Miracle-dz/UniFAR-FTUs huggingface dataset:
Early alterations of large-scale brain networks temporal dynamics in young children with autism

Autism spectrum disorders (ASD) are associated with disruption of large-scale brain network. Recently, we found that directed functional connectivity alterations of social brain networks are a core component of atypical brain development at early developmental stages in ASD. Here, we investigated the spatio-temporal dynamics of whole-brain neuronal networks at a subsecond scale in 113 toddlers and preschoolers (66 with ASD) using an EEG microstate approach. We first determined the predominant microstates using established clustering methods. We identified five predominant microstate (labeled as microstate classes A–E) with significant differences in the temporal dynamics of microstate class B between the groups in terms of increased appearance and prolonged duration. Using Markov chains, we found differences in the dynamic syntax between several maps in toddlers and preschoolers with ASD compared to their TD peers. Finally, exploratory analysis of brain–behavioral relationships within the ASD group suggested that the temporal dynamics of some maps were related to conditions comorbid to ASD during early developmental stages. To assess the association between Autism spectrum disorders (ASD) and the potential disruption of large-scale brain networks, Bochet, Sperdin et al investigated spatiotemporal dynamics of whole-brain neuronal networks in 113 toddlers and preschoolers (66 with ASD) using an EEG microstate approach. They found differences in the dynamic syntax between several maps in toddlers and pre-schoolers with ASD compared to their TD peers.
A Constrained Mixture Theory Model to Study Autoregulation in the Coronary Circulation

Coronary autoregulation is a short-term response manifested by a relatively constant flow over a wide range of perfusion pressures for a given metabolic state. This phenomenon is thought to be facilitated through a combination of mechanisms, including myogenic, shear dependent, and metabolic controls. The study of coronary autoregulation is challenging due to the coupled nature of the mechanisms and their differential effects through the coronary tree. In this paper, we developed a novel framework to study coronary autoregulation based on the constrained mixture theory. This structurally-motivated autoregulation model required calibration of anatomical and structural parameters of coronary trees via a homeostatic optimization approach using extensive literature data. Autoregulation was then simulated for two different coronary trees: subepicardial and subendocardial. The structurally calibrated model reproduced available baseline hemodynamics and autoregulation data for each coronary tree. The autoregulation analysis showed that the diameter of the intermediate and small arterioles varies the most in response to changes in perfusion pressure. Finally, we demonstrated the utility of the model in two application examples: 1) response to drops in epicardial pressure, and 2) response to drug infusion in the coronary arteries. The proposed structurally-motivated model could be extended to study long-term growth and remodeling in the coronary circulation in response to hypertension, atherosclerosis, etc. Key points Coronary autoregulation is defined as the capability of the coronary circulation to maintain the blood supply to the heart over a range of perfusion pressures. This phenomenon is facilitated through intrinsic mechanisms that control the vascular resistance by regulating the mechanical function of smooth muscle cells. Understanding the mechanisms involved in coronary autoregulation is one of the most fundamental questions in coronary physiology. This paper presents a structurally-motivated coronary autoregulation model that uses a nonlinear continuum mechanics approach to account for the morphometry and vessel wall composition in two coronary trees in the subepicardial and subendocardial layers. The model is calibrated against diverse experimental data from literature and is used to study heterogeneous autoregulatory response in the coronary trees. This model drastically differs from previous models, which relied on lumped parameter model formulations, and is suited to the study of long-term pathophysiological growth and remodeling phenomena in coronary vessels.
Steady state evoked potential (SSEP) responses in the primary and secondary somatosensory cortices of anesthetized cats: Nonlinearity characterized by harmonic and intermodulation frequencies

