Miracle-dz/UniFAR-FTUs huggingface dataset:
Amphibian larvae benefit from a warm environment under simultaneous threat from chytridiomycosis and ranavirosis

Rising temperatures can facilitate epizootic outbreaks, but disease outbreaks may be suppressed if temperatures increase beyond the optimum of the pathogens while still within the temperature range that allows for effective immune function in hosts. The two most devastating pathogens of wild amphibians, Batrachochytrium dendrobatidis (Bd) and ranaviruses (Rv), co-occur in large areas, yet little is known about the consequences of their co-infection and how these consequences depend on temperature. Here we tested how co-infection and elevated temperatures (28 and 30°C vs. 22°C) affected Bd and Rv prevalence, infection intensities, and resulting mortalities in larval agile frogs and common toads. We found multiple pieces of evidence that the presence of one pathogen influenced the prevalence and/or infection intensity of the other pathogen in both species, depending on temperature and initial Rv concentration. Generally, the 30°C treatment lowered the prevalence and infection intensity of both pathogens, and, in agile frogs, this was mirrored by higher survival. These results suggest that if temperatures naturally increase or are artificially elevated beyond what is ideal for both Bd and Rv, amphibians may be able to control infections and survive even the simultaneous presence of their most dangerous pathogenic enemies.
Femora from an exceptionally large population of coeval ornithomimosaurs yield evidence of sexual dimorphism in extinct theropod dinosaurs

Sexual dimorphism is challenging to detect among fossils, due to a lack of statistical representativeness. The Angeac-Charente Lagerstätte (France) represents a remarkable “snapshot” from a Berriasian (Early Cretaceous) ecosystem and offers a unique opportunity to study intraspecific variation among a herd of at least 61 coeval ornithomimosaurs. Herein, we investigated the hindlimb variation across the best-preserved specimens from the herd through 3D Geometric Morphometrics and Gaussian Mixture Modelling. Our results based on complete and fragmented femora evidenced a dimorphism characterized by variations in the shaft curvature and the distal epiphysis width. Since the same features vary between sexes among modern avian dinosaurs, crocodilians, and more distant amniotes, we attributed this bimodal variation to sexual dimorphism based on the extant phylogenetic bracketing approach. Documenting sexual dimorphism in fossil dinosaurs allows a better characterization and accounting of intraspecific variations, which is particularly relevant to address ongoing taxonomical and ecological questions relative to dinosaur evolution.
Transcription coactivator OCA-B/Pou2af1 is necessary and sufficient to promote T cell-intrinsic CD4 memory

The establishment of durable immunological memory remains a poorly understood aspect of lymphocyte biology and a limiting factor in vaccine development. Using a T cell-conditional OCA-B (Pou2af1) knockout model and a mouse viral pathogen, we show that expression of the transcription cofactor OCA-B within T cells is necessary for proper CD4+ memory T cell formation. We also show that ectopic OCA-B expression is sufficient to drive T cells towards a memory fate while having no effect on primary antiviral effector response. Bulk and single-cell gene expression profiling comparing cells transduced with OCA-B and empty vector at peak primary viral response identifies changes in gene expression consistent with later memory formation. Intersecting differentially expressed genes in bulk RNA-seq with prior ChIP-seq identifies direct targets increased (Tbx21, Zeb2, Gadd45b, Socs2) and decreased (Zbtb16, Ccr1) by ectopic OCA-B expression. Single-cell RNA-seq reveals expansion of short-lived effector T cell compartments with increased expression of Gadd45b and Socs2, as well as increased expression of memory-associated genes such as Slamf6, Il7r and Tcf1 in smaller clusters of effector cells with memory potential. We also describe a new OCA-B-mCherry reporter mouse that efficiently labels B and T lymphocytes and that shows high expression in CD4+ TCM cells. Cumulatively, the results demonstrate that OCA-B expression in T cells is necessary and sufficient to promote CD4 T cell memory in vivo. Supported by grants from NIH (R01 AI100873)
Sequential Activation and Local Unfolding Control Poly(A)-Binding Protein Condensation

