Miracle-dz/UniFAR-FTUs huggingface dataset:
Advances in mt-tRNA Mutation-Caused Mitochondrial Disease Modeling: Patients’ Brain in a Dish

Mitochondrial diseases are a heterogeneous group of rare genetic disorders that can be caused by mutations in nuclear (nDNA) or mitochondrial DNA (mtDNA). Mutations in mtDNA are associated with several maternally inherited genetic diseases, with mitochondrial dysfunction as a main pathological feature. These diseases, although frequently multisystemic, mainly affect organs that require large amounts of energy such as the brain and the skeletal muscle. In contrast to the difficulty of obtaining neuronal and muscle cell models, the development of induced pluripotent stem cells (iPSCs) has shed light on the study of mitochondrial diseases. However, it is still a challenge to obtain an appropriate cellular model in order to find new therapeutic options for people suffering from these diseases. In this review, we deepen the knowledge in the current models for the most studied mt-tRNA mutation-caused mitochondrial diseases, MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) and MERRF (myoclonic epilepsy with ragged red fibers) syndromes, and their therapeutic management. In particular, we will discuss the development of a novel model for mitochondrial disease research that consists of induced neurons (iNs) generated by direct reprogramming of fibroblasts derived from patients suffering from MERRF syndrome. We hypothesize that iNs will be helpful for mitochondrial disease modeling, since they could mimic patient’s neuron pathophysiology and give us the opportunity to correct the alterations in one of the most affected cellular types in these disorders.
Dynamics and Viability of a Small, Estuarine-Resident Population of Lahille’s Bottlenose Dolphins From Southern Brazil

Identifying threatened populations and quantifying their vulnerability is crucial for establishing priorities for conservation and providing robust information for decision-making. Lahille’s bottlenose dolphins have been long subjected to by-catch mortality in gillnet fisheries in coastal waters of southern Brazil, particularly in the Patos Lagoon estuary (PLE) and adjacent coastal waters, where dolphins from three populations (or Management Units) show overlapping home ranges. In this study we used a stage-classified matrix population model to conduct a demographic analysis of the PLE’s population with life-history data estimated through an 8 years mark-recapture study. A population viability analysis (PVA) was used to run a series of simulations where the risk was assessed under different by-catch scenarios, taking into account the effects of parameter uncertainty and stochasticity in the projections. In the absence of by-catch, we estimated that this dolphin population would growth at a rate of about 3% annually (95% CI: 1.2–5.8%). Under current by-catch rates, prognoses indicated high probabilities of viability over the next 60 years. These optimistic prognoses appear to be associated with the high survival of adult females. However, the eventual removal of very few mature females (one every year or two) would result in a prominent likelihood of decline from its current abundance at all pre-specified levels. The viability of the population would be substantially improved if the survival of juveniles/sub-adults could be increased. This may be achieved through the recently implemented dolphin protection area, which prohibits gillnet fisheries in the core area of this population. If the protection area reduces the entanglement rates of the most impacted life-stages (i.e., juvenile/sub-adult dolphins), there would be a substantial chance of the PLE’s dolphin population increasing above 20% of its current size, which is here proposed as conservation goal. If met, this goal has the potential to promote habitat quality, increase genetic diversity and connectivity with adjacent populations, enhancing the ability of bottlenose dolphins in southern Brazil to cope with environmental change and potential disease outbreaks.
The Scientific Contributions of Bernard Cohen (1929–2019)

Throughout Bernard Cohen's active career at Mount Sinai that lasted over a half century, he was involved in research on vestibular control of the oculomotor, body postural, and autonomic systems in animals and humans, contributing to our understanding of such maladies as motion sickness, mal de débarquement syndrome, and orthostatic syncope. This review is an attempt to trace and connect Cohen's varied research interests and his approaches to them. His influence was vast. His scientific contributions will continue to drive research directions for many years to come.
SARS-CoV-2 Causes a Systemically Multiple Organs Damages and Dissemination in Hamsters

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread across the world and impacted global healthcare systems. For clinical patients, COVID-19 not only induces pulmonary lesions but also affects extrapulmonary organs. An ideal animal model that mimics COVID-19 in humans in terms of the induced systematic lesions is urgently needed. Here, we report that Syrian hamster is highly permissive to SARS-CoV-2 and exhibit diffuse alveolar damage and induced extrapulmonary multi-organs damage, including spleen, lymph nodes, different segments of alimentary tract, kidney, adrenal gland, ovary, vesicular gland and prostate damage, at 3–7 days post inoculation (dpi), based on qRT-PCR, in situ hybridization and immunohistochemistry detection. Notably, the adrenal gland is a novel target organ, with abundant viral RNA and antigen expression detected, accompanied by focal to diffuse inflammation. Additionally, viral RNA was also detected in the corpus luteum of the ovary, vesicular gland and prostate. Focal lesions in liver, gallbladder, myocardium, and lymph nodes were still present at 18 dpi, suggesting potential damage after disease. Our findings illustrate systemic histological observations and the viral RNA and antigen distribution in infected hamsters during disease and convalescence to recapitulate those observed in humans with COVID-19, providing helpful data to the pathophysiologic characterization of SARS-CoV-2-induced systemic disease and the development of effective treatment strategies.
From Diversity Ideologies to the Expression of Stereotypes: Insights Into the Cognitive Regulation of Prejudice Within the Cultural-Ecological Context of French Laïcité

