• Topp Fitzsimmons opublikował 5 miesięcy, 1 tydzień temu

    The neuroprotective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) have been shown in numerous in vitro and in vivo models of Parkinson’s disease (PD) supporting the theory that PACAP could have an important role in the pathomechanism of the disorder affecting mostly older patients. Earlier studies found changes in PACAP levels in neurological disorders; therefore, the aim of our study was to examine PACAP in plasma samples of PD patients. Peptide levels were measured with ELISA and correlated with clinical parameters, age, stage of the disorder based on the Hoehn and Yahr (HY) scale, subtype of the disease, treatment, and specific scores measuring motor and non-motor symptoms, such as movement disorder society-unified Parkinson’s disease rating scale (MDS-UPDRS), Epworth sleepiness scale (ESS), Parkinson’s disease sleep scale (PDSS-2), and Beck depression inventory (BDI). Our results showed significantly decreased PACAP levels in PD patients without deep brain stimulation (DBS) therapy and in akinetic-rigid subtype; additionally we also observed a further decrease in the HY stage 3 and 4. Elevated PACAP levels were found in patients with DBS. There were no significant correlations between PACAP level with MDS-UPDRS, type of pharmacological treatment, PDSS-2 sleepiness, or depression (BDI) scales, but we found increased PACAP level in patients with more severe sleepiness problems based on the ESS scale. Based on these results, we suggest that following the alterations of PACAP with other frequently used clinical biomarkers in PD patients might improve strategic planning of further therapeutic interventions and help to provide a clearer prognosis regarding the future perspective of the disease.

    The N-myristoylation is required for BSK1 proper plasma membrane targeting and protein turnover. Brassinosteroid (BR) signaling kinase 1 (BSK1), with a myristoylation site at its N-terminus to anchor at plasma membrane (PM), is involved in BR-regulated plant growth and flg22-triggered immunity responses. However, little is known about the role of N-myristoylation in BSK1 protein homeostasis. Here, we revealed that N-myristoylation is critical to the PM targeting and protein stability of BSK1. The N-myristoylation-deficient mutant BSK1

    mainly distributed in the cytoplasm and retained in the endoplasmic reticulum. We further found that the BSK1

    proteins were unstable and degraded through ATG8e-labled autophagic pathway. This study provides a new insight into the regulation of plant protein homeostasis.

