bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone pain in Fibrous dysplasia does not rely on aberrant sensory nerve sprouting or neuroma formation
Authors: Palmisano Biagio , Tavanti Chiara , Farinacci Giorgia , Gosti Giorgio , Leonetti Marco , Donsante Samantha , Giannicola Giuseppe , Appelman-Dijkstra Natasha , Corsi Alessandro , Ippolito Ernesto , Riminucci Mara 
Published: July 2024

AbstractBone pain is a major symptom of many skeletal disorders. Fibrous dysplasia (FD) is a genetic disease with mono or polyostotic skeletal phenotype due to the post-zygotic occurrence of the causative Gsα mutation. Bone pain in FD often associates with skeletal deformities and fractures or nerve impingement by the pathological tissue. However, even in the absence of complications, FD patients often complain of a chronic pain that does not correlate with their disease burden. Multiple hypotheses have been made to explain this pain. However, its pathogenetic mechanisms remain, as yet, largely unexplored.In this study, we first demonstrate that the FD mouse model EF1α-GsαR201Cdevelops a painful-like behavior and an altered response to nociceptive stimuli that, as in FD patients, do not correlate with the severity of their phenotype, thus providing a reliable model to study bone pain in FD. Then, we show that in EF1α-GsαR201Cmice, the overall pattern of skeletal innervation is preserved and that within FD lesions, sensory fibers are variably and focally distributed, mainly at perivascular sites. Finally, we provide the first analysis of a series of human FD bone biopsies showing that sensory nerve fibers are rarely detected within the pathological tissue.These data confirm that bone pain is an intrinsic and reproducible feature of FD. They also show that, albeit sensory nerve fibers are found within FD lesions and may contribute to the unpleasant sensation that accompanies the disease, pathological sensory nerve sprouting or formation of neuromas are not detected in the Gsα-mutated skeleton.
Cell wall-resident PIR proteins show an inverted architecture inNeurospora crassa, but keep their role as wall stabilizers
Authors: Montaño-Silva Paul , Callejas-Negrete Olga A. , Pereira-Santana Alejandro , Verdín Jorge 
Published: July 2024

ABSTRACTProteins with internal repeats (PIRs) are the second most abundant class of fungal cell wall resident proteins. In yeasts, PIRs preserve the wall stability under stressful conditions. They are characterized by conserved N-terminal amino acid sequences repeated in tandem (PIR domains), and a Cys-rich C-terminal domain. Despite PIRs have been inferred in several filamentous fungi genomes, they have not been studied beyond yeasts. In this work, PIRs diversity, evolution and biological role, focused on a new PIRs class, were addressed. Bioinformatic inference of PIRs in fungi indicated they were an innovation in Ascomycota. Predicted PIRs clustered in two main groups: classical yeasts PIRs (N-terminal PIR domains; C-terminal Cys-rich domain), and PIRs from filamentous fungi with an inverted architecture (N-terminal Cys-rich domain; C-terminal PIR domains), which could harbor additional GPI-signals. As representatives of the second group,Neurospora crassa(Nc) PIR-1 (NCU04033) and PIR-2 (NCU07569) were studied. Confocal microscopy of eGFP-labeled PIR-1 and PIR-2 revealed they accumulate in apical plugs; additionally, PIR-1 requires the Kex2 processing site for correct maturation, and its predicted C-terminal GPI modification signal resulted functional. Moreover, Nc Δpir-1and Δpir-2single mutants showed a growth rate similar to that of Nc WT, but the double mutant Nc Δpir-1/Δpir-2grew significatively slower. Similarly, Nc Δpir-1and Nc Δpir-2were mildly sensitive to calcofluor white, although Nc Δpir-1/Δpir-2double mutant was severely impaired. Despite the inverted architecture of PIR-1 and PIR-2, they resulted in cell wall stabilizers as classical yeast PIRs.
Choose your partner: Social evaluation of skilfulness at cooperative co-action tasks in Tonkean macaques (Macaca tonkeana)
Authors: Hirel Marie , Meunier Hélène , Mundry Roger , Rakoczy Hannes , Fischer Julia , Keupp Stefanie 
Published: July 2024

