SARS-CoV-2 wastewater-based epidemiology in an enclosed compound: A 2.5-year survey to identify factors contributing to local community dissemination.

Long-term (>2.5 years) surveillance of SARS-CoV-2 RNA concentrations in wastewater was conducted within an enclosed university compound. This study aims to demonstrate how coupling wastewater-based epidemiology (WBE) with meta-data can identify which factors contribute toward the dissemination of SARS-CoV-2 within a local community.

Sparking a Movement, Not a Moment: Framework and Outcomes From a Pediatrics Department-Wide Coalition to Advance Anti-Racism.

Objective: The Stanford Pediatrics Advancing Anti-Racism Coalition (SPAARC) was created to promote a culture of anti-racism through immediate action, development of nimble systems, and longitudinal commitment toward equity. Evaluate gaps in the Stanford Department of Pediatrics (DoP) efforts to advance anti-racism and form a coalition of faculty, staff, and trainees to prioritize, design, and implement targeted activities with immediate and long-term measurable outcomes.

Methods: A needs assessment was conducted across all DoP members in July to August 2020 to identify gaps in anti-racism efforts.

General and Specific Aversive Modulation of Active Avoidance Require Central Amygdala.

Three studies provide evidence that the central nucleus of the amygdala, a structure with a well-established role in conditioned freezing, is also required for conditioned facilitation of instrumental avoidance in rats. First, the immediate early gene c-Fos was measured following the presentation of a previously shock-paired tone in subjects trained either on an unsignaled avoidance task or not (in addition to tone only presentations in naïve controls). Significantly elevated expression of c-Fos was found in both the avoidance trained and Pavlovian trained conditions relative to naïve controls (but with no difference between the two trained conditions).

The promise of the BRAIN initiative: NIH strategies for understanding neural circuit function.

New neurotechnologies fueled by the BRAIN Initiative now allow investigators to map, monitor and modulate complex neural circuits, enabling the pursuit of research questions previously considered unapproachable. Yet it is the convergence of molecular neuroscience with the new systems neuroscience that promises the greatest future advances. This is particularly true for our understanding of nervous system disorders, some of which have known molecular drivers or pathology but result in unknown perturbations in circuit function.

Increasing Health Care Workers' Proficiency With Using Professional Medical Interpretation: A Workshop.

Introduction: Families with limited English proficiency are at risk for poor outcomes and medical errors due to barriers in communication. The use of professional medical interpretation has been linked to improved access to care, improved patient satisfaction, and better outcomes. However, medical interpretation remains underutilized, and the literature lacks guidelines for training health care workers in its use.

Progression of proliferative glomerulonephritis with monoclonal IgG deposits in pediatric patients.

Background: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a glomerular disease defined by non-organized glomerular deposits of heavy and light chain-restricted immunoglobulin and is rarely reported in children.

Methods: We characterized a series of nine pediatric patients from two academic centers with biopsy-proven PGNMID and additionally describe two patients with monotypic IgG in the setting of IgM deposition.

Results: Each patient presented with hematuria and/or proteinuria; however, only five had elevated serum creatinine.

The State of the NIH BRAIN Initiative.

The BRAIN Initiative arose from a grand challenge to "accelerate the development and application of new technologies that will enable researchers to produce dynamic pictures of the brain that show how individual brain cells and complex neural circuits interact at the speed of thought." The BRAIN Initiative is a public-private effort focused on the development and use of powerful tools for acquiring fundamental insights about how information processing occurs in the central nervous system (CNS). As the Initiative enters its fifth year, NIH has supported >500 principal investigators, who have answered the Initiative's challenge via hundreds of publications describing novel tools, methods, and discoveries that address the Initiative's seven scientific priorities.

Motoneuronal TASK channels contribute to immobilizing effects of inhalational general anesthetics.

General anesthetics cause sedation, hypnosis, and immobilization via CNS mechanisms that remain incompletely understood; contributions of particular anesthetic targets in specific neural pathways remain largely unexplored. Among potential molecular targets for mediating anesthetic actions, members of the TASK subgroup [TASK-1 (K2P3.1) and TASK-3 (K2P9.

TASK channel deletion in mice causes primary hyperaldosteronism.

When inappropriate for salt status, the mineralocorticoid aldosterone induces cardiac and renal injury. Autonomous overproduction of aldosterone from the adrenal zona glomerulosa (ZG) is also the most frequent cause of secondary hypertension. Yet, the etiology of nontumorigenic primary hyperaldosteronism caused by bilateral idiopathic hyperaldosteronism remains unknown.

TASK channels determine pH sensitivity in select respiratory neurons but do not contribute to central respiratory chemosensitivity.

Central respiratory chemoreception is the mechanism by which the CNS maintains physiologically appropriate pH and PCO2 via control of breathing. A prominent hypothesis holds that neural substrates for this process are distributed widely in the respiratory network, especially because many neurons that make up this network are chemosensitive in vitro. We and others have proposed that TASK channels (TASK-1, K(2P)3.

Inhibition of a background potassium channel by Gq protein alpha-subunits.

