Miracle-dz/UniFAR-FTUs huggingface dataset:
Patient-Specific Network Connectivity Combined With a Next Generation Neural Mass Model to Test Clinical Hypothesis of Seizure Propagation

Dynamics underlying epileptic seizures span multiple scales in space and time, therefore, understanding seizure mechanisms requires identifying the relations between seizure components within and across these scales, together with the analysis of their dynamical repertoire. In this view, mathematical models have been developed, ranging from single neuron to neural population. In this study we consider a neural mass model able to exactly reproduce the dynamics of heterogeneous spiking neural networks. We combine the mathematical modelling with structural information from non-invasive brain imaging, thus building large-scale brain network models to explore emergent dynamics and test clinical hypothesis. We provide a comprehensive study on the effect of external drives on neuronal networks exhibiting multistability, in order to investigate the role played by the neuroanatomical connectivity matrices in shaping the emergent dynamics. In particular we systematically investigate the conditions under which the network displays a transition from a low activity regime to a high activity state, which we identify with a seizure-like event. This approach allows us to study the biophysical parameters and variables leading to multiple recruitment events at the network level. We further exploit topological network measures in order to explain the differences and the analogies among the subjects and their brain regions, in showing recruitment events at different parameter values. We demonstrate, along the example of diffusion-weighted magnetic resonance imaging (MRI) connectomes of 20 healthy subjects and 15 epileptic patients, that individual variations in structural connectivity, when linked with mathematical dynamic models, have the capacity to explain changes in spatiotemporal organization of brain dynamics, as observed in network-based brain disorders. In particular, for epileptic patients, by means of the integration of the clinical hypotheses on the epileptogenic zone (EZ), i.e. the local network where highly synchronous seizures originate, we have identified the sequence of recruitment events and discussed their links with the topological properties of the specific connectomes. The predictions made on the basis of the implemented set of exact mean-field equations turn out to be in line with the clinical pre-surgical evaluation on recruited secondary networks.
Synthesis and catalytic performance of MCM-41 modified with tetracarboxylphthalocyanine

A series of tetracarboxylphthalocyanines (MPc(COOH)4, M = H, Mn(II), Fe(II), Co(II), Ni(II), Cu(II), and Zn(II)) were anchored onto MCM-41 by the following procedures: functionalization of MCM-41 with (EtO)3SiCH2CH2CH2NH2 reacting with surface Si-OH, and anchoring MPc(COOH)4 onto MCM-41 with a substitution reaction between chloroformyl and amino groups. The samples were characterized by infrared spectroscopy, powder X-ray diffraction, scanning electron microscopy, N2 adsorption-desorption, and X-ray photoelectron spectroscopy. Catalytic activity of oxidation was tested using solutions of ethanethiol in petroleum ether and thiophene in octane; CoPc-CONH-MCM-41 displayed the highest conversion ratio of 90.15 % and 93.79 %, respectively.
A gelation transition enables the self-organization of bipolar metaphase spindles

The mitotic spindle is a highly dynamic bipolar structure that emerges from the self-organization of microtubules, molecular motors and other proteins. Sustained motor-driven poleward flows of dynamic microtubules play a key role in the bipolar organization of spindles. However, it is not understood how the local activity of motor proteins generates these large-scale coherent poleward flows. Here we show that a gelation transition enables long-range microtubule transport causing the spindles to self-organize into two oppositely polarized microtubule gels. Laser ablation experiments reveal that local active stresses generated at the spindle midplane propagate through the structure, thereby driving global coherent microtubule flows. Simulations show that microtubule gels undergoing rapid turnover can exhibit long stress relaxation times, in agreement with the long-range flows observed in experiments. Finally, our model predicts that in the presence of branching microtubule nucleation, either disrupting such flows or decreasing the network connectivity can lead to a microtubule polarity reversal in spindles. We experimentally confirm this inversion of polarity by abolishing the microtubule transport in spindles. Overall, we uncover a connection between spindle rheology and architecture in spindle self-organization. The activity of molecular motors drives the self-organization of cytoskeleton structures, leading to large-scale active flows. Now, experiments and simulations show how a gelation process enables such long-range transport in spindles.
Analysis and Implications of the Edge Structure of Dioctahedral Phyllosilicates

