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Even in the genomics era, the phylogeny of Neotropical small felids comprised in the genus Leopardus remains contentious. We used whole-genome resequencing data to construct a time-calibrated consensus phylogeny of this group, quantify phylogenomic discordance, test for interspecies introgression, and assess patterns of genetic diversity and demographic history. We infer that the Leopardus radiation started in the Early Pliocene as an initial speciation burst, followed by another in its subgenus Oncifelis during the Early Pleistocene. Our findings challenge the long-held notion that ocelot (Leopardus pardalis) and margay (L. wiedii) are sister species and instead indicate that margay is most closely related to the enigmatic Andean cat (L. jacobita), whose whole-genome data are reported here for the first time. In addition, we found that the newly sampled Andean tiger cat (L. tigrinus pardinoides) population from Colombia associates closely with Central American tiger cats (L. tigrinus oncilla). Genealogical discordance was largely attributable to incomplete lineage sorting, yet was augmented by strong gene flow between ocelot and the ancestral branch of Oncifelis, as well as between Geoffroy's cat (L. geoffroyi) and southern tiger cat (L. guttulus). Contrasting demographic trajectories have led to disparate levels of current genomic diversity, with a nearly tenfold difference in heterozygosity between Andean cat and ocelot, spanning the entire range of variability found in extant felids. Our analyses improved our understanding of the speciation history and diversity patterns in this felid radiation, and highlight the benefits to phylogenomic inference of embracing the many heterogeneous signals scattered across the genome., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

The New World Vultures (Cathartidae) include seven species of obligate scavengers that, despite their ecological relevance, present critical information gaps around their evolutionary history and conservation. Insights into their phylogenetic relationships in recent years has enabled the addressing of such information gaps through approaches based on phylogeny. We reconstructed the ancestral area in America of the current species using two regionalization schemes and methods: Biogeography with Bayesian Evolutionary Analysis (BioGeoBears) and Bayesian Binary Model-Monte Carlo Markov Chains (BBM-MCMC). Then, we identified the priority species and areas for conservation by means of the Evolutionary Distinctiveness index (ED), as a proxy of the uniqueness of species according to phylogeny, and the Global Endangerment index (GE), mapping phylogenetic diversity. We found that the ancestral area of New World Vultures in America corresponds to South America, with dispersal processes that led to a recolonization of North America by Coragyps atratus, Gymnogyps californianus and Cathartes aura. We identified the Black Vulture, G. californianus and Vultur gryphus as priority species based on ED and "Evolutionary Distinct Globally Endangered" (EDGE) indexes, and the lowlands of Amazon River basin and the Orinoco basin and some tributaries areas of the Guiana Shield were identified as the priority areas when mapping the phylogenetic diversity. This study highlights the importance of filling knowledge gaps of species of conservation concern through the integration of evolutionary and ecological information and tools and, thus, developing adequate strategies to enhance the preservation of these species in the face of the current loss of biodiversity.

Background: Spinocerebellar ataxia type 10 is a neurodegenerative disorder caused by the expansion of an ATTCT pentanucleotide repeat. Its clinical features include ataxia and, in some cases, epileptic seizures. There is, however, a dearth of information about its cognitive deficits and the neural bases underpinning them., Objectives: The objectives of this study were to characterize the performance of spinocerebellar ataxia type 10 patients in 2 cognitive domains typically affected in spinocerebellar ataxias, memory and executive function, and to correlate the identified cognitive impairments with ataxia severity and cerebral/cerebellar cortical thickness, as quantified by MRI., Methods: Memory and executive function tests were administered to 17 genetically confirmed Mexican spinocerebellar ataxia type 10 patients, and their results were compared with 17 healthy matched volunteers. MRI was performed in 16 patients., Results: Patients showed deficits in visual and visuospatial short-term memory, reduced storage capacity for verbal memory, and impaired monitoring, planning, and cognitive flexibility, which were ataxia independent. Patients with seizures (n = 9) and without seizures (n = 8) did not differ significantly in cognitive performance. There were significant correlations between short-term visuospatial memory impairment and posterior cerebellar lobe cortical thickness (bilateral lobule VI, IX, and right X). Cognitive flexibility deficiencies correlated with cerebral cortical thickness in the left middle frontal, cingulate, opercular, and temporal gyri. Cerebellar cortical thickness in several bilateral regions was correlated with motor impairment., Conclusions: Patients with spinocerebellar ataxia type 10 show significant memory and executive dysfunction that can be correlated with deterioration in the posterior lobe of the cerebellum and prefrontal, cingulate, and middle temporal cortices. © 2021 International Parkinson and Movement Disorder Society., (© 2021 International Parkinson and Movement Disorder Society.)

