Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic, genetic and phylogenetic evidence for a new falcon species using chromosome-level genome assembly of the gyrfalcon and population genomics

The taxonomic classification of a falcon population found in the Altai region in Asia has been heavily debated for two centuries and previous studies have been inconclusive, hindering a more informed conservation approach. Here, we generated a chromosome-level gyrfalcon reference genome using the Vertebrate Genomes Project (VGP) assembly pipeline. Using whole genome sequences of 44 falcons from different species and populations, including “Altai” falcons, we analyzed their population structure, admixture patterns and demographic history. We find that the Altai falcons are genomically mosaic of saker and gyrfalcon ancestries, and carry distinct W- and mitochondrial-haplotypes that cluster with the lanner falcon. The Altai haplotype diverged 422,000 years ago from the ancestor of sakers and gyrfalcons, both of which, in turn, split 109,000 years ago. The Altai W chromosome includes coding variants that may influence important structural, behavioral and reproductive traits. These findings support the designation of Altai falcons as a distinct falcon species (Falco altaicus).
A non-canonical Hippo pathway represses the expression of ΔNp63

The p63 transcription factor, a member of the p53 family, plays an oncogenic role in squamous cancers, while in breast cancers its expression is often repressed. In the canonical conserved Hippo pathway, known to play a complex role in regulating growth of cancer cells, the protein kinases MST1/2 and LATS1/2 act sequentially to phosphorylate and inhibit the YAP/TAZ transcription factors. We found that in the MCF10A mammary epithelial cell line as well as in squamous and breast cancer cell lines, expression of ΔNp63 RNA and protein is strongly repressed by inhibition of the Hippo pathway protein kinases in a manner that is independent of p53. While MST1/2 and LATS1 are required for p63 expression, the next step of the pathway, namely phosphorylation and degradation of the YAP/TAZ transcriptional activators is not required for repression of p63. This suggests that regulation of p63 expression occurs by a non-canonical version of the Hippo pathway. We additionally identified additional genes that were similarly regulated suggesting the broader importance of this pathway. Interestingly, we observed that experimentally lowering p63 expression leads to increased YAP protein levels, thereby constituting a feedback loop. These results, which reveal the intersection of the Hippo and p63 pathways, may prove useful for the control of their activities in cancer cells. One Sentence Summary Regulation of p63 expression occurs by a non-canonical version of the Hippo pathway in mammary epithelial, breast carcinoma and head and neck squamous carcinoma cells
Mutant fixation in the presence of a natural enemy

In the extensive literature about mutant invasion and fixation, populations are typically assumed to exist in isolation from their ecosystem. Yet, populations are part of ecological communities, and enemy-victim (e.g. predator-prey or pathogen-host) dynamics are particularly common. We use computational models to re-visit the established theory about mutant fixation in the presence of a natural enemy, which equally attacks both wild-type and mutant populations. We consider advantageous and disadvantageous mutants, whose fitness is unrelated to the infection. Using spatially structured agent-based as well as patch models of a population that is subject to infection, we investigate the fixation probability of a mutant that is introduced into the population at quasi-equilibrium. We find that infection significantly weakens selection. Thus, the presence of infection increases the fixation probability of disadvantageous mutants and decreases the fixation probability of advantageous mutants, with the magnitude of the effect rising with the infection rate. We show that this occurs because infection induces spatial structures, in which mutant and wild-type individuals are mostly spatially separated. Thus, instead of mutant and wild-type individuals competing with each other, it is mutant and wild-type “patches” that compete, resulting in smaller fitness differences and hence weakened selection. Because natural enemies such as infections are ubiquitous, this has broad applicability to natural systems. Our results imply that the burden of deleterious mutants in natural populations might be significantly higher than expected from mutant invasion theory developed in the absence of natural enemies.
Relaxational dynamics of the infinite-ranged spin glass with n-component spins

