Movement patterns of temperate wrasses (Labridae) within a small marine protected area

The movement patterns of three commercially important wrasse (Labridae) species inside a small marine protected area (~ 0.15 km²) on the west coast of Norway were analysed over a period of 21 months. The mean distance between capture and recapture locations varied between 10 and 187 m, and was species and season specific. The extent of movement was not related to body size or sex. These results imply that a network of small strategically located marine protected areas can be used as management tools to protect wrasses from size- and sex-selective fishing mortality.     

Population Dynamics of Intermediate-Host Snails in the White Nile River,Sudan: A Year-Round Observational Descriptive Study

We aimed to explore the population dynamics of snail in 3 sites of the White Nile in Sudan. More specifically, we aimed to investigate the annual patterns of snail populations that act as intermediate hosts of schistosomes and monthly snail infection rates and ecological characteristics presumably related to snail populations. We collected snails for 1 year monthly at 3 different shore sites in the vicinity of El Shajara along the White Nile river in Khartoum State, Sudan. In addition, we measured air and water temperatures, water turbidities, vegetation coverages, and water depths and current speeds. Most of the collected snails were Biomphalaria pfeifferi and Bulinus truncatus. The population densities of snails and their infection rates varied across survey sites. The collected snails liberated S. mansoni and S. haematobium cercariae as well as Amphistome and Echinostome cercariae. Infected snails were found during March–June. The ecological characteristics found to be associated with the absence of snails population were: high turbidity, deep water, low vegetation coverage (near absence of vegetation), high water temperature, and high current speed. To our knowledge, this is the first longitudinal study of the snail population and ecological characteristics in the main basin of the White Nile river.     

High Endemicity with Clonorchis sinensis Metacercariae in Fish from Yongjeon-cheon (Stream) in Cheongsong-gun,Gyeongsangbuk-do,Korea

The infection status with Clonorchis sinensis metacercariae (CsMc) was examined in freshwater fishes from Yongjeon-cheon (a branch of Nakdong-gang) located in Cheongsong-gun, Gyeongsangbuk-do, the Republic of Korea (Korea). A total of 750 fishes in 19 species were examined by the artificial digestion method for 2 years (2019 and 2020). CsMc were detected in 378 (51.4%) out of 735 fishes in 14 species (73.7%), and the infection intensity was 666 per fish infected. In 2019, CsMc were found in 172 (68.0%) out of 253 fishes in 10 species, and the infection intensity was 565 per fish infected. In 2020, CsMc were detected in 206 (62.2%) out of 331 fishes in 10 species, and the infection intensity was 751 per fish infected. The other zoonotic trematode, ie. Metagonimus spp., Centrocestus armatus, Echinostoma spp. and Clinostomum complanatum, metacercariae were also detected in fishes from the survey streams, but their endemicities were relatively low. Conclusively, it was first confirmed that CsMc are highly endemic in fishes from Yongjeon-cheon in Cheongsong-gun, Gyeongsangbuk-do, Korea.     

Ethanol inhibits Kv7.2/7.3 channel open probability by reducing the PI(4,5)P2 sensitivity of Kv7.2 subunit

Ethanol often causes critical health problems by altering the neuro-nal activities of the central and peripheral nerve systems. One of the cellular targets of ethanol is the plasma membrane proteins including ion channels and receptors. Recently, we reported that ethanol elevates membrane excitability in sympathetic neurons by inhibiting Kv7.2/7.3 channels in a cell type-specific manner. Even though our studies revealed that the inhibitory effects of ethanol on the Kv7.2/7.3 channel was diminished by the increase of plasma membrane phosphatidylinositol 4,5-bisphosphate (PI (4,5)P₂), the molecular mechanism of ethanol on Kv7.2/7.3 channel inhibition remains unclear. By investigating the kinetics of Kv7.2/7.3 current in high K⁺ solution, we found that ethanol inhibited Kv7.2/7.3 channels through a mechanism distinct from that of tetraethylammonium (TEA) which enters into the pore and blocks the gate of the channels. Using a non-stationary noise analysis (NSNA), we demonstrated that the inhibitory effect of ethanol is the result of reduction of open probability (P_O) of the Kv7.2/7.3 channel, but not of a single channel current (i) or channel number (N). Finally, ethanol selectively facilitated the kinetics of Kv7.2 current suppression by voltage-sensing phosphatase (VSP)-induced PI(4,5)P₂ depletion, while it slowed down Kv7.2 current recovery from the VSP-induced inhibition. Together our results suggest that ethanol regulates neuronal activity through the reduction of open probability and PI(4,5)P₂ sensitivity of Kv7.2/7.3 channels.     

A novel role of Hippo-Yap/TAZ signaling pathway in lymphatic vascular development

The lymphatic vasculature plays important role in regulating fluid homeostasis, intestinal lipid absorption, and immune surveillance in humans. Malfunction of lymphatic vasculature leads to several human diseases. Understanding the fundamental mechanism in lymphatic vascular development not only expand our knowledge, but also provide a new therapeutic insight. Recently, Hippo-YAP/TAZ signaling pathway, a key mechanism of organ size and tissue homeostasis, has emerged as a critical player that regulate lymphatic specification, sprouting, and maturation. In this review, we discuss the mechanistic regulation and pathophysiological significant of Hippo pathway in lymphatic vascular development.     

