Endocytosis of Wnt ligands from surrounding epithelial cells positions microtubule nucleation sites at dendrite branch points.

Microtubule nucleation is important for microtubule organization in dendrites and for neuronal injury responses. The core nucleation protein, γTubulin (γTub), is localized to dendrite branch points in Drosophila sensory neurons by Wnt receptors and scaffolding proteins on endosomes. However, whether Wnt ligands are important is unknown.

DSS1 restrains BRCA2's engagement with dsDNA for homologous recombination, replication fork protection, and R-loop homeostasis.

DSS1, essential for BRCA2-RAD51 dependent homologous recombination (HR), associates with the helical domain (HD) and OB fold 1 (OB1) of the BRCA2 DSS1/DNA-binding domain (DBD) which is frequently targeted by cancer-associated pathogenic variants. Herein, we reveal robust ss/dsDNA binding abilities in HD-OB1 subdomains and find that DSS1 shuts down HD-OB1's DNA binding to enable ssDNA targeting of the BRCA2-RAD51 complex. We show that C-terminal helix mutations of DSS1, including the cancer-associated R57Q mutation, disrupt this DSS1 regulation and permit dsDNA binding of HD-OB1/BRCA2-DBD.

Short report: Integrated evaluations for autism spectrum disorder in pediatric primary care clinics.

Primary care providers often screen for autism during well child visits in the first few years of life and refer children for diagnostic evaluations when needed. However, most children do not receive a diagnosis until years later which delays access to services. Racism, socioeconomic status, and other systemic inequalities that limit access to health care further delay diagnostic evaluations.

Linking Primary Care to Community-Based Mental Health Resources via Family Navigation and Phone-Based Care Coordination.

Family navigation (FN) and phone-based care coordination may improve linkages from primary care to community-based mental health referrals, but research on their differential impact is limited. This mixed-methods study compared FN and phone-based care coordination in connecting families to mental health services from primary care. Families of children (56.

A Multisystem Approach to Improving Autism Care.

Children with autism face significant barriers to accessing evaluations and intervention services often because of confusing referral processes, lack of centralized coordination across organizations serving children with autism, insurance coverage gaps, multiyear waitlists for diagnostic services, and limited provider knowledge about autism. Racism and systemic inequities exist and persist in autism care across the United States. This article reviews targeted initiatives implemented by a multidisciplinary team to advocate for, and address barriers faced, by autistic children and their families in Washington, DC.

Isradipine therapy in Cacna1dIle772Met/+ mice ameliorates primary aldosteronism and neurologic abnormalities.

Somatic gain-of-function mutations in the L-type calcium channel CaV1.3 (CACNA1D gene) cause adrenal aldosterone-producing adenomas and micronodules. De novo germline mutations are found in a syndrome of primary aldosteronism, seizures, and neurologic abnormalities (PASNA) as well as in autism spectrum disorder.

DC Mental Health Access in Pediatrics: Evaluating a Child Psychiatry Access Program in Washington, DC.

Introduction: Child psychiatry access programs (CPAPs) provide primary care providers (PCPs) with assistance in mental health diagnosis, management, and resource navigation.

Method: Data collected from DC Mental Health Access in Pediatrics (MAP) included PCPs and patient demographics, clinical encounter information, and provider satisfaction.

Results: DC MAP consult volume increased 349.

Mental Health Screening in Pediatric Primary Care: Factors Associated With Screening Completion and Elevated Scores.

This study aimed to examine predictors of complete and elevated youth mental health screens. Parents of 4- to 11-year-old children completed the Strengths and Difficulties Questionnaire (SDQ) during a routine, universal mental health screening initiative in primary care. Bivariate logistic regressions were run to examine associations between independent (visit age, sex, race/ethnicity, language, insurance, and guardian) and dependent variables (screening completion and elevated SDQ score).

Factors Associated With Psychiatric Readmission of Youths in a Racially Diverse and Urban Hospital Setting.

Objective: This study examined predictors of readmission to a psychiatric inpatient unit of an urban children's hospital within 1 year of discharge among a racially diverse sample of youths.

Methods: The authors retrospectively analyzed 2 years of electronic health record data of inpatient psychiatric unit admissions (N=1,604). Multivariate logistic regression and random-effects multinomial logistic regression were used for analyses.

A CRISPR-Cas9-engineered mouse model for GPI-anchor deficiency mirrors human phenotypes and exhibits hippocampal synaptic dysfunctions.

Pathogenic germline mutations in lead to glycosylphosphatidylinositol biosynthesis deficiency (GPIBD). Individuals with pathogenic biallelic mutations in genes of the glycosylphosphatidylinositol (GPI)-anchor pathway exhibit cognitive impairments, motor delay, and often epilepsy. Thus far, the pathophysiology underlying the disease remains unclear, and suitable rodent models that mirror all symptoms observed in human patients have not been available.

Abnormal brain structure and behavior in MyD88-deficient mice.