AbstractSocial evaluation – inferring individual characteristics of others from their past behaviours – is an adaptive strategy that helps to inform social decisions. However, how nonhuman primates form and use impressions about others to select their social partners strategically is still unclear. In this study, we investigated whether Tonkean macaques,Macaca tonkeana, can spontaneously use information, acquired by observation, to choose the optimal partners for cooperation in two co-action tasks from the same domain. The subjects (N=5) did not prefer to cooperate with the skilful partner compared to the unskilled partner, irrespective of the task or how much attention they paid to the partners’ actions solving a solo version of one task prior to the test. The probability of optimal choices did not increase through trials either, indicating no learning by experience with the partners across the 16 test trials. Our results contradict findings of previous studies that tested monkeys in different domains of competence and contexts, and thus encourage further investigation on monkeys’ social evaluation abilities. Our experimental design presents a promising way to investigate different contexts, the inter-individual differences, the different types of social information involved, and the cognitive mechanisms underlying social evaluation and partner selectivity in nonhuman primates.
Tumor-derived colorectal cancer organoids induce a unique Treg cell population through direct modulation of CD4+T cell differentiation
Authors: Aristin Revilla Sonia , Frederiks Cynthia Lisanne , Prekovic Stefan , Mocholi Enric , Kranenburg Onno , Coffer Paul James 
Published: July 2024

AbstractIn colorectal cancer (CRC), increased numbers of tumor-infiltrating CD4+regulatory T (Treg) cells correlate with tumor development and immunotherapy failure, leading to poor prognosis. However, the molecular and cellular mechanisms governing Treg recruitment, expansion, or differentiation remain unclear. Here, we developed anin vitroco-culture system to assess the capacity of CRC tumors to directly modulate Treg cell differentiation. CD4+T cells from Foxp3eGFP mice were co-cultured with murine tumor-derived CRC organoids, resulting in a significant increase in Treg cell numbers. This induction of Treg cells was not due to increased proliferation, but rather through differentiation of CD4+T cells in a TGFβ-dependent manner. Human CRC tumor organoids similarly induced Treg cells that exhibited enhanced suppressive capacity compared to TGFβ-induced Treg cells. RNA-sequencing analysis identified distinct transcriptional profiles between CRC organoid-induced Treg cells and TGFβ-induced Treg cells, with upregulation of key functional signature genes linked to CRC Treg cellsin vivo. High expression of genes upregulated in CRC organoid-induced Treg cells correlates with shorter progression free interval and overall survival of CRC patients, highlighting their prognostic potential. Taken together, CRC tumor organoids drive CD4+differentiation to Treg cells with a phenotype resembling tumor-infiltrating Treg cells. This model can be applied to both understand the molecular mechanisms by which tumors can directly modulate CD4+T cell differentiation and identify approaches to disrupt Treg cell function and stimulate anti-tumor immunity.
The temporal refinement ofDach1is a key step in the functional maturation of primary somatosensory neurons
Authors: Szemes Tünde , San José Alba Sabaté , Azouz Abdulkader , Sitte Maren , Salinas Gabriela , Achouri Younes , Kricha Sadia , Ris Laurence , Red-Horse Kristy , Bellefroid Eric J. , Desiderio Simon 
Published: July 2024

SummaryDuring somatosensory neurogenesis, neurons are born in an unspecialized transcriptional state, with several transcription factors following a broad-to-restricted expression dynamic as development proceeds, supporting neuron subtype identities. The relevance of this temporal refinement remains however unclear, these broad-to-restricted transcription factors being selectively involved in neurons in which they are ultimately maintained. Here we found thatDach1encodes for abona fidebroad-to-restricted transcription factor retained and required in tactile somatosensory neurons. Within developing nociceptors, we demonstrate that Prdm12 contributes toDach1extinction. Using genetic approaches to prevent its temporal restriction during somatosensory development, we reveal thatDach1refinement is a prerequisite for the appropriate transcriptional maturation of somatosensory subtypes from which it becomes ultimately excluded. These findings highlight the essential role played by Dach1 during somatosensory neuron development. They further demonstrate that the broad-to-restricted temporal pattern followed by several transcription factors is physiologically relevant to achieve appropriate transcriptional maturation of somatosensory neurons.
Thermal preconditioning modulates coral physiology and heat tolerance: A multi-species perspective
Authors: Ferrara Erik F. , Roik Anna , Wöhrmann-Zipf Franziska , Ziegler Maren 
Published: July 2024