When presented with an oscillatory sensory input at a particular frequency, F [Hz], neural systems respond with the corresponding frequency, f [Hz], and its multiples. When the input includes two frequencies (F1 and F2) and they are nonlinearly integrated in the system, responses at intermodulation frequencies (i.e., n1*f1+n2*f2 [Hz], where n1 and n2 are non-zero integers) emerge. Utilizing these properties, the steady state evoked potential (SSEP) paradigm allows us to characterize linear and nonlinear neural computation performed in cortical neurocircuitry. Here, we analyzed the steady state evoked local field potentials (LFPs) recorded from the primary (S1) and secondary (S2) somatosensory cortex of anesthetized (ketamine-xylazine) cats while we presented slow (F1=23Hz) and fast (F2=200Hz) somatosensory vibration to the contralateral paw pads and digits. Over 9 experimental sessions, we recorded LFPs from N=1620 and N=1008 bipolar-referenced sites in S1 and S2 using electrode arrays. Power spectral analyses revealed strong responses at 1) the fundamental (f1, f2), 2) its harmonic, 3) the intermodulation frequencies, and 4) broadband frequencies (50-150Hz). To compare the computational architecture in S1 and S2, we employed simple computational modeling. Our modeling results necessitate nonlinear computation to explain SSEP in S2 more than S1. Combined with our current analysis of LFPs, our paradigm offers a rare opportunity to constrain the computational architecture of hierarchical organization of S1 and S2 and to reveal how a large-scale SSEP can emerge from local neural population activities.
Outer membrane lipoprotein DolP interacts with the BAM complex and promotes fitness during envelope stress response

In Gram-negative bacteria, coordinated remodelling of the outer membrane (OM) and the peptidoglycan is crucial for envelope integrity. Envelope stress caused by unfolded OM proteins (OMPs) activates sigmaE(σE) in Enterobacteria. Whereas σE upregulates biogenesis factors, including the β-barrel assembly machinery (BAM) that catalyzes OMP-folding, elevated σE activity can be detrimental for OM integrity. We report that DolP (YraP), a σE-upregulated OM lipoprotein needed for envelope integrity, is a novel interactor of BAM and that BamA is a critical determinant of the BAM-DolP complex. Mid-cell recruitment of DolP had been reported to promote septal peptidoglycan remodelling during cell division, but the role of DolP during envelope stress was unknown. Using a synthetic-defect CRISPRi screen, we found that dolP is critical in cells with elevated or constitutive σE activation. Differently from other σE-upregulated proteins, DolP is not directly implicated in OMP assembly. Envelope stress or OM-overaccumulating BamA, however, interferes with DolP septal recruitment. Taken together, our results uncover DolP as a fitness factor during σE activation, and support a model where differential septal recruitment of DolP contributes to link envelope stress to a late step of cell division.
Impacts of sex ratio meiotic drive on genome structure and defense in a stalk-eyed fly

Some stalk-eyed flies in the genus Teleopsis carry selfish genetic elements that induce sex ratio meiotic drive (SR) and impact the fitness of male and female carriers. Here, we produced a chromosome-level genome assembly of the stalk-eyed fly, T. dalmanni, to elucidate patterns of genomic divergence associated with the presence of drive elements. We find evidence for multiple nested inversions along the sex ratio haplotype and widespread differentiation and divergence between XSR and XSR along the entire chromosome. These include a striking XSR-specific expansion of an array of partial copies of JASPer, a gene necessary for maintenance of euchromatin and regulation of transposable element expression (TEs). In addition, the genome contains tens of thousands of TE insertions and hundreds of transcriptionally and insertionally active TE families. Moreover, we find that several TE families are differentially expressed and/or present at a different copy number in SR male testes, suggesting an association between these two categories of selfish genetic elements in this species. We identify T. dalmanni orthologs of genes involved in genome defense via the piRNA pathway, including core members maelstrom, piwi and Argonaute3, that have diverged in sequence, expression or copy number between the SR and standard (ST) X chromosomes, consistent with altered TE regulation in flies carrying a sex ratio X chromosome. Overall, the evidence suggests that this ancient XSR polymorphism has had a variety of impacts on repetitive DNA and its regulation in this species.
Heterogeneity and ‘memory’ in stem cell populations

