Miracle-dz/UniFAR-FTUs huggingface dataset:
The Relevancy of Data Regarding the Metabolism of Iron to Our Understanding of Deregulated Mechanisms in ALS; Hypotheses and Pitfalls

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the loss of motor neurons. Its etiology remains unknown, but several pathophysiological mechanisms are beginning to explain motor neuronal death, as well as oxidative stress. Iron accumulation has been observed in both sporadic and familial forms of ALS, including mouse models. Therefore, the dysregulation of iron metabolism could play a role in the pathological oxidative stress in ALS. Several studies have been undertaken to describe iron-related metabolic markers, in most cases focusing on metabolites in the bloodstream due to few available data in the central nervous system. Reports of accumulation of iron, high serum ferritin, and low serum transferrin levels in ALS patients have encouraged researchers to consider dysregulated iron metabolism as an integral part of ALS pathophysiology. However, it appears complicated to suggest a general mechanism due to the diversity of models and iron markers studied, including the lack of consensus among all of the studies. Regarding clinical study reports, most of them do not take into account confusion biases such as inflammation, renal dysfunction, and nutritional status. Furthermore, the iron regulatory pathways, particularly involving hepcidin, have not been thoroughly explored yet within the pathogenesis of iron overload in ALS. In this sense, it is also essential to explore the relation between iron overload and other ALS-related events, such as neuro-inflammation, protein aggregation, and iron-driven cell death, termed ferroptosis. In this review, we point out limits of the designs of certain studies that may prevent the understanding of the role of iron in ALS and discuss the relevance of the published data regarding the pathogenic impact of iron metabolism deregulation in this disease and the therapeutics targeting this pathway.
Cannabinoid Ligands Targeting TRP Channels

Transient receptor potential (TRP) channels are a group of membrane proteins involved in the transduction of a plethora of chemical and physical stimuli. These channels modulate ion entry, mediating a variety of neural signaling processes implicated in the sensation of temperature, pressure, and pH, as well as smell, taste, vision, and pain perception. Many diseases involve TRP channel dysfunction, including neuropathic pain, inflammation, and respiratory disorders. In the pursuit of new treatments for these disorders, it was discovered that cannabinoids can modulate a certain subset of TRP channels. The TRP vanilloid (TRPV), TRP ankyrin (TRPA), and TRP melastatin (TRPM) subfamilies were all found to contain channels that can be modulated by several endogenous, phytogenic, and synthetic cannabinoids. To date, six TRP channels from the three subfamilies mentioned above have been reported to mediate cannabinoid activity: TRPV1, TRPV2, TRPV3, TRPV4, TRPA1, and TRPM8. The increasing data regarding cannabinoid interactions with these receptors has prompted some researchers to consider these TRP channels to be “ionotropic cannabinoid receptors. ” Although CB1 and CB2 are considered to be the canonical cannabinoid receptors, there is significant overlap between cannabinoids and ligands of TRP receptors. The first endogenous agonist of TRPV1 to be discovered was the endocannabinoid, anandamide (AEA). Similarly, N-arachidonyl dopamine (NADA) and AEA were the first endogenous TRPM8 antagonists discovered. Additionally, Δ9-tetrahydrocannabinol (Δ9-THC), the most abundant psychotropic compound in cannabis, acts most potently at TRPV2, moderately modulates TRPV3, TRPV4, TRPA1, and TRPM8, though Δ9-THC is not reported to modulate TRPV1. Moreover, TRP receptors may modulate effects of synthetic cannabinoids used in research. One common research tool is WIN55,212-2, a CB1 agonist that also exerts analgesic effects by desensitizing TRPA1 and TRPV1. In this review article, we aim to provide an overview and classification of the cannabinoid ligands that have been reported to modulate TRP channels and their therapeutic potential.
EEG Phase Synchronization in Persons With Depression Subjected to Transcranial Magnetic Stimulation