Eukaryotic cells form biomolecular condensates to sense and adapt to their environment1,2. Poly(A)-binding protein (Pab1), a canonical stress granule marker3,4, condenses upon heat shock or starvation, promoting adaptation5. The molecular basis of condensation has remained elusive due to a dearth of techniques to probe structure directly in condensates. Here we apply hydrogen-deuterium exchange/mass spectrometry (HDX-MS) to investigate the molecular mechanism of Pab1’s condensation. We find that Pab1’s four RNA recognition motifs (RRMs) undergo different levels of partial unfolding upon condensation, and the changes are similar for thermal and pH stresses. Although structural heterogeneity is observed, the ability of MS to describe individual subpopulations allows us to identify which regions become partially unfolded and contribute to the condensate’s interaction network. Our data yield a clear molecular picture of Pab1’s stress-triggered condensation, which we term sequential activation, wherein each RRM becomes activated at a temperature where it partially unfolds and associates with other likewise activated RRMs to form the condensate. This model thus implies that sequential activation is dictated by the underlying free energy surface, an effect we refer to as thermodynamic specificity. Our study represents a methodological advance for elucidating the interactions that drive biomolecular condensation that we anticipate will be widely applicable. Furthermore, our findings demonstrate how condensation can use thermodynamic specificity to perform an acute response to multiple, stresses, a potentially general mechanism for stress-responsive proteins.
Mitochondrial protein import clogging as a mechanism of disease

Mitochondrial biogenesis requires the import of >1,000 mitochondrial preproteins from the cytosol. Most studies on mitochondrial protein import are focused on the core import machinery. Whether and how the biophysical properties of substrate preproteins affect overall import efficiency is underexplored. Here, we show that protein traffic into mitochondria is disrupted by amino acid substitutions in a single substrate preprotein. Pathogenic missense mutations in adenine nucleotide translocase 1 (Ant1), and its yeast ortholog Aac2, cause the protein to accumulate along the protein import pathway, thereby obstructing general protein translocation into mitochondria. This impairs mitochondrial respiration, cytosolic proteostasis and cell viability independent of Ant1’s nucleotide transport activity. The mutations act synergistically, as double mutant Aac2/Ant1 cause severe clogging primarily at the Translocase of the Outer Membrane (TOM) complex. This confers extreme toxicity in yeast. In mice, expression of a super-clogger Ant1 variant led to an age-dependent dominant myopathy that phenocopies Ant1-induced human disease, suggesting clogging as a mechanism of disease. We propose that secondary structures of mitochondrial preproteins play an essential role in preventing clogging and disease.
Acquisition of emphatic consonants by Ammani Arabic-speaking children

ABSTRACT This article investigates the production of the emphatic consonants /ṭ, ḍ, ṣ/ by typically developing Jordanian children. Sixty typically developing monolingual Ammani Arabic-speaking children (30 boys and 30 girls) with ages ranging from 2 to 7;11 years were recruited in a production experiment. In the experiment, they were asked to produce 18 minimal pair words with emphatic consonants and their corresponding plain coronals in all word positions. Contrary to Amayreh & Dyson (1998) and Hamdan & Amayreh (2007), >50% of Ammani Arabic-speaking children produced emphatic consonants by the age of 3, >75% produced them by the age of 4, and >90% produced them by the age of 5. Acoustically, they produce them in an adult-like manner at the age of 6 word-initially and medially and at the age of 7 word-finally. The acoustic measurements confirm that children’s productions become increasingly adult-like with age. Compared with nonemphatic consonants, the appearance of emphatics tends to be delayed in Ammani Arabic. This delay in the production of emphatics, which are among the least frequently occurring consonants in Arabic, is likely due to their articulatory complexity, which involves a secondary co-articulation (the so-called pharyngealization). The current findings help clarify the developmental trajectory of children’s acquisition of emphatic consonants and should be informative for both researchers and clinicians.
Case report: The promising application of dynamic functional connectivity analysis on an individual with failed back surgery syndrome

