Miracle-dz/UniFAR-FTUs huggingface dataset:
Dopamine-dependent cerebellar dysfunction enhances beta oscillations and disrupts motor learning in a multiarea model

Parkinson’s disease (PD) is a chronic degenerative disorder of the central nervous system that affects the motor system. The discovery that PD motor symptoms result from the death of dopaminergic cells in the substantia nigra led to focus most of PD research on the basal ganglia. However, recent findings point to an active involvement of the cerebellum in PD. Here, we have developed a multiscale computational model of the rodent brain’s basal ganglia-cerebellar network. Simulations showed that a direct effect of dopamine depletion on the cerebellum must be taken into account to reproduce the alterations of PD neural activity, particularly the increased beta oscillations widely reported in PD patients. Moreover, dopamine depletion indirectly impacted spike-time-dependent plasticity at the parallel fiber-Purkinje cell synapses, degrading associative motor learning as observed in PD. Overall, these results suggest a relevant involvement of cerebellum in PD motor symptoms. Significance Statement This study highlights the role of cerebellum in Parkinson’s disease (PD). While most studies on PD concentrate on dopaminergic mechanisms in the basal ganglia, here we show that dopamine depletion impacts also on the cerebellum, generating a complex dysfunctional interaction between the two subcortical circuits. To investigate this interaction, we developed de novo a multiarea multiscale network model that mechanistically addresses the effects of dopamine depletionon the cerebellum. Our study demonstrates that this aspect is crucial to reproduce experimental data, particularly the increased beta wave activity. Moreover, alterations in spike-time-dependent plasticity at the parallel fibre – Purkinje cell synapse of cerebellum can explain the link between dopamine depletion to motor learning impairment. These simulations indicate that the cerebellum warrants more attention in future PD research.
A measure of the somatosensory blink reflex to parametric variation of mechanical stimulation

The primary goal of this study was to develop a parametric model that relates variation in stimulation of the trigeminal nerve to properties of the blink response. We measured blink responses in 17 healthy, adult participants to air puffs directed at the lateral canthus of the eye at five different, log-spaced intensities (3.5 - 60 PSI). Lid position over time was decomposed into amplitude and velocity components. We found that blink amplitude was systematically related to log stimulus intensity, with the relationship well described by a sigmoidal function. The parameters of the model fit correspond to the slope of the function and the stimulus intensity required to produce half of a maximal blink response (the half-response threshold). There was a reliable decrease in the half-response threshold for the contralateral as compared to the ipsilateral blink response. This decrease was consistent across participants despite substantial individual differences in the half-response threshold and slope parameters of the overall sensitivity function, suggesting that the laterality effect arises in the neural circuit subsequent to individual differences in sensitivity. Overall, we find that graded mechanical stimulation of the somatosensory trigeminal afferents elicits a graded response that is well described by a simple parametric model. We discuss the application of parametric measurements of the blink response to the detection of group differences in trigeminal sensitivity. Impact statement There has been limited study of how variation in stimulus intensity influences the cutaneous blink response. We describe how variation in the intensity of an air-puff stimulus relates to the amplitude of the blink response using a two-parameter model. The parameters of the model capture individual differences in response, which may be used in future studies to identify population differences in trigeminal sensitivity.
Typical Power Load Profiles Shape Clustering Analysis Based on Adaptive Piecewise Aggregate Approximation

With the trend of increasing dimensions of collected power load data, the data dimension reduction and classification become essential pre-processing steps for data mining and further application. On the basis of adaptive piecewise aggregate approximation(APAA) and k-Shape algorithm, a novel method is proposed. In light of the fluctuation degree and shape characteristics of the original load profiles, the new load dataset with variable temple resolution replace the old one by APAA, and further k-Shape algorithm is adopted for lower dimension load profiles clustering. K-Shape algorithm cluster curves with distance SBD as similarity measurement and also a novel method to extract the representative centroids is mentioned. The experiment testifies that APAA-kShape algorithm has shorter calculating time, higher accuracy and represent better load patterns than other cluster algorithms.
Alcohol-Induced Mucociliary Dysfunction: Role of Defective CFTR Channel Function