Crystal growth theory was applied to describe edge sites of phyllosilicates. Three face configurations were found to exist. One face has one tetrahedral site per tetrahedral sheet and two octahedral one-coordinated sites per crystallographic area ac sin β, where a and c are layer dimensions and β is the angle between them. The other two faces are similar except that they have one less octahedral site which is replaced by one SiIV-O-AlVI site in this same ac sin β area. A transfer of bonding energy from the remaining octahedral site to the SiIV-O-AlVI site is believed to neutralize all edge charge on faces containing these latter sites at normally encountered pHs (pH 3–9). A similar charge rearrangement along the edges results in an apparent decrease in the permanent charge of the mineral with an increase in edge area.On the basis of such an analysis, lath-shaped illite can be described as a very fine grained dioctahedral mica in which the apparent deficient occupancy of the octahedral sheet, presence of excess water, and measurable cation-exchange capacity may in part be the result of a large ratio of edge area to total volume, with no other chemical or structural change in the mica layers. The increasing importance of edge charge relative to layer charge produces erroneous formulae for 2:1 phyllosilicates in very fine grained samples containing fewer than 2 of 3 octahedral sites occupied by cations, on the basis of a 22-charge half cell.
How the healthy ageing brain supports semantic binding during language comprehension

Semantic binding refers to constructing complex meaning based on elementary building blocks. Using EEG, we investigated the age-related changes in modulations of oscillatory brain activity supporting lexical retrieval and semantic binding. Young and older adult participants were visually presented two-word phrases, which for the first word revealed a lexical retrieval signature (e.g. swift vs. swrfeq) and for the second word revealed a semantic binding signature (e.g. horse in a semantic binding “swift horse” vs. no binding “swrfeq horse” context). The oscillatory brain activity associated with lexical retrieval as well as semantic binding significantly differed between healthy older and young adults. Specifically for lexical retrieval, we found that different age groups exhibited opposite patterns of theta and alpha modulation, which as a combined picture suggest that lexical retrieval is associated with different and delayed signatures in older compared to young adults. For semantic binding, in young adults we found a signature in the low-beta range centred around the target word onset (i.e. a smaller low-beta increase for binding relative to no binding), while in healthy older adults we found an opposite binding signature about ~500ms later in the low- and high-beta range (i.e. a smaller low- and high-beta decrease for binding relative to no binding). The novel finding of a different and delayed oscillatory signature for semantic binding in healthy older adults reflects that the integration of word meaning into the semantic context takes longer and relies on different mechanisms in healthy older compared to young adults.
Layer 6A Pyramidal Cell Subtypes Form Synaptic Microcircuits with Distinct Functional and Structural Properties

Neocortical layer 6 plays a crucial role in sensorimotor coordination and integration through functionally segregated circuits linking intracortical and subcortical areas. However, because of the high neuronal heterogeneity and sparse intralaminar connectivity data on the cell-type specific synaptic microcircuits in layer 6 remain few and far between. To address this issue, whole-cell recordings combined with morphological reconstructions have been used to identify morpho-electric types of layer 6A pyramidal cells (PCs) in rat barrel cortex. Cortico-thalamic (CT), cortico-cortical (CC) and cortico-claustral (CCla) pyramidal cells have been distinguished based on to their distinct dendritic and axonal morphologies as well as their different electrophysiological properties. Here we demonstrate that these three types of layer 6A pyramidal cells innervate neighboring excitatory neurons with distinct synaptic properties: CT PCs establish weak facilitating synapses to other L6A PCs; CC PCs form synapses of moderate efficacy; while synapses made by putative CCla PCs display the highest release probability and a marked short-term depression. Furthermore, for excitatory-inhibitory synaptic connections in layer 6 we were able to show that both the presynaptic PC type and the postsynaptic interneuron type govern the dynamic properties of the of the respective synaptic connections. We have identified a functional division of local layer 6A excitatory microcircuits which may be responsible of the differential temporal engagement of layer 6 feed-forward and feedback networks. Our results provides a basis for further investigations on the long-range cortico-cortical, cortico-thalamic and cortico-claustral pathways.
Extended experience reveals distinct representational dynamics governing the CA1 spatial code