This theoretical paper examines the context-sensitivity of the impact of cultural norms on prejudice regulation. Granting the importance of understanding intergroup dynamics in cultural-ecological contexts, we focus on the peculiarities of the French diversity approach. Indeed, the major cultural norm, the Laïcité (i.e., French secularism) is declined today in two main variants: The Historic Laïcité, a longstanding egalitarian norm coexisting with its amended form: The New Laïcité, an assimilationist norm. In fact, these co-encapsulated Laïcité variants constitute a fruitful ground to cast light on the processes underlying prejudice regulation. Indeed, it is documented that the assimilationist New Laïcité is linked to higher levels of prejudice as compared to the egalitarian Historic Laïcité. To this day, research mainly explored interindividual determinants of Laïcité endorsements and specified how these endorsements shape prejudice. Crucially, this “indirect-endorsement path” does not account for the more straightforward causal relationship between Laïcité and prejudice. Moreover, recent experimental evidence suggests that the normative salience of both Laïcité norms shape intergroup attitudes beyond personal endorsement. Therefore, in this contribution, we complement previous work by investigating the possible socio-cognitive processes driving this “direct-contextual path. ” In doing so, we seek to bridge the gap of causality by investigating how the Laïcité norms can set the stage for specific regulatory strategies. Our reasoning derives from an application of the Justification-Suppression Model bolstered by classical work on mental control, modern racism and diversity ideology. From this, we sketch out the operative functioning of two distinct regulation processes: (a) one that prevents prejudicial attitudes but which can have unexpected consequences on stereotyping within the Historic Laïcité context (i.e., suppression) and (b) one that helps realize prejudice within the New Laïcité context (i.e., justification). From this analysis, we discuss the consequences for intergroup relations within and beyond the French context. In particular, we outline the importance of an adequate framing of egalitarian ideologies so that they achieve their goal to foster harmonious intergroup relations.
Relevance of Membrane Contact Sites in Cancer Progression

Membrane contact sites (MCS) are typically defined as areas of proximity between heterologous or homologous membranes characterized by specific proteins. The study of MCS is considered as an emergent field that shows how crucial organelle interactions are in cell physiology. MCS regulate a myriad of physiological processes such as apoptosis, calcium, and lipid signaling, just to name a few. The membranal interactions between the endoplasmic reticulum (ER)–mitochondria, the ER–plasma membrane, and the vesicular traffic have received special attention in recent years, particularly in cancer research, in which it has been proposed that MCS regulate tumor metabolism and fate, contributing to their progression. However, as the therapeutic or diagnostic potential of MCS has not been fully revisited, in this review, we provide recent information on MCS relevance on calcium and lipid signaling in cancer cells and on its role in tumor progression. We also describe some proteins associated with MCS, like CERT, STIM1, VDAC, and Orai, that impact on cancer progression and that could be a possible diagnostic marker. Overall, these information might contribute to the understanding of the complex biology of cancer cells.
Opportunistic Osteoporosis Screening Reveals Low Bone Density in Patients With Screw Loosening After Lumbar Semi-Rigid Instrumentation: A Case-Control Study