Background: With treatment for breast cancer, women treated may present significant sensory abnormalities in the upper extremity. However, there are no conclusive studies that have evaluated pressure pain thresholds (PPT) in the shoulder of postoperated women for breast cancer. The aim of this study was to compare PPT in the shoulder, stress, anxiety, depression symptoms, and quality of sleep among postoperated women for breast cancer (PO group) and asymptomatic women of shoulder pain (control group)., Methods: 40 women participated ( n = 20, PO group, age: average ± standard deviation, 49.2 ± 8.3 years; body mass index (BMI): 27.5 ± 3.0 kg/cm 2 ; surgery time: 22.2 ± 34.4 months; n = 20, control group, 46.9 ± 8.1 years; BMI: 26.8 ± 3.5 kg/cm 2 ). The PPT was evaluated with a digital algometer at 32 points in the shoulder region and one control point in the tibialis anterior. Stress, anxiety, and depression were evaluated with the Depression, Anxiety and Stress Scale 21 (DASS-21) and the quality of sleep by the Pittsburgh Sleep Quality Index., Results: Significant differences were observed over 1.5 kgf/cm 2 in 33 points evaluated ( p < 0.01) with a small to high effect size (Cliff's delta range = 0.16; 0.92) and higher levels of anxiety and stress in the PO group (anxiety: median [first; third quartile], 5[3; 12.5]; stress: 9.7 ± 4.7 (7.8; 11.8)) in comparison with the control group (anxiety: 2.5[1; 4.8]; stress: 6.7 ± 3.31 (5.2; 8.3), ( p < 0.05)). No significant differences were found between the groups in depression and sleep quality ( p > 0.05)., Conclusion: Postoperated women for breast cancer present hyperalgesia in the shoulder anterior and posterior region, low PPT in the tibialis anterior, and higher levels of stress and anxiety compared to the control group., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Ivana Leao Ribeiro et al.)

Objective: Dysfunction in emotional processes is a hypothesized contributor to functional neurological disorders (FNDs), yet few studies have evoked real-time emotion during multimethod assessment incorporating subjective, behavioral, and psychophysiological indicators. This approach may reveal clinical and neurobiological vulnerability to FND and clarify how dysfunctional emotional processes serve as perpetuating factors., Methods: Eleven participants with video-EEG-confirmed diagnoses of psychogenic nonepileptic seizures (PNES) were compared with 49 seizure-free trauma control subjects (TCs) with or without clinically elevated posttraumatic stress symptoms (25 clinically elevated [TC-clin], 24 not clinically elevated [TC-nonclin]). Participants recalled and described memories evoking anger, shame, happiness, and neutral feelings., Results: Even though PNES patients and TCs reported similar amounts of emotional experience, PNES patients reported more difficulty reliving emotions and were less likely to complete the relived shame task. During and after reliving happiness, PNES and TC-clin groups showed respiratory sinus arrhythmia (RSA) decreases, indicating parasympathetic withdrawal, whereas the TC-nonclin group showed RSA increases., Conclusions: Findings from this pilot study are consistent with previous research and clinical observations that emotional engagement may be more effortful for PNES patients. Patterns of RSA change, which may also point to greater effortful engagement, were similar in PNES and TC-clin groups, suggesting that traumatic stress reactions may play a part. At the same time, experience of greater difficulty or avoidance may be even greater among PNES patients. Especially when regulatory resources are already limited, accumulated effort, coupled with self-threatening contexts such as shame, may be particularly problematic for those with PNES and perhaps other FNDs.

Introduction: Spinocerebellar ataxia type 10 (SCA10) is a hereditary neurodegenerative disorder caused by repeat expansions in the ATXN10 gene. Patients present with cerebellar ataxia frequently accompanied by seizures. Even though loss of cerebellar Purkinje neurons has been described, its brain degeneration pattern is unknown. Our aim was to characterize the gray and white matter degeneration patterns in SCA10 patients and the association with clinical features., Methods: We enrolled 18 patients with molecular diagnosis of SCA10 and 18 healthy individuals matched for age and sex. All participants underwent brain MRI including high-resolution anatomical and diffusion images. Whole-brain Tract-Based Spatial Statistics (TBSS) and Voxel-Based Morphometry (VBM) were performed to identify white and grey matter degeneration respectively. A second analysis in the cerebellum identified the unbiased pattern of degeneration. Motor impairment was assessed using the SARA Scale., Results: TBSS analysis in the patient group revealed white matter atrophy exclusively in the cerebellum. VBM analysis showed extensive grey matter degeneration in the cerebellum, brainstem, thalamus, and putamen. Significant associations between cerebellar degeneration and SARA scores were found. Additionally, degeneration in thalamic GM and WM in the cerebellar lobule VI were significantly associated with the presence of seizures., Conclusion: The results show that besides cerebellum and brainstem, brain degeneration in SCA10 includes predominantly the putamen and thalamus; involvement of the latter is strongly associated with seizures. Analysis of the unbiased degeneration pattern in the cerebellum suggests lobules VIIIb, IX, and X as the primary cerebellar targets of the disease, which expands to the anterior lobe in later stages., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Anti-tumor efficacy of T cells engineered to express chimeric antigen receptors (CARs) is dependent on their specificity, survival, and in vivo expansion following adoptive transfer. Toll-like receptor (TLR) and CD40 signaling in T cells can improve persistence and drive proliferation of antigen-specific CD4 + and CD8 + T cells following pathogen challenge or in graft-versus-host disease (GvHD) settings, suggesting that these costimulatory pathways may be co-opted to improve CAR-T cell persistence and function. Here, we present a novel strategy to activate TLR and CD40 signaling in human T cells using inducible MyD88/CD40 (iMC), which can be triggered in vivo via the synthetic dimerizing ligand, rimiducid, to provide potent costimulation to CAR-modified T cells. Importantly, the concurrent activation of iMC (with rimiducid) and CAR (by antigen recognition) is required for interleukin (IL)-2 production and robust CAR-T cell expansion and may provide a user-controlled mechanism to amplify CAR-T cell levels in vivo and augment anti-tumor efficacy., (Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)