Hippocampal subregion CA1 is thought to support episodic memory through reinstatement of a stable spatial code. However, recent calcium imaging experiments demonstrate that the majority of this code changes rapidly, thus challenging this presumed function. Here we show that the mouse CA1 spatial code contains distinct representational components mediated by separate neural ensembles with different long-term dynamics, including a persistent representation of spatial geometry and prior experience.
Dengue virus 2 capsid protein chaperones strand displacement without altering the capsid-coding region hairpin element’s structural functionality

By virtue of its chaperone activity, the capsid protein of dengue virus strain 2 (DENV2C) promotes nucleic acid structural rearrangements. However, the role of DENV2C during the interaction of RNA elements involved in stabilizing the 5’-3’ panhandle structure of DENV RNA is still unclear. Therefore, we determined how DENV2C affects structural functionality of the capsid-coding region hairpin element (cHP) during RNA rearrangement of the 9-nt conserved sequence (5CS) to its complementary 3CS counterpart. The cHP element has two distinct functions: a role in translation start codon selection and a role in RNA synthesis. Our results showed that the cHP hairpin impedes annealing between the 5CS and the 3CS elements. Although DENV2C does not modulate structural functionality of the cHP hairpin, it accelerates annealing and specifically promotes strand displacement of 3CS during 5’-3’ panhandle formation. Furthermore, DENV2C exerts its chaperone activity by favoring one of the active conformations of the cHP element. Based on our results, we propose mechanisms for annealing and strand displacement involving the cHP element. Thus, our results provide mechanistic insights on how DENV2C regulates RNA synthesis by modulating essential RNA elements in the capsid-coding region, that in turn allow for DENV replication.
The impact of age and education on phonemic and semantic verbal fluency: Behavioral and fMRI correlates

The purpose of this study was to examine the impact of age and education on the neural and behavioral correlates of verbal fluency. Forty-eight healthy adult participants were included: high-educated young and elderly, low-educated young and elderly. Participants performed semantic and phonemic and a control task during fMRI scanning. The phonemic fluency data showed an education effect across age groups. As for the semantic fluency data, there was an education effect only in young participants. The second-level fMRI results showed, in phonemic fluency, a main effect of age in the left posterior cingulate, superior temporal gyrus (STG) and right caudate, whereas the main effect of education involved activation in the right semantic fluency, there were a main effect of age in the left paracentral lobule and posterior cingulate, a main effect of education in the left claustrum and an interaction in the right claustrum and STG and the hippocampus bilaterally.
A theoretical approach for quantifying the impact of changes in effective population size and expression level on the rate of coding sequence evolution

Molecular sequences are shaped by selection, where the strength of selection relative to drift is determined by effective population size (Ne). Populations with high Ne are expected to undergo stronger purifying selection, and consequently to show a lower substitution rate for selected mutations relative to the substitution rate for neutral mutations (ω). However, computational models based on biophysics of protein stability have suggested that ω can also be independent of Ne, a result proven under general conditions. Together, the response of ω to changes in Ne depends on the specific mapping from sequence to fitness. Importantly, an increase in protein expression level has been found empirically to result in decrease of ω, an observation predicted by theoretical models assuming selection for protein stability. Here, we derive a theoretical approximation for the response of ω to changes in Ne and expression level, under an explicit genotype-phenotype-fitness map. The method is generally valid for additive traits and log-concave fitness functions. We applied these results to protein undergoing selection for their conformational stability and corroborate out findings with simulations under more complex models. We predict a weak response of ω to changes in either Ne or expression level, which are interchangeable. Based on empirical data, we propose that fitness based on the conformational stability may not be a sufficient mechanism to explain the empirically observed variation in ω across species. Other aspects of protein biophysics might be explored, such as protein-protein interactions, which can lead to a stronger response of ω to changes in Ne.
Fibrin is a critical regulator of neutrophil effector function at mucosal barrier sites