Suppression of DRR1 results in the accumulation of insoluble ubiquitinated proteins,which impairs drought stress tolerance

Drought stress has detrimental effects on plants. Although the abscisic acid (ABA)‐mediated drought response is well established, defensive mechanisms to cope with dehydration‐induced proteotoxicity have been rarely studied. DRR1 was identified as an Arabidopsis drought‐induced gene encoding an ER‐localized RING‐type E3 Ub ligase. Suppression of DRR1 markedly reduced tolerance to drought and proteotoxic stress without altering ABA‐mediated germination and stomatal movement. Proteotoxicity‐ and dehydration‐induced insoluble ubiquitinated protein accumulation was more obvious in DRR1 loss‐of‐function plants than in wild‐type plants. These results suggest that DRR1 is involved in an ABA‐independent drought stress response possibly through the mitigation of dehydration‐induced proteotoxic stress.     

Efficacy of RyR2 inhibitor EL20 in induced pluripotent stem cell-derived cardiomyocytes from a patient with catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac arrhythmia syndrome that often leads to sudden cardiac death. The most common form of CPVT is caused by autosomal-dominant variants in the cardiac ryanodine receptor type-2 (RYR2) gene. Mutations in RYR2 promote calcium (Ca²⁺) leak from the sarcoplasmic reticulum (SR), triggering lethal arrhythmias. Recently, it was demonstrated that tetracaine derivative EL20 specifically inhibits mutant RyR2, normalizes Ca²⁺ handling and suppresses arrhythmias in a CPVT mouse model. The objective of this study was to determine whether EL20 normalizes SR Ca²⁺ handling and arrhythmic events in induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from a CPVT patient. Blood samples from a child carrying RyR2 variant RyR2 variant Arg-176-Glu (R176Q) and a mutation-negative relative were reprogrammed into iPSCs using a Sendai virus system. iPSC-CMs were derived using the Stemdiff^TM kit. Confocal Ca²⁺ imaging was used to quantify RyR2 activity in the absence and presence of EL20. iPSC-CMs harbouring the R176Q variant demonstrated spontaneous SR Ca²⁺ release events, whereas administration of EL20 diminished these abnormal events at low nanomolar concentrations (IC₅₀ = 82 nM). Importantly, treatment with EL20 did not have any adverse effects on systolic Ca²⁺ handling in control iPSC-CMs. Our results show for the first time that tetracaine derivative EL20 normalized SR Ca²⁺ handling and suppresses arrhythmogenic activity in iPSC-CMs derived from a CPVT patient. Hence, this study confirms that this RyR2-inhibitor represents a promising therapeutic candidate for treatment of CPVT.     

Effect of mesenchymal stromal cells encapsulated within polyethylene glycol-collagen hydrogels formed in situ on alkali-burned corneas in an ex vivo organ culture model

Background aimsCorneal inflammation after alkali burns often results in vision loss due to corneal opacification and neovascularization. Mesenchymal stem cells (MSCs) and their secreted factors (secretome) have been studied for their anti-inflammatory and anti-angiogenic properties with encouraging results. However, topical instillation of MSCs or their secretome is often accompanied by issues related to delivery or rapid washout. Polyethylene glycol (PEG) and collagen are well-known biomaterials used extensively in scaffolds for tissue engineering. To effectively suppress alkaline burn-induced corneal injury, the authors proposed encapsulating MSCs within collagen gels cross-linked with multi-functional PEG-succinimidyl esters as a means to deliver the secretome of immobilized MSCs.MethodsHuman MSCs were added to a neutralized collagen solution and mixed with a solution of four-arm PEG-N-hydroxysuccinimide. An ex vivo organ culture was conducted using rabbit corneas injured by alkali burn. MSCs were encapsulated within PEG-collagen hydrogels and injected onto the wounded cornea immediately following alkali burn and washing. Photographs of the ocular surface were taken over a period of 7 days after the alkali burn and processed for immunohistochemical evaluation. Samples were split into three groups: injury without treatment, MSCs alone, and MSCs encapsulated within PEG-collagen hydrogels.ResultsAll corneas in ex vivo organ culture lost their transparency immediately after alkali burn, and only the groups treated with MSCs and MSCs encapsulated within PEG-collagen hydrogels recovered some transparency after 7 days. Immunohistochemical analysis revealed increased expression of vimentin in the anterior corneal stroma of the group without treatment indicative of fibrotic healing, whereas less stromal vimentin was detected in the group containing MSCs encapsulated within the PEG-collagen hydrogels.ConclusionsPEG-collagen hydrogels enable the encapsulation of viable MSCs capable of releasing secreted factors onto the ocular surface. Encapsulating MSCs within PEG-collagen hydrogels may be a promising method for delivering their therapeutic benefits in cases of ocular inflammatory diseases, such as alkali burn injuries.     

Relationship of the lung microbiome with PD-L1 expression and immunotherapy response in lung cancer

IL-35 subunit EBI3 is up-regulated in pulmonary fibrosis tissues. In this study, we investigated the pathological role of EBI3 in pulmonary fibrosis and dissected the underlying molecular mechanism. Bleomycin-induced pulmonary fibrosis mouse model was established, and samples were performed gene expression analyses through RNAseq, qRT-PCR and Western blot. Wild type and EBI3 knockout mice were exposed to bleomycin to investigate the pathological role of IL-35, via lung function and gene expression analyses. Primary lung epithelial cells were used to dissect the regulatory mechanism of EBI3 on STAT1/STAT4 and STAT3. IL-35 was elevated in both human and mouse with pulmonary fibrosis. EBI3 knockdown aggravated the symptoms of pulmonary fibrosis in mice. EBI3 deficiency enhanced the expressions of fibrotic and extracellular matrix-associated genes. Mechanistically, IL-35 activated STAT1 and STAT4, which in turn suppressed DNA enrichment of STAT3 and inhibited the fibrosis process. IL-35 might be one of the potential therapeutic targets for bleomycin-induced pulmonary fibrosis.