Miracle-dz/UniFAR-FTUs huggingface dataset:
Induction of muscle-regenerative multipotent stem cells from human adipocytes by PDGF-AB and 5-azacytidine

Human adipocytes are a source of tissue-regenerative multipotent stem cells. Terminally differentiated murine osteocytes and adipocytes can be reprogrammed using platelet-derived growth factor–AB and 5-azacytidine into multipotent stem cells with stromal cell characteristics. We have now optimized culture conditions to reprogram human adipocytes into induced multipotent stem (iMS) cells and characterized their molecular and functional properties. Although the basal transcriptomes of adipocyte-derived iMS cells and adipose tissue–derived mesenchymal stem cells were similar, there were changes in histone modifications and CpG methylation at cis-regulatory regions consistent with an epigenetic landscape that was primed for tissue development and differentiation. In a non-specific tissue injury xenograft model, iMS cells contributed directly to muscle, bone, cartilage, and blood vessels, with no evidence of teratogenic potential. In a cardiotoxin muscle injury model, iMS cells contributed specifically to satellite cells and myofibers without ectopic tissue formation. Together, human adipocyte–derived iMS cells regenerate tissues in a context-dependent manner without ectopic or neoplastic growth.
Small dendritic synapses enhance temporal coding in a model of cochlear nucleus bushy cells

Spherical bushy cells (SBC) in the the anteroventral cochlear nucleus can improve the temporal precision of the auditory nerve spiking activity despite receiving sometimes only a single suprathreshold axosomatic input. The interaction with small dendritic inputs could provide a possible explanation for this phenomenon. In a compartment model of spherical bushy cells with a stylized or realistic three-dimensional representation of the bushy dendrite we explored this proposal. Phase-locked dendritic inputs caused both a tonic depolarization and a modulation of the SBC membrane potential at the frequency of the stimulus but for plausible model parameters do not cause output action potentials (AP). The tonic depolarization increased the excitability of the SBC model. The modulation of the membrane potential caused a phase-dependent increase in the efficacy of the main axosomatic input to cause output AP. These effects increased the rate and the temporal precision of output AP. Rate was mainly increased for stimulus frequencies at and below the characteristic frequency of the main input. Precision mostly increased for higher frequencies above about 1 kHz. Dendritic morphological parameters, biophysical parameters of the dendrite and the synaptic inputs and tonotopic parameters of the inputs all affected the impact of dendritic synapses. This suggested the possibility of fine tuning of the effect the dendritic inputs have for different coding demands or input frequency ranges. Excitatory dendritic inputs modulate the processing of the main input and are thus a plausible mechanism for the improvement of temporal precision in spherical bushy cells.
Brain Tumor IDH, 1p/19q, and MGMT Molecular Classification Using MRI-based Deep Learning: Effect of Motion and Motion Correction

Deep learning has shown promise for predicting glioma molecular profiles using MR images. Before clinical implementation, ensuring robustness to real-world problems, such as patient motion, is crucial. We sought to evaluate the effects of motion artifact on glioma marker classifier performance and develop a deep learning motion correction network to restore classification accuracies. T2w images and molecular information were retrieved from the TCIA and TCGA databases. Three-fold cross-validation was used to train and test the motion correction network on artifact-corrupted images. We then compared the performance of three glioma marker classifiers (IDH mutation, 1p/19q codeletion, and MGMT methylation) using motion-corrupted and motion-corrected images. Glioma marker classifier performance decreased markedly with increasing motion corruption. Applying motion correction effectively restored classification accuracy for even the most motion-corrupted images. For IDH classification, an accuracy of 99% was achieved, representing a new benchmark in non-invasive image-based IDH classification and exceeding the original performance of the network. Robust motion correction can enable high accuracy in deep learning MRI-based molecular marker classification rivaling tissue-based characterization. STATEMENT OF SIGNIFICANCE Deep learning networks have shown promise for predicting molecular profiles of gliomas using MR images. We demonstrate that patient motion artifact, which is frequently encountered in the clinic, can significantly impair the performance of these algorithms. The application of robust motion correction algorithms can restore the performance of these networks, rivaling tissue-based characterization.
Short Chain Fatty Acids Enhance Expression and Activity of the Umami Taste Receptor in Enteroendocrine Cells via a Gαi/o Pathway