Tissue-specific cues are critical for homeostasis at mucosal barriers. Here, we document that the clotting factor fibrin is a critical regulator of neutrophil function at mucosal barriers. We demonstrate that fibrin engages neutrophils through the αMβ2 integrin receptor and activates effector functions, including the production of reactive oxygen species and NET formation. These immune-protective neutrophil functions become tissue damaging in the context of impaired plasmin-mediated fibrinolysis. Indeed, the accumulation of fibrin due to Mendelian genetic defects in plasmin leads to severe oral mucosal immunopathology in mice and humans. Concordantly, genetic polymorphisms in the human PLG gene, encoding plasminogen, are associated with common forms of the oral mucosal disease periodontitis. Our work uncovers fibrin as a critical regulator of neutrophil effector function within the mucosal tissue microenvironment and suggests fibrin-neutrophil engagement as a pathogenic instigator and therapeutic target in common mucosal disease.
Mice in a labyrinth: Rapid learning, sudden insight, and efficient exploration

Animals learn certain complex tasks remarkably fast, sometimes after a single experience. What behavioral algorithms support this efficiency? Many contemporary studies based on two-alternative-forced-choice (2AFC) tasks observe only slow or incomplete learning. As an alternative, we study the unconstrained behavior of mice in a complex labyrinth and measure the dynamics of learning and the behaviors that enable it. A mouse in the labyrinth makes ~2000 navigation decisions per hour. The animal quickly discovers the location of a reward in the maze and executes correct 10-bit choices after only 10 reward experiences – a learning rate 1000-fold higher than in 2AFC experiments. Many mice improve discontinuously from one minute to the next, suggesting moments of sudden insight about the structure of the labyrinth. The underlying search algorithm does not require a global memory of places visited and is largely explained by purely local turning rules.
Photochemical Formation of the Anion Radical of Zinc Phthalocyanine and Analysis of the Absorption and Magnetic Circular Dichroism Spectral Data. Assignment of the Optical Spectrum of [ZnPc(-3)]-

An extensive analysis of the optical absorption and magnetic circular dichroism (MCD) spectra of the anion radical of zinc phthalocyanine ([(ZnPc(-3)] - ) is described. Novel photochemical formation of the ring-reduced [ZnPc-(-3)] - from (hydrazine)Zn II Pc(-2) is reported for reactions carried out at room temperature using visible-wavelength light and hydrazine as the electron donor. Absorption and MCD spectra of the radical anion species have been obtained at both room and cryogenic temperatures. Phosphorescence and fluorescence lifetime studies of ZnPc(-2) show that the photoexcited (hydrazine)ZnPc(-2) complex reacts via the triplet state to form the ring reduced anion radical, [ZnPc(-3)] -
Reticulate Evolutionary History in a Recent Radiation of Montane Grasshoppers Revealed by Genomic Data

Inferring the ecological and evolutionary processes underlying lineage and phenotypic diversification is of paramount importance to shed light on the origin of contemporary patterns of biological diversity. However, reconstructing phylogenetic relationships in recent evolutionary radiations represents a major challenge due to the frequent co-occurrence of incomplete lineage sorting and introgression. In this study, we combined high throughput sequence data (ddRADseq), geometric morphometric information, and novel phylogenetic inference methods that explicitly account for gene flow to infer the evolutionary relationships and the timing and mode of diversification in a complex of Ibero-Maghrebian montane grasshoppers of the subgenus Dreuxius (genus Omocestus). Our analyses supported the phenotypic distinctiveness of most sister taxa, two events of historical introgression involving lineages at different stages of the diversification continuum, and the recent Pleistocene origin (< 1 Ma) of the complex. Phylogenetic analyses did not recover the reciprocal monophyly of taxa from Iberia and northwestern Africa, supporting overseas migration between the two continents during the Pleistocene. Collectively, these results indicate that periods of isolation and secondary contact linked to Pleistocene glacial cycles likely contributed to both allopatric speciation and post divergence gene flow in the complex. This study exemplifies how the integration of multiple lines of evidence can help to reconstruct complex histories of reticulated evolution and highlights the important role of Quaternary climatic oscillations as a diversification engine in the Ibero-Maghrebian biodiversity hotspot.
Sub-lethal aquatic doses of pyriproxyfen may increase pyrethroid resistance in malaria mosquitoes

