In budding yeast, the Rho-family GTPase Cdc42 has several functions that depend on its subcellular localization and the cell cycle stage. During bud formation, Cdc42 localizes to the plasma membrane at the bud tip and bud neck where it carries out functions in actin polymerization, spindle positioning, and exocytosis to ensure proper polarity development. Recent live-cell imaging analysis revealed a novel localization of Cdc42 to a discrete intracellular focus associated with the vacuole and nuclear envelope. The discovery of this novel Cdc42 localization led to the identification of a new function in ESCRT-mediated nuclear envelope sealing. However, other aspects of this intracellular localization and its functional implications were not explored. Here, we further characterize the Cdc42 focus and present several novel observations that suggest possible additional Cdc42 functions at the nucleus, including nucleus-vacuole junction formation, nuclear envelope tethering, nuclear migration, and nucleopodia formation.
Contrasting findings have been reported regarding a possible constitutive expression of inducible nitric oxide synthase (iNOS) in a normal mammalian bladder. The current study was designed to further investigate such putative iNOS expression.
The experiments were conducted with paraffin-embedded archival material from the urinary bladder of 6 normal, male Sprague-Dawley rats. In addition, two normal female mice (C57BL/6) were sacrificed and the urinary bladders were harvested. The occurrence of iNOS mRNA was examined by the RNAScope
hybridization method. https://www.selleckchem.com/products/ijmjd6.html Protein expression of iNOS and 3-nitrotyrosine (the latter used as an indicator of oxidative stress) was investigated by immunohistochemistry.
No expression of iNOS mRNA was observed in the bladder tissue. iNOS protein and 3-nitrotyrosine were strongly expressed in the urothelium. iNOS was also expressed perinuclearly in the detrusor.
Although the RNAScope methodology could not demonstrate mRNA for iNOS in the normal urinary bladder, the results by immunohistochemistry strongly suggest the occurrence of iNOS in particular, in the urothelium. Positive reactivity for 3-nitrotyrosine may indicate ongoing oxidative stress of the urothelium. The finding of perinuclear iNOS immunoreactivity could suggest an intracrine signaling function by iNOS to the nucleus.
Although the RNAScope methodology could not demonstrate mRNA for iNOS in the normal urinary bladder, the results by immunohistochemistry strongly suggest the occurrence of iNOS in particular, in the urothelium. Positive reactivity for 3-nitrotyrosine may indicate ongoing oxidative stress of the urothelium. The finding of perinuclear iNOS immunoreactivity could suggest an intracrine signaling function by iNOS to the nucleus.
This study employed network analysis to characterize central autism spectrum disorder (ASD) traits and suicide symptoms within an active duty military sample as well as to identify symptoms that may bridge between ASD traits and suicidality (i.e., suicidal ideation and behaviors).
Participants were active duty U.S. military service members (
= 287). Autism spectrum traits, suicidality, depression, and suicide related constructs were assessed online via self-report.
Within the combined ASD trait-suicidality network, suicide rumination, suicide behaviors, and depression had the highest strength centrality. The most central bridge symptoms between ASD and suicidality were thwarted belongingness, social skills deficits, and depressive symptoms.
Social skills deficits and thwarted belongingness may function as a meaningful bridge between ASD symptoms and suicidality within active duty members. Individuals with ASD symptoms who additionally present with high levels of thwarted belongingness and/or consides did not.Suicide rumination, suicide behaviors, and depression were the most central symptom in an ASD-suicidality network.Symptoms related to social skills deficits may connect ASD traits and suicidality.
To investigate whether a combination of dry-needling treatments and upper extremity neuromuscular reeducation exercises can significantly improve neck pain and/or headache-related disability, joint position error, cervical range of motion, and pain pressure threshold in individuals suffering from cervicogenic headache (CGH).
This study is a quasi-experimental design. Seven participants met the inclusion criteria and received dry needling to three muscles that reproduced the participant's headache symptoms and completed the Neck Disability Index (NDI), Headache Disability Inventory (HDI), Visual Analog Scale (VAS), and Numeric Pain Rating Scale (NPRS). Participants performed an exercise regimen designed to address strength and mobility of cervical and scapulothoracic musculature.
There were significant improvements seen in cervical range of motion and neck pain-related disability (NDI) during the 4-week treatment period.
Dry needling and neuromuscular re-education (NMR) exercises could be effective components of treatment for individuals suffering from CGH to reduce disability and pain.