The short chain fatty acids (SCFAs) acetate, butyrate and propionate, are produced by the fermentation of non-digestible carbohydrates by the gut microbiota. SCFAs are of interest because they regulate appetite, adiposity, metabolism, glycemic control and immunity. SCFAs act at two distinct G protein-coupled receptors (GPCRs), FFAR2 and FFAR3. These are expressed in intestinal enteroendocrine cells (EECs), where they mediate SCFA-driven anorectic gut hormone release. EECs also express other GPCRs that act as nutrient sensors, in a manner that is plastic and adaptable to the environment. SCFAs may elicit some of their health-promoting effects by altering levels of GPCRs in EECs, thus, enhancing gut sensitivity to dietary molecules. Here, we identified that exposure of the murine EEC STC-1 cell-line to a concentration of SCFAs found in the colon, specifically enhances mRNA levels of the umami taste receptors TASR1 and TASR3, without altering levels of the SCFA GPCRs, FFAR2 and FFAR3. Interestingly, treatment of EECs with propionate or butyrate, but not acetate, increased levels of umami receptor transcripts. This phenomenon was reversed by inhibiting Gαi/o signaling with pertussis toxin, suggesting that SCFAs act through FFAR2/3 to alter gene expression. Surprisingly, neither a FFAR3-nor a FFAR2-selective synthetic ligand could increase TASR1/TASR3 mRNA levels. We assessed the functional impact of increases in TASR1/TASR3 expression using unique pharmacological properties of the umami taste receptor; namely, the potentiation of signaling by inosine monophosphate. We found that the umami taste receptor induced inosine-1-phosphate and calcium signaling in response to L-alanine and L-monosodium glutamate, and that butyrate pretreatment significantly enhanced such signaling. Our study reveals that SCFAs may contribute to EEC adaptation and alter EEC sensitivity to bioactive nutrients.
The rise and fall of novel ecological communities

Local and global environmental change is transforming ecological assemblages into new configurations, resulting in ecosystems with novel communities. Here we develop a robust methodology for the identification of novel communities, examine patterns in their natural chance of occurrence, and quantify the probability of local extinction, emigration, local origination and immigration in transitions to and from novel communities. Using a global dataset of Cenozoic marine plankton communities, we found the probability of local extinction, origination and emigration during transitions to a novel community increased up to four times that of background community changes, with the probability of species loss about equal to that of species gain. Although rare, once a novel community state emerged, the chance of shifting into another novel community state was five times greater than expected by chance. Thus, for marine planktonic communities at 100K year time scales, novel communities are particularly sensitive to further extinctions and community shift. One Sentence Summary Once developed, novel ecological communities face increased susceptibility to further shifts in species composition, with heightened extinction risk.
Central processing of leg proprioception in Drosophila

Proprioception, the sense of self-movement and position, is mediated by mechanosensory neurons that detect diverse features of body kinematics. Although proprioceptive feedback is crucial for accurate motor control, little is known about how downstream circuits transform limb sensory information to guide motor output. Here, we investigate neural circuits in Drosophila that process proprioceptive information from the fly leg. We identify three cell-types from distinct developmental lineages that are positioned to receive input from proprioceptor subtypes encoding tibia position, movement, and vibration. 13Bα neurons encode femur-tibia joint angle and mediate postural changes in tibia position. 9Aα neurons also drive changes in leg posture, but encode a combination of directional movement, high frequency vibration, and joint angle. Activating 10Bα neurons, which encode tibia vibration at specific joint angles, elicits pausing in walking flies. Altogether, our results reveal that central circuits integrate information across proprioceptor subtypes to construct complex sensorimotor representations that mediate diverse behaviors, including reflexive control of limb posture and detection of leg vibration.
A simple and effective F0 knockout method for rapid screening of behaviour and other complex phenotypes