Two-pore-domain K(+) channels provide neuronal background currents that establish resting membrane potential and input resistance; their modulation provides a prevalent mechanism for regulating cellular excitability. The so-called TASK channel subunits (TASK-1 and TASK-3) are widely expressed, and they are robustly inhibited by receptors that signal through Galphaq family proteins. Here, we manipulated G protein expression and membrane phosphatidylinositol 4,5-bisphosphate (PIP(2)) levels in intact and cell-free systems to provide electrophysiological and biochemical evidence that inhibition of TASK channels by Galphaq-linked receptors proceeds unabated in the absence of phospholipase C (PLC) activity, and instead involves association of activated Galphaq subunits with the channels.

HCN subunit-specific and cAMP-modulated effects of anesthetics on neuronal pacemaker currents.

General anesthetics have been a mainstay of surgical practice for more than 150 years, but the mechanisms by which they mediate their important clinical actions remain unclear. Ion channels represent important anesthetic targets, and, although GABA(A) receptors have emerged as major contributors to sedative, immobilizing, and hypnotic effects of intravenous anesthetics, a role for those receptors is less certain in the case of inhalational anesthetics. The neuronal hyperpolarization-activated pacemaker current (Ih) is essential for oscillatory and integrative properties in numerous cell types.

Motoneurons express heteromeric TWIK-related acid-sensitive K+ (TASK) channels containing TASK-1 (KCNK3) and TASK-3 (KCNK9) subunits.

Background potassium currents carried by the KCNK family of two-pore-domain K+ channels are important determinants of resting membrane potential and cellular excitability. TWIK-related acid-sensitive K+ 1 (TASK-1, KCNK3) and TASK-3 (KCNK9) are pH-sensitive subunits of the KCNK family that are closely related and coexpressed in many brain regions. There is accumulating evidence that these two subunits can form heterodimeric channels, but this evidence remains controversial.

Tyrosinase expression during neuroblast divisions affects later pathfinding by retinal ganglion cells.

Occulocutaneous albinism is caused by mutations in the gene encoding the enzyme tyrosinase. Individuals with this disorder are predisposed to visual system deficits. We determined the critical period during development when tyrosinase expression is essential for the appropriate pathfinding of ganglion cell axons from the retina to the dorsal lateral geniculate nucleus.

Functional expression of TASK-1/TASK-3 heteromers in cerebellar granule cells.

TASK-1 and TASK-3 are functional members of the tandem-pore K+ (K2P) channel family, and mRNAs for both channels are expressed together in many brain regions. Although TASK-1 and TASK-3 subunits are able to form heteromers when their complementary RNAs are injected into oocytes, whether functional heteromers are present in the native tissue is not known. Using cultured cerebellar granule (CG) neurones that express mRNAs of both TASK-1 and TASK-3, we studied the presence of heteromers by comparing the sensitivities of cloned and native K+ channels to extracellular pH (pHo) and ruthenium red.

Molecular mechanisms mediating inhibition of G protein-coupled inwardly-rectifying K+ channels.

Neuronal G protein-coupled inwardly-rectifying potassium channels (GIRKs, Kir3.x) can be activated or inhibited by distinct classes of receptors (Galphai/o and Galphaq/11-coupled, respectively), providing dynamic regulation of neuronal excitability. In this mini-review, we highlight findings from our laboratory in which we used a mammalian heterologous expression system to address mechanisms of GIRK channel regulation by Galpha and Gbetagamma subunits.

Two-pore-Domain (KCNK) potassium channels: dynamic roles in neuronal function.

Leak K+ currents contribute to the resting membrane potential and are important for modulation of neuronal excitability. Within the past few years, an entire family of genes has been described whose members form leak K+ channels, insofar as they generate potassium-selective currents with little voltage- and time-dependence. They are often referred to as "two-pore-domain" channels because of their predicted topology, which includes two pore-forming regions in each subunit.

Modulation of TASK-1 (Kcnk3) and TASK-3 (Kcnk9) potassium channels: volatile anesthetics and neurotransmitters share a molecular site of action.

TASK-1 and TASK-3, members of the two-pore-domain channel family, are widely expressed leak potassium channels responsible for maintenance of cell membrane potential and input resistance. They are sites of action for a variety of modulatory agents, including volatile anesthetics and neurotransmitters/hormones, the latter acting via mechanisms that have remained elusive. To clarify these mechanisms, we generated mutant channels and found that alterations disrupting anesthetic (halothane) activation of these channels also disrupted transmitter (thyrotropin-releasing hormone, TRH) inhibition and did so to a similar degree.

Serotonergic raphe neurons express TASK channel transcripts and a TASK-like pH- and halothane-sensitive K+ conductance.

The recently described two-pore-domain K+ channels, TASK-1 and TASK-3, generate currents with a unique set of properties; specifically, the channels produce instantaneous open-rectifier (i.e., "leak") K+ currents that are modulated by extracellular pH and by clinically useful anesthetics.

TASK-1 is a highly modulated pH-sensitive 'leak' K(+) channel expressed in brainstem respiratory neurons.

Central respiratory chemoreceptors adjust respiratory drive in a homeostatic response to alterations in brain pH and/or P(CO(2)). Multiple brainstem sites are proposed as neural substrates for central chemoreception, but molecular substrates that underlie chemosensitivity in respiratory neurons have not been identified. In rat brainstem neurons expressing transcripts for TASK-1, a two-pore domain K(+) channel, we characterized K(+) currents with kinetic and voltage-dependent properties identical to cloned rat TASK-1 currents.