wall of each mouse was assessed histologically, followed by spatial transcriptomic analysis andRaman microscopy measurements. Multivariate data analysis was performed on the obtained Ramanspectra. Mass spectrometry (MS) imaging was utilized for lipidome analysis. Results: Label-free imaging of extracellular substrates (collagen fibres, elastic fibres, versican, andaggrecan), lipids, and cells was produced in WT, Fbn1 mgR/mgR and Fbn1 mgR/mgR - AAD aortic tissue. Spatialtranscriptomic analysis identified differentially expressed genes among these aortas. We identified markedlipid accumulations in the acute aortic dissection models with Raman and MS imaging.
Report on scipost_202304_00007v1
2023-08-04

We calculate the quantum Fisher information for a generic many-body fermionic system in a pure state depending on a parameter.We discuss the situations where the parameter is imprinted in the basis states, in the state coefficients, or both.In the case where the parameter dependence of coefficients results from a Hamiltonian evolution, we derive a particularly simple expression for the quantum Fisher information.We apply our findings to the quantum Hall effect, and evaluate the quantum Fisher information associated with the optimal measurement of the magnetic field for a system in the ground state of the effective Hamiltonian.The occupation of electron states with high momentum enforced by the Pauli principle leads to a super-Heisenberg scaling of the sensitivity with a power law that depends on the geometry of the sensor.
IntronicFGF14GAA repeat expansions are a common cause of downbeat nystagmus syndromes: frequency, phenotypic profile, and 4-aminopyridine treatment response
2023-08-05

Abstract The cause of downbeat nystagmus (DBN) remains unknown in approximately 30% of patients (idiopathic DBN). Here, we hypothesized that: (i) FGF14 (GAA) ≥250 repeat expansions represent a frequent genetic cause of idiopathic DBN syndromes, (ii) are treatable with 4-aminopyridine (4-AP), and (iii) FGF14 (GAA) 200-249 alleles are potentially pathogenic. We conducted a multi-modal cohort study of 170 patients with idiopathic DBN that comprised: in-depth ocular motor, neurological, and disease evolution phenotyping; assessment of 4-AP treatment response, including re-analysis of placebo-controlled video-oculography treatment response data from a previous randomized double-blind 4-AP trial; and genotyping of the FGF14 repeat. Frequency of FGF14 (GAA) ≥250 expansions was 48% (82/170) in the entire idiopathic DBN cohort. Additional cerebellar ocular motor signs were observed in 100% (82/82), cerebellar ataxia in 43% (35/82), and extracerebellar features in 21% (17/82) of (GAA) ≥250 - FGF14 patients. Alleles of 200 to 249 GAA repeats were enriched in patients with DBN (12%; 20/170) compared to controls (0.87%; 19/2,191; OR, 15.20; 95% CI, 7.52-30.80; p =9.876e-14). The phenotype of (GAA) 200-249 - FGF14 patients closely mirrored that of (GAA) ≥250 - FGF14 patients. (GAA) ≥250 - FGF14 and (GAA) 200-249 - FGF14 patients had a significantly greater clinician-reported (80% vs 31%; p =0.0011) and self-reported (59% vs 11%; p =0.0003) response rate to 4-AP treatment compared to (GAA) &lt;200 - FGF14 patients. This included a treatment response with high relevance to everyday living, as exemplified by an improvement of 2 FARS stages in some cases. Placebo-controlled video-oculography data of four (GAA) ≥250 - FGF14 patients previously enrolled in a 4-AP randomized double-blind trial showed a significant decrease in slow phase velocity of DBN with 4-AP, but not placebo. This study shows that FGF14 GAA repeat expansions are a highly frequent genetic cause of DBN syndromes, especially when associated with additional cerebellar features. Moreover, they genetically stratify a subgroup of patients with DBN that appear to be highly responsive to 4-AP, thus paving the way for a “theranostics” approach in DBN syndromes.