Hundreds of human genes are associated with neurological diseases, but translation into tractable biological mechanisms is lagging. Larval zebrafish are an attractive model to investigate genetic contributions to neurological diseases. However, current CRISPR-Cas9 methods are difficult to apply to large genetic screens studying behavioural phenotypes. To facilitate rapid genetic screening, we developed a simple sequencing-free tool to validate gRNAs and a highly effective CRISPR-Cas9 method capable of converting >90% of injected embryos directly into F0 biallelic knockouts. We demonstrate that F0 knockouts reliably recapitulate complex mutant phenotypes, such as altered molecular rhythms of the circadian clock, escape responses to irritants, and multi-parameter day-night locomotor behaviours. The technique is sufficiently robust to knockout multiple genes in the same animal, for example to create the transparent triple knockout crystal fish for imaging. Our F0 knockout method cuts the experimental time from gene to behavioural phenotype in zebrafish from months to one week.
IV. EXPERIMENTAL CONDITIONS FOR THE INDUCTION OF HAPTEN-SPEcIFIC TOLERANCE OR FOR THE STIMULATION OF ANTI-HAPTEN ANAMNESTIC RESPONSES BY "NoNIMMUNOGENIC" HAPTEN-POLYPEPTIDE CONJUGATES

There is now a considerable body of evidence demonstrating that two types of specific lymphoid cells are involved in the antibody response to a variety of antigens (1-10). One of these cells appears to be derived largely from the bone marrow cell population, to be the direct precursor of antibody-secreting cells, and to possess membrane-associated antigen-binding receptors, immunoglobulin in nature and similar (or identical) in specificity with the antibody produced (3, 11-13 and footnote 1). The activation of these antibody-forming cell precursors (AFCP) 2 either requires or is markedly enhanced by the activity of another specific cell type which appears to neither secrete detectable immunoglobulin nor to differentiate into an immunoglobulin-secreting cell (2, 3, 14). This latter cell type has been referred to as a "helper" cell and has been shown in the mouse to be derived from thymus cells and to bear the isoantigen ~ (15, 16). Its activity, although undefined in mechanism, has been demonstrated to be resistant to X-irradiation (16a) and to account for the "carrierspecificity" of anamnestic antibody responses to hapten-carrier conjugates (8, 15, 17). Recent studies in the mouse have demonstrated that specific immunologic tolerance is relatively easy to induce in the helper cell population and that such a state of unresponsiveness may also be induced in bone marrow lymphocytes, although in this population induction of tolerance is more difficult to achieve and the duration of un-
Oropouche virus glycoprotein topology and cellular requirements for virus-like particle assembly

Oropouche virus (OROV; Genus: Orthobunyavirus) is the etiological agent of Oropouche fever, a debilitating febrile illness common in South America. To facilitate studies of OROV budding and assembly, we developed a system for producing OROV virus-like particles (VLPs). Using this system we show that the OROV surface glycoproteins Gn and Gc self-assemble to form VLPs independently of the non-structural protein NSm. Mature OROV Gn has two trans-membrane domains that are crucial for glycoprotein translocation to the Golgi complex and VLP production. Inhibition of Golgi function using the drugs brefeldin A and monensin inhibit VLP secretion, with monensin treatment leading to an increase in co-localisation of OROV glycoproteins with the cis-Golgi marker protein GM130. Infection studies have previously shown that the cellular Endosomal Sorting Complexes Required for Transport (ESCRT) machinery is recruited to Golgi membranes during OROV assembly and that ESCRT activity is required for virus secretion. We demonstrate that a dominant negative form of the ESCRT-associated ATPase VPS4 significantly reduces Gn secretion in our VLP assay. Proteasome inhibition using the drug MG132 also disrupts VLPs secretion, suggesting that ubiquitylation promotes ESCRT-mediated VLP release. Additionally, we observe co-localisation between OROV glycoproteins and a specific subset of fluorescently-tagged ESCRT-III components, providing the first insights into which ESCRT-III components are required for OROV assembly. Our in vitro assay for OROV VLP production has allowed us to define molecular interactions that promote OROV release and will facilitate future studies of orthobunyavirus assembly. Importance Oropouche virus is the etiological agent of Oropouche fever, a debilitating febrile illness common in South America. The tripartite genome of this zoonotic virus is capable of reassortment and there have been multiple epidemics of Oropouche fever in South America over the last 50 years, making Oropouche virus infection a significant threat to public health. However, the molecular characteristics of this arbovirus are poorly understood. We have developed an in vitro virus-like particle production assay for Oropouche virus, allowing us to study the assembly and release of this dangerous pathogen without high-containment biosecurity. We determined the polyprotein sites that are cleaved to yield the mature Oropouche virus surface glycoproteins and characterised the cellular machinery required for glycoprotein secretion. Our study provides important insights into the molecular biology of Oropouche virus infection, in addition to presenting a robust virus-like particle production assay that should facilitate future functional and pharmacological inhibition studies.
Large-scale color biases in the retinotopic functional architecture are region specific and shared across human brains