The dynamic mean field theory of the spin glass phase is generalised to n-component spins. Exact averaged equations of motion are derived within a purely relaxational model. It is shown that dynamic stability enforces a violation of the fluctuation-dissipation theorem for any finite n and T<Tc. The marginally stable state is characterised by algebraic decay of correlations t- nu with an exponent which depends continuously on temperature and the number of components, nu (T,n)=1/2-3 mod T-Tc mod / pi n(n+2)+O( mod T-Tc mod 2)+O(1/n3).
Cooperative super-enhancer inactivation caused by heterozygous loss of CREBBP and KMT2D skews B cell fate decisions and yields T cell-depleted lymphomas

Mutations affecting enhancer chromatin regulators CREBBP and KMT2D are highly co-occurrent in germinal center (GC)-derived lymphomas and other tumors, even though regulating similar pathways. Herein, we report that combined haploinsufficiency of Crebbp and Kmt2d (C+K) indeed accelerated lymphomagenesis. C+K haploinsufficiency induced GC hyperplasia by altering cell fate decisions, skewing B cells away from memory and plasma cell differentiation. C+K deficiency particularly impaired enhancer activation for immune synapse genes involved in exiting the GC reaction. This effect was especially severe at super-enhancers for immunoregulatory and differentiation genes. Mechanistically, CREBBP and KMT2D formed a complex, were highly co-localized on chromatin, and were required for each-other’s stable recruitment to enhancers. Notably, C+K lymphomas in mice and humans manifested significantly reduced CD8+ T-cell abundance. Hence, deficiency of C+K cooperatively induced an immune evasive phenotype due at least in part to failure to activate key immune synapse super-enhancers, associated with altered immune cell fate decisions. SIGNIFICANCE Although CREBBP and KMT2D have similar enhancer regulatory functions, they are paradoxically co-mutated in lymphomas. We show that their combined loss causes specific disruption of super-enhancers driving immune synapse genes. Importantly, this leads to reduction of CD8 cells in lymphomas, linking super-enhancer function to immune surveillance, with implications for immunotherapy resistance.
High occupancy of European leaf-toed gecko Euleptes europaea in two island stands of Eucalyptus sp.: tree selection, co-occurrence and habitat effect

The effective conservation of a species requires a thorough knowledge of its ecology. Long considered to live exclusively in rocky habitats, the European leaf-toed gecko (Euleptes europaea) has in fact been observed in vegetated and wooded habitats at several locations throughout its range. The tendency of this species to use these habitats seems to be clearly supported by its prehensile tail characteristic of geckos with arboreal behaviour. To better assess tree occupation by E. europaea and other co-occurring geckos, a site-occupancy survey was conducted in 2022 on the testing site of DGA (French MoD the Procurement Agency) of Levant Island (Hyères, France). Two stands of Eucalyptus sp. containing 68 trees were selected to monitor. One stand lies in an anthropised context, consisting of scattered woodland and clear ground (stand 1), and the other represents a ‘natural’ forest context with dense ground vegetation (stand 2). The results revealed high occupancy by E. europaea in both stands, with an average occupancy probability of 0.57 (CI 0.40–0.72). The Mediterranean house gecko (Hemidactylus turcicus) and Moorish gecko (Tarentola mauritanica) had an average occupancy probability of 0.28 (CI 0.16–0.44) and 0.07 (CI 0.03–0.16) respectively. In stand 2, E. europaea was the only gecko species found, suggesting that it is better adapted to this type of forest habitat, which may represent a refuge for this species. In view of these results, the ecology of this species should be reconsidered and the research broadened by systematically including vegetated and forest habitats.
Gene-signatures for early detection of cancers

Background Gene signatures represents set of molecular modulations in disease genomes or in cells at specific conditions, and are frequently used to classify samples into different groups for better research or clinical treatment. Multiple methods and applications are available in the literature, but powerful ones that can account for early detection of cancer are still lacking. Method In this article, gene-signatures identified through new in-house algorithm (NCT method) by processing transcriptome data (DEGs extracted from RNA-seq dataset) from population. NCT-Method utilized for processing population dataset, from 28 different human cancer from TCGA & GTEx databases, as empirical background. NCT-score used for optimal clustering of gene-set. The identified gene clusters evaluated through survival analysis. Gene-sets with disease-vs-normal survival plot with logPvalue < 0.05 represented as reliable gene signatures. Results We applied NCT algorithm to the 28 different cancers, and identified novel gene-signatures as well as inter-relation between different cancers in reference of identified signatures. Conclusions The algorithm uses population data, and provides validated gene signatures with reliable capacity to discriminate the cancer and normal samples with higher classification performance. The algorithm will be useful to find signature for any RNA-seq data.
Immp2l knockdown increases stimulus-driven instrumental behaviour but does not alter goal-directed learning or neuron density in cortico-striatal circuits in a mouse model of Tourette syndrome and autism spectrum disorder

