Buschdunn0279

© 2020, Martinez et al.G protein-coupled receptors (GPCRs) signal through allostery, and it is increasingly clear that chemically distinct agonists can produce different receptor-based effects. It has been proposed that agonists selectively promote receptors to recruit one cellular interacting partner over another, introducing allosteric 'bias' into the signaling system. However, the underlying hypothesis - that different agonists drive GPCRs to engage different cytoplasmic proteins in living cells - remains untested due to the complexity of readouts through which receptor-proximal interactions are typically inferred. We describe a cell-based assay to overcome this challenge, based on GPCR-interacting biosensors that are disconnected from endogenous transduction mechanisms. Focusing on opioid receptors, we directly demonstrate differences between biosensor recruitment produced by chemically distinct opioid ligands in living cells. We then show that selective recruitment applies to GRK2, a biologically relevant GPCR regulator, throu can not only communicate that a signaling molecule is binding but can respond differently to convey what molecule it is more specifically. This could be important in developing drugs, particularly to specifically trigger the desired response and reduce side effects. Stoeber et al. suggest that an important next step for research is to understand how the GPCRs preferentially bind to different proteins. © 2020, Stoeber et al.A truncated version of the only insulin receptor in C. elegans has been discovered. © 2020, Murphy.Cryptosporidiosis is a parasitic diarrheal infection that is transmitted by the fecal-oral route. We assessed trends in incidence and demographic characteristics for the 3,984 cases diagnosed during 1995-2018 in New York City, New York, USA, and reported to the New York City Department of Health and Mental Hygiene. Reported cryptosporidiosis incidence decreased with HIV/AIDS treatment rollout in the mid-1990s, but the introduction of syndromic multiplex diagnostic panels in 2015 led to a major increase in incidence and to a shift in the demographic profile of reported patients. Incidence was highest among men 20-59 years of age, who consistently represented most (54%) reported patients. In addition, 30% of interviewed patients reported recent international travel. The burden of cryptosporidiosis in New York City is probably highest among men who have sex with men. Prevention messaging is warranted for men who have sex with men and their healthcare providers, as well as for international travelers.Bentonite is an inorganic clay material that is often easily dispersed as fine particles by air and water circulation, and most people are exposed to different concentrations of bentonite particles. Therefore, the inhaled effects of bentonite nanoparticles (BNPs) were studied in Wistar rats. Seventy-five rats were divided into five groups of 15 four exposure groups (0.1, 0.5, 2, and 10 mg/m3 of BNPs) and one control group. The rats were exposed for 30, 60, and 90 days to BNPs for 5 days a week (6 h/day) in whole-body inhalation chambers. Blood samples were collected to measure the levels of antioxidant activity of the contents such as total antioxidant capacity (TAC) and malondialdehyde (MDA). X-ray diffraction and scanning electron microscopy were used to identify nanoparticles. The results showed no significant difference in the effect of nanoparticles on levels of TAC and MDA in the studied groups based on the concentrations of nanoparticles. However, the level of MDA increased significantly with extending exposure time; there was a significant increase in the level of MDA content 90 days postexposure compared to 30 days postexposure at concentrations of 0.5, 2, and 10 mg/m3. Histopathological examination showed that inhalation exposure of rats to BNPs led to different histopathologic responses in the lung tissue, such as inflammatory infiltration, granulomatous inflammation, acute neutrophilic reaction in the early stages, and lung fibrosis. At the lowest concentration, BNPs have low or no toxicity, and inhalation of these nanoparticles at low concentrations does not affect the levels of MDA and TAC content. However, increased concentration and exposure time caused correspondingly greater increases in MDA and more damage to lung tissue.BACKGROUND In recent years, nanoparticles have been widely used in many fields, ranging from cosmetics, agriculture, environment, and biomedical areas. The increasing use of nanoproducts induces a potential increasing exposure to human body, and then, unknown pathological consequences could increase. METHODS The database was searched from 2008 to 2018 by the Web of Science Core Collection. The bibliometric methods, CiteSpace and HistCite, were used for analysis and visualization of the data. Selleck OSS_128167 RESULTS The 2932 publications were analyzed and the annual publications grew from 78 to 512 in a decade. The United States and China mainly contribute to this research area, which accounted for 29.5% and 22.9%, respectively. PLoS One, Scientific Reports, and Nanoscale were the three journals that published the most articles. Keyword analysis indicated that the major research direction was the mechanisms of nanoneurotoxicity, which included oxidative stress, inflammation, astrocyte activation, and the fibrillation of amyloid β protein. CONCLUSION This bibliometric study revealed that nanoneurotoxicity was still a research hot topic and could be a promising area of research in the next few years. Nanoparticles play a role in neurodegenerative diseases by inducing reactive oxygen species production, inflammation, alterations of gene expression, and signal pathways.As a general alternative, diisononyl phthalate (DINP) has gradually replaced di(2-ethylhexyl) phthalate (DEHP) as the main plasticizer used in polyvinyl chloride. Like DEHP, DINP can also be released into the environment, resulting in humans