Excessive alcohol use is thought to increase the risk of respiratory infections by impairing mucociliary clearance (MCC). In this study, we investigate the hypothesis that alcohol reduces the function of CFTR, the protein that is defective in individuals with cystic fibrosis, thus altering mucus properties to impair MCC and the airway’s defense against inhaled pathogens. Methods Sprague Dawley rats with wild type CFTR (+/+), matched for age and sex, were administered either a Lieber-DeCarli alcohol diet or a control diet with the same number of calories for eight weeks. CFTR activity was measured using nasal potential difference (NPD) assay and Ussing chamber electrophysiology of tracheal tissue samples. In vivo MCC was determined by measuring the radiographic clearance of inhaled Tc99 particles and the depth of the airway periciliary liquid (PCL) and mucus transport rate in excised trachea using micro-optical coherence tomography (µOCT). The levels of rat lung MUC5b and CFTR were estimated by protein and mRNA analysis. Results Alcohol diet was found to decrease CFTR ion transport in the nasal and tracheal epithelium in vivo and ex vivo. This decrease in activity was also reflected in partially reduced full-length CFTR protein levels but not, in mRNA copies, in the lungs of rats. Furthermore, alcohol-fed rats showed a significant decrease in MCC after 8 weeks of alcohol consumption. The trachea from these rats also showed reduced PCL depth, indicating a decrease in mucosal surface hydration that was reflected in delayed mucus transport. Diminished MCC rate was also likely due to the elevated MUC5b expression in alcohol-fed rat lungs. Conclusions Excessive alcohol use can decrease the expression and activity of CFTR channels, leading to reduced airway surface hydration and impaired mucus clearance. This suggests that CFTR dysfunction plays a role in the compromised lung defense against respiratory pathogens in individuals who drink alcohol excessively. What is the current scientific knowledge on this subject? Excessive alcohol is associated with delayed mucociliary clearance (MCC) and an increased risk of respiratory infections among heavy drinkers. What does this study add to the field? Chronic alcohol use reduces CFTR activity and airway surface hydration explaining the mechanisms underlying mucociliary dysfunction. Acquired CFTR dysfunction may be a suitable target to improve host immunity in those affected by prolonged alcohol use.
Hundreds of independent midsize deletions mediate DNA loss in wild relatives of Red Jungle Fowl

Small and midsize deletions and insertions (InDels) are major events that play a crucial role in the evolution of genome size and contribute to the genetic and phenotypic diversity of species. In recent years, considerable attention has been given to studying small indels associated with various developmental, growth, and production traits in domestic chicken breeds. Additionally, small and midsize indels have been studied between chicken and phylogenetically more distant species such as duck, turkey, rock pigeon, and other passerine birds. However, the investigation of small and midsize deletions in the wild relatives of chickens has been relatively overlooked until now. To address this gap, our study aimed to identify the presence and distribution of midsize deletions (> 1 Kb) in the wild relatives of chickens. We conducted a comparative genomic analysis using high-quality genomic data from four species belonging to the Gallus genus. Our analysis revealed the existence of more than 125 midsize deletions in the three other species compared to Gallus gallus (red junglefowl). These midsize deletions were found to be distributed in intergenic regions and within introns of various protein-coding genes but not in the exonic regions of protein-coding genes. Furthermore, we observed a trend between the number of midsize deletions and the phylogenetic distance in the phylogeny of the Gallus genus. The most ancestral species, Gallus varius (green junglefowl), exhibited the highest deletions, followed by Gallus lafayettii (Ceylon junglefowl) and Gallus sonneratii (grey junglefowl). Some protein-coding genes harboring deletions in their introns and upstream regions were associated with body development, production, growth traits, abdominal fat deposition, behavioral patterns such as stress, fear, anxiety, plumage color, and adaptation to extreme climatic conditions. Our study finds that the midsize deletions identified in wild relatives of red junglefowl contribute less than 1% of DNA loss with a rate of 8-44 Kb/My during the evolution of the Gallus genus.
Predicting cell morphological responses to perturbations using generative modeling