Cortico-striatal neurocircuits mediate goal-directed and habitual actions which are necessary for adaptive behaviour. It has recently been proposed that some of the core symptoms of autism spectrum disorder (ASD) and Gilles de la Tourette syndrome (GTS), such as tics and repetitive behaviours, may emerge because of imbalances in these neurocircuits. We have recently developed a model of ASD and GTS by knocking down Immp2l, a mitochondrial gene frequently associated with these disorders. The current study sought to determine whether Immp2l knockdown (KD) in male mice alters flexible, goal- or cue-driven behaviour using procedures specifically designed to examine response-outcome and stimulus-response associations, which underlie goal-directed and habitual behaviour, respectively. Whether Immp2l KD alters neuron density in cortico-striatal neurocircuits known to regulate these behaviours was also examined. Immp2l KD mice and wild type-like mice (WT) were trained on Pavlovian and instrumental learning procedures where auditory cues predicted food delivery and lever-press responses earned a food outcome. It was demonstrated that goal-directed learning was not changed for Immp2l KD mice compared to WT mice, as lever-press responses were sensitive to changes in the value of the food outcome, and to contingency reversal and degradation. There was also no difference in the capacity of KD mice to form habitual behaviours compared to WT mice following extending training of the instrumental action. However, Immp2l KD mice were more responsive to auditory stimuli paired with food as indicated by a non-specific increase in lever response rates during Pavlovian-to-instrumental transfer. Finally, there were no alterations to neuron density in striatum or any prefrontal cortex or limbic brain structures examined. Thus, the current study suggests that Immp2l is not necessary for learned maladaptive goal or stimulus driven behaviours in ASD or GTS, but that it may contribute to increased capacity for external stimuli to drive behaviour. Alterations to stimulus-driven behaviour could potentially influence the expression of tics and repetitive behaviours, suggesting that genetic alterations to Immp2l may contribute to these core symptoms in ASD and GTS. Given that this is the first application of this battery of instrumental learning procedures to a mouse model of ASD or GTS, it is an important initial step in determining the contribution of known risk-genes to goal-directed versus habitual behaviours, which should be more broadly applied to other rodent models of ASD and GTS in the future.
Continuum and Kinetic Simulation of Laminar Separated Flow at Hypersonic Speeds

The continuum and kinetic approaches were used to study the shock wave/boundary-layer interaction for monoatomic and diatomic gases. The effect of the translational/rotational exchange and gas/surface interaction models forthe kinetic approach on thee owstructure was analyzed. Theine uenceof slip conditions forthe Navier ‐ Stokes solver on the shock wave position and separation region length was studied. A comparison with available experimental data was performed.
Phosphoproteomics of cellular mechanosensing reveals NFATC4 as a regulator of myofibroblast activity