AbstractGlobal warming threatens reef-building corals by challenging their natural adaptive capacity. Therefore, interventions such as stress hardening by thermal preconditioning could become crucial for their survival. Stress-hardening approaches recognize that organisms living in thermally variable environments are better able to withstand marine heat waves. However, a systematic assessment of preconditioning effects on the baseline physiology and thermal tolerance across coral species is lacking. We assessed the changes of thermal tolerance in six stony coral species (Galaxea fascicularis, Porites rus, Acropora muricata, Montipora digitata, andStylophora pistillata) in three thermal preconditioning treatments of stable-high 29 °C and variable-high 29 °C with a daily oscillation of ± 1.5 °C, compared to corals in stable-ambient 26 °C. We quantified changes in photosynthetic efficiency and coral bleaching intensity before and after a short-term heat stress assay and up to 30 days later. Stress-hardening success after preconditioning was observed in nearly all preconditioned corals, but the increases in thermal tolerance were species-specific. The greatest increase was recorded inG. fascicularisandA. muricata, with stress responses reduced by over 80 %. In contrast, preconditioning regimes had minor effects on stress tolerance ofS. pistillata, making it least receptive to this intervention. After 30 days, most stress-hardened species demonstrated higher survival and recovery rates than their conspecifics from the stable-ambient regime. Notably, both preconditioning regimes affected baseline physiology, especially in the branching species, as indicated by minor tissue paling and decreased photosynthetic efficiency. We conclude that implementing thermal stress hardening protocols will require careful consideration of the species-specific receptiveness and evaluation of the potential trade-offs that can be inflicted with the post-conditioning shifts in physiological baselines.
Metabolites reflect variability introduced by mesoscale eddies in the North Pacific Subtropical Gyre
Authors: Kumler William , Qin Wei , Lundeen Rachel A. , Barone Benedetto , Carlson Laura T. , Ingalls Anitra E. 
Published: July 2024

AbstractMesoscale eddies significantly alter open ocean environments such as those found in the subtropical gyres that cover a large fraction of the global ocean. Previous studies have explored eddy effects on biogeochemistry and microbial community composition but not on the molecular composition of particulate organic matter. This study reports the absolute concentration of 67 metabolites and relative abundances for 640 molecular features to understand how mesoscale eddies impact the metabolome of the North Pacific Subtropical Gyre during two cruises in 2017 and 2018. We find that many metabolites track biomass trends, but metabolites like isethionic acid, homarine, and trigonelline linked to eukaryotic phytoplankton were enriched at the deep chlorophyll maximum of the cyclonic features, while degradation products such as arsenobetaine were enriched in anticyclones. In every analysis, metabolites with the strongest responses were detected via untargeted mass spectrometry, indicating that the molecules most sensitive to environmental perturbation were not among the characterized metabolome. By analyzing depth variability (accounting for 20-40% of metabolomic variability across ∼150 meters) and the vertical displacement of isopycnal surfaces (explaining 10-20% of variability across a sea level anomaly range of 40 centimeters and a spatial distance of 300 kilometers), this analysis constrains the importance of mesoscale eddies in shaping the chemical composition of particulate matter in the largest biomes on the planet.ImportanceMesoscale eddies are common ocean surface currents that circulate seawater vertically and horizontally. This stirring effect alters biogeochemistry and planktonic community composition. Here, we use metabolomics to determine how these eddy-induced changes influence the nature of organic carbon across an eddy dipole. We found that many small, polar molecules track with the overall particulate carbon in the system and that there were significant differences in metabolite composition between eddy states. A few metabolites reflected the increased importance of eukaryotic phytoplankton that were enriched by the higher nutrient supply from depth in the cyclonic eddies. Anticyclones contained more compounds that reflected a higher degree of degradation. This work answers outstanding questions about the importance of these common ocean features in shaping microbial community function.
Reproductive resource allocation correlates with successful global invasion of a mosquito species
Authors: Khorramnejad Ayda , Alfaro Claudia , Quaranta Stefano , Lozada-Chávez Alejandro Nabor , Gasmi Laila , Perdomo Hugo D. , Chiarelli Laurent Roberto , Bonizzoni Mariangela 
Published: July 2024

