Miracle-dz/UniFAR-FTUs huggingface dataset:
Implicit food odour priming effects on reactivity and inhibitory control towards foods

The food environment can interact with cognitive processing and influence eating behaviour. Our objective was to characterize the impact of implicit olfactory priming on inhibitory control towards food, in groups with different weight status. Ninety-one adults completed a modified Affective Shifting Task: they had to detect target stimuli and ignore distractor stimuli while being primed with non-attentively perceived odours. We measured reactivity and inhibitory control towards food pictures. Priming effects were observed on reactivity: participants with overweight and obesity were slower when primed with pear and pound cake odour respectively. Common inhibitory control patterns toward foods were observed between groups. We suggest that non-attentively perceived food cues influence bottom-up processing by activating distinguished mental representations according to weight status. Also, our data show that cognitive load influences inhibitory control toward foods. Those results contribute to understanding how the environment can influence eating behaviour in individuals with obesity.
Two dynamical behaviours of the microtubules at cell cortex reveal pulling and pushing forces that position the spindle in C. elegans embryo

In the Caenorhabditis elegans zygote, astral microtubules generate forces, pushing against and pulling from the cell periphery. They are essential to position the mitotic spindle and in turn the cytokinesis furrow, ensuring the proper distribution of fate determinants to the daughter cells. By measuring the dynamics of astral microtubules, we revealed the presence of two populations, residing at the cortex during 0.4 s and 1.8 s, proposed to reflect the pulling and pushing events, respectively. This is a unique opportunity to unravel the time and space variations of these both spindle-positioning forces, to study their regulation under physiological conditions. By an investigation at the microscopic level, we first confirmed that the asymmetry in pulling forces was encoded by an anteroposterior imbalance in dynein-engaging rate, and that this asymmetry exists from early metaphase on and accounts for the final spindle position. More importantly, we obtained direct proof of the temporal control of pulling forces through the force-generator processivity increase during anaphase. Lastly, we discovered an anti-correlation between the long-lived population density and the stability of the spindle position during metaphase, which strongly suggests that the pushing forces contribute to maintaining the spindle at the cell centre.
Areas of global importance for terrestrial biodiversity, carbon, and water

To meet the ambitious objectives of biodiversity and climate conventions, countries and the international community require clarity on how these objectives can be operationalized spatially, and multiple targets be pursued concurrently1. To support governments and political conventions, spatial guidance is needed to identify which areas should be managed for conservation to generate the greatest synergies between biodiversity and nature’s contribution to people (NCP). Here we present results from a joint optimization that maximizes improvements in species conservation status, carbon retention and water provisioning and rank terrestrial conservation priorities globally. We found that, selecting the top-ranked 30% (respectively 50%) of areas would conserve 62.4% (86.8%) of the estimated total carbon stock and 67.8% (90.7%) of all clean water provisioning, in addition to improving the conservation status for 69.7% (83.8%) of all species considered. If priority was given to biodiversity only, managing 30% of optimally located land area for conservation may be sufficient to improve the conservation status of 86.3% of plant and vertebrate species on Earth. Our results provide a global baseline on where land could be managed for conservation. We discuss how such a spatial prioritisation framework can support the implementation of the biodiversity and climate conventions.
Employing NaChBac for cryo-EM analysis of toxin action on voltage-gated Na+ channels in nanodisc

Significance NaChBac was the first bacterial Nav channel to be characterized and has been a prototype in the study of the structure–function relationship of Nav and Cav channels. Despite advances in the structural biology of prokaryotic and eukaryotic Nav channels, the structure of NaChBac had not been determined. Here we present single particle electron cryomicroscopy (cryo-EM) structures of NaChBac in detergent micelles and in nanodiscs, which exhibit identical conformation. NaChBac can be engineered to be a surrogate to study the interactions between gating modifier toxins (GMTs) and targeted segments on eukaryotic Nav channels. Our comparative structural characterizations emphasize the significance of the membrane environment in the structural study of Nav channels and GMTs. NaChBac, the first bacterial voltage-gated Na+ (Nav) channel to be characterized, has been the prokaryotic prototype for studying the structure–function relationship of Nav channels. Discovered nearly two decades ago, the structure of NaChBac has not been determined. Here we present the single particle electron cryomicroscopy (cryo-EM) analysis of NaChBac in both detergent micelles and nanodiscs. Under both conditions, the conformation of NaChBac is nearly identical to that of the potentially inactivated NavAb. Determining the structure of NaChBac in nanodiscs enabled us to examine gating modifier toxins (GMTs) of Nav channels in lipid bilayers. To study GMTs in mammalian Nav channels, we generated a chimera in which the extracellular fragment of the S3 and S4 segments in the second voltage-sensing domain from Nav1.7 replaced the corresponding sequence in NaChBac. Cryo-EM structures of the nanodisc-embedded chimera alone and in complex with HuwenToxin IV (HWTX-IV) were determined to 3.5 and 3.2 Å resolutions, respectively. Compared to the structure of HWTX-IV–bound human Nav1.7, which was obtained at an overall resolution of 3.2 Å, the local resolution of the toxin has been improved from ∼6 to ∼4 Å. This resolution enabled visualization of toxin docking. NaChBac can thus serve as a convenient surrogate for structural studies of the interactions between GMTs and Nav channels in a membrane environment.
Severe asthma is associated with a remodeling of the pulmonary arteries in horses