Failed back surgery syndrome (FBSS), a chronic neuropathic pain condition, is a common indication for spinal cord stimulation (SCS). However, the mechanisms of SCS, especially its effects on supraspinal/brain functional connectivity, are still not fully understood. Resting state functional magnetic resonance imaging (rsfMRI) studies have shown characteristics in patients with chronic low back pain (cLBP). In this case study, we performed rsfMRI scanning (3.0 T) on an FBSS patient, who presented with chronic low back and leg pain following her previous lumbar microdiscectomy and had undergone permanent SCS. Appropriate MRI safety measures were undertaken to scan this subject. Seed-based functional connectivity (FC) was performed on the rsfMRI data acquired from the FBSS subject, and then compared to a group of 17 healthy controls. Seeds were identified by an atlas of resting state networks (RSNs), which is composed of 32 regions grouped into 8 networks. Sliding-window method and k-means clustering were used in dynamic FC analysis, which resulted in 4 brain states for each group. Our results demonstrated the safety and feasibility of 3T MRI scanning in a patient with implanted SCS system. Compared to the brain states of healthy controls, the FBSS subject presented very different FC patterns in less frequent brain states. The mean dwell time of brain states showed distinct distributions: the FBSS subject seemed to prefer a single state over the others. Although future studies with large sample sizes are needed to make statistical conclusions, our findings demonstrated the promising application of dynamic FC to provide more granularity with FC changes associated with different brain states in chronic pain.
Lévy process conditioned by its height process

In the present work, we consider spectrally positive Levy processes $(X_t,t\geq0)$ not drifting to $+\infty$ and we are interested in conditioning these processes to reach arbitrarily large heights (in the sense of the height process associated with $X$) before hitting $0$. This way we obtain a new conditioning of Levy processes to stay positive. The (honest) law $\pfl$ of this conditioned process is defined as a Doob $h$-transform via a martingale. For Levy processes with infinite variation paths, this martingale is $\left(\int\tilde\rt(\mathrm{d}z)e^{\alpha z}+I_t\right)\2{t\leq T_0}$ for some $\alpha$ and where $(I_t,t\geq0)$ is the past infimum process of $X$, where $(\tilde\rt,t\geq0)$ is the so-called \emph{exploration process} defined in \cite{Duquesne2002} and where $T_0$ is the hitting time of 0 for $X$. Under $\pfl$, we also obtain a path decomposition of $X$ at its minimum, which enables us to prove the convergence of $\pfl$ as $x\to0$. When the process $X$ is a compensated compound Poisson process, the previous martingale is defined through the jumps of the future infimum process of $X$. The computations are easier in this case because $X$ can be viewed as the contour process of a (sub)critical \emph{splitting tree}. We also can give an alternative characterization of our conditioned process in the vein of spine decompositions.
The application of collagen in the repair of peripheral nerve defect

Collagen is a natural polymer expressed in the extracellular matrix of the peripheral nervous system. It has become increasingly crucial in peripheral nerve reconstruction as it was involved in regulating Schwann cell behaviors, maintaining peripheral nerve functions during peripheral nerve development, and being strongly upregulated after nerve injury to promote peripheral nerve regeneration. Moreover, its biological properties, such as low immunogenicity, excellent biocompatibility, and biodegradability make it a suitable biomaterial for peripheral nerve repair. Collagen provides a suitable microenvironment to support Schwann cells’ growth, proliferation, and migration, thereby improving the regeneration and functional recovery of peripheral nerves. This review aims to summarize the characteristics of collagen as a biomaterial, analyze its role in peripheral nerve regeneration, and provide a detailed overview of the recent advances concerning the optimization of collagen nerve conduits in terms of physical properties and structure, as well as the application of the combination with the bioactive component in peripheral nerve regeneration.
Identification of Leuconostoc species based on novel marker genes identified using real-time PCR via computational pangenome analysis