AbstractThe understanding of traits favoring biological invasions has been considered an essential step to predict which species would become successful invaders. Classical approaches test for differences between invasive vs. not invasive species and emphasize reproduction as a critical phenotype for successful establishment of an invasive species. However, cross-species comparisons underestimate intraspecies differences, which may be relevant in invasive species with highly genetically diverse populations. Here we capitalize on the well-characterized invasion history of the arboviral vectorAedes albopictus, which resulted in genetically-distinct native, old and invasive populations, and compared the reproductive capacity (fertility and fecundity), development (timing of egg development, oviposition patterns and egg hatching) and physiology (blood digestion and nutrient movement during oogenesis) across populations. We observed that invasive mosquitoes optimize their nutrient investment during development and oogenesis, which leads to increased egg production with respect to native and long adapted laboratory mosquitoes. This higher fecundity results from a delay in oogenesis and is accompanied by higher fertility. We further tested inheritance of reproductive traits via reciprocal crosses, which showed a higher fertility and fecundity in hybrids with respect to parental strains and a potential contribution of males to the reproductive success of invasive mosquitoes. Our results provide evidence that resource allocation during development and oogenesis influences the reproductive capacity ofAe. albopictusand manifests in population differences that correlate with their invasion success.Significance StatementIn addition to being an essential process to ensure the survival of a species, reproduction is a key determinant for a species invasion success because it facilitates a species’ ability to establish in a new area. Reproduction is a complex phenotype that relies on intricate and timely interactions between genetic and physiological factors. Here we combined molecular, biochemical, and genetic approaches to show that efficient allocation of energetic resources during development and oogenesis fosters the reproductive output ofAe. albopictusmosquitoes and manifests as variation in the reproductive capacity of its geographic populations. These results are critical for predicting the invasion success of this species and tailoring effective control strategies.
Identification and characterization of thiamine analogues with antiplasmodial activity
Authors: Fathoni Imam , Ho Terence C. S. , Chan Alex H. Y. , Leeper Finian J. , Matuschewski Kai , Saliba Kevin J. 
Published: July 2024

AbstractThiamine is metabolized into thiamine pyrophosphate (TPP), an essential enzyme cofactor. Previous work has shown that oxythiamine, a thiamine analogue, is metabolized by thiamine pyrophosphokinase (TPK) into oxythiamine pyrophosphate (OxPP) within the malaria parasitePlasmodium falciparum, and then inhibits TPP-dependent enzymes, killing the parasitein vitroandin vivo. To identify a more potent antiplasmodial thiamine analogue, 11 commercially available compounds were tested againstP. falciparumandP. knowlesi. Five active compounds were identified, but only N3-pyridyl thiamine (N3PT), a potent transketolase inhibitor and candidate anticancer lead compound, was found to suppressP. falciparumproliferation with an IC50value 10-fold lower than that of oxythiamine. N3PT was active againstP. knowlesiand was >17 times less toxic to human fibroblast, as compared to oxythiamine. Increasing the extracellular thiamine concentration reduced the antiplasmodial activity of N3PT, consistent with N3PT competing with thiamine/TPP. A transgenicP. falciparumline overexpressing TPK was found to be hypersensitized to N3PT. Docking studies showed an almost identical binding mode in TPK between thiamine and N3PT. Furthermore, we show that [3H]thiamine accumulation, resulting from a combination of transport and metabolism, in isolated parasites is reduced by N3PT. Treatment ofP. berghei-infected mice with 200 mg/kg/day N3PT reduced their parasitemia, prolonged their time to malaria symptoms, and appeared to be non-toxic to mice. Collectively, our studies are consistent with N3PT competing with thiamine for TPK binding and inhibiting parasite proliferation by reducing TPP production, as well as being converted into a TPP antimetabolite that inhibits TPP-dependent enzymes.
Tubules, rods and spirals: diverse modes of SepF-FtsZ assembling
Authors: Choudhury Jagrity , Chaudhuri Barnali N. 
Published: July 2024