Modern single cell experiments have revealed unexpected heterogeneity in apparently functionally ‘pure’ cell populations. However, we are still lacking a conceptual framework to understand this heterogeneity. Here, we propose that cellular memories—changes in the molecular status of a cell in response to a stimulus, that modify the ability of the cell to respond to future stimuli—are an essential ingredient in any such theory. We illustrate this idea by considering a simple age-structured model of stem cell proliferation that takes account of mitotic memories. Using this model we argue that asynchronous mitosis generates heterogeneity that is central to stem cell population function. This model naturally explains why stem cell numbers increase through life, yet regenerative potency simultaneously declines.
Kinetics of self-assembly of inclusions due to lipid membrane thickness interactions

Self-assembly of proteins on lipid membranes underlies many important processes in cell biology, such as, exo- and endo-cytosis, assembly of viruses, etc. An attractive force that can cause self-assembly is mediated by membrane thickness interactions between proteins. The free energy profile associated with this attractive force is a result of the overlap of thickness deformation fields around the proteins. The thickness deformation field around proteins of various shapes can be calculated from the solution of a boundary value problem and is relatively well understood. Yet, the time scales over which self-assembly occurs has not been explored. In this paper we compute this time scale as a function of the initial distance between two inclusions by viewing their coalescence as a first passage time problem. The first passage time is computed using both Langevin dynamics and a partial differential equation, and both methods are found to be in excellent agreement. Inclusions of three different shapes are studied and it is found that for two inclusions separated by about hundred nanometers the time to coalescence is hundreds of milliseconds irrespective of shape. Our Langevin dynamics simulation of self-assembly required an efficient computation of the interaction energy of inclusions which was accomplished using a finite difference technique. The interaction energy profiles obtained using this numerical technique were in excellent agreement with those from a previously proposed semi-analytical method based on Fourier-Bessel series. The computational strategies described in this paper could potentially lead to efficient methods to explore the kinetics of self-assembly of proteins on lipid membranes. Author summary Self-assembly of proteins on lipid membranes occurs during exo- and endo-cytosis and also when viruses exit an infected cell. The forces mediating self-assembly of inclusions on membranes have therefore been of long standing interest. However, the kinetics of self-assembly has received much less attention. As a first step in discerning the kinetics, we examine the time to coalescence of two inclusions on a membrane as a function of the distance separating them. We use both Langevin dynamics simulations and a partial differential equation to compute this time scale. We predict that the time to coalescence is on the scale of hundreds of milliseconds for two inclusions separated by about hundred nanometers. The deformation moduli of the lipid membrane and the membrane tension can affect this time scale.
Chitin Biosynthesis Genes in Diaphorina citri

The polysaccharide chitin is critical for the formation of many insect structures, including the exoskeleton, and is required for normal development. Here we report the annotation of three genes from the chitin synthesis pathway in the Asian citrus psyllid, Diaphorina citri. Most insects have two chitin synthase (CHS) genes but, like other hemipterans, D. citri has only one. In contrast, D. citri is unusual among insects in having two UDP-N-acetylglucosamine pyrophosphorylase (UAP) genes. One of the D. citri UAP genes is broadly expressed, while the other is expressed predominantly in males. Our work helps pave the way for potential utilization of these genes as pest control targets.
Eye-head coordination and dynamic visual scanning as indicators of visuo-cognitive demands in driving simulator

