julilili42/papers huggingface dataset:
Influence of Unidirectional Vacuum Application on Bone Healing in Maxillofacial Surgery
2025-05-21

Negative-pressure wound therapy (NPWT) using vacuum-assisted closure (VAC) is a well known tissue defect bridging method that applies a vacuum pump to sterile, open-cell foam dressings via suction tubes. Although it has mostly been described for soft tissue use, there are also a few studies concerning its use on hard tissue. However, as oral and maxillofacial surgery has to deal with both soft and hard tissue, which lie next to each other in these regions, there is a particular need to assess the influence of negative pressure on bone. Therefore, the effects of different negative pressure levels (530 mbar and 725 mbar) and atmospheric pressure (1013 mbar) on bone tissue cultures and osteoblast cell cultures were investigated over periods of 1, 3, and 6 weeks. During the culture period, osteoblast growth and the tissue regeneration of bone defects were studied in vitro using tissue cultures that were histologically supplemented by cytological investigations and quantitative RNA expression studies. In the bone defect model, there was a faster defect reduction using NPWT; the effect was especially strong for 530 mbar. Compared to the control group, up to 30% more newly generated bone tissue was detected. This effect on the mineralization capacity was assessed by the mRNA expression of osteogenic marker genes, as well as the receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG), two multifaceted cytokines that regulate bone metabolism. The influence of negative pressure consequently resulted in a decreased RANKL/OPG ratio in osteoblasts. Associated with the upregulation of marker genes to up to 400%, including Col1, BMP4, OCN, and RUNX2, the decrease in the RANKL/OPG ratio to 41% indicates the stimulation of osteogenesis. Since VAC has been shown to be a safe and effective method to close wounds in general, these data suggest that patients suffering from compound bone and soft tissue defects in the maxillofacial area may benefit from an adapted therapy approach accelerating both soft and hard tissue regeneration.
Two-Dimensional Perisaccadic Visual Mislocalization in Rhesus Macaque Monkeys
2025-05-21

Perceptual localization of brief, high-contrast perisaccadic visual probes is grossly erroneous. While this phenomenon has been extensively studied in humans, more needs to be learned about its underlying neural mechanisms. This ideally requires running similar behavioral paradigms in animals. However, during neurophysiology, neurons encountered in the relevant sensory and sensory–motor brain areas for visual mislocalization can have arbitrary, noncardinal response field locations. This necessitates using mislocalization paradigms that can work with any saccade direction. Here, we first established such a paradigm in three male rhesus macaque monkeys. In every trial, the monkeys generated a saccade toward an eccentric target. Once a saccade onset was detected, we presented a brief flash at one of three possible locations ahead of the saccade target location. After an experimentally imposed delay, we removed the saccade target, and the monkeys were then required to generate a memory-guided saccade toward the remembered flash location. All three monkeys readily learned the task, and, like humans, they all showed strong backward mislocalization toward the saccade target, which recovered for later flashes from the saccade time. Importantly, we then replicated a known property of human perisaccadic mislocalization, as revealed by two-dimensional mislocalization paradigms: that mislocalization is the strongest for upward saccades. For horizontal saccades, we additionally found stronger mislocalization for upper visual field flashes, again consistent with humans. Our results establish a robust two-dimensional mislocalization paradigm in monkeys, and they pave the way for exploring the neural mechanisms underlying the dependence of perisaccadic mislocalization strength on saccade direction.
Microglia activation orchestrates CXCL10-mediated CD8+ T cell recruitment to promote aging-related white matter degeneration
2025-05-22