Advancements in high-throughput screening have enabled the exploration of rich phenotypic readouts like high-content microscopy, expediting drug target identification and mode of action studies. However, scaling these experiments to the vast space of drug or genetic manipulations poses challenges, as only a small subset of compounds show activity in screenings. Despite being widely used in various applications, machine learning methods have not shown a reliable ability to extrapolate predictions to scenarios involving unseen phenomena, specifically transforming an unseen control cell image into a desired perturbation. We present a generative model, the IMage Perturbation Autoencoder (IMPA), which predicts cellular morphological effects of chemical and genetic perturbations using untreated cells as input. IMPA learns perturbation-specific styles from generalized embeddings and generates counterfactual treatment response predictions in control cells. We demonstrate IMPA can predict morphological changes caused by small molecule perturbations on breast cancer cells. Additionally, we test IMPA on the unseen drug effect prediction task, showing improved performance over state-of-the-art generative models when compounds are structurally related to the training set. Finally, generalizability and capability to predict more subtle effects are showcased through its application to large microscopy datasets with hundreds of genetic perturbations on U2OS cells. We envision IMPA to become a valuable tool in computational microscopy for aiding phenotypic drug discovery, facilitating navigation of the perturbation space, and rational experimental design.
A Streamlined Method to Obtain Biologically Active TcdA and TcdB Toxins from Clostridioides difficile

The major virulence factors of Clostridioides difficile (C. difficile) are enterotoxin A (TcdA) and cytotoxin B (TcdB). The study of toxins is a crucial step in exploring the virulence of this pathogen. Currently, the toxin purification process is either laborious and time-consuming in C. difficile or performed in heterologous hosts. Therefore, we propose a streamlined method to obtain functional toxins in C. difficile. Two C. difficile strains were generated each harboring a sequence encoding a His-tag at the 3’ end of C. difficile 630Δerm tcdA or tcdB genes. Each toxin gene is expressed using the Ptet promoter inducible by anhydro-tetracycline. The purification yields were estimated to be 0.28 mg per liter and 0.1 mg per liter for rTcdA and rTcdB, respectively. In this study, we successfully developed a simple routine method that allows the production and purification of biologically rTcdA and rTcdB active toxins with similar activities compared to native toxins.
Vertical and oblique ionospheric soundings performance comparison over the 12,760 km transequatorial HF link between Antarctica and Spain

This paper presents the second part of the study of the oblique sounding of a 12,760 km transequatorial ionospheric link between Livingston Island (Antarctica) and Cambrils in Spain. The study consists of the comparison among the oblique sounding results using an inverted V as receiver antenna, the International Telecommunication Union Rec533 HF prediction model, and the vertical sounding results on the path of the long haul channel. The data were collected the last consecutive surveys, when the inverted V antenna was operative (2010–2011, 2011–2012, 2012–2013, and 2013–2014). The ionospheric channel is studied in terms of frequency availability depending on time using the measurements of an oblique incidence sounder (OIS) and also measurements of several vertical incidence sounding stations (VIS) on the path of the long haul channel. The results obtained show similarities between the VIS and the OIS measurements; following previous studies preliminary results, the experiments conducted led us to think that the frequency of large availability can be estimated depending on the VIS sounding results.
Risk of Cesarean Delivery When Second-Trimester Ultrasound Dating Disagrees with Definite Last Menstrual Period