Feedback connections between tissue stiffness and cellular contractile forces can instruct cell identity and activity via a process referred to as mechanosensing. Specific phosphoproteome changes during mechanosensing are poorly characterized. In this work, we chart the global phosphoproteome dynamics of primary human lung fibroblasts sensing the stiffness of injury relevant fibronectin coated Poly(dimethylsiloxane) substrates. We discovered a key signaling threshold at a Young’s modulus of eight kPa stiffness, above which cells activated a large number of pathways including RhoA, CK2A1, PKA, AMPK, AKT1, and Hippo-YAP1/TAZ mediated signaling. Time-resolved phosphoproteomics of cell spreading on stiff substrates revealed the temporal dynamics of these stiffness-sensitive signaling pathways. ECM substrate stiffness above eight kPA induced fibroblast contractility, cytoskeletal rearrangements, ECM secretion, and a fibroblast to myofibroblast transition. Our data indicate that phosphorylation of the transcriptional regulator NFATC4 at S213/S217 enhances myofibroblast activity, which is the key hallmark of fibrotic diseases. NFATC4 knock down cells display reduced stiffness induced collagen secretion, cell contractility, nuclear deformation and invasion, suggesting NFATC4 as a novel target for antifibrotic therapy. Synopsis How tissue stiffness regulates identity and activity of tissue fibroblasts is unclear. Mass spectrometry based analysis of tissue stiffness dependent phosphoproteome changes reveals how primary lung fibroblasts sense the mechanical properties of their environment and identifies NFATC4 as a novel regulator of the stiffness dependent transition of fibroblasts to ECM secreting myofibroblasts. Mass spectrometry analysis reveals the signaling landscape of fibroblast mechanosensing Time-resolved phosphoproteomic analysis of cell spreading on fibronectin NFATC4 regulates myofibroblast collagen secretion, cell contractility and invasion
A comparative study of low-pH tolerance and chitinase activity between toxigenic and non-toxigenic strains of Vibrio cholerae

Cholera toxin, encoded by the ctx gene, is a key virulence factor in toxigenic Vibrio cholerae (ctx+) strains. However, some non-toxigenic V. cholerae (ctx-) strains are also pathogenic to humans and the mechanism involved in low-pH tolerance and pathogenicity in these strains remains unclear. To address this, we profiled the growth and chitinase activity in different pH of two clinical isolates of V. cholerae: VC20, a ctx+ strain, and WO5, a ctx- strain. We also compared the expression level of key genes involved in pathogenesis between the strains. WO5, the non-toxigenic strain had robust growth and greater chitinase activity across a wide pH range, in comparison to VC20. Additionally, WO5 expressed higher levels of transcripts from genes implicated in host cell adhesion and virulence, namely ompK and toxT, respectively. Notably, we propose that lower hapR levels in WO5 contrary to VC20 is key to its low-pH tolerance. To systematically identify genes involved in low pH tolerance, we used a sequence-based homology search and found a widespread presence of low-pH adaptation modules, lysine-cadaverine, and ornithine-putrescine in multiple representative species of the Vibrio phylum. Furthermore, our analysis suggests that the loss of a gene encoding nitrite reductase that confers low pH tolerance is specific to V. cholerae and V. mimicus. Together, these findings reveal that the low-pH tolerance enhances the chitinase activity of the non-toxigenic strain that could help V. cholerae to survive the acidic environment of the stomach and readily colonize the intestine.
Systematic review and meta-analysis of transcriptomic studies on different brain regions reveals different sex-based profiles in schizophrenic patients

Schizophrenia is a severe neuropsychiatric disorder characterised by altered perception, mood and behaviour that, despite its relatively low prevalence, causes a profound impact in patients and society. Regarding genetic factors, previous studies have related dopamine receptor D2, different genes involved in glutamatergic neurotransmission, synaptic plasticity, and several immune functions. Sex differences have been clearly established in the epidemiology, symptomatology and outcome of schizophrenia. Nevertheless, the effects of schizophrenia in the transcriptome considering sex and the cerebral regions are barely explored. In this study, we performed a systematic review and sex-based meta-analysis using RNAseq studies of postmortem brain samples. Here we show that genes related to immune response functions are overexpressed in cortical regions of males and hippocampus of females, whereas cortical regions of females overexpressed genes related to neurotransmission and synapses. Regarding the meta-analysis of all brain regions available, we found again that genes related to synaptic plasticity and transmission were enriched in females, while those involved in the organisation of genetic information and protein folding were more expressed in males. Our results suggest multiple sex-based transcriptomic profiles as a consequence of schizophrenia on the brain. These results provide new insights into the role of sex in the effects of schizophrenia and facilitates the exploration of sex-specific markers of the disease.
The Cross-Lagged Correlation Technique: Reconsideration in Terms of Exploratory Utility, Assumption Specification and Robustness