Driving is an everyday task involving a complex interaction between visual and cognitive processes. As such, an increase in the cognitive and/or visual demands can lead to a mental overload which can be detrimental for driving safety. Compiling evidence suggest that eye and head movements are relevant indicators of visuo-cognitive demands and attention allocation. This study aims to investigate the effects of visual degradation on eye-head coordination as well as visual scanning behavior during a highly demanding task in a driving simulator. A total of 21 emmetropic participants (21 to 34 years old) performed dual-task driving in which they were asked to maintain a constant speed on a highway while completing a visual search and detection task on a navigation device. Participants did the experiment with optimal vision and with contact lenses that introduced a visual perturbation (myopic defocus). The results indicate modifications of eye-head coordination and the dynamics of visual scanning in response to the visual perturbation induced. More specifically, the head was more involved in horizontal gaze shifts when the visual needs were not met. Furthermore, the evaluation of visual scanning dynamics, based on time-based entropy which measures the complexity and randomness of scanpaths, revealed that eye and gaze movements became less explorative and more stereotyped when vision was not optimal. These results provide evidence for a reorganization of both eye and head movements in response to increasing visual-cognitive demands during a driving task. Altogether, these findings suggest that eye and head movements can provide relevant information about visuo-cognitive demands associated with complex tasks. Ultimately, eye-head coordination and visual scanning dynamics may be good candidates to estimate drivers’ workload and better characterize risky driving behavior.
Insights into the diversity and survival strategies of soil bacterial isolates from the Atacama Desert

The Atacama Desert, the driest and oldest desert in the world, is a hostile environment for life. Despite the inhospitable conditions, bacterial sequences detected in this location suggest rich bacterial life. This study tested the idea that certain bacteria would thrive in this location and that some of them could be cultivated permitting further characterization. Environmental surface soil samples from 1-5 cm deep were collected from 18 diverse locations within the Atacama Desert. To assess the bacterial taxa, diversity, and abundance, Illumina 16S rRNA gene sequencing was performed directly on soil samples. Bacteria were also cultured from the samples. We have a collection of 74 unique bacterial isolates after cultivation and confirmation by 16S rRNA gene sequencing. Pigmentation, biofilm formation, antibiotic production against Escherichia coli MG1655 and Staphylococcus aureus HG003, and antibiotic resistance were assessed on these isolates. We found that approximately a third of the colonies produced pigments, 80% of isolates formed biofilms, many isolates had antibiotic activity against E. coli and/or S. aureus, and many were resistant to commercial antibiotics. The functional characterization of these isolates gives us insight into the adaptive bacterial strategies in harsh environments and enables us to learn about their possible use in agriculture, healthcare, or biotechnology. Originality-Significant Statement This study provides the first microbial diversity analysis from Atacama Desert soil, presents the cultivation and isolation of 74 unique bacterial isolates, many of which may be novel genera and species, and explores pigment production, antibiotic production and resistance, and unique biofilm development as bacterial survival strategies for living within extreme environments.
Functional monovalency amplifies the pathogenicity of anti-MuSK IgG4 in myasthenia gravis

Significance An expanding group of autoimmune diseases is now recognized to be hallmarked by pathogenic IgG4 autoantibodies. IgG4 has the unique ability to exchange Fab-arms, rendering it bispecific and functionally monovalent. Here we show that autoantibody functional monovalency significantly amplifies the pathogenicity of IgG4 autoantibodies using patient-derived monoclonal antibodies in an in vivo model of MuSK myasthenia gravis. Therefore, subclass switching to predominant IgG4 autoantibodies is a critical step in the development of MuSK myasthenia gravis. This new mechanism in autoimmunity is also potentially relevant to 29 other IgG4-mediated autoimmune diseases known to date, allergy and other disease settings where IgG4 antibodies contribute to pathology. Human immunoglobulin (Ig) G4 usually displays antiinflammatory activity, and observations of IgG4 autoantibodies causing severe autoimmune disorders are therefore poorly understood. In blood, IgG4 naturally engages in a stochastic process termed “Fab-arm exchange” in which unrelated IgG4s exchange half-molecules continuously. The resulting IgG4 antibodies are composed of two different binding sites, thereby acquiring monovalent binding and inability to cross-link for each antigen recognized. Here, we demonstrate that this process amplifies autoantibody pathogenicity in a classic IgG4-mediated autoimmune disease: muscle-specific kinase (MuSK) myasthenia gravis. In mice, monovalent anti-MuSK IgG4s caused rapid and severe myasthenic muscle weakness, whereas the same antibodies in their parental bivalent form were less potent or did not induce a phenotype. Mechanistically this could be explained by opposing effects on MuSK signaling. Isotype switching to IgG4 in an autoimmune response thereby may be a critical step in the development of disease. Our study establishes functional monovalency as a pathogenic mechanism in IgG4-mediated autoimmune disease and potentially other disorders.
A speech production model including the nasal Cavity: A novel approach to articulatory analysis of speech signals.