Objective Decreased bone mineral density (BMD) impairs screw purchase in trabecular bone and can cause screw loosening following spinal instrumentation. Existing computed tomography (CT) scans could be used for opportunistic osteoporosis screening for decreased BMD. Purpose of this case-control study was to investigate the association of opportunistically assessed BMD with the outcome after spinal surgery with semi-rigid instrumentation for lumbar degenerative instability. Methods We reviewed consecutive patients that had primary surgery with semi-rigid instrumentation in our hospital. Patients that showed screw loosening in follow-up imaging qualified as cases. Patients that did not show screw loosening or—if no follow-up imaging was available (n = 8)—reported benefit from surgery ≥ 6 months after primary surgery qualified as controls. Matching criteria were sex, age, and surgical construct. Opportunistic BMD screening was performed at L1 to L4 in perioperative CT scans by automatic spine segmentation and using asynchronous calibration. Processing steps of this deep learning-driven approach can be reproduced using the freely available online-tool Anduin (https://anduin.bonescreen.de). Area under the curve (AUC) was calculated for BMD as a predictor of screw loosening. Results Forty-six elderly patients (69.9 ± 9.1 years)—23 cases and 23 controls—were included. The majority of surgeries involved three spinal motion segments (n = 34). Twenty patients had low bone mass and 13 had osteoporotic BMD. Cases had significantly lower mean BMD (86.5 ± 29.5 mg/cm³) compared to controls (118.2 ± 32.9 mg/cm³, p = 0.001), i.e. patients with screw loosening showed reduced BMD. Screw loosening was best predicted by a BMD < 81.8 mg/cm³ (sensitivity = 91.3%, specificity = 56.5%, AUC = 0.769, p = 0.002). Conclusion Prevalence of osteoporosis or low bone mass (BMD ≤ 120 mg/cm³) was relatively high in this group of elderly patients undergoing spinal surgery. Screw loosening was associated with BMD close to the threshold for osteoporosis (< 80 mg/cm³). Opportunistic BMD screening is feasible using the presented approach and can guide the surgeon to take measures to prevent screw loosening and to increase favorable outcomes.
Electroplating Copper onto Resistive Barrier Films

An analytical solution for the metal resistance-controlled plating current distribution on circular wafers is obtained for determining the conditions under which a uniform metal film can be electrodeposited on a resistive film. Results indicate that, when using conventional copper plating solutions, uniform films cannot be deposited on 500 A thick barrier layers consisting of Ta (or more resistive metals) on 200 mm wafers, regardless of plating current density or the use of pulse reverse plating. Uniformity can be characterized by a dimensionless polarization parameter that reflects the influences of current density and physical and chemical properties. Of these properties, the only one that can be varied enough to allow Cu plating on a barrier film is the plating exchange current density, i 0 . By lowering the copper concentration and thus i 0 in the plating bath by one or two orders of magnitude below levels that are commonly employed, the terminal effect can be reduced to the point where a uniform conformal conduction layer can be electrodeposited. Subsequently, the bulk copper film can be plated at high rates.
A Circadian Clock in the Retina Regulates Rod-Cone Gap Junction Coupling and Neuronal Light Responses via Activation of Adenosine A2A Receptors

Adenosine, a major neuromodulator in the central nervous system (CNS), is involved in a variety of regulatory functions such as the sleep/wake cycle. Because exogenous adenosine displays dark- and night-mimicking effects in the vertebrate retina, we tested the hypothesis that a circadian (24 h) clock in the retina uses adenosine to control neuronal light responses and information processing. Using a variety of techniques in the intact goldfish retina including measurements of adenosine overflow and content, tracer labeling, and electrical recording of the light responses of cone photoreceptor cells and cone horizontal cells (cHCs), which are post-synaptic to cones, we demonstrate that a circadian clock in the retina itself—but not activation of melatonin or dopamine receptors—controls extracellular and intracellular adenosine levels so that they are highest during the subjective night. Moreover, the results show that the clock increases extracellular adenosine at night by enhancing adenosine content so that inward adenosine transport ceases. Also, we report that circadian clock control of endogenous cone adenosine A2A receptor activation increases rod-cone gap junction coupling and rod input to cones and cHCs at night. These results demonstrate that adenosine and A2A receptor activity are controlled by a circadian clock in the retina, and are used by the clock to modulate rod-cone electrical synapses and the sensitivity of cones and cHCs to very dim light stimuli. Moreover, the adenosine system represents a separate circadian-controlled pathway in the retina that is independent of the melatonin/dopamine pathway but which nevertheless acts in concert to enhance the day/night difference in rod-cone coupling.
Conflict and resources in post‐genocide Rwanda and the Great Lakes region

The legacy of the genocide of 1994 has spread from Rwanda to the wider Great Lakes region, and its most damaging effects have been felt in Eastern Democratic Republic of Congo (DRC), former Zaire. Here an economy based on pillage and force of arms has been organized by local elites, and the Rwandan state, ensuring also on behalf of the West that it is not excluded from the scramble to extract rare mineral deposits, obtain forest products and otherwise exploit the resources of the DRC. The most noticeable after‐effect of the genocide has been mass refugee movements and internal displacement. The damage to environments throughout the region has been dramatic, and has been exacerbated by patterns of growing social inequality. In addition, social institutions that might be able to both manage resource use and resolve conflicts, have all but collapsed under the weight of a violent form of ethnic politics. The main hope for the future lies in reviving some of these community‐level institutions in ways that can overcome some of the more poisonous effects of racial identity politics throughout the Great Lakes region. The necessity for political solutions to environmental and resource problems is very clear; what is less clear is how such solutions can be formulated and implemented.
Why and how the brain weights contributions from a mixture of experts