The cross-lagged correlation technique (CLC) for assessing causality from passive observational data has been the subject of much recent criticism. CLC compares cross correlations between variables across time points of measurement and attributes differences in correlations to causal effects. Some of the major areas of criticism have to do with: (a) lack of a no-cause baseline, (b) spurious effects of mediating variables, and (c) obscuring effects of heterogeneous stabilities. The present author attempts to show that while these criticisms are valid, CLC should not be rejected outright as a tool in social science research. CLC has some utility as an exploratory technique. Furthermore, if certain assumptions are specified and these assumptions are correct, valid inferences can be made from CLC. Lastly, some assumptions for CLC are not as stringent as implied by critics and CLC is robust to minor violations of assumptions.
Computation of Bio-Fluid Sounds

A hybrid method is proposed for prediction of bio-fluid sounds at very low Mach numbers. The unsteady hydrodynamic flow field is computed by the incompressible Navier-Stokes equations (INS), while the sound field is obtained by solving the linearized perturbed compressible equations (LPCE) with sound sources represented by a total derivative of the hydrodyanmic pressure, DP/Dt. With the present INS/LPCE hybrid method, the vocal sound in human larynx and the buzz sound of bumblebee are computed with more clear understanding on the sound generation processes associated with their characteristic motions such as the self-sustained oscillatory motions of the vocal folds and the figure-eight motion of the flapping wings.
Control of the resistive wall mode with internal coils in the DIII–D tokamak

Internal coils, ‘I-Coils’, were installed inside the vacuum vessel of the DIII–D device to generate non-axisymmetric magnetic fields to act directly on the plasma. These fields are predicted to stabilize the resistive wall mode (RWM) branch of the long-wavelength external kink mode with plasma beta close to the ideal wall limit. Feedback using these I-Coils was found to be more effective as compared to using external coils located outside the vacuum vessel. Locating the coils inside the vessel allows for a faster response and the coil geometry also allows for better coupling to the helical mode structure. Initial results were reported previously (Strait E.J. et al 2004 Phys. Plasmas 11 2505). This paper reports on results from extended feedback stabilization operations, achieving plasma parameters up to the regime of Cβ ≈ 1.0 and open loop growth rates of γopenτw ≳ 25 where the RWM was predicted to be unstable with only the ‘rotational viscous stabilization mechanism’. Here Cβ ≈ (β − βno−wall.limit)/(βideal.wall.limit − βno−wall.limit) is a measure of the beta relative to the stability limits without a wall and with a perfectly conducting wall, and τw is the resistive flux penetration time of the wall. These feedback experimental results clarified the processes of dynamic error field correction and direct RWM stabilization, both of which took place simultaneously during RWM feedback stabilization operation. MARS-F modelling provides a critical rotation velocity in reasonable agreement with the experiment and predicts that the growth rate increases rapidly as rotation decreases below the critical. The MARS-F code also predicted that for successful RWM magnetic feedback, the characteristic time of the power supply should be limited to a fraction of the growth time of the targeted RWM. The possibility of further improvements in the presently achievable range of operation of feedback gain values is also discussed.
The Scattering of Fast Electrons by Atomic Nuclei

Section 1 . — The hypothesis that the electron has a magnetic moment was, as is well known, first introduced to account for the duplexity phenomena of atomic spectra. More recently, however, Dirac has succeeded in accounting for these same phenomena by the introduction of a modified wave equation, which conforms both to the principle of relativity and to the general transformation theory. Formally, at least, on the new theory also, the electron has a magnetic moment of eh/mc , but when the electron is in an atom we cannot observe this magnetic moment directly; we can only observe the foment of the whole atom, or, of course, the splitting of the spectral lines, which we may say is “caused” by this moment. The question arises, has the free electron "really” got a magnetic moment, a magnetic moment that we can by any conceivable experiment observe? The question is not so simple as it might seem, because a magnetic moment eh/mc can never be observed directly, e.g . , with a magnetometer; there is always an uncertainty in the eternal electromagnetic field, due to the uncertainty in the position and velocity of the electron, and this uncertainty is greater than the effect of the electron magnet which we are trying to observe.