Pulmonary hypertension and cor pulmonale are complications of severe equine asthma, as a consequence of pulmonary hypoxic vasoconstriction. However, as pulmonary hypertension is only partially reversible by oxygen administration, other etiological factors are likely involved. In human chronic obstructive pulmonary disease, pulmonary artery remodeling contributes to the development of pulmonary hypertension. In rodent models, pulmonary vascular remodeling is present as a consequence of allergic airway inflammation. The present study investigated the presence of remodeling of the pulmonary arteries in severe equine asthma, its distribution throughout the lungs, and its reversibility following long-term antigen avoidance strategies and inhaled corticosteroid administration. Using histomorphometry, the total wall area of pulmonary arteries from different regions of the lung of asthmatic horses and controls was measured. The smooth muscle mass of pulmonary arteries was also estimated on lung sections stained for α-smooth muscle actin. Reversibility of vascular changes in asthmatic horses was assessed after 1 year of antigen avoidance alone or treatment with inhaled fluticasone. Pulmonary arteries showed increased wall area in apical and caudodorsal lung regions of asthmatic horses in both exacerbation and remission. The pulmonary arteries smooth muscle mass was similarly increased. Both treatments reversed the increase in wall area. However, normalization of the vascular smooth muscle mass was observed only after treatment with antigen avoidance, but not with fluticasone. In conclusion, severe equine asthma is associated with remodeling of the pulmonary arteries consisting in an increased smooth muscle mass. The resulting narrowing of the artery lumen could enhance hypoxic vasoconstriction, contributing to pulmonary hypertension. Vascular smooth muscle mass normalization is better achieved by antigen avoidance than with inhaled corticosteroids.
Tuning trophoblast invasion in a gelatin hydrogel via soluble cues from the maternal-fetal interface

Trophoblast cells play multiple critical roles in pregnancy, notably modulating blastocyst attachment to the endometrium as well as invading into and actively remodeling the endometrium to facilitate biotransport needs of the growing embryo. Despite the importance of trophoblast invasion for processes essential at early stages of pregnancy, much remains unknown regarding the balance of signaling molecules that may influence trophoblast invasion into the endometrium. The goal of this study was to use a three-dimensional trophoblast spheroid invasion assays to examine the effect of cues from the maternal-fetal interface on trophoblast invasion. We report use of a methacrylamide-functionalized gelatin (GelMA) hydrogel to support quantitative analysis of trophoblast outgrowth area and cell viability. We show this multidimensional model of trophoblast invasion can resolve quantifiable differences in outgrowth area and viability in the presence of a known invasion promoter, epidermal growth factor, and a known invasion inhibitor, transforming growth factor β1. We then investigate the sensitivity of trophoblast invasion to cortisol, a hormone associated with exogenous stressors. Together, this approach provides a toolset to investigate the coordinated action of physiological and pathophysiological processes on early stages of trophoblast invasion. IMPACT STATEMENT Trophoblast cells from the invading blastocyst play crucial roles in pregnancy, including remodeling endometrial structure to support embryonic biotransport needs; however, much remains unknown regarding the balance of signaling molecules that may influence trophoblast invasion. We show this multidimensional model of invasion can resolve quantifiable differences in outgrowth area and viability in the presence of known invasion promoters and inhibitors and then investigate invasion sensitivity to cortisol, a hormone associated with exogenous stressors. This approach provides a toolset to investigate the coordinated action of molecules from the maternal-fetal interface on trophoblast invasion that may be challenging to study in humans.
The Medial Temporal Lobe Supports Mnemonic Discrimination For Event Duration

Time has an integral role in episodic memory and previous work has implicated the medial temporal lobe in both representing time and discriminating between similar memory traces. Here we developed a novel paradigm to test mnemonic discrimination for temporal duration, as previous temporal work has largely focused on order or maintaining information over time. Thirty-five healthy, young adults completed a continuous-recognition temporal discrimination task in which participants were tasked with detecting a change of stimulus duration on the order of 0.5 seconds and whole-brain high-resolution fMRI data were acquired during this process. Analyses of behavioral results indicate that participants were successful at detecting whether the stimulus duration changed. Further, fMRI analyses revealed that successful trial performance was associated with differential processes in the left entorhinal and perirhinal cortices. Specifically, the left entorhinal cortex was differentially engaged during encoding trials that preceded Target detection, and the left perirhinal cortex was differentially engaged during successful test phase Target and Lure detections. These findings suggest that the entorhinal cortex is involved in the encoding of temporal context information and that the perirhinal cortex is representing the conjunction of item and context during retrieval.
The prevalence and importance of malaria infections during pregnancy not detected by microscopy or rapid diagnostic testing

