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Among the pH regulatory genes upregulated by Mgrn1 knockdown, we identified those encoding several subunits of the vacuolar adenosine triphosphatase V-ATPase (mostly Atp6v0d2) and a calcium channel of the transient receptor potential channel family, Mucolipin 3 (Mcoln3). Manipulation of expression of the Mcoln3 gene showed that overexpression of Mcoln3 played a significant role in neutralization of the pH of acidic organelles and activation of tyrosinase in MGRN1-depleted cells. Therefore, lack of MGRN1 led to cell-autonomous stimulation of pigment production in melanocytes mostly by increasing tyrosinase specific activity through neutralization of the melanosomal pH in a MCOLN3-dependent manner.The initial identification of long non-coding RNA myocardial infarction associated transcript (MIAT) as a genetic risk factor of myocardial infarction has made this lncRNA (designated as lncR-MIAT here) a focus of intensive studies worldwide. Emerging evidence supports that lncR-MIAT is susceptible in its expression to multiple deleterious factors like angiotensin II, isoproterenol, hypoxia, and infection and is anomaly overexpressed in serum, plasma, blood cells and myocardial tissues under a variety of cardiovascular conditions including myocardial infarction, cardiac hypertrophy, diabetic cardiomyopathy, dilated cardiomyopathy, sepsis cardiomyopathy, atrial fibrillation and microvascular dysfunction. Experimental results consistently demonstrated that upregulation of lncR-MIAT plays active roles in the pathological processes of the cardiovascular system and knockdown of this lncRNA effectively ameliorates the adverse conditions. The available data revealed that lncR-MIAT acts through multiple mechanisms such as competitive endogenous RNA, natural antisense RNA and RNA/protein interactions. Moreover, the functional domains of lncR-MIAT accounting for certain specific cellular functions of the full-length transcript have been identified and characterized. These insights will not only tremendously advance our understanding of lncRNA biology and pathophysiology, but also offer good opportunities for more innovative and precise design of agents that have the potential to be developed into new drugs for better therapy of cardiovascular diseases (CVDs) in the future. Herein, we provide an overview of lncR-MIAT, focusing on its roles in cardiovascular diseases, underline the unique cellular/molecular mechanisms for its actions, and speculate the perspectives about the translational studies on the potential diagnostic and therapeutic applications of lncR-MIAT.

The 2019 ESC-guidelines on chronic coronary syndromes (ESC-CCS) recommend computed tomographic coronary angiography (CTCA) or non-invasive functional imaging instead of exercise ECG as initial test to diagnose obstructive coronary artery disease. Since impact and challenges of these guidelines are unknown, we studied the current utilisation of CTCA-services, status of CTCA-protocols and modeled the expected impact of these guidelines in the Netherlands.

A survey on current practice and CTCA utilisation was disseminated to every Dutch hospital organisation providing outpatient cardiology care and modeled the required CTCA capacity for implementation of the ESC guideline, based on these national figures and expert consensus. Survey response rate was 100% (68/68 hospital organisations). In 2019, 63 hospital organisations provided CTCA-services (93%), CTCA was performed on 99 CTCA-capable CT-scanners, and 37,283 CTCA-examinations were performed. Between the hospital organisations, we found substantial variatition and reporting of CTCA, as well as to establish interdisciplinary collaboration and organisational alignment.The quality of spring water and its suitability for human consumption is determined by examining its physicochemical and microbiological characteristics. Preliminary investigations were conducted to determine the potability of seven traditionally used springs in the highly populated hill town of Bhaderwah in Union Territory of Jammu and Kashmir, India. The water analysis was performed for various physico-chemical and microbial parameters during April 2019-March 2020. Water temperature, TDS, EC, pH, DO, free CO2, total alkalinity, total hardness, Ca2+, Mg2+, Na+, K+, CO32-, HCOֿ3, Cl‾, NOֿ3, PO43-, SO42-, total coliforms, and thermotolerant coliforms were all measured. Eleven physical and chemical characteristics were used to generate the Water Quality Index. The Piper diagram demonstrated the predominance of Ca2+-HCOֿ3 water types, whereas the Schoeller diagram indicated that all springs had a similar lithological origin. The chemical composition of springs tested met the required criteria for drinking water quality. The microbiological indicators, on the other hand, did not satisfy the criteria except for Eidgah spring, which lacked thermotolerant coliforms. Our results on spring water potability indicate that the town's most dependable springs are susceptible to anthropogenic contamination and therefore need treatment prior to use. Apart from frequent monitoring, the responsible municipal corporation is expected to develop comprehensive plans to rehabilitate and revitalise these vulnerable drinking water sources.

Obesity-associated difficult asthma continues to be a substantial problem and, despite a move to address treatable traits affecting asthma morbidity and mortality, it remains poorly understood with limited phenotype-specific treatments. The complex association between asthma, obesity, and inflammation is highlighted and recent advances in treatment options explored.