Dry needling and neuromuscular re-education (NMR) exercises could be effective components of treatment for individuals suffering from CGH to reduce disability and pain.Platelets mediate central aspects of host responses during sepsis, an acute profoundly systemic inflammatory response due to infection. Macroautophagy/autophagy, which mediates critical aspects of cellular responses during inflammatory conditions, is known to be a functional cellular process in anucleate platelets, and is essential for normal platelet functions. Nevertheless, how sepsis may alter autophagy in platelets has never been established. Using platelets isolated from septic patients and matched healthy controls, we show that during clinical sepsis, the number of autophagosomes is increased in platelets, most likely due to an accumulation of autophagosomes, some containing mitochondria and indicative of mitophagy. Therefore, autophagy induction or early-stage autophagosome formation (as compared to decreased later-stage autophagosome maturation or autophagosome-late endosome/lysosome fusion) is normal or increased. This was consistent with decreased fusion of autophagosomes with lysosomes in platelets. EPG5 (ectopic P-granules autophagy protein 5 homolog), a protein essential for normal autophagy, expression did increase, while protein-protein interactions between EPG5 and MAP1LC3/LC3 (which orchestrate the fusion of autophagosomes and lysosomes) were significantly reduced in platelets during sepsis. Furthermore, data from a megakaryocyte model demonstrate the importance of TLR4 (toll like receptor 4), LPS-dependent signaling for regulating this mechanism. Similar phenotypes were also observed in platelets isolated from a patient with Vici syndrome an inherited condition caused by a naturally occurring, loss-of-function mutation in EPG5. Together, we provide evidence that autophagic functions are aberrant in platelets during sepsis, due in part to reduced EPG5-LC3 interactions, regulated by TLR4 engagement, and the resultant accumulation of autophagosomes.In 2016, in Switzerland, we implemented transitional interprofessional and interinstitutional shared decision-making processes (IIPs) between a short-stay inpatient care unit (SSU) and primary care professionals. Between 2018 and 2019, we evaluated this intervention using a realist design to answer the following questions for whom, with whom, in which context and how have IIPs been implemented? Our initial theory was tested via interviews with patients, primary care professionals and staff from the SSU. Results showed that a patient's stay at the SSU, with actors committed to facilitating IIPs, reinforced the perceived appropriateness and implementation of those IIPs. However, this appropriateness varied according to different contextual elements, such as the complexity of needs, preexisting collaborative practices and the purpose of the inpatient stay. Since IIPs occurred in a context of fragmented practices, proactive and sustained efforts are required of the actors implementing them and the organizations supporting them.ZO-2 is a peripheral tight junction (TJ) protein whose silencing in renal epithelia induces cell hypertrophy. Here, we found that in ZO-2 KD MDCK cells, in compensatory renal hypertrophy triggered in rats by a unilateral nephrectomy and in liver steatosis of obese Zucker (OZ) rats, ZO-2 silencing is accompanied by the diminished activity of LATS, a kinase of the Hippo pathway, and the nuclear concentration of YAP, the final effector of this signaling route. ZO-2 appears to function as a scaffold for the Hippo pathway as it associates to LATS1. ZO-2 silencing in hypertrophic tissue is due to a diminished abundance of ZO-2 mRNA, and the Sp1 transcription factor is critical for ZO-2 transcription in renal cells. Treatment of OZ rats with metformin, an activator of AMPK that blocks JNK activity, augments ZO-2 and claudin-1 expression in the liver, reduces the paracellular permeability of hepatocytes, and serum bile acid content. Our results suggest that ZO-2 silencing is a common feature of hypertrophy, and that ZO-2 is a positive regulator of the Hippo pathway that regulates cell size. Moreover, our observations highlight the importance of AMPK, JNK, and ZO-2 as therapeutic targets for blood-bile barrier dysfunction.Physical/cognitive limitations associated with the aging process place older adults at disproportionate risk of negative consequences during disasters. Guided by the profession's commitment to supporting vulnerable populations, gerontological social workers have long been on the frontlines supporting older adults during disasters. Yet, disaster social work practice remains an undeveloped and under-researched area. Thus, we asked "what is the current role of gerontological social workers in disaster preparedness with older adults in the United States, and potential areas for improvement?" This paper systematically reviews the literature discussing social work and disaster preparedness/response with older adults in the U.S., to identify needs and inform future directions. PRISMA guidelines were followed to conduct a systematic search across relevant databases for peer-reviewed-publications between January 1, 2009-June 12, 2020. Eleven articles met inclusion criteria. This body of literature is small and covers two broad areas (1) charging the social work profession to engage in this work, and (2) describing current efforts and unique challenges of older adults during disasters. Only three empirical studies were identified. Future educational efforts should formalize training to prepare social workers for this practice area. Research should detail the roles of social workers in disaster preparedness/response, and factors that predict involvement.The aim is to investigate the effect of irrigation of subcutaneous tissue with saline, rifampicin, or povidone-iodine on incisional surgical site infections following caesarean section. Three hundred patients scheduled for caesarean section were randomly assigned into one of three groups of 100 members each, as follows the subcutaneous tissue was irrigated with saline in group 1 (control); saline + rifampicin in group 2; saline + 10% povidone-iodine in group 3. Patients who developed a superficial incisional surgical site infection within 30 days were recorded. The surgical site infection rate did not differ when using rifampicin or povidone-iodine (p = .202). It was observed that there was a statistically significant increase in the rate of incisional surgical site infections as the existence of comorbidities (p = .001), perioperative blood transfusion (p = .020), and midline incision (p = .004). Irrigation of subcutaneous tissue with rifampicin or 10% povidone-iodine is not effective in preventing surgical site infections after caesarean section.