Leuconostoc species are important microorganisms in food fermentation but also cause food spoilage. Although these species are commercially important, their taxonomy is still based on inaccurate identification methods. Here, we used computational pangenome analysis to develop a real-time PCR-based method for identifying and differentiating the 12 major Leuconostoc species found in food. Analysis of pan and core-genome phylogenies showed clustering of strains into 12 distinct groups according to the species. Pangenome analysis of 130 Leuconostoc genomes from these 12 species enabled the identification of each species-specific gene. In silico testing of the species-specific genes against 143 publicly available Leuconostoc and 100 other lactic acid bacterial genomes showed that all the assays had 100% inclusivity/exclusivity. We also verified the specificity for each primer pair targeting each specific gene using 23 target and 124 non-target strains and found high specificity (100%). The sensitivity of the real-time PCR method was 102 colony forming units (CFUs)/ml in pure culture and spiked food samples. All standard curves showed good linear correlations, with an R2 value of ≥0.996, suggesting that screened targets have good specificity and strong anti-interference ability from food sample matrices and non-target strains. The real-time PCR method can be potentially used to determine the taxonomic status and identify the Leuconostoc species in foods.
Conditional deletion of MAD2B in forebrain neurons enhances hippocampus-dependent learning and memory in mice

Mitotic arrest deficient 2-like protein 2 (MAD2B) is not only a DNA damage repair agent but also a cell cycle regulator that is widely expressed in the hippocampus and the cerebral cortex. However, the functions of MAD2B in hippocampal and cerebral cortical neurons are poorly understood. In this study, we crossed MAD2Bflox/flox and calcium/calmodulin-dependent protein kinase II alpha (Camk2a)-Cre mice to conditionally knock out MAD2B in the forebrain pyramidal neurons by the Cre/loxP recombinase system. First, RNA sequencing suggested that the differentially expressed genes in the hippocampus and the cerebral cortex between the WT and the MAD2B cKO mice were related to learning and memory. Then, the results of behavioral tests, including the Morris water maze test, the novel object recognition test, and the contextual fear conditioning experiment, suggested that the learning and memory abilities of the MAD2B cKO mice had improved. Moreover, conditional knockout of MAD2B increased the number of neurons without affecting the number of glial cells in the hippocampal CA1 and the cerebral cortex. At the same time, the number of doublecortin-positive (DCX+) cells was increased in the dentate gyrus (DG) of the MAD2B cKO mice. In addition, as shown by Golgi staining, the MAD2B cKO mice had more mushroom-like and long-like spines than the WT mice. Transmission electron microscopy (TEM) revealed that spine synapses increased and shaft synapses decreased in the CA1 of the MAD2B cKO mice. Taken together, our findings indicated that MAD2B plays an essential role in regulating learning and memory.
The functional connectivity of language network across the life span: Disentangling the effects of typical aging from Alzheimer’s disease

Language is usually characterized as the most preserved cognitive function during typical aging. Several neuroimaging studies have shown that healthy aging is characterized by inter-network compensation which correlates with better language performance. On the contrary, language deficits occur early in the course of Alzheimer’s disease (AD). Therefore, this study compares young participants, healthy older participants, and prodromal AD participants, to characterize functional connectivity changes in language due to healthy aging or prodromal AD. We first compared measures of integrated local correlations (ILCs) and fractional amplitude of low-frequency oscillations (fALFFs) in language areas. We showed that both groups of older adults had lower connectivity values within frontal language-related areas. In the healthy older group, higher integrated local correlation (ILC) and fALFF values in frontal areas were positively correlated with fluency and naming tasks. We then performed seed-based analyses for more precise discrimination between healthy aging and prodromal AD. Healthy older adults showed no functional alterations at a seed-based level when the seed area was not or only slightly impaired compared to the young adults [i.e., inferior frontal gyrus (IFG)], while prodromal AD participants also showed decreased connectivity at a seed-based level. On the contrary, when the seed area was similarly impaired in healthy older adults and prodromal AD participants on ILC and fALFF measures, their connectivity maps were also similar during seed-to-voxel analyses [i.e., superior frontal gyrus (SFG)]. Current results show that functional connectivity measures at a voxel level (ILC and fALFF) are already impacted in healthy aging. These findings imply that the functional compensations observed in healthy aging depend on the functional integrity of brain areas at a voxel level.
Integrated metabolomic and transcriptomic analyses reveal molecular response of anthocyanins biosynthesis in perilla to light intensity

