Rab7a is an enhancer of TPC2 activity regulating melanoma progression through modulation of the GSK3β/β-Catenin/MITF-axis.

Melanoma arising from pigment-producing melanocytes is the deadliest form of skin cancer. Extensive ultraviolet light exposure is a major cause of melanoma and individuals with low levels of melanin are at particular risk. Humans carrying gain-of-function polymorphisms in the melanosomal/endolysosomal two-pore cation channel TPC2 present with hypopigmentation, blond hair, and albinism.

Metrological realization of the radon activity concentration in air.

In the framework of the EMPIR research project Metrology for Radon, a facility was devised that provides stable and traceable atmospheres for the realization of radon activity concentration at a high metrological level. The facility is used to calibrate and test devices for measuring radon in the air. It enables precise long-term exposures in the range between 100 Bq/m and 1000 Bq/m.

Widening Our Lane: How Child and Adolescent Psychiatrists Can Embrace the Full Spectrum of Mental Health.

The majority of a psychiatrist's training and clinical attention is devoted to mental illness rather than mental health. This article suggests a broader understanding and application of mental well-being that can benefit both those already struggling with mental health challenges and those trying to stay well. Recommendations for being a well-being-oriented psychiatrist include increasing one's knowledge about well-being and health promotion and adjusting one's practice to incorporate these principles.

Pacemaker Channels and the Chronotropic Response in Health and Disease.

Loss or dysregulation of the normally precise control of heart rate via the autonomic nervous system plays a critical role during the development and progression of cardiovascular disease-including ischemic heart disease, heart failure, and arrhythmias. While the clinical significance of regulating changes in heart rate, known as the chronotropic effect, is undeniable, the mechanisms controlling these changes remain not fully understood. Heart rate acceleration and deceleration are mediated by increasing or decreasing the spontaneous firing rate of pacemaker cells in the sinoatrial node.

OCaR1 endows exocytic vesicles with autoregulatory competence by preventing uncontrolled Ca2+ release, exocytosis, and pancreatic tissue damage.

Regulated exocytosis is initiated by increased Ca2+ concentrations in close spatial proximity to secretory granules, which is effectively prevented when the cell is at rest. Here we showed that exocytosis of zymogen granules in acinar cells was driven by Ca2+ directly released from acidic Ca2+ stores including secretory granules through NAADP-activated two-pore channels (TPCs). We identified OCaR1 (encoded by Tmem63a) as an organellar Ca2+ regulator protein integral to the membrane of secretory granules that controlled Ca2+ release via inhibition of TPC1 and TPC2 currents.

Sustainable Soil Additives for Water and Micronutrient Supply: Swelling and Chelating Properties of Polyaspartic Acid Hydrogels Utilizing Newly Developed Crosslinkers.

Drought and water shortage are serious problems in many arid and semi-arid regions. This problem is getting worse and even continues in temperate climatic regions due to climate change. To address this problem, the use of biodegradable hydrogels is increasingly important for the application as water-retaining additives in soil.

Missing Heritability in Albinism: Deep Characterization of a Hungarian Albinism Cohort Raises the Possibility of the Digenic Genetic Background of the Disease.

Albinism is characterized by a variable degree of hypopigmentation affecting the skin and the hair, and causing ophthalmologic abnormalities. Its oculocutaneous, ocular and syndromic forms follow an autosomal or X-linked recessive mode of inheritance, and 22 disease-causing genes are implicated in their development. Our aim was to clarify the genetic background of a Hungarian albinism cohort.

Reaching "The Other Half": Teacher Referral Increases Inclusivity in Intervention Research for Neurodivergent School-Age Children.

Objective: Researchers employed two recruitment strategies in a school-based comparative effectiveness trial for students with a diagnosis of attention-deficit/hyperactivity disorder (ADHD) or autism. This study assessed the: 1) effectiveness of school-based referrals for identifying students meeting diagnostic criteria and 2) impact of eliminating requirements for existing diagnoses on recruitment, sample characteristics, and intervention response.

Method: Autistic students and students with ADHD in schools serving underresourced communities were recruited for an executive functioning (EF) intervention trial over 2 years.

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.

The Concise Guide to PHARMACOLOGY 2023/24: Ion channels.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.

A Conjoined Rectilinear Collision Cell and Pulsed Extraction Ion Trap with Auxiliary DC Electrodes.

Ion traps are routinely directly coupled to mass analyzers, where they serve to suitably cool and shape an ion population prior to pulsed extraction into the analyzer proper. Such devices benefit from high duty cycle and transmission but suffer slow ion processing times caused by a compromise in the buffer gas pressure range that suitably dampens the ion kinetic energy without causing excessive scatter during extraction or within the analyzer. A rectilinear RF quadrupole ion trap has been characterized, conjoining a pressurized collision region with a pumped extraction region, and an unbroken RF interface for seamless ion transfer between them.

Editorial: Cash Transfers to Families Living in Poverty: Can Benefits for Children Extend to the Next Generation?

Childhood poverty is the most widespread and important modifiable risk factor for the development of a range of health outcomes, including childhood-onset mental health problems. In the United States, 30 million children are growing up impoverished, which ranks among the highest per capita rates of child poverty among high-income countries. As a nation, the United States does less to support its poor children and their families than any other wealthy country, despite scientific evidence that growing up in poverty significantly increases lifetime risk of physical and mental health problems, reduces likelihood of academic and vocational success, and leads to poorer social outcomes for children.

mRNA trans-splicing dual AAV vectors for (epi)genome editing and gene therapy.