Background Pyriproxyfen (PPF), an insect growth hormone mimic is widely used as a larvicide and in some second-generation bed nets, where it is combined with pyrethroids to improve impact. It has also been evaluated as a candidate for auto-dissemination by adult mosquitoes to control Aedes and Anopheles species. We examined whether PPF added to larval habitats of pyrethroid-resistant malaria vectors can modulate levels of resistance among emergent adult mosquitoes. Methodology Third-instar larvae of pyrethroid-resistant Anopheles arabiensis (both laboratory-reared and field-collected) were reared in different PPF concentrations, between 1×10-9 milligrams active ingredient per litre of water (mgAI/L) and 1×10-4 mgAI/L, or no PPF at all. Emergent adults escaping these sub-lethal exposures were tested using WHO-standard susceptibility assays on pyrethroids (0.75% permethrin and 0.05% deltamethrin), carbamates (0.1% bendiocarb) and organochlorides (4% DDT). Biochemical basis of pyrethroid resistance was investigated by pre-exposure to 4% PBO. Bio-efficacies of long-lasting insecticide-treated nets, Olyset® and PermaNet 2.0 were also examined against adult mosquitoes with or without previous aquatic exposure to PPF. Results Addition of sub-lethal doses of PPF to larval habitats of pyrethroid-resistant An. arabiensis, consistently resulted in significantly reduced mortalities of emergent adults when exposed to pyrethroids, but not to bendiocarb or DDT. Mortality rates after exposure to Olyset® nets, but not PermaNet 2.0 were also reduced following aquatic exposures to PPF. Pre-exposure to PBO followed by permethrin or deltamethrin resulted in significant increases in mortality, compared to either insecticide alone. Conclusions Partially-resistant mosquitoes exposed to sub-lethal aquatic concentrations of PPF may become more resistant to pyrethroids than they already are without such pre-exposures. Studies should be conducted to examine whether field applications of PPF, either by larviciding or other means actually excercebates pyrethroid-resistance in areas where signs of such resistance already exist in wild the vector populations. The studies should also investigate mechanisms underlying such magnification of resistance, and how this may impact the potential of PPF-based interventions in areas with pyrethroid resistance.
Identifying long non-coding RNAs and characterizing their functional roles in swine mammary gland from colostrogenesis to lactogenesis

Long non-coding RNAs (lncRNAs) play important regulatory roles in milk biological processes. While, little is known about the identification and function of swine lncRNAs in response to mammary gland development. Here, we identified 286 differentially expressed (DE) lncRNAs in mammary gland at different stages from 14 days prior to (-) parturition to day 1 after (+) parturition using the published RNA-seq data. The expression pattern of these DE lncRNAs was examined, and most of lncRNAs expressions were strongly changed from Day −2 to Day +1. Functional annotation revealed that the DE lncRNAs were mainly involved in the mammary gland developing, lactation developing, milk composition metabolism and colostrum function. By performing the weighted gene co-expression network analysis (WGCNA), we identified 7 out of 12 lncRNA-mRNA modules, including 35 lncRNAs and 319 mRNAs, which were highly associated with the mammary gland at Day −14, Day −2 and Day +1. Integrated analysis of the DE lncRNAs expression pattern examination, targets prediction, function annotation and WGCNA suggested that 18 lncRNAs (such as, XLOC_020627, ENSSSCG00000051193, XLOC_025150, ENSSSCG00000042618, XLOC_963181, ENSSSCG00000051701, XLOC_018030, and XLOC_025146) and their 20 target genes (such as, ACTN4, ADCY1, CSN3, SMO, CSN2, PRKAG2, FIBCD1, and GALNT7), were considered as the promising candidates for swine parturition and colostrum occurrence processes. Our research provided the insights into lncRNA profiles and their regulating mechanisms from colostrogenesis to lactogenesis in swine.