Aim: The main objective of this work was to study the impact of repetitive Transcranial Magnetic Stimulation (rTMS) treatment on brain activity in 8 patients with major depressive disorder (MDD) and 10 patients with bipolar disorder (BP). Changes due to rTMS stimulation of the left dorsolateral prefrontal cortex (DLPFC) were investigated considering separately responders and non-responders to therapy in each of both groups. The aim of the research is to determine whether non-responders differ from responders suffered from both diseases, as well as if any change occurred due to rTMS across consecutive rTMS sessions. Methods: The graph-theory-based connectivity analysis of non-linearity measure of phase interdependencies—Phase Locking Value (PLV)—was examined from EEG data. The approximately 15-min EEG recordings from each of participants were recorded before and after 1st, 10th, and 20th session, respectively. PLV calculated from data was analyzed using principal graph theory indices (strength and degree) within five physiological frequency bands and in individual channels separately. The impact of rTMS on the EEG connectivity in every group of patients evaluated by PLV was assessed. Results: Each of four groups reacted differently to rTMS treatment. The strength and degree of PLV increased in gamma band in both groups of responders. Moreover, an increase of indices in beta band for BP-responders was observed. While, in MDD-non-responders the indices decreased in gamma band and increased in beta band. Moreover, the index strength was lower in alpha band for BP- non-responders. The rTMS stimulation caused topographically specific changes, i.e., the increase of the activity in the left DLPFC as well as in other brain regions such as right parieto-occipital areas. Conclusions: The analysis of PLV allowed for evaluation of the rTMS impact on the EEG activity in each group of patients. The changes of PLV under stimulation might be a good indicator of response to depression treatment permitting to improve the effectiveness of therapy.
CRISPR/Cas9: A Novel Weapon in the Arsenal to Combat Plant Diseases

Plant pathogens like virus, bacteria, and fungi incur a huge loss of global productivity. Targeting the dominant R gene resulted in the evolution of resistance in pathogens, which shifted plant pathologists’ attention toward host susceptibility factors (or S genes). Herein, the application of sequence-specific nucleases (SSNs) for targeted genome editing are gaining more importance, which utilize the use of meganucleases (MN), zinc finger nucleases (ZFNs), transcription activator-like effector-based nucleases (TALEN) with the latest one namely clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9). The first generation of genome editing technologies, due to their cumbersome nature, is becoming obsolete. Owing to its simple and inexpensive nature the use of CRISPR/Cas9 system has revolutionized targeted genome editing technology. CRISPR/Cas9 system has been exploited for developing resistance against virus, bacteria, and fungi. For resistance to DNA viruses (mainly single-stranded DNA viruses), different parts of the viral genome have been targeted transiently and by the development of transgenic plants. For RNA viruses, mainly the host susceptibility factors and very recently the viral RNA genome itself have been targeted. Fungal and bacterial resistance has been achieved mainly by targeting the host susceptibility genes through the development of transgenics. In spite of these successes CRISPR/Cas9 system suffers from off-targeting. This and other problems associated with this system are being tackled by the continuous discovery/evolution of new variants. Finally, the regulatory standpoint regarding CRISPR/Cas9 will determine the fate of using this versatile tool in developing pathogen resistance in crop plants.
The Neurobiology of Fear Generalization

The generalization of fear memories is an adaptive neurobiological process that promotes survival in complex and dynamic environments. When confronted with a potential threat, an animal must select an appropriate defensive response based on previous experiences that are not identical, weighing cues and contextual information that may predict safety or danger. Like other aspects of fear memory, generalization is mediated by the coordinated actions of prefrontal, hippocampal, amygdalar, and thalamic brain areas. In this review article, we describe the current understanding of the behavioral, neural, genetic, and biochemical mechanisms involved in the generalization of fear. Fear generalization is a hallmark of many anxiety and stress-related disorders, and its emergence, severity, and manifestation are sex-dependent. Therefore, to improve the dialog between human and animal studies as well as to accelerate the development of effective therapeutics, we emphasize the need to examine both sex differences and remote timescales in rodent models.
Ambient Odor Exposure Affects Food Intake and Sensory Specific Appetite in Obese Women