While the original protein Toll in Drosophila melanogaster regulates both host defense and morphogenesis, the role of its ortholog Toll-like receptors (TLRs), the interleukin 1 receptor (IL-1R) family, and the associated signaling pathways in mammalian brain development and structure is poorly understood. Because the adaptor protein myeloid differentiation primary response protein 88 (MyD88) is essential for downstream signaling of most TLRs and IL-1R, we systematically investigated the effect of MyD88 deficiency on murine brain structure during development and on behavior. In neonatal Myd88 mice, neocortical thickness was reduced, while density of cortical neurons was increased.

Pediatric Provider Experiences with Implementation of Routine Mental Health Screening.

Objective: Despite the utility of universal screening, most pediatric providers rarely use mental health (MH) screening tools. As such, provider descriptions of their experiences with universal screening are limited. The goal of this study was to describe barriers to, and facilitators of, universal MH screening implementation, the perceived impact of such screening, impressions of a screening-focused quality improvement (QI) Learning Collaborative, and lessons learned.

Human gestational N-methyl-d-aspartate receptor autoantibodies impair neonatal murine brain function.

Objective: Maternal autoantibodies are a risk factor for impaired brain development in offspring. Antibodies (ABs) against the NR1 (GluN1) subunit of the N-methyl-d-aspartate receptor (NMDAR) are among the most frequently diagnosed anti-neuronal surface ABs, yet little is known about effects on fetal development during pregnancy.

Methods: We established a murine model of in utero exposure to human recombinant NR1 and isotype-matched nonreactive control ABs.

Increasing Mental Health Engagement From Primary Care: The Potential Role of Family Navigation.

Early engagement in mental health intervention is critical, yet the vast majority of children who are experiencing mental health concerns are not receiving needed services. Pediatric primary care clinics have been recognized as an ideal setting in which to identify and address mental health problems early, although engagement in mental health services within primary care and in community-based settings remains low. Navigators, or individuals with experience in navigating the mental health system, have been highlighted as promising partners in efforts to improve engagement in mental health services.

Mesenchymal stem cell‑derived extracellular vesicles promote the in vitro proliferation and migration of breast cancer cells through the activation of the ERK pathway.

Mesenchymal stem cells (MSCs) have been demonstrated to be involved in tumor progression and the modulation of the tumor microenvironment, partly through their secretome. Extracellular vesicles (EVs) are membranous nanovesicles secreted by multiple types of cells and have been demonstrated to mediate intercellular communication in both physiological and pathological conditions. However, numerous questions still remain regarding the underlying mechanisms and functional consequences of these interactions.

Nesfatin-1 Injected Intracerebroventricularly Increases Anxiety, Depression-Like Behavior, and Anhedonia in Normal Weight Rats.

Nesfatin-1 is a well-established anorexigenic peptide. Recent studies indicated an association between nesfatin-1 and anxiety/depression-like behavior. However, it is unclear whether this effect is retained in obesity.

Electronic and Steric Tuning of Catalytic H Evolution by Cobalt Complexes with Pentadentate Polypyridyl-Amine Ligands.

Structural modifications of molecular cobalt catalysts have provided important insights into the structure-function relationship for the hydrogen evolution reaction. We have shown that replacement of equatorial pyridines with more basic and conjugate isoquinoline groups of a pentadentate ligand results in lower overpotential and higher catalytic activity for electro- and photolytic H production in aqueous solutions. To fully understand the electronic and steric effects of the axial group that lies trans to the proposed cobalt hydride intermediate, isoquinoline groups were introduced in two new pentadentate ligands, N, N-bis(2-pyridinylmethyl)[3-(2-pyridinyl)isoquinoline)]-1-methanamine (DPA-1-MPI) and N, N-bis(2-pyridinylmethyl)[1-(2-pyridinyl)-isoquinoline)]-3-methanamine (DPA-3-MPI).

Mental Health Screening Quality Improvement Learning Collaborative in Pediatric Primary Care.

Background: In the United States, up to 20% of children experience a mental health (MH) disorder in a given year, many of whom remain untreated. Routine screening during annual well visits is 1 strategy providers can use to identify concerns early and facilitate appropriate intervention. However, many barriers exist to the effective implementation of such screening.

Behavioral Health Integration in Health Care Settings: Lessons Learned from a Pediatric Hospital Primary Care System.

Behavioral health integration within primary care has been evolving, but literature traditionally focuses on smaller scale efforts. We detail how behavioral health has been integrated across a large, urban pediatric hospital system's six primary care clinics (serving over 35,000 children annually and insured predominately through Medicaid) and discuss strategies for success in sustaining and expanding efforts to achieve effective integration of behavioral health into primary care. In a time span of 3 years, the clinics have implemented routine, universal behavioral health screening at well child visits, participated in a 15-month behavioral health screening quality improvement learning collaborative, and integrated the work of psychologists and psychiatrists.