Miracle-dz/UniFAR-FTUs huggingface dataset:
Gain of PITRM1 peptidase in cortical neurons affords protection of mitochondrial and synaptic function in an advanced age mouse model of Alzheimer’s disease

Mitochondrial dysfunction is one of the early pathological features of Alzheimer's disease (AD). Accumulation of cerebral and mitochondrial Aβ links to mitochondrial and synaptic toxicity. We have previously demonstrated the mechanism by which presequence peptidase (PITRM1)‐mediated clearance of mitochondrial Aβ contributes to mitochondrial and cerebral amyloid pathology and mitochondrial and synaptic stress in adult transgenic AD mice overexpressing Aβ up to 12 months old. Here, we investigate the effect of PITRM1 in an advanced age AD mouse model (up to 19–24 months) to address the fundamental unexplored question of whether restoration/gain of PITRM1 function protects against mitochondrial and synaptic dysfunction associated with Aβ accumulation and whether this protection is maintained even at later ages featuring profound amyloid pathology and synaptic failure. Using newly developed aged PITRM1/Aβ‐producing AD mice, we first uncovered reduction in PITRM1 expression in AD‐affected cortex of AD mice at 19–24 months of age. Increasing neuronal PITRM1 activity/expression re‐established mitochondrial respiration, suppressed reactive oxygen species, improved synaptic function, and reduced loss of synapses even at advanced ages (up to 19–24 months). Notably, loss of PITRM1 proteolytic activity resulted in Aβ accumulation and failure to rescue mitochondrial and synaptic function, suggesting that PITRM1 activity is required for the degradation and clearance of mitochondrial Aβ and Aβ deposition. These data indicate that augmenting PITRM1 function results in persistent life‐long protection against Aβ toxicity in an AD mouse model. Therefore, augmenting PITRM1 function may enhance Aβ clearance in mitochondria, thereby maintaining mitochondrial integrity and ultimately slowing the progression of AD.
Use of neck circumference as a predictor of cardiovascular risk in chronic kidney patients undergoing hemodialysis candidates for transplantation.

INTRODUCTION Patients undergoing hemodialysis have a great cardiovascular risk. Neck circumference is a simple and low-cost measure that can estimate this risk precociously. OBJECTIVE To evaluate whether the cardiovascular risk obtained by Neck Circumference (NC) is associated with the main cardiometabolic risk factors in patients on hemodialysis treatment on waiting list for transplantation. METHODS cross-sectional study including 96 patients in a single transplantation center. Sociodemographic, clinical-laboratory and anthropometric data were collected. NC was considered as a dependent variable and the independent variables were body mass index (BMI), biochemical tests of fasting glycemia and lipid profile, triglyceride ratio and high density lipoprotein cholesterol (TGL / HDL-C) and triglyceride Index and glycemia (TyG). For the comparison of averages, we used the Mann Whitney and Students t Tests, as well as the one-way ANOVA and Kruskal Wallis tests. Bivariate and multivariate logistic regression was performed for the association between NC and cardiometabolic risk factors. A significance level of 5% was assumed. RESULTS There were higher BMI averages, blood glucose, triglycerides (TGL), TGL/HDL-C ratio and TyG index in the tertile 3 of the NC, whereas the HDL-c decreased as the tertile increased. There was a statistically significant risk of cardiovascular disease, according to NC, with overweight, high levels of TGL, TGL/HDL-c, TyG index, and low HDL-c. CONCLUSION NC has been shown to be associated with cardiometabolic risk factors in kidney patients undergoing hemodialysis on transplant waiting lists.
Locomotion of an adult female and juvenile male aye‐aye (Daubentonia madagascariensis) in Torotorofotsy, Madagascar