Despite the functional specialization in visual cortex, there is growing evidence that the processing of chromatic and spatial visual features is intertwined. While past studies focused on visual field biases in retina and behaviour, large-scale dependencies between coding of color and retinotopic space are largely unexplored in the cortex. Here we asked whether spatial color biases are shared across different human observers, and whether they are idiosyncratic for distinct areas. We tested this by predicting the color a person was seeing using a linear classifier that has never been trained on chromatic responses from that same brain, solely by taking into account: (1) the chromatic responses in other individuals’ brains and (2) commonalities between the spatial coding in brains used for training and the test brain. We were able to predict the color (and luminance) of stimuli seen by an observer based on other subjects’ activity patterns in areas V1-V3, hV4 and LO1. In addition, we found that different colors elicited systematic, large-scale retinotopic biases that were idiosyncratic for distinct areas and common across brains. The area-specific spatial color codes and their conservation across individuals suggest functional or evolutionary organization pressures that remain to be elucidated. Significance statement Does a color elicit comparable neural activity in two different observers? We addressed these questions, which involved the central test to predict what color someone is seeing based on their brain activity if it is only known how other brains respond to color. We estimated the commonalities across brains in the way they respond to achromatic, spatial stimulation, which allowed us to retinotopically align different brain responses to each other in a common response space. In this space derived without any color responses we could decode across brains what color an observer was seeing and found that spatial color biases differed between areas. Our results demonstrate systematic dependencies between chromatic and visual field representations that are area-specific and preserved across observers.
Population dynamics of brown trout, Salmo trutta L., in a tributary in Brittany (France): spawning and juveniles

The colonization by both resident and migrating spawner populations of brown trout and the characteristics of resident and migrating juveniles derived from the two populations have been studied in a brook and its tributary over 4 years. Resident trout spawns mainly in the upstream part of the brook and migrating trout in the downstream part. There are density and growth variations for the two age classes (0+ and 1 +) of juveniles in autumn according to the year and the environment. In the brook, the population of 0 + fish increases from downstream to upstream while the density of other age classes decreases. The migrating juvenile population of the brook changes annually and consists mainly of 1 s (one summer) individuals coming from the upper part. These individuals migrate generally in autumn and winter while young trout produced in the middle and downstream parts of the brook migrate mainly in the spring. The emigration process of the 0 + population decreases markedly from upstream to downstream and appears to be independent of the autumn length and sex ratio. In the tributary, most trout are 0+ years old, the population structure is different, and no migrating fish is observed. The results are discussed and a colonization strategy of the brown trout population in this brook is suggested.
Evolutionary genetics of Drosophila melanogaster immunity: role of the X chromosome and sex-specific dominance