AbstractZ-ring formation by FtsZ, the master assembler of divisome, is a key step in bacterial cell division. Both formation and membrane anchoring of the Z-ring requires assistance of a number of Z-ring binding proteins, such as FtsA, EzrA, SepF, SepH and ZipA. SepF participates in bundling and membrane anchoring of FtsZ in gram-positive bacteria. We reportin vitrobiophysical studies of the interactions between FtsZ and cytoplasmic component of cognate SepF from three different bacteria:Mycobacterium tuberculosis,Staphylococcus aureusandEnterococcus gallinarum.While the cytosolic domain of SepF fromM. tuberculosisis a dimer, those fromS. aureusandE. gallinarumpolymerize to form ring-like structures. Mycobacterial SepF helps in bundling of FtsZ filaments to form thick filaments and large spirals. On the other hand, ring-forming SepF from theFirmicutesbundle FtsZ into tubules.
Evaluating the Efficacy of AI-Based Interactive Assessments Using Large Language Models for Depression Screening
Authors: Jin Zheng , Bi Dandan , Hu Jiaxing , Zhao Kaibin 
Published: July 2024

ABSTRACTThe evolution of language models, particularly the development of Large Language Models like ChatGPT, has opened new avenues for psychological assessment, potentially revolutionizing the rating scale methods that have been used for over a century. This study introduces a new Automated Assessment Paradigm (AAP), which aims to integrate natural language processing (NLP) techniques with traditional measurement methods. This integration enhances the accuracy and depth of mental health evaluations, while also addressing the acceptance and subjective experience of participants—areas that have not been extensively measured before. A pilot study was conducted with 32 participants, seven of whom were diagnosed with depression by licensed psychiatrists using the Clinical Interview Schedule-Revised (CIS-R). The participants completed the BDI-Fast Screen (BDI-FS) using a custom ChatGPT (GPTs) interface and the Chinese version of the PHQ-9 in a private setting. Following these assessments, participants also completed the Subjective Evaluation Scale. Spearman’s correlation analysis showed a high correlation between the total scores of the PHQ-9 and the BSI-FS-GPTs. The agreement of diagnoses between the two measures, as measured by Cohen’s kappa, was also significant. BSI-FS-GPTs diagnosis showed significantly higher agreement with the current diagnosis of depression. However, given the limited sample size of the pilot study, the AUC value of 1.00 and a sensitivity of 0.80 at a cutoff of 0.5, with zero false positive rate, likely overstate the classifier’s performance. Bayesian factors suggest that participants may feel more comfortable expressing their true feelings and opinions through this method. For ongoing follow-up research, a total sample size of approximately 104 participants, including about 26 diagnosed individuals, may be required to ensure the analysis maintains a necessary power of 0.80 and an alpha level of 0.05. Nonetheless, these findings provide a promising foundation for the ongoing validation of the new AAP in larger-scale studies, aiming to confirm its validity and reliability.
Health-Related Quality of Life Perception Among Older Persons with Non-Communicable Diseases in Primary Healthcare Facilities: A Qualitative Inquiry
Authors: Fiona Atim , Regina Ndagire , Nampima Chloe , Kiyinji Frank , Lwanira Catherine , Nanyonga Rose Clarke , Orach-Meza Faustino 
Published: July 2024

AbstractBackgroundUnveiling the understanding of older persons with non-communicable diseases (NCDs) regarding health well-being is paramount and can translate to increased self-efficiency, independence, and enhanced well-being. However, little is known about older persons’ understanding of the concept of health-related quality of life (HRQoL) in Uganda. The study explored perceptions of older persons with NCDs on HRQoL in central Uganda.MethodsThis exploratory qualitative study design involved 23 participants recruited from selected Primary healthcare facilities in Central Uganda. Thematic analysis using an inductive approach generated themes that informed the study’s qualitative findings.ResultsThe key themes that emerged from the study include holistic well-being, lifestyle modification, and financial stability. The key component of HRQoL that came out clearly from the study was the physical domain. There is a need to embrace a person-centered approach based on the perceptions of older persons on HRQoL, which has the potential to improve well-being and enhance a healthy aging journey.