Paxillin facilitates timely neurite initiation on soft-substrate environments by interacting with the endocytic machinery.

Neurite initiation is the first step in neuronal development and occurs spontaneously in soft tissue environments. Although the mechanisms regulating the morphology of migratory cells on rigid substrates in cell culture are widely known, how soft environments modulate neurite initiation remains elusive. Using hydrogel cultures, pharmacologic inhibition, and genetic approaches, we reveal that paxillin-linked endocytosis and adhesion are components of a bistable switch controlling neurite initiation in a substrate modulus-dependent manner. On soft substrates, most paxillin binds to endocytic factors and facilitates vesicle invagination, elevating neuritogenic Rac1 activity and expression of genes encoding the endocytic machinery. By contrast, on rigid substrates, cells develop extensive adhesions, increase RhoA activity and sequester paxillin from the endocytic machinery, thereby delaying neurite initiation. Our results highlight paxillin as a core molecule in substrate modulus-controlled morphogenesis and define a mechanism whereby neuronal cells respond to environments exhibiting varying mechanical properties

One-pot synthesis of poly (3,4-ethylenedioxythiophene)-Pt nanoparticle composite and its application to electrochemical H2O2 sensor.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Poly(3,4-ethylenedioxythiophene)-Pt nanoparticle composite was synthesized in one-pot fashion using a photo-assisted chemical method, and its electrocatalytic properties toward hydrogen peroxide (H2O2) was investigated. Under UV irradiation, the rates of the oxidative polymerization of EDOT monomer along with the reduction of Pt4+ ions were accelerated. In addition, the morphology of PtNPs was also greatly influenced by the UV irradiation; the size of PtNPs was reduced under UV irradiation, which can be attributed to the faster nucleation rate. The immobilized PtNPs showed excellent electrocatalytic activities towards the electroreduction of hydrogen peroxide. The resultant amperometric sensor showed enhanced sensitivity for the detection of H2O2 as compared to that without PtNPs, i.e., only with a layer of PEDOT. Amperometric determination of H2O2 at -0.55 V gave a limit of detection of 1.6 μM (S / N = 3) and a sensitivity of 19.29 mA cm-2 M-1 up to 6 mM, with a response time (steady state, t95) of 30 to 40 s. Energy dispersive X-ray analysis, transmission electron microscopic image, cyclic voltammetry (CV), and scanning electron microscopic images were utilized to characterize the modified electrode. Sensing properties of the modified electrode were studied both by CV and amperometric analysis

Pharmacokinetics and tissue depletion of doxycycline administered at high dosage to broiler chickens via the drinking water

The recommended use of doxycycline (DC) to broiler chicken is 100 mg/L via the drinking water and a 7-day withdrawal time (WDT). However, study of a higher dosage is desirable because of the possible increase of antimicrobial resistance and disease spectrum. Tissue DC residues exceeding the current maximum residue levels (MRL) was our major concern. Therefore, serum concentration and tissue depletion of DC hyclate after administration of 200 mg/L of DC in the drinking water for five consecutive days were studied. The steady-state DC concentration (8.3 ± 0.9 μg/mL) was reached on the third day of medication. The elimination constant (0.05 ± 0.01 1/h), half-life (14.9 ± 1.4 h), area under concentration versus time curve (81.0 ± 9.9 h·μg/mL) and mean residence time (22.7 ± 2.5 h) were obtained using a non-compartmental pharmacokinetic model. It was determined that the current 7-day WDT regulation was still legitimate for the kidney and liver as well as for the breast and leg muscles, which were estimated by linear regression analysis of the 99% upper distribution limit. The unregulated heart and gizzard were considered safe even when the lowest MRL of muscle (100 ng/g) was applied. While at the present time the extra-label use of drugs is only allowed under specific conditions, in the future it may become necessary to increase the general dosage of DC, and the current results suggest a safe range of DC hyclate in chicken; however, skin/fat tissue residues warrant further studies

Using the computer-based feedback (CBF) system to investigate the juniorphysicians’s and clinical-instructors perceptions for the benefits of general medicine clinical-instructors training program