    The N-myristoylation is required for BSK1 proper plasma membrane targeting and protein turnover. Brassinosteroid (BR) signaling kinase 1 (BSK1), with a myristoylation site at its N-terminus to anchor at plasma membrane (PM), is involved in BR-regulated plant growth and flg22-triggered immunity responses. However, little is known about the role of N-myristoylation in BSK1 protein homeostasis. Here, we revealed that N-myristoylation is critical to the PM targeting and protein stability of BSK1. The N-myristoylation-deficient mutant BSK1G2A mainly distributed in the cytoplasm and retained in the endoplasmic reticulum. We further found that the BSK1G2A proteins were unstable and degraded through ATG8e-labled autophagic pathway. This study provides a new insight into the regulation of plant protein homeostasis.Despite various efforts to produce potent recombinant bio-adhesive proteins for medical purposes, efficient production of a safe and feasible bio-glue is not yet a commercial reality due to the weak properties or low expression levels. Here, a feasible expression system has been developed to produce strong recombinant fusion bioinspired protein using mussel foot protein 3 and 5 (Mfps) along with gas vesicle protein A (GvpA) of Anabaena flos-aquae, and a curli protein CsgA from E. coli, expressed under the control of alcohol oxidase (AOX1) promoter for high-level production in yeast P. pastoris using pPICZα vector. Purified chimeric proteins were first evaluated using western blotting, and their remaining dihydroxyphenylalanine (DOPA) was measured in the modified proteins by NBT assay. We further elucidated the mechanistic properties of obtained adhesive protein assembly in various pH levels based on its different subunits using atomic force microscopy (AFM) when adsorbed onto the mica surface. We found that both combinational structural features of subunits and post-translational changes during expression in yeast host have led to potent adherence due to higher DOPA residues specially in acidic condition and tetrad complex which is higher than that of earlier reports in prokaryotic systems. We believe that our obtained chimeric protein resulted from the fusion of GvpA and CsgA proteins with DOPA-containing Mfp proteins, expressed in the methylotrophic yeast, P. pastoris, not only presents a candidate for future biomedical applications but also provides novel biological clues used for high-performance bioinspired biomaterial designation.Chronic kidney disease (CKD) can progress to kidney failure and require dialysis or transplantation, while early diagnosis can alter the course of disease and lead to better outcomes in both pediatric and adult patients. Significant CKD comorbidities include the manifestation of cardiovascular disease, heart failure, coronary disease, and hypertension. The pathogenesis of chronic kidney diseases can present as subtle and especially difficult to distinguish between different glomerular pathologies. Early detection of adult and pediatric CKD and detailed mechanistic understanding of the kidney damage can be helpful in delaying or curtailing disease progression via precise intervention toward diagnosis and prognosis. Clinically, serum creatinine and albumin levels can be indicative of CKD, but often are a lagging indicator only significantly affected once kidney function has severely diminished. The evolution of proteomics and mass spectrometry technologies has begun to provide a powerful research tool in defining these mechanisms and identifying novel biomarkers of CKD. Many of the same challenges and advances in proteomics apply to adult and pediatric patient populations. Additionally, proteomic analysis of adult CKD patients can be transferred directly toward advancing our knowledge of pediatric CKD as well. In this review, we highlight applications of proteomics that have yielded such biomarkers as PLA2R, SEMA3B, and other markers of membranous nephropathy as well as KIM-1, MCP-1, and NGAL in lupus nephritis among other potential diagnostic and prognostic markers. The potential for improving the clinical toolkit toward better treatment of pediatric kidney diseases is significantly aided by current and future development of proteomic applications.Lakes throughout the globe have been gravely altered or degraded at a pace much more significant than their restoration. In the heart of Srinagar, the summer capital of Jammu and Kashmir, Dal Lake, has witnessed extreme loss in water quality during the last four decades because of anthropogenic pressures. The lake is unique in that over 50,000 people inhabit the lake itself in houseboats, dongas, or islands within the lake. These people derive their livelihood from the lake in terms of tourism, agriculture, fishing, and vegetable farming. The countless ways people use the lake have led to an extreme load of pollution in the lake. Encroachment in and around the lake has led to the loss of volume of water in the lake and consequently increased the concentration of pollutants. Discharge of untreated sewage, agricultural runoff, and sediments from adjoining catchments have further degraded the lake water quality. The changes in water quality are clear from the physio-chemical properties of the lake waters. While transparency and dissolved oxygen in the lake have decreased drastically during the last 40 years, the concentration of harmful substances like phosphates, nitrates, and chlorides has increased. The hardness of water has also increased due to higher levels of carbonates and bicarbonates in the lake. This paper details the changes in the water quality of Dal Lake over the recent past. The paper analyses the strategies that can be implemented to manage the lake and restore its quality if appropriately implemented.Emergency department (ED) nurses and emergency medical services (EMS) staff have been recently exposed to high levels of stress due to the new Coronavirus (COVID-19) pandemic. This increased stress level may influence the physical and mental health of ED nurses and EMS staff and the quality of caregiving to the patients. A spiritual coping approach is one of the most commonly used strategies to help healthcare workers manage stressful events or situations. This study explores the spiritual coping (positive or negative) among ED nurses and EMS staff during the COVID-19 pandemic. A descriptive cross-sectional study was performed on 494 ED/EMS nurses in Ardabil Province in the northwest of Iran, using a convenience sampling method. The spiritual coping questionnaire (SCQ) was used to assess spiritual coping in the subjects. The results of this study showed that ED nurses and EMS staff generally used positive spiritual coping methods to reduce stress during the COVID-19 pandemic. Multiple linear regression indicated that workplace (β = 0.22, p  less then  0.001), service location (β = 0.16, p  less then  0.001), and type of employment (β = - 0.13, p = 0.012) were significant predictors of positive spiritual coping, and older age (β = 0.13, p = 0.045), overtime work (β = 0.12, p = 0.01), and marital status (β = - 0.12, p = 0.021) were predictors of negative spiritual coping. Our findings indicated that positive religious behavior was the main spiritual coping strategy used by healthcare workers. The findings could help emergency nurse managers to propose future strategies to minimize stress based on the use of spiritual coping strategies and provide time and facilities to pray.

    Acute or regular stretching exercises reduce arterial stiffness, but whether stretching exercises per se can reduce central arterial stiffness remain controversial. Recent studies have suggested that mechanical stimulation of arteries can directly modulate arterial stiffness, rather than causing systemic effects. Thus, this study aimed to examine the effects of trunk stretching using an exercise ball on central arterial stiffness and carotid arterial compliance.

    Twelve healthy young adults participated in two different trials for 30min each in random order on separate days a resting and sitting trial (CON); and supervised passive trunk stretching using the exercise ball (EB). In EB, subjects preformed six types of passive trunk stretching using the exercise ball. At each site, passive stretching was held for 30s followed by a 30-s relaxation period, repeated 5 times during the 30-min trial. In CON, subjects rested on a comfortable chair for 30min.

    After the experiment, carotid-femoral pulse wave velocity was significantly reduced in EB, but not in CON (EB vs. CON -4.5 ± 1.2% vs. 0.2 ± 0.9%; P < 0.05). Carotid arterial compliance was also significantly increased in EB, but not in CON (EB vs. CON 38.4 ± 11.4% vs. 4.1 ± 9.4%; P < 0.05). Supplemental experiments also confirmed that stretching of lower extremity did not reduce carotid-femoral pulse wave velocity.

    Our findings indicate that acute, direct trunk stretching using an exercise ball reduces central arterial stiffness and increases carotid arterial compliance in young healthy men.

    Our findings indicate that acute, direct trunk stretching using an exercise ball reduces central arterial stiffness and increases carotid arterial compliance in young healthy men.

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