Obesity negatively impacts asthma outcomes and has a causal link in the pathogenesis of adult-onset asthma. KRpep-2d cell line Imbalance in the adipose organ found in obesityfavours a pro-inflammatory state both systemically and in airways. Obesity may impact currently available asthma biomarkers, and obesity-associated asthma specific biomarkers are needed. Whilst surgical weight loss interventions are associated with improvements in asthma control and quality of life, evidence for pragmatic conservative options are sparse. Innovative approaches tackling obesity-mediated airway inflammation may provide novel therapies. The immunopathological mechanisms underlyic options for this disease. However, weight loss appears to be effective in improving asthma in this cohort and focus is also needed on non-surgical treatments applicable in the real-world setting.

Excision of the posterior cruciate ligament (PCL) is recommended when implanting a medial pivot (MP) total knee arthroplasty (TKA) to reduce the risk of limiting flexion by over-tensioning the flexion space. The present study determined whether PCL retention (1) limits internal tibial rotation and (2) causes anterior lift-off of the insert in 90° flexion after implantation of an MP design with unrestricted caliper verified kinematic alignment (KA).

Four surgeons implanted an MP TKA design with medial ball-in-socket and lateral flat tibial insert in ten fresh-frozen cadaveric knees. Before and after PCL excision, trial inserts with medial goniometric markings measured the angular I-E tibial orientation relative to the trial femoral component's medial condyle in extension and at 90° flexion, and the surgeon recorded the occurrence of anterior lift-off of the insert at 90° flexion.

PCL retention resulted in greater internal tibial rotation than PCL excision, with mean values of 15° vs 7° degrees from maximum extension to 90° flexion, respectively (p < 0.0007). At 90° flexion, no TKAs with PCL retention and one TKA with PCL excision had anterior lift-off of the insert (N.S.).

This preliminary study of ten cadaveric knees showed that PCL retention restored more passive internal tibial rotation than PCL excision with a negligible risk of anterior lift-off. However,in vivoanalysis from multiple authors with a larger sample size is required to recommend PCL retention with an MP TKA design implanted with unrestricted caliper verified KA.

This preliminary study of ten cadaveric knees showed that PCL retention restored more passive internal tibial rotation than PCL excision with a negligible risk of anterior lift-off. However, in vivo analysis from multiple authors with a larger sample size is required to recommend PCL retention with an MP TKA design implanted with unrestricted caliper verified KA.Staphylococcus aureus possesses an extraordinary ability to deal with a wide range of osmotic pressure. This study performed transcriptomic and metabolomic analyses on the potential mechanism of gradient salinity stress adaptation in S. aureus ZS01. The results revealed that CPS biosynthetic protein genes were candidate target genes for directly regulating the phenotypic changes of biofilm. Inositol phosphate metabolism was downregulated to reduce the conversion of functional molecules. The gluconeogenesis pathway and histidine synthesis were downregulated to reduce the production of endogenous glucose. The pyruvate metabolism pathway was upregulated to promote the accumulation of succinate. TCA cycle metabolism pathway was downregulated to reduce unnecessary energy loss. L-Proline was accumulated to regulate osmotic pressure. Therefore, these self-protection mechanisms can protect cells from hypertonic environments and help them focus on survival. In addition, we identified ten hub genes. The findings will aid in the prevention and treatment strategies of S. aureus infections.Emergent patterns of collective motion are thought to arise from local rules of interaction that govern how individuals adjust their velocity in response to the relative locations and velocities of near neighbours. Many models of collective motion apply rules of interaction over a metric scale, based on the distances to neighbouring group members. However, empirical work suggests that some species apply interactions over a topological scale, based on distance determined neighbour rank. Here, we modify an important metric model of collective motion (Couzin et al. in J Theor Biol 218(1)1-11, 2002), so that interactions relating to orienting movements with neighbours and attraction towards more distant neighbours operate over topological scales. We examine the emergent group movement patterns generated by the model as the numbers of neighbours that contribute to orientation- and attraction-based velocity adjustments vary. Like the metric form of the model, simulated groups can fragment (when interactions are influenced by less than 10-15% of the group), swarm and move in parallel, but milling does not occur. The model also generates other cohesive group movements including cases where groups exhibit directed motion without strong overall alignment of individuals. Multiple emergent states are possible for the same set of underlying model parameters in some cases, suggesting sensitivity to initial conditions, and there is evidence that emergent states of the system depend on the history of the system. Groups that do not fragment tend to stay relatively compact in terms of neighbour distances. Even if a group does fragment, individuals remain relatively close to near neighbours, avoiding complete isolation.The aim of this study was to evaluate the probiotic potential of Bacillus strains with antibacterial activity against Vibrio spp. in vitro. 13 Bacillus strains were selected using Bacillus-selective agar. Among the strains elected in the preliminary screening for antagonistic effect, only the strain PJ_11 with better antibacterial ability was selected and used in further experiments. Based on the morphological and biochemical features with phylogenetic analysis of the 16S rRNA sequencing, selected strain was identified as B. pumilus. PJ_11 showed probiotic properties such as able to survive in wide range of temperatures and salinity, tolerance to 0.3% oxgal and pH 2.0, and high cell-adhesion activity. In this study, there was no special feature regarding the inhibitory effect of the isolate against Gram-positive or Gram-negative indicator bacteria. However, the inhibition effect of the culture was found to be greater than that of the supernatant. PJ_11 exhibited strong antibacterial activity against Vibrio vulnificus, Vibrio parahaemolyticus and Vibrio anguillarum that were isolated from fish (Dicentrarchus labrax) with disease symptoms.

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