Background: The purpose of this study is to examine the clinical-instructors and junior-physicians (residents and interns) perceptions for the general-medicine training program by using bi-directional interactive and self-assessments computer-based feedback (CBF) and paper-based multisource feedback assessment (PBMFA) systems for the efficiency and benefit evaluation.Methods: Between 2011 January to 2013 December, junior-physicians and their clinical-instructors in the same medical team were enrolled consecutively for monitoring the CBF scores gave by each other after each clinical course. A total of 321 residents, 298 interns and 110 clinical-instructors who participated in the core competency general-medicine training program in 6-months period were included in the study. The CBF and PBMFA evaluations are undergone paralleled to gather the suggested information in different levels of Kirkpatrick evolutional theory.Results: The results showed that lecturers, being 5-10 years as attending physicians, internal medicine sub-specialty clinical-instructors are most benefit from the general medicine training program. Accordingly, the CBF scores of junior-physicians was positively correlated with the times (> 3-times) of exposure to the medical teams that leaded by qualified clinical-instructors. Both clinical-instructors and junior-physicians have positive attitude to the value of the general-medicine training program. Interestingly, a good consistency was existed between residents CBF scores and PBMFA grades for their core-competency performance. Comparatively, the overall perception of clinical-instructors and junior-physicians for the general-medicine training was very positive.Conclusions: Clinical-instructors and junior-physicians had positive perception of CBF and PBMFA systems which could give us different information to improve and strength the further core-competency general-medicine training program by appropriate utilization

The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia

Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10−7 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30×10−11). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38×10−11). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60×10−20, allelic risk = 1.54, 95% Confidence Interval (CI) 1.41–1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40–1.87), and 2.35 (95% CI: 1.95–2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma

Seizing the window of opportunity to mitigate the impact of climate change on the health of Chinese residents

The health threats posed by climate change in China are increasing rapidly. Each province faces different health risks. Without a timely and adequate response, climate change will impact lives and livelihoods at an accelerated rate and even prevent the achievement of the Healthy and Beautiful China initiatives. The 2021 China Report of the Lancet Countdown on Health and Climate Change is the first annual update of China’s Report of the Lancet Countdown. It comprehensively assesses the impact of climate change on the health of Chinese households and the measures China has taken. Invited by the Lancet committee, Tsinghua University led the writing of the report and cooperated with 25 relevant institutions in and outside of China. The report includes 25 indicators within five major areas (climate change impacts, exposures, and vulnerability; adaptation, planning, and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement) and a policy brief. This 2021 China policy brief contains the most urgent and relevant indicators focusing on provincial data: The increasing health risks of climate change in China; mixed progress in responding to climate change. In 2020, the heatwave exposures per person in China increased by 4.51 d compared with the 1986–2005 average, resulting in an estimated 92% increase in heatwave-related deaths. The resulting economic cost of the estimated 14500 heatwave-related deaths in 2020 is US$176 million. Increased temperatures also caused a potential 31.5 billion h in lost work time in 2020, which is equivalent to 1.3% of the work hours of the total national workforce, with resulting economic losses estimated at 1.4% of China’s annual gross domestic product. For adaptation efforts, there has been steady progress in local adaptation planning and assessment in 2020, urban green space growth in 2020, and health emergency management in 2019. 12 of 30 provinces reported that they have completed, or were developing, provincial health adaptation plans. Urban green space, which is an important heat adaptation measure, has increased in 18 of 31 provinces in the past decade, and the capacity of China’s health emergency management increased in almost all provinces from 2018 to 2019. As a result of China’s persistent efforts to clean its energy structure and control air pollution, the premature deaths due to exposure to ambient particulate matter of 2.5 μm or less (PM2.5) and the resulting costs continue to decline. However, 98% of China’s cities still have annual average PM2.5 concentrations that are more than the WHO guideline standard of 10 μg/m3. It provides policymakers and the public with up-to-date information on China’s response to climate change and improvements in health outcomes and makes the following policy recommendations. (1) Promote systematic thinking in the related departments and strengthen multi-departmental cooperation. Sectors related to climate and development in China should incorporate health perspectives into their policymaking and actions, demonstrating WHO’s and President Xi Jinping’s so-called health-in-all-policies principle. (2) Include clear goals and timelines for climate-related health impact assessments and health adaptation plans at both the national and the regional levels in the National Climate Change Adaptation Strategy for 2035. (3) Strengthen China’s climate mitigation actions and ensure that health is included in China’s pathway to carbon neutrality. By promoting investments in zero-carbon technologies and reducing fossil fuel subsidies, the current rebounding trend in carbon emissions will be reversed and lead to a healthy, low-carbon future. (4) Increase awareness of the linkages between climate change and health at all levels. Health professionals, the academic community, and traditional and new media should raise the awareness of the public and policymakers on the important linkages between climate change and health.</p