Food odors are important in food perception not only during consumption, but also in anticipation of food. Even though it is well established that smell is involved in eating behavior, its role in affecting actual food consumption is still unclear, especially in morbidly obese subjects, who are reported to be more affected by sensory cues than lean subjects. The aim of the present study was to investigate the influence of ambient odor exposure on ad libitum food intake and on sensory specific appetite in obese women. Thirty obese women (BMI: 34.9 ± 0.8 kg m-2; age: 50.8 ± 1.8) attended two sessions in which they were exposed to a bread odor dispersed, in a detectable but mild concentration, in the test room (“scented” condition) and to a control condition (“unscented” condition). Participants filled out a questionnaire on general appetite before entering the test room and completed a sensory specific appetite questionnaire (including 12 specific products) about 10 min after entering the test room. After approximately 15 min of exposure, the ad libitum intake of a low energy dense food product (vegetable soup) was measured. The “scented” condition significantly (p < 0.01) increased the amount of soup eaten compared to the “unscented” condition (466.4 ± 33.1 g; 368.9 ± 33.2 g, respectively). Moreover, the odor exposure induced sensory specific appetite for congruent food products in term of taste and energy density, as well as a significant increase in general appetite scores (p < 0.001). In conclusion, ambient odor exposure to a food odor affected the intake of a low energy food in obese women and stimulated appetite for congruent products. This could have important implications for influencing energy intake of individuals.
Guidance of Navigating Honeybees by Learned Elongated Ground Structures

Elongated landscape features like forest edges, rivers, roads or boundaries of fields are particularly salient landmarks for navigating animals. Here, we ask how honeybees learn such structures and how they are used during their homing flights after being released at an unexpected location (catch-and-release paradigm). The experiments were performed in two landscapes that differed with respect to their overall structure: a rather feature-less landscape, and one rich in close and far distant landmarks. We tested three different forms of learning: learning during orientation flights, learning during training to a feeding site, and learning during homing flights after release at an unexpected site within the explored area. We found that bees use elongated ground structures, e.g., a field boundary separating two pastures close to the hive (Experiment 1), an irrigation channel (Experiment 2), a hedgerow along which the bees were trained (Experiment 3), a gravel road close to the hive and the feeder (Experiment 4), a path along an irrigation channel with its vegetation close to the feeder (Experiment 5) and a gravel road along which bees performed their homing flights (Experiment 6). Discrimination and generalization between the learned linear landmarks and similar ones in the test area depend on their object properties (irrigation channel, gravel road, hedgerow) and their compass orientation. We conclude that elongated ground structures are embedded into multiple landscape features indicating that memory of these linear structures is one component of bee navigation. Elongated structures interact and compete with other references. Object identification is an important part of this process. The objects are characterized not only by their appearance but also by their alignment in the compass. Their salience is highest if both components are close to what had been learned. High similarity in appearance can compensate for (partial) compass misalignment, and vice versa.
Environnement de Réalité Augmentée Collaboratif : Manipulation d'Objets Réels et Virtuels

La realite augmentee est un outil indispensable pour certaines situations collaboratives. Nous proposons un environnement multi-utilisateurs, multi-peripheriques dedie aux applications collaboratives. Il repose sur une architecture modulaire et facilement configurable pour une mise en place rapide d'une session de travail. Cette plate-forme est utilisee pour demontrer des techniques d'interactions tres intuitives pour la manipulation d'objets reels et virtuels et la visualisation a plusieurs echelles. On introduit egalement des methodes pour ajouter de facon dynamique des objets reels et virtuels, qui s'integrent alors dans le meme espace. Base sur des concepts de vue privee et de droits d'acces aux elements de la scene, l'environnement gere l'interaction multi-utilisateurs.
Predictors of Evolution Into Multiple Sclerosis After a First Acute Demyelinating Syndrome in Children and Adolescents