Abstract Aging is the major risk factor for neurodegeneration and is associated with structural and functional alterations in white matter. Myelin is particularly vulnerable to aging, resulting in white matter-associated microglia activation. Here we used pharmacological and genetic approaches to investigate microglial functions related to aging-associated changes in myelinated axons of mice. Our results reveal that maladaptive microglia activation promotes the accumulation of harmful CD8 + T cells, leading to the degeneration of myelinated axons and subsequent impairment of brain function and behavior. We characterize glial heterogeneity and aging-related changes in white matter by single-cell and spatial transcriptomics and reveal elaborate glial–immune interactions. Mechanistically, we show that the CXCL10–CXCR3 axis is crucial for the recruitment and retention of CD8 + T cells in aged white matter, where they exert pathogenic effects. Our results indicate that myelin-related microglia dysfunction promotes adaptive immune reactions in aging and identify putative targets to mitigate their detrimental impact.
Turf algae redefine the chemical landscape of temperate reefs, limiting kelp forest recovery
2025-05-22

In temperate regions experiencing rapid ocean warming, kelp forests are being replaced by chemically rich turf algae. However, the extent to which these turf algae alter the surrounding chemical environment or affect the rebound potential of kelp forests (through chemically mediated interactions) remains unknown. Here, we used underwater visual surveys, comprehensive chemical profiling, and laboratory experiments to reveal that turf algae release bioactive compounds into the water that fundamentally alter the reef “chemical landscape” and directly suppress kelp recruitment. Therefore, our study reveals that chemical ecology is critical in shaping modern kelp forest ecosystems and their resilience. Further, it demonstrates that reversing climate-driven state shifts will require not only curbing global carbon emissions but also implementing targeted local interventions that break harmful ecological feedback loops and foster recovery.
Heterogeneity in response to GLP-1 receptor agonists in type 2 diabetes in real-world clinical practice: insights from the DPV register – an IMI-SOPHIA study
2025-05-22

Abstract Aims/hypothesis Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a cornerstone in type 2 diabetes management. In this study we evaluated heterogeneity in body weight and glycaemic responses to the initiation of liraglutide, semaglutide or dulaglutide in real-world clinical practice. Methods Data from 4467 adults with type 2 diabetes in the Diabetes Patient Follow-up (DPV) registry were analysed, focusing on changes in HbA 1c and body weight over 6 months following initiation of a GLP-1 RA. We categorised participants based on their response: HbA 1c reduction only, weight loss only, both or neither. This analysis was part of the IMI-Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy (IMI-SOPHIA) project. Results At 6 months’ follow-up the median absolute HbA 1c reduction was 5.3 mmol/mol (IQR 13.9, −1.0) (0.49% [1.27, −0.09]) and relative body weight reduction was 1.43% (4.26, 0). Only 14% of participants achieved meaningful reductions in both HbA 1c (absolute reduction ≥5.5 mmol/mol [0.5%]) and body weight (relative reduction ≥5%). Men and those with a higher baseline HbA 1c were more likely to show an HbA 1c only response (36% of participants; both p &lt;0.001), while older individuals and those with a longer diabetes duration were more likely to experience a weight-only response (7% of participants; both p &lt;0.001). Higher baseline body weight and lower eGFR (both p &lt;0.05) correlated with greater weight reduction, whereas lower baseline HbA 1c and longer diabetes duration were linked to smaller HbA 1c reductions (both p &lt;0.001). Conclusions/interpretation There is significant heterogeneity in responses to GLP-1 RA therapy among individuals with type 2 diabetes in routine clinical practice. However, in our study a substantial proportion achieved a reduction in either body weight or HbA 1c . Future studies should explore why some individuals achieve either weight loss or HbA 1c reduction but not both. Graphical Abstract
Application of IVDr NMR spectroscopy to stratify Parkinson’s disease with absolute quantitation of blood serum metabolites and lipoproteins
2025-05-22

