Assessing One Health capacities for transboundary zoonotic diseases at the Libya-Tunisia border.

Background: The dynamic nature of zoonotic emergence, spillover and spread necessitates multisectoral coordination beyond national borders to encompass cross-boundary and regional cooperation. Designated points of entry (POEs), specifically ground crossings, serve as critical locales for establishing and maintaining robust prevention, detection, notification, coordination, and response mechanisms to transboundary emerging and re-emerging disease threats. In order to better assess One Health capacities for transboundary zoonotic diseases (TZD) prevention, detection and response we adapted an existing tool, One Health Systems Assessment for Priority Zoonoses (OHSAPZ), for a cross-border, POE setting in North Africa.

Single-Cell Analysis of Rohon-Beard Neurons Implicates Fgf Signaling in Axon Maintenance and Cell Survival.

Peripheral sensory neurons are a critical part of the nervous system that transmit a multitude of sensory stimuli to the central nervous system. During larval and juvenile stages in zebrafish, this function is mediated by Rohon-Beard somatosensory neurons (RBs). RBs are optically accessible and amenable to experimental manipulation, making them a powerful system for mechanistic investigation of sensory neurons.

One Health Systems Assessments for Sustainable Capacity Strengthening to Control Priority Zoonotic Diseases Within and Between Countries.

One Health is increasingly recognized as an important approach for health systems, particularly with respect to strengthening prevention, detection and response to zoonotic and other emerging disease threats. While many global health security frameworks reference the importance of One Health, there are fewer existing methodologies, tools, and resources for supporting countries and other regional or sub-national authorities in systematically assessing their One Health capabilities. We describe here two methodologies, One Health Systems Assessment for Priority Zoonoses (OHSAPZ) and One Health Transboundary Assessment for Priority Zoonoses (OHTAPZ), which have been developed to assist with creating consensus lists of priority zoonotic diseases for cross-sectoral consideration; identification of current strengths and gaps in One Health communication and coordination between sectors (and, in the case of OHTAPZ, between countries); and the development and dissemination of prioritized recommendations for future capacity strengthening.

Single-cell analysis of Rohon-Beard neurons implicates Fgf signaling in axon maintenance and cell survival.

Peripheral sensory neurons are a critical part of the nervous system that transmit a multitude of sensory stimuli to the central nervous system. During larval and juvenile stages in zebrafish, this function is mediated by Rohon-Beard somatosensory neurons (RBs). RBs are optically accessible and amenable to experimental manipulation, making them a powerful system for mechanistic investigation of sensory neurons.

Using One Health assessments to leverage endemic disease frameworks for emerging zoonotic disease threats in Libya.

Continued emergence, re-emergence and spread of zoonotic diseases demonstrates the imperative need for multisectoral communication and joint coordination of disease detection and response. While there are existing international frameworks underpinning One Health capacity building for pandemic prevention and response, often guidance does not account for challenges faced by countries undergoing long-term conflict and sociopolitical instability. The purpose of this research was to identify Libya's laboratory and surveillance networks and routes of inter- and multisectoral communication and coordination for priority zoonotic diseases.

Combined Kelch-like 3 and Cullin 3 Degradation is a Central Mechanism in Familial Hyperkalemic Hypertension in Mice.

Background: Mutations in the ubiquitin ligase scaffold protein Cullin 3 () gene cause the disease familial hyperkalemic hypertension (FHHt). In the kidney, mutant () increases abundance of With-No-Lysine (K) Kinase 4 (WNK4), inappropriately activating sterile 20/SPS-1-related proline/alanine-rich kinase (SPAK), which then phosphorylates and hyperactivates the NaCl cotransporter (NCC). The precise mechanism by which causes FHHt is unclear.

Identification and characterization of diverse OTU deubiquitinases in bacteria.

Manipulation of host ubiquitin signaling is becoming an increasingly apparent evolutionary strategy among bacterial and viral pathogens. By removing host ubiquitin signals, for example, invading pathogens can inactivate immune response pathways and evade detection. The ovarian tumor (OTU) family of deubiquitinases regulates diverse ubiquitin signals in humans.

WNK bodies cluster WNK4 and SPAK/OSR1 to promote NCC activation in hypokalemia.

K deficiency stimulates renal salt reuptake via the Na-Cl cotransporter (NCC) of the distal convoluted tubule (DCT), thereby reducing K losses in downstream nephron segments while increasing NaCl retention and blood pressure. NCC activation is mediated by a kinase cascade involving with no lysine (WNK) kinases upstream of Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress-responsive kinase-1 (OSR1). In K deficiency, WNKs and SPAK/OSR1 concentrate in spherical cytoplasmic domains in the DCT termed "WNK bodies," the significance of which is undetermined.

Mg restriction downregulates NCC through NEDD4-2 and prevents its activation by hypokalemia.

Hypomagnesemia is associated with reduced kidney function and life-threatening complications and sustains hypokalemia. The distal convoluted tubule (DCT) determines final urinary Mg excretion and, via activity of the Na-Cl cotransporter (NCC), also plays a key role in K homeostasis by metering Na delivery to distal segments. Little is known about the mechanisms by which plasma Mg concentration regulates NCC activity and how low-plasma Mg concentration and K concentration interact to modulate NCC activity.

With no lysine kinase 4 modulates sodium potassium 2 chloride cotransporter activity in vivo.

With no lysine kinase 4 (WNK4) is essential to activate the thiazide-sensitive NaCl cotransporter (NCC) along the distal convoluted tubule, an effect central to the phenotype of familial hyperkalemic hypertension. Although effects on potassium and sodium channels along the connecting and collecting tubules have also been documented, WNK4 is typically believed to have little role in modulating sodium chloride reabsorption along the thick ascending limb of the loop of Henle. Yet wnk4 mice (knockout mice lacking WNK4) do not demonstrate the hypocalciuria typical of pure distal convoluted tubule dysfunction.

Mutant Cullin 3 causes familial hyperkalemic hypertension via dominant effects.

Mutations in the ubiquitin ligase scaffold protein Cullin 3 (CUL3) cause the disease familial hyperkalemic hypertension (FHHt). In the kidney, mutant CUL3 (CUL3-Δ9) increases abundance of With-No-Lysine [K] Kinase 4 (WNK4), with excessive activation of the downstream Sterile 20 (STE20)/SPS-1-related proline/alanine-rich kinase (SPAK) increasing phosphorylation of the Na+-Cl- cotransporter (NCC). CUL3-Δ9 promotes its own degradation via autoubiquitination, leading to the hypothesis that Cul3 haploinsufficiency causes FHHt.