Background/Objective: The aim of the study was to estimate the rate of evolution or for multiple sclerosis (MS), after a first acute demyelinating event (ADE) in pediatric patients, and to investigate the variables that predict this evolution. Methods: We retrospectively evaluated the clinical and neuroradiological features of children who presented a first ADE between January 2005 and April 2017. All patients included underwent a baseline MRI, a cerebrospinal fluid and blood analysis, including virological examinations. The evolution into MS was determined by the 2013 International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria. Clinical and radiological features predictive of MS were determined using multivariate analyses. Results: Ninety-one patients were selected (mean age at onset: 10.11 ± 4.6). After a mean follow-up of 5.6 ± 2.3 years, 35% of patients' conditions evolved to MS. In the logistic multivariate analysis of clinical and laboratory data, the best predictors of evolution into MS were: the presence of oligoclonal bands in CSF (p < 0.001), past infection with EBV (p < 0.001), periventricular lesions (p < 0.001), hypointense lesions on T1 (p < 0.001), and lesions of the corpus callosum (p < 0.001) including Dawson fingers (p < 0.001). Conclusion: Our findings suggest that a pattern of neuroimaging and laboratory findings may help to distinguish between, at clinical onset, children with a monophasic syndrome (clinically isolated syndrome or acute disseminated encephalomyelitis) from those who will develop MS.
Visual and Vestibular Inputs Affect Muscle Synergies Responsible for Body Extension and Stabilization in Sit-to-Stand Motion

The sit-to-stand motion is a common movement in daily life and understanding the mechanism of the sit-to-stand motion is important. Our previous study shows that four muscle synergies can characterize the sit-to-stand motion, and they have specific roles, such as upper body flexion, rising from a chair, body extension, and posture stabilization. The time-varying weight of these synergies are changed to achieve adaptive movement. However, the relationship between sensory input and the activation of the muscle synergies is not completely understood. In this paper, we aim to clarify how vestibular and visual inputs affect the muscle synergy in sit-to-stand motion. To address this, we conducted experiments as follows. Muscle activity, body kinematics, and ground reaction force were measured for the sit-to-stand motion under three different conditions: control, visual-disturbance, and vestibular-disturbance conditions. Under the control condition, the participants stood without any intervention. Under the visual-disturbance condition, the participants wore convex lens glasses and performed the sit-to-stand motion in a dark room. Under the vestibular-disturbance condition, a caloric test was performed. Muscle synergies were calculated for these three conditions using non-negative matrix factorization. We examined whether the same four muscle synergies were employed under each condition, and the changes in the time-varying coefficients were determined. These experiments were conducted on seven healthy, young participants. It was found that four muscle synergies could explain the muscle activity in the sit-to-stand motion under the three conditions. However, there were significant differences in the time-varying weight coefficients. When the visual input was disturbed, a larger amplitude was found for the muscle synergy that activated mostly in the final posture stabilization phase of the sit-to-stand motion. Under vestibular-disturbance condition, a longer activation was observed for the synergies that extended the entire body and led to posture stabilization. The results implied that during human sit-to-stand motion, visual input has less contribution to alter or correct activation of muscle synergies until the last phase. On the other hand, duration of muscle synergies after the buttocks leave are prolonged in order to adapt to the unstable condition in which sense of verticality is decreased under vestibular-disturbance.
Potential Utility of Protein Targets of Cysteine-S-Nitrosylation in Identifying Clinical Disease Status in Human Chagas Disease