Abstract The challenge of early detection and stratification in Parkinson’s disease (PD) is urgent due to the current emergence of mechanism-based disease-modifying treatments. In here, metabolomic and lipidomic parameters obtained by a standardized and targeted in vitro diagnostic research (IVDr) platform have a significant potential to address therapy-related questions and generate improved biomarker panels. Our study aimed to use IVDr nuclear magnetic resonance (NMR) spectroscopy to quantify metabolites and lipoproteins in PD blood serum from different cohorts to stratify metabolically driven subtypes of idiopathic and genetic PD. Serum aliquots from three neurodegeneration biobank cohorts (287 samples in total, including 62 PD patient samples with GBA mutation, 98/43 PD patient samples of early/late stages of disease duration, 20 PD samples from patients with mutations in recessive PD genes and some smaller subgroups of mitochondrial and double mutation cases) were prepared and analyzed with IVDr NMR spectroscopy, covering 39 blood serum metabolites and 112 lipoprotein parameters. Uni- and multivariate statistics were used to identify metabolism-driven changes under consideration of typical confounders such as age, sex and disease duration and set into context with clinical biomarkers such as CSF concentrations of alpha-synuclein, neurofilament light chain, and tau protein. Based on the different PD subgroups we performed a total of eight different comparisons. Highlights from these comparisons include increased citrate and dimethylglycine with a decrease of creatinine and methionine in healthy controls and early PD group compared to GBA, PD late and recessive PD. We furthermore identified decreased HDL-3 free cholesterol in genetic PD cases compared to sporadic subject samples (sum of the PD early and PD late groups). Considering medication, we found that the levodopa equivalent daily dose (LEDD) is mostly positively correlated with tyrosine and citrate in sporadic PD compared to pyruvate and phenylalanine in genetic PD. Cerebrospinal fluid levels of alpha-synuclein were negatively correlated with alanine. Further metabolites and lipoproteins with discriminatory power for double mutation PD cases involved ornithine, 2-aminobutyrate and 2-hydroxybutyrate as well as for mitochondrial phenotypes via LDL phospholipid, apolipoprotein and cholesterol subfractions. Quantitative IVDr NMR serum spectroscopy is able to stratify PD patient samples of different etiology and can contribute to a wider understanding of the underlying metabolism-driven alterations e.g. in energy, amino acid, and lipoprotein metabolism. Though our overall cohort was large, major confounders such as age, sex and medication have a strong impact. That is why absolute quantification and detailed patient knowledge about metabolic confounders, is a premise for future translation of NMR serum spectroscopy to routine PD diagnostics.
Emergence of multiple collective motility modes in a physical model of cell chains
2025-05-22

Collective cell migration is central to processes like development and cancer metastasis. While mechanisms of collective motility are increasingly understood, their classification remains incomplete. Here, we study the migration of small cell chains, namely cohesive pairs. Experiments with Dictyostelium discoideum (Dd) revealed two motility modes: the individual contributor (IC) mode, where each cell generates its own traction dipole, and the supracellular (S) mode, characterized by a single dipole. Dd pairs favored the IC mode, while Madin-Darby canine kidney (MDCK) doublets predominantly used the S mode. A 2D biophysical model recapitulated many experimental observations; the IC mode emerged naturally in ameboid Dd doublets when both cells exerted similar traction stresses, while the S mode dominated with stronger leaders. Contrary to amebas, MDCK-like cell chains showed a bias towards the IC mode when increasing cell-cell adhesion. Extending the model to longer chains, we show its potential for understanding emergent migration patterns across cell types and scales.
Hominin tool evolution and its (surprising) relation to language origins
2025-05-22

Abstract This chapter examines the evolution of human culture and communication using a novel social learning framework. We hypothesize that human apes show a unique propensity for a type of social learning we call ‘know-how copying’. As we explain, know-how copying is integral to language evolution. Various methodologies for testing whether a given type of human or animal culture depends on know-how copying are discussed. We then consider the hominin technological record with an eye towards identifying signatures of know-how copying. We suggest a much later date for the origins of know-how copying than is typical. This poses a puzzle, namely: there is good reason to think that hominins had considerably expanded their communicative repertoire prior to the evolution of know-how copying. How was this possible in the seeming absence of know-how copying? We sketch a solution that provides new support for a gestural–iconic origins scenario for language.
Why modelling space is hard: no evidence for a serial founder effect in Polynesian phoneme inventories
2025-05-22