Aye‐ayes (Daubentonia madagascariensis) locate and acquire invertebrates from within woody substrates at all levels of the rainforest; yet how their locomotion helps them accommodate this diet has not been explored in detail. We studied the locomotor behavior of an adult female (N = 1,085) and juvenile male (N = 708) aye‐aye in the undisturbed forest of Torotorofotsy, Madagascar from May to December 2017. We used bout sampling to record locomotion during foraging and travel of the two radio‐collared individuals. We used χ 2 tests to compare overall locomotion, travel, and foraging, as well as strata and support use. We performed a correspondence analysis to examine relationships between individual behaviors, strata, and support types. Leaping accounted for 47.9% and 50.1% of all locomotor activity in the adult female and juvenile male, respectively. Leaping was the most common behavior during travel in both individuals (59.2% and 53.9%, respectively), whereas head‐first descent was most frequent during foraging (35.0% and 48.0%, respectively). For all three locomotor categories, the main canopy (40.3%–79.6%) was used most frequently and trunks were the most frequently used support type (50.7%–60.0%). There is a strong association between strata and support use overall and during travel. Quadrupedal walking was significantly associated with the main canopy, as was head‐first descent with the low canopy. Our analysis demonstrates that aye‐ayes use a variety of locomotor behaviors to forage for invertebrates. Aye‐ayes’ ability to repurpose their positional repertoire to acquire other resources in degraded forests should not obscure the importance of invertebrates to this species.
Concentration‐ and time‐dependent induction of Cyp1a and DNA damage response by benzo(a)pyrene in LMH three‐dimensional spheroids

In vitro liver toxicity tests performed using cell lines cultured as two‐dimensional (2D) monolayer have limited CYP450 activity and may be inadequate for screening chemicals that require activation to exert toxicity. Metabolic competence is greatly improved using three‐dimensional (3D) cell culture. In this study, Cyp1a induction, and subsequent DNA damage response induced by benzo(a)pyrene (BaP) were compared in 2D monolayer cells and 3D spheroids of the chicken hepatic cell line, LMH. Cells were exposed to BaP (0.1–100 μM) for different durations: 8, 24, 35, or 48 hr. Cyp1a activity, mRNA expression of Cyp1a and DNA damage response (DDR) genes, and phosphorylation of H2AX (γH2AX) were determined using the EROD assay, a customized PCR array, and flow cytometry, respectively. EROD activity was induced at 8 hr and achieved maximal induction at 24 hr in spheroids; earlier time points than for monolayer cells. In spheroids, BaP exposure resulted in a concentration‐dependent increase in Cyp1a4 mRNA expression at 8 hr followed by upregulation of DDR genes at 24 hr, whereas Cyp1a4 mRNA induction was only observed at 48 hr in monolayer cells. Cyp1a5 mRNA was induced at 8 hr in monolayer cells but maximum induction was greater in spheroids. An increase in γH2AX was observed at 24 hr in spheroids; this endpoint was not evaluated in monolayer cells. These results suggest that BaP metabolism precedes the DNA damage response and occurs earlier in 3D spheroids. This study demonstrates that LMH 3D spheroids could be a suitable metabolically‐competent in vitro model to measure genotoxicity of chemicals that require metabolic activation by Cyp1a.
Epidemiologic case investigation on the zoonotic transmission of Staphylococcus aureus infection from goat to veterinarians

Staphylococcus aureus infection led to a case of goat abortion, and four veterinarians contracted S. aureus infection from the goat during and after the abortion. Three veterinarians assisted a doe during the dystocic delivery of a dead foetus. Seventy‐two hours after the dystocia, which ended with the goat's death, the veterinarians who assisted during the kidding and the veterinarian who performed the necropsy showed the presence of multiple, isolated, painful pustules 1–5 mm in diameter located along their forearms and knees. S. aureus was isolated from the pustules of the veterinarians, the placenta and uterus of the goat, the organs (brain, thymus gland, abomasum, liver and spleen) of the foetus, the scrotum and eye swabs of the buck, and mammary pustules of another goat from the same herd. Histological analysis revealed purulent metritis and inflammation of the placental cotyledons. Additional investigations eliminated the chances of other infections. S. aureus isolates recovered from the veterinarians, goats, foetus and buck were sensitive to the tested anti‐microbials and did not encode staphylococcal enterotoxin genes (sea, ser, sep, see, seg and sei). The isolates were closely related, as indicated by the results of Fourier‐transform infrared spectroscopy and comparative whole‐genome sequencing analysis. The results of this study clearly support the hypothesis that an episode of professional zoonosis was caused by S. aureus infection during the abortion and also highlight the need for bacterial subtyping in epidemiological surveys.
Application of Four Genotyping Methods to Mycoplasma bovis Isolates Derived from Western Canadian Feedlot Cattle