Estimates of gestational age based on early second-trimester ultrasound often differ from that based on the last menstrual period (LMP) even when a woman is certain about her LMP. Discrepancies in these gestational age estimates may be associated with an increased risk of cesarean section and low birth weight. We analyzed 7228 singleton, low-risk, white women from The Routine Antenatal Diagnostic Imaging with Ultrasound trial. The women were recruited at less than 14 weeks of gestation and received ultrasound exams between 15 and 22 weeks. Our results indicate that among nulliparous women, the risk of cesarean section increased from 10% when the ultrasound-based gestational age exceeded the LMP-based estimate by 4 days to 60% when the discrepancy increased to 21 days. Moreover, for each additional day the ultrasound-based estimate exceeded the LMP-based estimate, birth weight was higher by 9.6 g. Our ﬁndings indicate that a positive discrepancy (i.e., ultrasound-based estimate exceeds LMP-based estimate) in gestational age is associated with an increased risk of cesarean section. A negative discrepancy, by contrast, may reﬂect early intrauterine growth restriction and an increased risk of low birth weight.
Percepción de los alumnos acerca del teorema de Pitágoras

espanolLa ensenanza del teorema de Pitagoras pretende tanto su comprension como su aplicacion. Este articulo profundiza en el teorema de Pitagoras a partir del Analisis Didactico, y plantea una tarea para la comprension del teorema. Hemos llevado esta tarea a una clase de secundaria y analizado la forma en que los alumnos comprenden el teorema de Pitagoras, apreciandose que esta muy ligada a la formula. EnglishThe teaching of the Pythagorean theorem seeks both its understanding and its application. This article delves into Pythagorean theorem of didactic analysis, and shows a task for the understanding of the theorem. We have taken this task to a high school class and analyzed how students understand the Pythagorean theorem, appreciating that it is closely linked to the formula.
Pax37 gene function in Oikopleura dioica supports a neuroepithelial-like origin for its house-making Fol territory

Larvacean tunicates feature a spectacular innovation not seen in other animals - the trunk oikoplastic epithelium (OE). This epithelium produces a house, a large and complex extracellular structure used for filtering and concentrating food particles. Previously we have shown that several homeobox transcription factors may play a role in patterning the OE. Among these are two Pax3/7 duplicates that we named Pax37A and Pax37B. The vertebrate homologs, PAX3 and PAX7, are involved in developmental processes related to neural crest and muscles. In the ascidian tunicate Ciona robusta, Pax3/7 has been given a role in development of cells deriving from the neural plate border including trunk epidermal sensory neurons and tail nerve cord neurons as well as in neural tube closure. Here we have investigated the roles of Pax37A and Pax37B in the development of the OE using CRISPR-Cas9, analyzing scRNA-seq data from wild-type animals that were compared with scRNA-seq data from C. robusta. We revealed that Pax37B but not Pax37A is essential for the differentiation of cell fields that produce the food concentrating filter of the house: the anterior Fol, giant Fol and Nasse cells. Lineage analysis supports that expression of Pax37 is under influence of Wnt signaling and that Fol cells have a neuroepithelial-like transcriptional signature. We propose that the highly specialized secretory epithelial cells of the Fol region either maintained or evolved neuroepithelial features as do “glue” secreting collocytes of ascidians. Their development seems to be controlled by a GRN that also operates in some ascidian neurons.
The Genomic Legacy of Human Management and sex-biased Aurochs hybridization in Iberian Cattle

Cattle have been a valuable economic resource and cultural icon since prehistory. From the initial expansion of domestic cattle into Europe during the Neolithic period, taurine cattle (Bos taurus) and their wild ancestor, the aurochs (B. primigenius), had overlapping ranges leading to ample opportunities for intentional and unintentional hybridization. We performed a bioarchaeological analysis of 24 Bos remains from Iberia dating from the Mesolithic to the Roman period. The archaeogenomic dataset allows us to investigate the extent of domestic-wild hybridization over time, providing insight into the species’ behavior and human management by aligning changes with cultural and genomic transitions in the archaeological record. Our results show frequent hybridization during the Neolithic and Chalcolithic, likely reflecting a mix of hunting and herding or relatively unmanaged herds, with mostly male aurochs and female domestic cattle involved in hybridization. This is supported by isotopic evidence of ecological niche sharing, with only a few domestic cattle possibly being managed. The proportion of aurochs ancestry in domestic cattle remains relatively constant from about 4000 years ago, probably due to herd management and selection against hybrids, coinciding with other cultural transitions. The constant level of wild ancestry (~20%) continues into modern western European breeds including the Spanish Lidia breed which is bred for its aggressiveness and fighting ability, but does not display elevated levels of aurochs ancestry. This study takes a genomic glance at the impact of human actions and wild introgression in the establishment of cattle as one of the most important domestic species today.
Spin-wave excitations and electron-magnon scattering in elementary ferromagnets from ab initio many-body perturbation theory