Abstract In recent years there has been an increased interest in computational modeling of spatial phenomena in typology. While the main focus of most work so far has been on direct language contact, there are two different types of spatial dynamics of interest to typologists and areal linguists: language expansion, and asymmetric contact effects. In this paper we present five statistical techniques to model phylogenetic and spatial relations between languages. We illustrate these techniques with a case study on Polynesian phoneme inventory sizes, and show that there is robust evidence for asymmetric contact effects from Non-Polynesian on Polynesian, but little evidence for expansion effects within Polynesian. In other words, we do not find convincing evidence for a serial founder effect in Polynesian phoneme inventory sizes. We also argue that we are still far from having a complete understanding of how to model all spatial dynamics that can affect language contact, and that more attention should be paid to these issues.
Exoskeletal cuticle proteins enable Drosophila locomotion
2025-05-22

Exo- and Endoskeleton function enables muscle-mediated locomotion in animals. In mammals, the defective protein matrix of bones found in systematic skeletal disorders such as osteoporosis causes fractures and severe skeletal deformations under high muscle tension. We identified an analogous mechanism for integrating muscle-mediated tension into the apical extracellular matrix (aECM) of the invertebrate body wall exoskeleton. Obstructor chitin-binding proteins, the chitin deacetylases, Chitinases, and the matrix-protecting proteins Knickkopf and Retroactive are epidermally expressed during late embryogenesis. Their control of forming epidermal chitinous structures protects the exoskeletal aECM from collapsing when embryos start moving and hatch as larvae. In a larval locomotion assay we tested the function of these cuticle related genes. Gene mutations and knockdowns caused changes in normal movement behavior and lower the speed of larvae. Moreover, we found that the transmembrane Zona Pellucida domain protein Piopio provides the adhesion between the epidermal apical membrane and the overlaying chitinous aECM in a matriptase-dependent manner. A failure of Piopio and chitin-associated proteins leads to exoskeletal deformations and detachment from the epidermal membrane, destabilizing muscle forces and impairing larval mobility. Our data identifies a protein network that transforms the chitinous aECM into a stable exoskeleton that directly resists muscle impact at epidermal tendon cells, thereby serving locomotion. Demonstrating the importance of these proteins in producing aECM as a three-dimensional cuticular scaffold for exoskeletal function opens up opportunities for the development of biomimetic applications of synthetic materials. STATEMENT OF SIGNIFICANCE: Chitin-based materials include hydrogels, microcapsules, membranous films, sponges, tubes, and various porous structures. In nature, chitin structures form cuticles, which serves as the exoskeleton of arthropods. Using Drosophila melanogaster, we have performed systematic analyses to identify the proteins and enzymes that organize chitin polymers in 3D structures of the cuticle exoskeleton. Three-dimensional laser-scanning and ultrastructural electron microscopy revealed deformations of the cuticle structure, lack of cellular cuticle adhesion, and overall changes in the flexibility of the chitin-based material, leading to insufficient function of the exoskeleton. Components such as the identified proteins and enzymes, which play a unique role in the organization of the chitin fibers and the formation of the exoskeleton, offer suitable materials for tissue engineering for biomimetic applications.
A task-invariant prior explains trial-by-trial active avoidance behaviour across gain and loss tasks
2025-05-22