With the advent of rapid diagnostic tests (RDT) for malaria detection, parasitological confirmation of malaria diagnoses has become more readily accessible and increasingly more affordable. However, questions are being asked about how useful they are in screening programmes, particularly for pregnant women who very often may harbour placental malaria infections which may not be detected by peripheral blood smear microscopy. It is also necessary to examine how many malaria infections go undetected by RDTs and whether such undetected infections have any negative consequences for women who carry such RDT-negative infections. This sub-study was conducted as part of a large multi-country trial of intermittent preventive treatment with sulfadoxine pyrimethamine versus intermittent screening and treatment of malaria in pregnancy which in Burkina Faso, Gambia, Ghana and Mali. The study enrolled 5,354 primi- and secundigravidae who attended antenatal clinics at study sites in the four countries from May 2010 to October 2011. The sensitivity of the RDT to detect peripheral malaria in pregnancy using PCR as the reference declined from 89.3% (95% CI 85.5-92.4) on the day of enrollment to 57.7% (95% CI 46.5-73.0) at delivery. However, the sensitivity of the RDT to detect placental malaria was lower when placental histology was used as the reference ranging from 72% (95% CI 63.3-79.7) for any woman who tested RDT positive at any scheduled ANC visit, to 35.4% (95% CI 26.6-45.0) at the delivery visit. The prevalence of sub-RDT malaria was highest at delivery (6.3%). There was no significant association between sub-RDT malaria infection and low birth weight. Of the women in a sub-sample who were seen at first ANC visit, 39.0% had malaria infections out of which 1.7% were non-falciparum infections presenting as mono-infections or mixed infections with P. falciparum. Clinical symptoms and signs were not sensitive enough to predict a positive RDT test and therefore the presence of malaria parasites. Women whose malaria infections get missed by RDTs are not at great risk of developing adverse pregnancy outcomes when compared with women who had no malaria. All pregnant women should be screened with RDT if IST was considered to replace IPTp-SP in areas where SP resistance is too high or transmission intensity is very low.
Genome based Evolutionary study of SARS-CoV-2 towards the Prediction of Epitope Based Chimeric Vaccine

SARS-CoV-2 is known to infect the neurological, respiratory, enteric, and hepatic systems of human and has already become an unprecedented threat to global healthcare system. COVID-19, the most serious public condition caused by SARS-CoV-2 leads the world to an uncertainty alongside thousands of regular death scenes. Unavailability of specific therapeutics or approved vaccine has made the recovery of COVI-19 more troublesome and challenging. The present in silico study aimed to predict a novel chimeric vaccines by simultaneously targeting four major structural proteins via the establishment of ancestral relationship among different strains of coronaviruses. Conserved regions from the homologous protein sets of spike glycoprotein (S), membrane protein (M), envelope protein and nucleocapsid protein (N) were identified through multiple sequence alignment. The phylogeny analyses of whole genome stated that four proteins (S, E, M and N) reflected the close ancestral relation of SARS-CoV-2 to SARS-COV-1 and bat coronavirus. Numerous immunogenic epitopes (both T cell and B cell) were generated from the common fragments which were further ranked on the basis of antigenicity, transmembrane topology, conservancy level, toxicity and allergenicity pattern and population coverage analysis. Top putative epitopes were combined with appropriate adjuvants and linkers to construct a novel multiepitope subunit vaccine against COVID-19. The designed constructs were characterized based on physicochemical properties, allergenicity, antigenicity and solubility which revealed the superiority of construct V3 in terms safety and efficacy. Essential molecular dynamics and Normal Mode analysis confirmed minimal deformability of the refined model at molecular level. In addition, disulfide engineering was investigated to accelerate the stability of the protein. Molecular docking study ensured high binding affinity between construct V3 and HLA cells, as well as with different host receptors. Microbial expression and translational efficacy of the constructs were checked using pET28a(+) vector of E. coli strain K12. The development of preventive measures to combat COVID-19 infections might be aided the present study. However, the in vivo and in vitro validation might be ensured with wet lab trials using model animals for the implementation of the presented data.
Synchronized cardiac impulses emerge from multi-scale, heterogeneous local calcium signals within and among cells of heart pacemaker tissue