The perilla anthocyanins have important medicinal and ornamental value, and their contents are significantly affected by light intensity. In view of their molecular mechanisms were not well understood, we integrated the metabolomic and transcriptomic analyses of the light-sensitive perilla variety under different light intensity. The perilla leave color were obviously affected under different treatments. Totally 140 flavonoid metabolites and 2461 genes showed steady change, among which 60 flavonoid metabolites were increased accumulation and 983 genes were upregulated expression under elevated light intensity treatment. Light treatment prominently affected the expression of genes involved in the main anthocyanin metabolites accumulation in perilla leaves. Using WGCNA analysis, we identified 4 key genes in anthocyanin biosynthesis pathway (CHI, DFR, and ANS) and 147 transcription factors (MYB, bHLH, bZIP, ERF, and NAC) involved in malonylshisonin biosynthesis. Among them, 6 MYBs and 4 bZIPs were predicted to play important roles in light regulation of malonylshisonin biosynthesis based on phylogenetic construction, correlation analysis, cis-acting element identification and qPCR verification. The identified key genes and regulatory factors will help us to understand the potential mechanism of photo-regulated anthocyanin accumulation in perilla.
Endodermal apoplastic barriers are linked to osmotic tolerance in meso-xerophytic grass Elymus sibiricus

Drought is the most serious adversity faced by agriculture and animal husbandry industries. One strategy that plants use to adapt to water deficits is modifying the root growth and architecture. Root endodermis has cell walls reinforced with apoplastic barriers formed by the Casparian strip (CS) and suberin lamellae (SL) deposits, regulates radial nutrient transport and protects the vascular cylinder from abiotic threats. Elymus sibiricus is an economically important meso-xerophytic forage grass, characterized by high nutritional quality and strong environmental adaptability. The purpose of this study was to evaluate the drought tolerance of E. sibiricus genotypes and investigate the root structural adaptation mechanism of drought-tolerant genotypes’ responding to drought. Specifically, a drought tolerant (DT) and drought sensitive (DS) genotype were screened out from 52 E. sibiricus genotypes. DT showed less apoplastic bypass flow of water and solutes than DS under control conditions, as determined with a hydraulic conductivity measurement system and an apoplastic fluorescent tracer, specifically PTS trisodium-8-hydroxy-1,3,6-pyrenetrisulphonic acid (PTS). In addition, DT accumulated less Na, Mg, Mn, and Zn and more Ni, Cu, and Al than DS, regardless of osmotic stress. Further study showed more suberin deposition in DT than in DS, which could be induced by osmotic stress in both. Accordingly, the CS and SL were deposited closer to the root tip in DT than in DS. However, osmotic stress induced their deposition closer to the root tips in DS, while likely increasing the thickness of the CS and SL in DT. The stronger and earlier formation of endodermal barriers may determine the radial transport pathways of water and solutes, and contribute to balance growth and drought response in E. sibiricus. These results could help us better understand how altered endodermal apoplastic barriers in roots regulate water and mineral nutrient transport in plants that have adapted to drought environments. Moreover, the current findings will aid in improving future breeding programs to develop drought-tolerant grass or crop cultivars.
Candida guilliermondii as an agent of postpartum subacute mastitis in Rio de Janeiro, Brazil: Case report

Candida spp. can cause mild-to-severe human infections. Certain species have been described as the etiologic agent of human mastitis, inflammation of the breast tissue. Mastitis affects millions of lactating women and can be a source of disease transmission to the infant. In this work, we report the detection of the unusual etiologic agent of human mastitis, Candida guilliermondii, isolated from the milk of a puerperal woman with subacute mastitis in Rio de Janeiro, Brazil. Species identification was performed by MALDI-TOF MS and genetic sequencing. The patient had a full recovery after antifungal therapy.