In this thesis, an ab initio theoretical framework for the investigation of spin excitations and the electron-magnon scattering is developed within many-body perturbation theory and implemented in the full-potential linearized augmented-plane-wave method. The spin excitations, including single-particle Stoner excitations and collective spin waves, are accessible through the magnetic response function, which is obtained by the solution of a Bethe-Salpeter equation employing four-point functions. These four-point functions are represented in a Wannier-function basis, which allows to exploit the short-range behavior of the screened interaction in metallic systems by truncating the matrices in real space. The spin excitation spectrum of ferromagnetic materials contains an acoustic magnon mode whose energy, in the absence of spin-orbit coupling, vanishes in the long-wavelength limit as a consequence of the spontaneously broken spin-rotation symmetry in these materials according to the Goldstone theorem. However, in numerical realizations of the magnetic response function the acoustic magnon mode exhibits a small but finite gap in the Goldstonemode limit. We investigate this violation of the Goldstone theorem and present an approach that implements the magnetic response function employing the properly renormalized Green function instead of the Kohn-Sham one. This much more expensive approach shows a substantial reduction of the gap error. In addition, we discuss a correction scheme motivated by the one-band Hubbard model that cures the fundamental inconsistency of using the Kohn-Sham Green function by adjusting the exchange splitting. We present corrected magnon spectra for the elementary ferromagnets iron, cobalt, and nickel. We then employ the T-matrix approach for the description of the electron-magnon interaction within the GT approximation, which can be combined with the GW approximation without the need of double-counting corrections. The multiple-scattering T matrix is part of the four-point magnetic response function and describes the correlated propagation of electron-hole pairs with opposite spins from which the collective spin excitations arise. We apply the GT
Can food and temperature influence regional connectivity patterns of Bivalvia in fragmented archipelagos? Evidence from biophysical modeling applied to French Polynesia

Larval dispersal and connectivity are key processes that drive marine metapopulation dynamics, and therefore should be well characterized when designing effective management strategies. While temperature and food availability can structure marine species connectivity patterns, their relative contribution has not been thoroughly investigated in highly fragmented archipelagos. We used biophysical modeling of larval dispersal to explore the connectivity patterns of species with complex life-cycles across French Polynesia (FP), a territory formed by more than a hundred small, geographically isolated islands covering an area as large as Europe. We first simulated ten years of larval dispersal to investigate the spatial and temporal (seasonal and interannual) variability in larval dispersal pathways for different hypothetical species exhibiting a range of Larval Precompetency Period (LPP) values. Then, using the black-lip pearl oyster (Pinctada margaritifera) as a model species, we accounted for variability in the LPP induced by temperature and food availability, as derived from a Dynamic Energy Budget (DEB) model. The model showed that food availability and meso-scale turbulence (eddies) in the Marquesas jointly constrained larval dispersal, reducing its potential connectivity with other archipelagos in FP. However, accounting for food and temperature effects on larval development, barely changed the connectivity pattern at regional scale due to the remoteness of this archipelago. The DEB simulations further revealed seasonal and interannual variability in connectivity driven by environmental conditions. Our results highlight the importance of considering temperature and food in biophysical models to adequately capture dispersal, connectivity and to identify appropriate management units at the regional scale.