Mycoplasma bovis is a significant pathogen of feedlot cattle, responsible for chronic pneumonia and polyarthritis syndrome (CPPS). M. bovis isolates (n = 129) were used to compare four methods of phylogenetic analysis and to determine if the isolates’ genotypes were associated with phenotypes. Metadata included the health status of the animal from which an isolate was derived (healthy, diseased, or dead), anatomical location (nasopharynx, lung, or joint), feedlot, and production year (2006 to 2018). ABSTRACT Mycoplasma bovis is a significant pathogen of feedlot cattle, responsible for chronic pneumonia and polyarthritis syndrome (CPPS). M. bovis isolates (n = 129) were used to compare four methods of phylogenetic analysis and to determine if the isolates’ genotypes were associated with phenotypes. Metadata included the health status of the animal from which an isolate was derived (healthy, diseased, or dead), anatomical location (nasopharynx, lung, or joint), feedlot, and production year (2006 to 2018). Four in silico phylogenetic typing methods were used: multilocus sequence typing (MLST), core genome MLST (cgMLST), core genome single nucleotide variant (cgSNV) analysis, and whole-genome SNV (wgSNV) analysis. Using Simpson’s diversity index (D) as a proxy for resolution, MLST had the lowest resolution (D = 0.932); cgSNV (D = 0.984) and cgMLST (D = 0.987) generated comparable results; and wgSNV (D = 1.000) provided the highest resolution. Visual inspection of the minimum spanning trees found that the memberships of the clonal complexes and clades had similar structural appearances. Although MLST had the lowest resolution, this methodology was intuitive and easy to apply, and the PubMLST database facilitates the comparison of sequence types across studies. The cg methods had higher resolution than MLST, and the graphical interface software was user-friendly for nonbioinformaticians, but the proprietary software is relatively expensive. The wgSNV approach was the most robust for processing poor-quality sequence data while offering the highest resolution; however, application of its software requires specialized training. None of the four methods could associate genotypes with phenotypes.
Autonomic Nervous Function in Patients with Sudden Sensorineural Hearing Loss and Its Association with Prognosis and Disease Severity

Introduction: Vascular disorder is considered one of the main mechanisms of sudden sensorineural hearing loss (SSNHL) due to the anatomy of the inner ear. One factor that can contribute to vascular disorder is impairment in the autonomic nervous system. This study aims to investigate autonomic function in patients with SSNHL and its association with prognosis and disease severity from January 2018 to October 2019. Methods: We conducted a cross-sectional study involving 40 healthy controls and 55 subjects with SSNHL. We compared the autonomic function of controls and patients using heart rate variability (HRV). SSNHL patients were divided into improvement and no-improvement groups and into mild and severe groups according to pure-tone audiometry results. Results: The SSNHL group had significantly decreased total power (TP), low frequency (LF), and high frequency (HF) compared to the control group. However, there were no significant differences between the mild and severe groups. In the no-improvement group, LF was significantly higher and normalized HF was significantly lower than in the improvement group. According to a multiple logistic regression analysis, age and LF were significantly correlated with improvement. Conclusion: This is the first study to evaluate the significance of HRV in patients with SSNHL, according to prognosis and disease severity. Further studies about the relationship between autonomic nervous system and SSNHL with larger sample size and prospective design are needed.
Zebrafish as a Translational Model: An Experimental Alternative to Study the Mechanisms Involved in Anosmia and Possible Neurodegenerative Aspects of COVID-19?

Visual Abstract The Coronavirus disease-2019 (COVID-19) presents a variability of clinical symptoms, ranging from asymptomatic to severe respiratory and systemic conditions. In a cohort of patients, the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), beyond the classical respiratory manifestations, induces anosmia. Evidence has suggested SARS-CoV-2-induced anosmia can be the result of neurodegeneration of the olfactory pathway. Neurologic symptoms associated with COVID-19 have been reported; however, the precise mechanism and possible long-lasting effects remain poorly investigated. Preclinical models are valuable tools for describing and testing new possible treatments for neurologic disorders. In this way, the zebrafish (Danio rerio) organism model represents an attractive tool in the field of neuroscience, showing economic and logistic advantages besides genetic and physiologic similarities with mammalian, including the brain structure and functions. Besides, its external embryonic development, high availability of eggs, and fast development allows easy genetic manipulation and fast replications. In the present review, we suggest that the zebrafish model can be advantageous to investigate the neurologic features of COVID-19.
Role of the Srs2–Rad51 Interaction Domain in Crossover Control in Saccharomyces cerevisiae