Background The current paradigm of Sinoatrial Node (SAN) impulse generation: (i) is that full-scale action potentials (APs) of a common frequency are initiated at one site and are conducted within the SAN along smooth isochrones; and (ii) does not feature fine details of Ca2+ signalling present in isolated SAN cells, in which small subcellular, subthreshold local Ca2+ releases (LCRs) self-organize to generate cell-wide APs. Objectives To study subcellular Ca2+ signals within and among cells comprising the SAN tissue. Methods We combined immunolabeling with a novel technique to detect the occurrence of LCRs and AP-induced Ca2+ transients (APCTs) in individual pixels (chonopix) across the entire mouse SAN images. Results At high magnification, Ca2+ signals appeared markedly heterogeneous in space, amplitude, frequency, and phase among cells comprising an HCN4+/CX43- cell meshwork. The signalling exhibited several distinguishable patterns of LCR/APCT interactions within and among cells. Apparently conducting rhythmic APCTs of the meshwork were transferred to a truly conducting HCN4-/CX43+ network of straited cells via narrow functional interfaces where different cell types intertwine, i.e. the SAN anatomical/functional unit. At low magnification, the earliest APCT of each cycle occurred within a small area of the HCN4 meshwork and subsequent APCT appearance throughout SAN pixels was discontinuous. Conclusions We have discovered a novel, microscopic Ca2+ signalling paradigm of SAN operation that has escaped detection using low-resolution, macroscopic tissue isochrones employed in prior studies: APs emerge from heterogeneous subcellular subthreshold Ca2+ signals, resembling multiscale complex processes of impulse generation within clusters of neurons in neuronal networks. Condensed abstract By combining immunolabeling with a novel optical technique we detected markedly heterogenous Ca2+signals within and among cell clusters of an HCN4+/CX43- meshwork in mouse sinoatrial node. These Ca2+ signals self-organized and transferred, throughout the node, to projections from an HCN4-/CX43+ network connected to a highly organized, rapidly conducting part of the CX43+ network. Thus, APs emerge from heterogeneous, subthreshold Ca2+ signaling not detected in low-resolution macroscopic isochrones. Our discovery requires a fundamental paradigm shift from concentric impulse propagation initiated within a leading site, to a multiscale/complex process, resembling the emergence of organized signals from heterogeneous local signals within neuronal networks.
A Variable Clock Underlies Internally Generated Hippocampal Sequences

Humans have the ability to store and retrieve memories with various degrees of specificity, and recent advances in reinforcement learning have identified benefits to learning when past experience is represented at different levels of temporal abstraction. How this flexibility might be implemented in the brain remains unclear. We analyzed the temporal organization of male rat hippocampal population spiking to identify potential substrates for temporally flexible representations. We examined activity both during locomotion and during memory-associated population events known as sharp-wave ripples (SWRs). We found that spiking during SWRs is rhythmically organized with higher event-to-event variability than spiking during locomotion-associated population events. Decoding analyses using clusterless methods further indicate that a similar spatial experience can be replayed in multiple SWRs, each time with a different rhythmic structure whose periodicity is sampled from a log-normal distribution. This variability increases with experience despite the decline in SWR rates that occurs as environments become more familiar. We hypothesize that the variability in temporal organization of hippocampal spiking provides a mechanism for storing experiences with various degrees of specificity. SIGNIFICANCE STATEMENT One of the most remarkable properties of memory is its flexibility: the brain can retrieve stored representations at varying levels of detail where, for example, we can begin with a memory of an entire extended event and then zoom in on a particular episode. The neural mechanisms that support this flexibility are not understood. Here we show that hippocampal sharp-wave ripples, which mark the times of memory replay and are important for memory storage, have a highly variable temporal structure that is well suited to support the storage of memories at different levels of detail.
A truncated form of HpARI stabilises IL-33, amplifying responses to the cytokine

The murine intestinal nematode Heligmosomoides polygyrus releases the H. polygyrus Alarmin Release Inhibitor (HpARI) - a protein which binds to IL-33 and to DNA, effectively tethering the cytokine in the nucleus of necrotic cells. Previous work showed that a non-natural truncation consisting of the first 2 domains of HpARI (HpARI_CCP1/2) retains binding to both DNA and IL-33, and inhibited IL-33 release in vivo. Here, we show that the affinity of HpARI_CCP1/2 for IL-33 is significantly lower than that of the full-length protein, and that HpARI_CCP1/2 lacks the ability to prevent interaction of IL-33 with its receptor. When HpARI_CCP1/2 was applied in vivo it potently amplified IL-33-dependent immune responses to Alternaria alternata allergen, Nippostrongylus brasiliensis infection and recombinant IL-33 injection. Mechanistically, we found that HpARI_CCP1/2 is able to bind to and stabilise IL-33, preventing its degradation and maintaining the cytokine in its active form. This study highlights the importance of IL-33 inactivation, the potential for IL-33 stabilisation in vivo, and describes a new tool for IL-33 research.