HGA and human babesiosis ZINB models indicated similar associations with forest cover, forest land cover change, and winter minimum temperature; and differing associations with elevation, urban land cover change, and winter precipitation. These results indicate that tick-borne disease ecology varies between pathogens spread by I. scapularis.To determine the functional organization of premotor areas in the cat pericruciate cortex we applied intracortical microstimulation (ICMS) within multiple cytoarchitectonically identified subregions of areas 4 and 6 in the awake cat, both at rest and during treadmill walking. ICMS in most premotor areas evoked clear twitch responses in the limbs and/or head at rest. During locomotion, these same areas produced phase-dependent modifications of muscle activity. ICMS in the primary motor cortex (area 4γ) produced large phase-dependent responses, mostly restricted to the contralateral forelimb or hindlimb. Stimulation in premotor areas also produced phase-dependent responses that, in some cases, were as large as those evoked from area 4γ. selleck products However, responses from premotor areas had more widespread effects on multiple limbs, including the ipsilateral limbs, than did stimulation in 4γ. During locomotion, responses in both forelimb and hindlimb muscles were evoked from cytoarchitectonic areas 4γ, 4δ, 6aα, and 6aγ. However, the prevalence of effects in a given limb varied from one area to another. The results suggest that premotor areas may contribute to the production, modification, and coordination of activity in the limbs during locomotion and may be particularly pertinent during modifications of gait.We explored minimal residual disease (MRD) in relapsed/refractory multiple myeloma (RRMM) and transplant-ineligible newly diagnosed multiple myeloma (TIE NDMM) using data from four phase 3 studies (POLLUX, CASTOR, ALCYONE, and MAIA). Each study previously demonstrated that daratumumab-based therapies improved MRD-negativity rates and reduced the risk of disease progression or death by approximately half versus standards of care. We conducted a large-scale pooled analysis for associations between patients achieving complete response (CR) or better with MRD-negative status, and progression-free survival (PFS). MRD was assessed via next-generation sequencing (10‒5 threshold). Patient-level data were pooled from all four studies, and for patients with TIE NDMM plus patients with RRMM who received ≤2 prior lines of therapy (≤2PL). PFS was evaluated by response and MRD status. Median follow-up (months) was POLLUX, 54.8; CASTOR, 50.2; ALCYONE, 40.1; and MAIA, 36.4. Patients who achieved ≥CR and MRD negativity had improved PFS versus those who failed to reach CR or were MRD positive (TIE NDMM and RRMM hazard ratio [HR] 0.20, P less then .0001; TIE NDMM and RRMM ≤2PL HR 0.20, P less then .0001). This benefit occurred irrespective of therapy or disease setting. A time-varying Cox proportional hazard model confirmed that ≥CR with MRD negativity was associated with improved PFS. Daratumumab-based treatment was associated with more patients reaching ≥CR and MRD negativity. These findings represent the first large-scale analysis with robust methodology to support ≥CR with MRD negativity as a prognostic factor for PFS in RRMM and TIE NDMM. These trials were registered at http://www.ClinicalTrials.gov NCT02076009/NCT02136134/NCT02195479/NCT02252172.The prevailing coronavirus disease (COVID-19) caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has presented some neurological manifestations including hyposmia, hypogeusia, headache, stroke, encephalitis, Guillain‒Barre syndrome, and some neuropsychiatric disorders. Although several cell types in the brain express angiotensin converting enzyme-2 (ACE2), the main SARS-CoV-2 receptor, and other related proteins, it remains unclear whether the observed neurological manifestations are attributed to virus invasion into the brain or just comorbidities caused by dysregulation of systemic factors. Here, we briefly review the neurological manifestations of SARS-CoV-2, summarize recent evidence for the potential neurotropism of SARS-CoV-2, and discuss the potential mechanisms of COVID-19-associated neurological diseases.Tests based on the dN/dS statistic are used to identify positive selection of nonsynonymous polymorphisms. Using these tests on alignments of all orthologs from related species can provide insights into which gene categories have been most frequently positively selected. However, longer alignments have more power to detect positive selection, creating a detection bias that could create misleading results from functional enrichment tests. Most studies of positive selection in plant pathogens focus on genes with specific virulence functions, with little emphasis on broader molecular processes. Furthermore, no studies in plant pathogens have accounted for detection bias due to alignment length when performing functional enrichment tests. To address these research gaps, we analyze 12 genomes of the phytopathogenic fungal genus Botrytis, including two sequenced in this study. To establish a temporal context, we estimated fossil-calibrated divergence times for the genus. We find that Botrytis likely originated 16-18 Ma in the Miocene and underwent continuous radiation ending in the Pliocene. An untargeted scan of Botrytis single-copy orthologs for positive selection with three different statistical tests uncovered evidence for positive selection among proteases, signaling proteins, CAZymes, and secreted proteins. There was also a strong overrepresentation of transcription factors among positively selected genes. This overrepresentation was still apparent after two complementary controls for detection bias due to sequence length. Positively selected sites were depleted within DNA-binding domains, suggesting changes in transcriptional responses to internal and external cues or protein-protein interactions have undergone positive selection more frequently than changes in promoter fidelity.Progranulin (PGRN) is a multifunctional growth factor expressed in central nervous system. Although PGRN expression is regulated by various stressors, its precise role(s) and regulatory mechanism(s) remain elusive. In this study, we used HT22 cells to investigate the physiological implications of oxidative stress-induced PGRN expression and the regulation of PGRN expression by oxidative stress. We observed that p38 MAP kinase was activated upon the addition of H2O2, and a selective p38 MAP kinase inhibitor, attenuated PGRN induction by H2O2. To explore the physiological role(s) of the PGRN induction, we first confirmed H2O2-dependent responses of HT22 cells and found that the length and number of neurites were increased by H2O2. Pgrn knockdown experiments suggested these changes were mediated by H2O2-induced PGRN expression, at least in part. Overall, the results suggested that an increase in oxidative stress in HT22 cells induced PGRN expression via p38 MAP kinase pathway, thereby controlling neurite outgrowth.