Saccharomyces cerevisiae Srs2, in addition to its well-documented antirecombination activity, has been proposed to play a role in promoting synthesis-dependent strand annealing (SDSA). Here we report the identification and characterization of an SRS2 mutant with a single amino acid substitution (srs2-F891A) that specifically affects the Srs2 pro-SDSA function. This residue is located within the Srs2–Rad51 interaction domain and embedded within a protein sequence resembling a BRC repeat motif. The srs2-F891A mutation leads to a complete loss of interaction with Rad51 as measured through yeast two-hybrid analysis and a partial loss of interaction as determined through protein pull-down assays with purified Srs2, Srs2-F891A, and Rad51 proteins. Even though previous work has shown that internal deletions of the Srs2–Rad51 interaction domain block Srs2 antirecombination activity in vitro, the Srs2-F891A mutant protein, despite its weakened interaction with Rad51, exhibits no measurable defect in antirecombination activity in vitro or in vivo. Surprisingly, srs2-F891A shows a robust shift from noncrossover to crossover repair products in a plasmid-based gap repair assay, but not in an ectopic physical recombination assay. Our findings suggest that the Srs2 C-terminal Rad51 interaction domain is more complex than previously thought, containing multiple interaction sites with unique effects on Srs2 activity.
How Protein Methylation Regulates Steroid Receptor Function

Abstract Steroid receptors (SRs) are members of the nuclear hormonal receptor family, many of which are transcription factors regulated by ligand binding. SRs regulate various human physiological functions essential for maintenance of vital biological pathways, including development, reproduction, and metabolic homeostasis. In addition, aberrant expression of SRs or dysregulation of their signaling has been observed in a wide variety of pathologies. SR activity is tightly and finely controlled by post-translational modifications (PTMs) targeting the receptors and/or their coregulators. Whereas major attention has been focused on phosphorylation, growing evidence shows that methylation is also an important regulator of SRs. Interestingly, the protein methyltransferases depositing methyl marks are involved in many functions, from development to adult life. They have also been associated with pathologies such as inflammation, as well as cardiovascular and neuronal disorders, and cancer. This article provides an overview of SR methylation/demethylation events, along with their functional effects and biological consequences. An in-depth understanding of the landscape of these methylation events could provide new information on SR regulation in physiology, as well as promising perspectives for the development of new therapeutic strategies, illustrated by the specific inhibitors of protein methyltransferases that are currently available.
Off-label tocilizumab and adjuvant iron chelator effectiveness in a group of severe COVID-19 pneumonia patients

Abstract Tocilizumab (TCZ), a monoclonal recombinant antibody against IL-6 receptor, is currently used in managing the cytokine release syndrome (CRS) that occurred in coronavirus disease 2019 (COVID-19) selected cases. The primary objective of our study was to establish the effectiveness of TCZ in patients with severe or critical severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pneumonia. We retrospectively analyzed 25 consecutive patients, admitted in the Academic Emergency Hospital Sibiu, Romania from April 1, 2020 until May 25, 2020, all with confirmed SARS-CoV-2 infection and severe pneumonia. All patients were treated off-label with TCZ, beside their standard care. Adjuvant iron chelator was associated in 11 patients. Six female and 19 male patients admitted in our hospital all with confirmed SARS-CoV-2 infection and severe pneumonia as defined by Chinese Centers for Disease Control and Prevention were enrolled in this study. Seventeen of the 25 enrolled patients (68%) were seriously ill requiring noninvasive ventilation or oxygen mask, and 8 cases (32%) were critically ill requiring invasive mechanical ventilation. All patients received TCZ, and also received hydroxychloroquine, and lopinavir/ritonavir 200/50 mg for 10 days. Adjuvant iron chelator (deferasirox – marketed as Exjade) was associated in 11 patients who had ferritin serum levels above 1000 ng/mL. No side effects were encountered during infusions or after TCZ. We observed a rapid increase in arterial oxygen saturation for 20 of the 25 cases (80%) with a favorable evolution toward healing. Survivors were younger than 60 years old (80%), had less comorbidities (10% no comorbidities, 70% with 1 or 2 comorbidities), lower serum ferritin levels (30% under 1000 ng/mL), and 50% had no serum glucose elevation. Our patients with CRS had no response to corticosteroid therapy. Five out of the 25 patients had an unfavorable evolution to death. The off-label use of TCZ in patients with severe or critically ill form of SARS-CoV-2 infection had good results in our study. Off-label use of TCZ in severe and critical cases of COVID-19 pneumonia is effective in managing the “cytokine storm. ” Better outcomes were noted in younger patients. Associated adjuvant iron chelators may contribute to a good outcome and needs to be confirmed in larger studies.
Model for the Effect of Pressure on Light Scattering from Biological Tissue Containing Glucose