Trypanosoma cruzi (Tc) infection causes Chagas disease (ChD) presented by dilated cardiomyopathy and heart failure. During infection, oxidative and nitrosative stresses are elicited by the immune cells for control the pathogen; however, excess nitric oxide and superoxide production can result in cysteine S-nitrosylation (SNO) of host proteins that affects cellular homeostasis and may contribute to disease development. To identify the proteins with changes in SNO modification levels as a hallmark of ChD, we obtained peripheral blood mononuclear cells (PBMC) from seronegative, normal healthy (NH, n = 30) subjects, and from seropositive clinically asymptomatic (ChD CA, n = 25) or clinically symptomatic (ChD CS, n = 28) ChD patients. All samples were treated (Asc+) or not-treated (Asc−) with ascorbate (reduces nitrosylated thiols), labeled with the thiol-labeling BODIPY FL-maleimide dye, resolved by two-dimensional electrophoresis (total 166 gels), and the protein spots that yielded significant differences in abundance or SNO level at p-value of ≤ 0.05t−test/Welch/BH were identified by MALDI-TOF/TOF MS or OrbiTrap LC-MS/MS. Targeted analysis of a new cohort of PBMC samples (n = 10–14/group) was conducted to verify the differential abundance/SNO levels of two of the proteins in ChD (vs. NH) subjects. The multivariate adaptive regression splines (MARS) modeling, comparing differences in relative SNO level (Asc−/Asc+ ratio) of the protein spots between any two groups yielded SNO biomarkers that exhibited ≥90% prediction success in classifying ChD CA (582-KRT1 and 884-TPM3) and ChD CS (426-PNP, 582-KRT1, 486-ALB, 662-ACTB) patients from NH controls. Ingenuity Pathway Analysis (IPA) of the SNO proteome dataset normalized to changes in protein abundance suggested the proteins belonging to the signaling networks of cell death and the recruitment and migration of immune cells were most affected in ChD CA and ChD CS (vs. NH) subjects. We propose that SNO modification of the select panel of proteins identified in this study have the potential to identify ChD severity in seropositive individuals exposed to Tc infection.
Abnormal Cortico-Cerebellar Functional Connectivity in Autism Spectrum Disorder

The cerebral cortex and the cerebellum are spatially remote areas that are connected by complex circuits that link both primary and associative areas. Previous studies have revealed abnormalities in autism spectrum disorder (ASD); however, it is not clear whether cortico-cerebellar connectivity is differentially manifested in the disorder. To explore this issue, we investigated differences in intrinsic cortico-cerebellar functional connectivity between individuals with typical development (TD) and those with ASD. To this end, we used functional magnetic resonance imaging (fMRI) of 708 subjects under a resting state protocol provided by the ABIDE I Consortium. We found that people with ASD had diminished functional connectivity between the cerebellum and the following cortical regions: (i) right fusiform gyrus, (ii) right postcentral gyrus, (iii) right superior temporal gyrus, (iv) right middle temporal gyrus, and (v) left middle temporal gyrus. All of these regions are involved in many cognitive systems that contribute to commonly affected functions in ASD. For right fusiform gyrus, right superior temporal gyrus, and left middle temporal gyrus, we reproduced the results in an independent cohort composed of 585 subjects of the ABIDE II Consortium. Our results points toward a consistent atypical cortico-cerebellar connectivity in ASD.
Executive Function in Relation to White Matter in Preterm and Full Term Children

Background: Executive function (EF) refers to cognitive abilities used to guide goal-directed behavior. Diffusion Tensor Imaging (DTI) provides quantitative characterization of white matter tracts in the brain. Children with preterm birth often have EF impairments and white matter injury. Aim: To examine the degree of association between EF scores and white matter fractional anisotropy (FA) as measured by DTI in children born preterm and term Study design: Cross-sectional study Subjects: Participants, 9–16 years of age, born preterm (n = 25; mean gestational age 28.6 weeks; mean birth weight 1,191 grams), and full term (n = 20) Outcome measures: White matter FA analyzed with Tract-Based Spatial Statistics, a technique that generates a skeleton representing the core of white matter tracts throughout the brain. Behavioral scores from EF tasks examining working memory, spatial memory capacity, and multiple skills from the Stockings of Cambridge. Results: The groups performed comparably on all tasks. In both groups, unfavorable working memory strategy scores were associated with lower FA. Other measures of EF were not associated with whole skeleton FA in either group in either direction. Conclusions: Strategy score on a spatial working memory task was associated with FA in preterm and full term children, suggesting common underlying neurobiology in both groups. Associations were found in frontal-parietal connections and other major tracts. Lack of associations between other EF tasks and FA may be due to variation in how children accomplish these EF tasks. Future research is required to fully understand the neurobiology of EF in children born preterm.