being exposed through skin contact. This study aims to explore whether oxidative damage to hepatic and renal tissues can be induced by dermal exposure to DINP in mice. Forty-two male Balb/c mice were divided into six groups. The five DINP dermal exposure groups were exposed to different doses of DINP (0.02, 0.2, 2, 20, and 200 mg/kg) for 28 consecutive days. The pathological alterations to the skin, liver, and kidney in the mice were examined. Levels of reactive oxygen species (ROS), reduced glutathione (GSH), malondialdehyde (MDA), and DNA-protein cross-links (DPC) in the liver and kidney were also determined to investigate oxidative damage. The experimental results showed that the levels of ROS, MDA, and DPC coefficients increased gradually in a dose-dependent manner, whereas the level of GSH decreased accordingly. When the exposure dose was ≥20 mg/kg, ROS, GSH, MDA content, and the DPC coefficient were significantly different compared to the control group (p less then 0.05). These results suggest that a high dose of DINP can induce oxidative stress and histopathological alterations in the liver and kidney via dermal exposure.Cefoperazone-sulbactam (CS) and piperacillin-tazobactam (TZP) are used in the treatment of Gram-negative nosocomial infections (NIs). We aimed to compare the effects of these two antibiotics on mortality and treatment success. Patients treated with CS or TZP empirically for at least three days with suspicion of NI were included in this retrospective study. In total, 308 (154 patients in both treatment arms) patients were analyzed. Treatment success rate in CS and TZP group respectively (50% vs 51.2%, p = 0.18), 28-day mortality rate (46.1% vs 42.8%, p = 0.56) and antibiotic-related side effects (50.6% vs 46.1%, p = 0.42) were similar except prolonged prothrombin time (19.4% vs 6.4%; p = 0.001). According to this study results, CS and TZP have equal effectivity and safety for the empirical treatment of Gram-negative NIs. CS may be an appropriate alternative to TZP for antibiotic cycling or mixing strategy to reduce antibiotic resistance.Healthy eating among young people may curb obesity and improve health, but strong messaging is needed for healthy eating interventions. In the current work, we evaluated the usefulness of visual appeals in a pilot text message-based healthy eating intervention among college students. A 2 (gain vs. loss) × 2 (image vs. no image) design with pretest and posttest questionnaires (N = 111) revealed text-only messages with loss frames had an influence on affective risk response, while both gain- and loss-framed text messages with visual appeals had positive effects on attitudes and intentions. This pilot study provides evidence to support the feasibility of using visual appeals in text message-based health interventions. The implications of the current study are discussed.This study investigated the association between talent selection criteria, draft order and match performance in professional Australian Football players. Physical performance results from the Australian Football League (AFL) National Draft combine and non-performance based talent selection criteria were collated for all players drafted in the National Draft with selections 1-80 between 2003 and 2008 (n = 318). Match performance was assessed via the AFL Player Ranking metric that was provided by a commercial statistical provider (Champion Data Pty Ltd). A combination of stepwise multiple regression and linear mixed model analyses examined the influence of National Draft combine physical performance assessments and non-performance based talent selection criteria on draft order and future match performance. Earlier draft selection was associated with Under-18 all Australian team selection, height, Under-18 National Championship participation and indigenous status. The 20 m sprint and state of origin were associated with later draft selection. Under-18 all Australian team selection increased both Player Ranking/game and total Player Ranking. Under-18 all Australian team selection displays efficacy for selecting players with the potential for success.Purpose To investigate the efficacy and sustainability of drug-coated balloon (DCB) treatment of femoropopliteal in-stent restenosis (ISR). Materials and Methods An investigator-initiated, prospective, multicenter, 11 randomized study enrolled 88 patients for treatment of ISR with DCB (n=47; mean age 68.3±9.6 years; 26 men) or uncoated balloon (n=41; mean age 67.6±10.2 years; 26 men) angioplasty (ClinicalTrials.gov identifier NCT01594684). Additionally, the protocol provided for an observational arm composed of patients from either randomized arm who experienced recurrent ISR ≥30 days after the index treatment. Redo treatment consisted of 2 DCBs sequentially inflated at the same location (double dose therapy). The majority of patients (66, 78%) had Rutherford category 3 ischemia. The mean lesion length was 140 mm; a third (27, 31%) were total occlusions. The primary endpoint was angiographic late lumen loss (LLL) at 6 months evaluated by an independent core laboratory. Results Twenty-two patients (7 DCB +15 uncoated) were treated for recurrence with fully overlapping double DCB angioplasty. Six-month LLL was lower after DCB (0.34±1.12 mm) treatment than after angioplasty with an uncoated balloon (1.58±1.10 mm, p less then 0.001). At the 12-month follow-up, target lesion revascularization (TLR) was performed in 18 (49%) of 37 patients in the uncoated group, 6 (14%) of 43 patients in the single-dose DCB group (p=0.001), and no patients from the recurrent ISR group. At ~2 years after treatment, a remarkable number (14/27, 52%) of TLRs were recorded in the single-dose DCB group. Conclusion Treatment with DCBs resulted in significantly less 6-month LLL and fewer TLRs up to 24 months than treatment with uncoated balloons. The double dose for treating recurrent ISR did not cause recognizable adverse events or require TLR up to 24 months.