Estimate of glucose level in biological tissue can be obtained by measuring the reduced-scattering coefficient. However, external physical factors like pressure or compression can influence measured values. Using Mie scattering theory and simple fluid mechanical arguments, the paper model the dependency of pressure, glucose concentration and light-wavelength on reduced-scattering coefficient of biological tissue. The authors show that the model is in very good agreement with experimental results
Redox kinetics and oxygen diffusion in a borosilicate melt

On a etabli un modele mathematique pour relier le coefficient, de diffusion de l'oxygene a la cinetique d'oxydoreduction des elements multivalents. Le coefficient de diffusion chimique de l'oxygene obtenu a partir de la cinetique d'oxydoreduction doit etre differencie du coefficient de l'oxygene dans le reseau determine par des methodes de traceurs radioactifs
Interpolation and extrapolation in a 51-dimensional variable space: system-agnostic construction of high-dimensional PES

Machine learning is becoming an increasingly powerful tool for physics research. High-dimensional physics problems are generally modelled by neural networks (NNs). However, NNs require large data and are problem-specific. An alternative approach is probabilistic modelling based on Gaussian processes (GPs), which are system-agnostic and can be fully automated. However, GPs suffer from the numerical complexity and have been limited to low-dimensional physics problems. Here, we illustrate that it is possible to build an accurate GP model of a 51-dimensional physical system based on $5000$ inputs, using the fragmentation of the input space and entropy-based enhancement of the model complexity. We demonstrate the potency of these algorithms by constructing the global potential energy surface (PES) for a molecular system with $19$ atoms. We illustrate that GP models thus constructed have generalization power, allowing us to extrapolate the PES from low energies ($<10,000$ cm$^{-1}$), yielding a PES at high energies ($>20,000$ cm$^{-1}$). This opens the prospect for building machine-learning models that can be used to search for new physics, such as phase transitions, in high-dimensional physics problems with unknown property landscapes by extrapolation.
Evolution of vision and hearing modalities in theropod dinosaurs

Revealing behavioral secrets in extinct species Extinct species had complex behaviors, just like modern species, but fossils generally reveal little of these details. New approaches that allow for the study of structures that relate directly to behavior are greatly improving our understanding of the lifestyles of extinct animals (see the Perspective by Witmer). Hanson et al. looked at three-dimensional scans of archosauromorph inner ears and found clear patterns relating these bones to complex movement, including flight. Choiniere et al. looked at inner ears and scleral eye rings and found a clear emergence of patterns relating to nocturnality in early theropod evolution. Together, these papers reveal behavioral complexity and evolutionary patterns in these groups. Science, this issue p. 601, p. 610; see also p. 575 Low-light vision and increased hearing sensitivity in the nonavialan lineage Alvarezsauroidea suggest nocturnal predation. Owls and nightbirds are nocturnal hunters of active prey that combine visual and hearing adaptations to overcome limits on sensory performance in low light. Such sensory innovations are unknown in nonavialan theropod dinosaurs and are poorly characterized on the line that leads to birds. We investigate morphofunctional proxies of vision and hearing in living and extinct theropods and demonstrate deep evolutionary divergences of sensory modalities. Nocturnal predation evolved early in the nonavialan lineage Alvarezsauroidea, signaled by extreme low-light vision and increases in hearing sensitivity. The Late Cretaceous alvarezsauroid Shuvuuia deserti had even further specialized hearing acuity, rivaling that of today’s barn owl. This combination of sensory adaptations evolved independently in dinosaurs long before the modern bird radiation and provides a notable example of convergence between dinosaurs and mammals.