It has long been suggested that human behavior reflects the contributions of multiple systems that cooperate or compete for behavioral control. Here we propose that the brain acts as a "Mixture of Experts" in which different expert systems propose strategies for action. It will be argued that the brain determines which experts should control behavior at any one moment in time by keeping track of the reliability of the predictions within each system, and by allocating control over behavior in a manner that depends on the relative reliabilities across experts. fMRI and neurostimulation studies suggest a specific contribution of the anterior prefrontal cortex in this process. Further, such a mechanism also takes into consideration the complexity of the expert, favoring simpler over more cognitively complex experts. Results from the study of different expert systems in both experiential and social learning domains hint at the possibility that this reliability-based control mechanism is domain general, exerting control over many different expert systems simultaneously in order to produce sophisticated behavior.
The Persistence of Neuromyths in the Educational Settings: A Systematic Review

Neuroscience influences education, and these two areas have converged in a new field denominated “Neuroeducation. ” However, the growing interest in the education–brain relationship does not match the proper use of research findings. In 2007, the Organization for Economic Cooperation and Development (OECD) warned of the misunderstandings about the brain among teachers, labeling them as neuromyths. The main objective here is to observe the prevalence of the neuromyths in educators over time. After two decades of publications of research on neuromyths among in-service or prospective teachers, this work presents a systematic scientific review. To select the articles, we used the words: “teachers,” “preservice teachers,” “neuromyths” combined with the Boolean data type “and. ” The search was filtered according to the following criteria: (a) identifiable author, (b) written in English, Spanish, French, Italian, or Portuguese, (c) word neuromyth in title, abstract, or keywords, (d) research with a participant's survey, (e) sample focused on educators, (f) peer-review publication index in JCR, SJR, or ESCI. The documents were found through Web of Science, Scopus, PubMed, Dialnet, ProQuest, EBSCO-host, and Google Scholar. After the search, 24 articles were identified as being of sufficiently high quality for this systematic review. This result highlights that neuromyths are still the subject of attention almost two decades after their definition. The findings present neuromyths as the consequence of a lack of scientific knowledge, a communicative gap between scientists and teachers, and the low-quality information sources consulted by teachers. In addition, the data on protectors and predictors of neuromyths is inconsistent. There is also no standard scientific methodology nor a guideline to determine a new neuromyth. The results show the need to improve the scientific content in higher education and the importance of in-service teacher training. This research justifies the requirement for university professors to be active researchers and to establish a close link with educators from other fields and levels. Neuroeducation will be the bridge that unites scientific knowledge and practical application in education, with a rigorous, standard method for the entire scientific-educational community.
Resistance Distances in Linear Polyacene Graphs

The resistance distance between any two vertices of a connected graph is defined as the net effective resistance between them in the electrical network constructed from the graph by replacing each edge with a unit resistor. In this article, using electric network approach and combinatorial approach, we derive exact expression for resistance distances between any two vertices of polyacene graphs.
Modeling Uremic Vasculopathy With Induced Pluripotent Stem Cell-Derived Endothelial Cells as a Drug Screening System

Background: Cardiovascular complications are the leading cause of mortality in patients with chronic kidney disease (CKD). Uremic vasculopathy plays a crucial role in facilitating the progression of cardiovascular complications in advanced CKD. However, the improvement of conventional research methods could provide further insights into CKD. Objectives: In this study, we aimed to develop a novel model of uremic vasculopathy as a potential drug screening system. Methods and Results: The effects of uremic serum and different combinations of uremic toxins on induced pluripotent stem cell (iPSC)-derived endothelial cells (ECs) of a normal control and a CKD patient were investigated using several functional assays. We found that a mixture of uremic toxins composed of high urea, creatinine, uric acid, and indoxyl sulfate exerted deleterious effects on normal control iPSC-ECs that were comparable to uremic serum by increasing reactive oxygen species and apoptosis, as well as suppression of tube formation. Additional characterization revealed a potential involvement of dysregulated TGF-β signaling as treatment with either losartan or TGF-β inhibitors led to the attenuation of adverse effects induced by uremic toxins. Importantly, impaired wound healing potential seen in CKD patient-specific iPSC-ECs was rescued by treatment with losartan and TGF-β inhibitors. Conclusion: Our study demonstrated that simplified uremic toxin mixtures can simulate the uremic micromilieu reproducibly and CKD patient-specific iPSC-ECs can potentially recapitulate susceptibility to uremic vasculopathy. This novel model of uremic vasculopathy may provide a new research tool as a drug screening system.