Intralocus Sexual Conflict (IaSC) ensues when males and females of the same species experience divergent selection on shared traits. A large number of traits have been implicated in IaSC and there is growing evidence for sexual antagonism associated with immunity. X chromosomes are thought to be hotspots of sexually antagonistic genetic variation and have been shown to harbour substantial immunity-related genetic variation. Here, using interpopulation crosses and cytogenetic cloning, we investigated the role of the X chromosome in improved immune response of laboratory populations of the fruit-fly Drosophila melanogaster selected against systemic infection by Pseudomonas entomophila. We could not detect any contribution of the X chromosome in the evolved immune response of our selected populations. However, we found strong evidence of sex-specific dominance related to immunity in our populations. Our results indicate that alleles that confer a superior immune response to the selected populations are, on average, partially dominant in females but partially recessive in males. We argue that sex-specific dominance over immunity evolved as a by-product of sexually antagonistic selection in the wild ancestors of our populations. We also highlight sex-specific dominance as a potential mechanism of sex differences in immunity, with population-level sex differences primarily driven by sex differences in heterozygotes.
Effects of Taurine on Sperm Characteristics during In vitro Storage of Boar Semen

The objective of this study was to investigate the anti-oxidative effects of taurine on sperm characteristics for in vitro storage of boar semen. Semen was randomly divided into 10 groups in conical tubes and treated with different concentrations oftaurine (25-100 mM) with or without 250 μM H 2 O 2 . The percentage of motile spermatozoa in taurine groups after 6 and 9 h were significantly higher at >94% and 87%, respectively, compared to the control group (85.1±0.5 and 72.4±0.3, p<0.05). The sperm motility in taurine with H 2 O 2 after 6 h incubation was slightly decreased compared to the taurine alone treatment, but after 9 and 12 h incubation % sperm motility dropped sharply in taurine with H 2 O 2 (75.3±0.3 and 69.6±2.9, p<0.05). For 3, 9 and 12 h incubation, sperm viability in the control was lower than in taurine groups, irrespective of taurine concentration. In eosin Y and nigrosin staining (ENS), the sperm survival rates (%) for 6 h incubation were significantly higher in 25 mM (76.0±0.6) and 50 mM taurine groups (78.0±0.7), respectively. Sperm survival rates for 9 and 12 h incubation were higher in taurine groups (≥48% in 9 h and ≥42% in 12 h) compared to controls (43.0±2.1 and 31.0±0.6, respectively). In the hyoosmotic swelling test (HOST), sperm membrane integrity was similar to the results of sperm survival. These experiments indicate that supplementation of taurine to the semen extender can increase the sperm characteristics (motility, viability, survival and membrane integrity).
Mutations in BBS2 Cause Apparent Nonsyndromic Retinitis Pigmentosa

Purpose To identify and functionally test the causative mutations in the BBS2 gene in a family presenting with retinitis pigmentosa and infertility and to generate a bbs2−/− mutant zebrafish. Methods A female proband and her male sibling were clinically evaluated and genetic testing with targeted next-generation sequencing was performed. Mutations were verified by Sanger sequencing. Protein localization was examined by transient expression and immunocytochemistry in cultured HEK-293T cells. Mutations in the zebrafish bbs2 gene were generated by CRISPR/Cas9 and retinal phenotypes were examined by immunohistochemistry. Results The proband and her brother exhibited reduced visual fields, retinal degeneration, and bone spicule deposits, consistent with retinitis pigmentosa. The brother also reported symptoms consistent with infertility. Compound heterozygous mutations in the BBS2 gene; namely NM_031885. 4 (BBS2):c.823C>T (p.R275X) and NM_031885. 4 (BBS2):c.401C>G (p.P134R), were identified in the proband and her brother. Both mutations interfered with ciliary localization of Bbs2 in cell culture. Mutation of the zebrafish bbs2 gene resulted in progressive cone degeneration and rhodopsin mislocalization. Conclusion Missense mutations of BBS2 leads to non-syndromic retinitis pigmentosa, but not Bardet-Biedl Syndrome, even though Bbs2 fails to localize to cilia. In zebrafish, the complete loss of bbs2 results in cone degeneration and ciliopathy phenotypes, indicating a requirement for Bbs2 in photoreceptor survival.