We also found interesting differences; for example, latencies of initial saccades to moving Gaussian blob targets were significantly faster compared to saccades to moving objects in video scenes, whereas pursuit accuracy was significantly higher in video scenes. These findings suggest a lower processing demand for simple target conditions during saccade preparation and an advantage for tracking behavior in natural scenes due to higher predictability provided by the context information.

Physicians have an increased rate of depression and suicide compared with nonphysician peers. State medical licensure questions about mental health deter physicians from seeking mental health care. Several previous studies have examined state medical licensing board compliance with the Americans with Disabilities Act (ADA) of 1990, but none have included osteopathic licensing boards.

To evaluate compliance of state osteopathic medical licensing boards with ADA requirements regarding mental health.

State medical licensing applications for 51 states, including the District of Columbia (DC), and 16 states with osteopathic licensing entities were reviewed for ADA compliance in questions about mental health. In states where both osteopathic and allopathic applications were available, questions and compliance were compared.

Fourteen of 51 states (including DC) were grossly out of compliance with ADA statutes. In states where osteopathic and allopathic licensing were both available, 7 of 16 asked different mental health questions of osteopathic physicians than their allopathic physician counterparts. Of those 7 states, 6 of the osteopathic boards were out of compliance with ADA, while their allopathic counterparts were either compliant or intermediately compliant.

To improve physician wellbeing, corrective action must be taken to create ADA-compliant language in medical licensing so physicians can seek treatment for mental health conditions without discrimination by licensing boards. Osteopathic physicians should be aware that there is a discrepancy in state licensure compliance compared with allopathic requirements in some states.

To improve physician wellbeing, corrective action must be taken to create ADA-compliant language in medical licensing so physicians can seek treatment for mental health conditions without discrimination by licensing boards. Osteopathic physicians should be aware that there is a discrepancy in state licensure compliance compared with allopathic requirements in some states.Failure of neural tube closure during embryonic development can result in anencephaly, one of the most common birth defects in humans. A family with recurrent anencephalic fetuses was investigated to understand its etiology and pathogenesis. Exome sequencing revealed a recessive germline 21-bp in-frame deletion in NUAK2 segregating with the disease. In vitro kinase assays demonstrated that the 7-amino acid truncation in NUAK2, a serine/threonine kinase, completely abrogated its catalytic activity. Patient-derived disease models including neural progenitor cells and cerebral organoids showed that loss of NUAK2 activity led to decreased Hippo signaling via cytoplasmic YAP retention. In neural tube-like structures, endogenous NUAK2 colocalized apically with the actomyosin network, which was disrupted in patient cells, causing impaired nucleokinesis and apical constriction. Our results establish NUAK2 as an indispensable kinase for brain development in humans and suggest that a NUAK2-Hippo signaling axis regulates cytoskeletal processes that govern cell shape during neural tube closure.IKAROS is a transcription factor forming homo- and heterodimers and regulating lymphocyte development and function. Germline mutations affecting the IKAROS N-terminal DNA binding domain, acting in a haploinsufficient or dominant-negative manner, cause immunodeficiency. learn more Herein, we describe 4 germline heterozygous IKAROS variants affecting its C-terminal dimerization domain, via haploinsufficiency, in 4 unrelated families. Index patients presented with hematologic disease consisting of cytopenias (thrombocytopenia, anemia, neutropenia)/Evans syndrome and malignancies (T-cell acute lymphoblastic leukemia, Burkitt lymphoma). These dimerization defective mutants disrupt homo- and heterodimerization in a complete or partial manner, but they do not affect the wild-type allele function. Moreover, they alter key mechanisms of IKAROS gene regulation, including sumoylation, protein stability, and the recruitment of the nucleosome remodeling and deacetylase complex; none affected in N-terminal DNA binding defects. These C-terminal dimerization mutations are largely associated with hematologic disorders, display dimerization haploinsufficiency and incomplete clinical penetrance, and differ from previously reported allelic variants in their mechanism of action. Dimerization mutants contribute to the growing spectrum of IKAROS-associated diseases displaying a genotype-phenotype correlation.

Proper balance between cell proliferation and differentiation is essential for corneal epithelial (CE) stratification and homeostasis. Although bone morphogenetic protein-6 (BMP6) is known to be expressed in the CE for over 25 years, its function in this tissue remains unknown. Here, we test the hypothesis that BMP6 promotes CE cell stratification and homeostasis by regulating their proliferation and differentiation.

We employed postnatal day-12 (PN-12), PN-14, PN-20, and PN-90 mouse eyes; human corneal limbal epithelial (HCLE) cells; and ocular surface fibrovascular disease pterygium tissues to evaluate the role of BMP6 in CE proliferation, differentiation, and pathology by RT-qPCR, immunoblots, and/or immunofluorescent staining. Cell proliferation was quantified by immunostaining for Ki67.

Coincident with the mouse CE stratification between PN-12 and PN-20, BMP6 was significantly upregulated and the BMP6 antagonist Noggin downregulated. Mature CE retained high BMP6 and low Noggin expression at PN-90. BMP6 and its receptors BMPR1A and BMPR2 were upregulated during in vitro stratification of HCLE cells. Consistent with its anti-proliferative role, exogenous BMP6 suppressed HCLE cell proliferation, downregulated cyclin-D1 and cyclin-D2, and upregulated cell-cycle inhibitors Krüppel-like factor 4 (KLF4) and p21. BMP6 also upregulated the desmosomal cadherins desmoplakin and desmoglein in HCLE cells, consistent with its pro-differentiation role. Human pterygium displayed significant upregulation of BMP6 coupled with downregulation of Noggin and cell-cycle suppressors KLF4 and p21.

BMP6 coordinates CE stratification and homeostasis by regulating their proliferation and differentiation. BMP6 is significantly upregulated in human pterygium concurrent with downregulation of Noggin, KLF4, and p21.

BMP6 coordinates CE stratification and homeostasis by regulating their proliferation and differentiation. BMP6 is significantly upregulated in human pterygium concurrent with downregulation of Noggin, KLF4, and p21.