Abstract Failing to make decisions that would actively avoid negative outcomes is central to helplessness. In a Bayesian framework, deciding whether to act is informed by beliefs about the world that can be characterised as priors. However, these priors have not been previously quantified. Here we administered two tasks in which 279 participants decided whether to attempt active avoidance actions. In both tasks, participants decided between a passive option that would for sure result in a negative outcome of varying size, and a costly active option that allowed them a probability of avoiding the negative outcome. The tasks differed in framing and valence, allowing us to test whether the prior generating biases in behaviour is problem-specific or task-independent and general. We performed extensive comparisons of models offering different structural explanations of the data, finding that a Bayesian model with a task-invariant prior for active avoidance provided the best fit to participants’ trial-by-trial behaviour. The parameters of this prior were reliable, and participants’ self-rated positive affect was weakly correlated with this prior such that participants with an optimistic prior reported higher levels of positive affect. These results show that individual differences in prior beliefs can explain decisions to engage in active avoidance of negative outcomes, providing evidence for a Bayesian conceptualization of helplessness.
A “Ligand First” Approach toward Selective, Covalent JNK2/3 Inhibitors
2025-05-22

All JNK isoforms play a specific role in various diseases. The role of the JNK2 isoform has so far received little attention compared to its JNK1 and JNK3 counterparts with JNK3 being a potential target for neurodegenerative diseases and an inhibitor with JNK1 bias being currently investigated in clinical trials. Using an iterative, structure-guided optimization approach starting from a reported reversible binding aminopyrazole-derived scaffold, novel highly potent JNK2/3 selective inhibitors were generated ("ligand-first approach"). These reversible inhibitors were further transformed to covalent inhibitors by attaching an electrophilic warhead moiety, able to address a conserved cysteine side chain present in JNKs. Reversible and covalent inhibitors presented in this study show high JNK2/3 isoform selectivity and activity in cells. The covalently acting lead compound <b>56d</b> shows good kinetic data with a <i>k</i><sub>inact</sub>/<i>K</i><sub>I</sub> (JNK2) = 38,200 M<sup>-1</sup> s<sup>-1</sup> as well as cellular isoform selectivity and a clean kinome profile.
Multi-Level Approaches to Assessing Flexibility in Great Ape Communication
2025-05-22

Abstract Human language is an exceptionally plastic and productive signalling system. We can explore the origins of our communicative innovativeness by examining the extent to which non-human species flexibly adjust their communication in response to both immediate and persistent changes in the socioecological environment. One fruitful research avenue is to compare how interactions of individuals of the same species vary dependent on population or setting, interaction partners, and social context. These contrasts allow us to test directly how the use and repertoire of signals respond to the relevant differences in socioecological conditions. Here, we summarize our recent work on wild and zoo-housed orang-utans of two species, showing that individuals facing more sociable and terrestrial conditions exhibit remarkable plasticity in their non-vocal communication. Because great apes are also highly innovative in the non-communicative domain, this general plasticity may have facilitated the evolution of language in the hominin lineage.
Long-Read Sequencing Identifies Mosaic Sequence Variations in Friedreich’s Ataxia-GAA Repeats
2025-05-22

Friedreich’s ataxia (FRDA) is an autosomal recessive neurodegenerative disorder characterized by ataxia, sensory loss and pyramidal signs. While the majority of FRDA cases are caused by biallelic GAA trinucleotide repeat expansions in intron 1 of FXN, there is a subset of patients harboring a heterozygous pathogenic small variant compound-heterozygous with a GAA repeat expansion. We report on the diagnostic journey of a 21-year-old patient who was clinically suspected of having FRDA at the age of 12 years. Genetic testing included fragment analysis, gene panel analysis and exome sequencing, which only detected one pathogenic heterozygous missense variant (c.389 G&gt;T,p.Gly130Val) in FXN. Although conventional repeat analyses failed to detect GAA expansions in our patient, subsequent short-read genome sequencing (GS) indicated a potential GAA repeat expansion. This finding was confirmed by long-read GS, which in addition revealed a complex pattern of interruptions. Both large and small GAA expansions with divergent interruptions containing G, A, GA, GAG and/or GAAG sequences were present within one allele, indicating mosaic sequence variations. Our findings underscore the complexity of repeat expansions which can exhibit both interruptions and somatic instability. We also highlight the utility of long-read GS in unraveling intricate genetic profiles, ultimately contributing to more accurate diagnoses in clinical practice.