Large genes including several CRISPR-Cas modules like gene activators (CRISPRa) require dual adeno-associated viral (AAV) vectors for an efficient in vivo delivery and expression. Current dual AAV vector approaches have important limitations, e.g.

Parallelized Acquisition of Orbitrap and Astral Analyzers Enables High-Throughput Quantitative Analysis.

The growing trend toward high-throughput proteomics demands rapid liquid chromatography-mass spectrometry (LC-MS) cycles that limit the available time to gather the large numbers of MS/MS fragmentation spectra required for identification. Orbitrap analyzers scale performance with acquisition time and necessarily sacrifice sensitivity and resolving power to deliver higher acquisition rates. We developed a new mass spectrometer that combines a mass-resolving quadrupole, the Orbitrap, and the novel Asymmetric Track Lossless (Astral) analyzer.

Hyperpolarization-activated cyclic nucleotide-gated cation channel 3 promotes HCC development in a female-biased manner.

Sex differences in hepatocellular carcinoma (HCC) development are regulated by sex and non-sex chromosomes, sex hormones, and environmental factors. We previously reported that Ncoa5 mice develop HCC in a male-biased manner. Here we show that NCOA5 expression is reduced in male patient HCCs while the expression of an NCOA5-interacting tumor suppressor, TIP30, is lower in female HCCs.

Bighorn sheep associations: understanding tradeoffs of sociality and implications for disease transmission.

Sociality directly influences mating success, survival rates, and disease, but ultimately likely evolved for its fitness benefits in a challenging environment. The tradeoffs between the costs and benefits of sociality can operate at multiple scales, resulting in different interpretations of animal behavior. We investigated the influence of intrinsic (, relatedness, age) and extrinsic factors (, land cover type, season) on direct contact (simultaneous GPS locations ≤ 25 m) rates of bighorn sheep () at multiple scales near the Waterton-Glacier International Peace Park.

The Effects of Social Determinants of Health on Child and Family Mental Health: Implications of the COVID-19 Pandemic and Beyond.

Purpose Of Review: This review aims to expand understanding of the effect of SDOH on youth and family mental health outcomes. The review highlights significant findings from recent literature across SDOH categories (Economic Stability, Education Access/Quality, Health Care Access/Quality, Neighborhood/Built Environment, and Social/Community Context). This review also aims to demonstrate how the COVID-19 pandemic influences these effects.

"It was Just Good to Have an Outlet for Other Parents to Talk to": Feasibility and Acceptability of Integrating Mental Health and Wellness Services into Predominantly Black Early Childhood Education Centers During the COVID-19 Pandemic.

Racial disparities in mental health care access and quality are associated with higher levels of unmet need for Black parents and families, a population disproportionately affected by the COVID-19 pandemic. Integrating services within early childhood education centers may increase mental health care access for Black families with young children. The current study examined the feasibility, acceptability, and perceived impact of an integrated program offering mental health care for parents, children, and dyads during the pandemic.

Leveraging the Expertise of the Community: A Case for Expansion of a Peer Workforce in Child, Adolescent, and Family Mental Health.

The rise in child and adolescent mental health concerns has led to the need for an expanded workforce to meet the needs of our nation's families. Peer paraprofessionals (PPs) have proven to be impactful in the areas of adult mental health (MH) and substance use disorders, and for persons with chronic medical conditions. PPs can contribute to addressing child, adolescent, and family MH needs by being deployed in community settings and providing both emotional and tangible support to families and children.

Human variation impacting restricts Typhi replication by magnesium deprivation.

Human genetic diversity can reveal critical factors in host-pathogen interactions. This is especially useful for human-restricted pathogens like serovar Typhi ( Typhi), the cause of typhoid fever. One key defense during bacterial infection is nutritional immunity: host cells attempt to restrict bacterial replication by denying bacteria access to key nutrients or supplying toxic metabolites.

Considerations in implementation of social risk factor screening and referral in maternal and infant care in Washington, DC: A qualitative study.

Background: The District of Columbia (DC) has striking disparities in maternal and infant outcomes comparing Black to White women and babies. Social determinants of health (SDoH) are widely recognized as a significant contributor to these disparities in health outcomes. Screening for social risk factors and referral for appropriate services is a critical step in addressing social needs and reducing outcome disparities.

Motivation in Aphasia Treatment: Self-Determination Theory Applied to the FOURC Model.

Purpose: Although the importance of motivation to successful rehabilitation is frequently acknowledged in the aphasia literature, little evidence-based guidance has been provided on how to support it. The purpose of this tutorial is to introduce a well-validated theory of motivation, self-determination theory (SDT); explain its role as the foundation for the FOURC model of collaborative goal setting and treatment planning; and explain how it may be applied during rehabilitation to support the motivation of people with aphasia.

Method: We provide an overview of SDT, explore the link between motivation and psychological wellness, and discuss how psychological needs are addressed in SDT and the FOURC model.

Biology, Pathobiology and Gene Therapy of CNG Channel-Related Retinopathies.

The visual process begins with the absorption of photons by photopigments of cone and rod photoreceptors in the retina. In this process, the signal is first amplified by a cyclic guanosine monophosphate (cGMP)-based signaling cascade and then converted into an electrical signal by cyclic nucleotide-gated (CNG) channels. CNG channels are purely ligand-gated channels whose activity can be controlled by cGMP, which induces a depolarizing Na/Ca current upon binding to the channel.