In order to obtain articulatory analysis of speech signals the standard speech production model is improved. The standard model, as used in LPC analysis, to a large extent only models the acoustic properties of the speech signal as opposed to articulatory modelling of the speech production. In spite of this the LPC model is by far the most widely used model in speech technology. The thesis presents research in which the standard model is enhanced in two respects: Firstly the nasal cavity in the human speech production system is incorporated into the model and the corresponding mathematical model, which contains both poles and zeros, is established. The transfer function is determined as a fairly complex expression, but using a program for symbolic mathematics the order is determined. Once the order is known, system identification techniques are applied to determine the transfer function on normal form, from which the poles and zeros are obtainable. Secondly a signal analysis algorithm corresponding to the extended speech production model is described. The algorithm extracts the glottal signal contribution from the speech signal by estimating the parameters of a glottal signal model, thereby obtaining the transfer function of the vocal tract. It is desired to determine the transfer function of the vocal tract isolated from excitation signal characteristics because the transfer function closely corresponds to the vocal tract shape. The algorithm is improved to allow frequency weighting of the error spectrum without sacrificing the time resolution of the analysis. The described components contribute to the research in articulatory speech analysis rather than being an attempt to find a complete and final solution to the problem.
The proapoptotic effect of combination PI3K p85α depletion and 5-FU treatment on colorectal cancer cells

Objective To investigate the proapoptotic effect of combination PI3K p85α depletion via RNA interference and 5-FU treatment on colorectal cancer cells. MethodsPI3K p85α/RNAi-LoVo cells and LoVo control cells were recovered and cultured in RPMI1640,supplemented with 10% fetal calf serum and 500 μg/mL G418.Western blot analysis was used to determine the RNA interference effect.The 50% inhibitory concentration(IC50) value of 5-FU was evaluated by MTT assay.Annexin V-FITC Kit was used to determine the apoptosis. ResultsWestern blot analysis showed that the inhibited rate of PI3K p85α protein was 59%. Compared with the control cells,IC50 of 5-FU in PI3K p85α/RNAi-LoVo cells obviously decreased(P=0.000). Depletion of PI3K p85α sensitized LoVo cells to 5-FU induced apoptosis(P=0.000). ConclusionCombination PI3K p85α depletion and 5-FU treatment could promote apoptosis of LoVo cells.It may be a new therapeutic strategy for gene therapy and chemotherapy of colorectal cancer.
Uta stansburiana: una ventana a la evolución de las estrategias reproductivas Uta stansburiana: a window to evolution of reproductive strategies

In his famous phrase, Dobzhansky said "nothing in biology makes sense except in the light of evolution". By extension, in Neurosciences it could be interpreted as "nothing in neurosciences makes sense except in the light of behavior". The side blotched lizard Uta stansburiana has been widely used as a model organism to understand variation in reproductive strategies, which has greatly contributed to enrich the debate on the genetic basis of behavior and its consequences on the evolution of populations. Moreover, researching of Uta stransburiana has yielded interesting results about the modulation of behavior through conserved neuroendocrine pathways through the species; these data allow to establish the neuroendocrine substrate of conserved behavioral among several groups. This review synthesizes some behaviors that have contributed to the understanding of the evolution of morphological and behavioral traits sexual selection and can help to understand reproductive behavior observed in other vertebrate groups.
Producing sustainable competitive advantage through the effective management of people

Executive Overview Achieving competitive success through people involves fundamentally altering how we think about the workforce and the employment relationship. It means achieving success by working with people, not by replacing them or limiting the scope of their activities. It entails seeing the workforce as a source of strategic advantage, not just as a cost to be minimized or avoided. Firms that take this different perspective are often able to successfully outmaneuver and outperform their rivals.