Optogenetically engineered Ca2+ oscillation-mediated DRP1 activation promotes mitochondrial fission and cell death.

Mitochondrial dynamics regulate the quality and morphology of mitochondria. Calcium (Ca2+) plays an important role in regulating mitochondrial function. Here, we investigated the effects of optogenetically engineered Ca2+ signaling on mitochondrial dynamics. More specifically, customized illumination conditions could trigger unique Ca2+ oscillation waves to trigger specific signaling pathways. In this study, we found that modulating Ca2+ oscillations by increasing the light frequency, intensity and exposure time could drive mitochondria toward the fission state, mitochondrial dysfunction, autophagy and cell death. Moreover, illumination triggered phosphorylation at the Ser616 residue but not the Ser637 residue of the mitochondrial fission protein, dynamin-related protein 1 (DRP1, encoded by DNM1L), via the activation of Ca2+-dependent kinases CaMKII, ERK and CDK1. However, optogenetically engineered Ca2+ signaling did not activate calcineurin phosphatase to dephosphorylate DRP1 at Ser637. In addition, light illumination had no effect on the expression levels of the mitochondrial fusion proteins mitofusin 1 (MFN1) and 2 (MFN2). Overall, this study provides an effective and innovative approach to altering Ca2+ signaling for controlling mitochondrial fission with a more precise resolution than pharmacological approaches in the temporal dimension.

Microplastic accumulation in bivalves collected from different coastal areas of Vietnam and an assessment of potential risks.

Microplastic (MP) pollution is an emerging problem in many areas around the world and in coastal areas of Vietnam, requiring more studies dedicated to the accumulation of this pollutant in the food chain as well as its potential risk to human health. This study investigated MP levels in tissues of five common bivalve species collected from aquaculture areas along the coast of Vietnam. MPs were found in all bivalve samples, with average values of 10.84 ± 2.61 items/individual or 2.40 ± 1.34 items/g wet weight. Impacts of feeding habits of bivalves showed influences on MP abundance in the samples. Fibers were the dominant shape of MPs recorded, most of which accumulated in the gills and digestive glands of all bivalve samples, with the majority falling within the size range of 300-2000 µm. MPs found in all studied species had relatively similar chemical compositions, mainly composed of polypropylene (PP) and polyethylene (PE). In this study, a diverse diet consisting of different bivalve species and detailed data on the consumption rate of these species were used to assess the human health risk of MPs dedicated to the coastal communities of Vietnam. The results suggested a significant part of MP uptake by human could be via bivalve consumption, in which removing viscera and proper depuration should be applied prior to eating, thereby reducing the risk.

A case-control study of agricultural and behavioral factors associated with leptospirosis in Vietnam.

INTRODUCTION: Leptospirosis is a neglected disease in Vietnam. Until now, there has been limited knowledge about risk factors of this disease in Vietnam. The study was carried out to identify agricultural and behavioral factors associated with the transmission of leptospirosis in Vietnam. METHODS: This matched retrospective hospital-community-based case-control study was conducted from 1 October 2018 to 31 October 2019. We recruited cases from 11 selected government hospitals in three provinces of Vietnam, while controls were selected from the same communes of cases and matched by age (± 2 years) and sex. Microscopic agglutination test (MAT) and enzyme-linked immunosorbent assay (ELISA) were applied to determine confirmed cases, while only MAT was used to identify controls with a single high MAT titer < 1:100. RESULTS: 504 participants (252 cases and 252 controls) were identified. Cultivating (OR 2.83, CI 1.38-5.79), animal farming (OR 8.26, CI 2.24-30.52), pig owners (OR 10.48, CI 5.05-21.73), cat owners (OR 2.62, CI 1.49-4.61) and drinking unboiled water (OR 1.72, CI 1.14 -2.59, p = 0.010) were significantly associated with human leptospirosis in Vietnam. Hand washing after farming/ gardening (OR 0.57, CI 0.38-0.86, p = 0.007) and bathing after farming, gardening, contact with cattle and poultry (OR 0.33, CI 0.19-0.58, p = 0.000) were determined as protective factors for this disease. CONCLUSIONS: In short, the case-control study has revealed the risks in agricultural and animal practices and protective behavioral factors related to human leptospirosis in Vietnam. The findings suggested promotion of communication and health education programs targeting health behaviors in daily life and agricultural practices. Using personal protective equipment such as gowns, gloves, and boots during agricultural practices, especially cultivating and animal farming, is most recommended.

Seasonal changes in phytoplankton assemblages and environmental variables in highly turbid tropical estuaries of the Mekong River, Vietnam.

The distribution of phytoplankton assemblages in response to physicochemical variables was assessed using Spearman's correlation and canonical correspondence analysis in four highly turbid estuaries of the Mekong River (MKR) system in Ben Tre Province, Vietnam. During two surveys (September 2017 and April 2018) at 20 sampling sites, a total of 162 species were recorded, with a dominance of diatoms (> 50%). Phytoplankton abundance varied from 3.01 × 105 to 11.85 × 105 cells/L, with the highest cell densities found at the BL2 station in the rainy season, mainly attributed to cyanobacteria during the rainy period, whereas diatoms were dominant in the dry season. Chlorophyll-a concentration in this area was low and decreased from the mouth stations. Similarity analysis distinguished the freshwater and oligohaline regions (characterized by lower phytoplankton abundance in the oligohaline areas) from the mesohaline and polyhaline zones (characterized by higher phytoplankton density in the polyhaline sections), based on the salinity gradient, which mostly explained the spatio-temporal distribution of phytoplankton. In which, freshwater and oligohaline sites were dominated by the diatom Coscinodiscus, the euglenoids Lepocinclis, and the green alga Scenedesmus in the rainy season, while mesohaline and polyhaline stations were dominated only by diatom species (Thalassionema and Skeletonema) in the dry season. High salinity and total dissolved solutes, and low nutrients are the major factors affecting phytoplankton growth and lead to low density and low primary biomass in turbid estuarine systems like the MKR estuaries. Our results further emphasize the importance of taking into account of salinity in understanding seasonal changes of phytoplankton communities, which can provide a valuable baseline data for ecological management strategies in tropical estuarine ecosystems.

The effect of a dam on the copper accumulation in estuarine sediment and associated nematodes in a Mekong estuary.

Dam construction across the main flow of an estuary can greatly contribute to a high accumulation of inorganic contaminants. However, it remains unknown to what extend externally available heavy metals are incorporated into biota living in those contaminated environments. In this study, the heavy metal copper was investigated both in the sediment and in the tissues of nematodes taken from the subtidal zone in the Ba Lai estuary where a dam is present, and compared with samples from the dam-free Ham Luong estuary, both part of the Mekong Delta. Samples were taken in the dry season of 2017 in four stations in the Ba Lai estuary with two stations in the downstream part from the dam and two upstream. Similar locations with respect to the distance were sampled in the dam-free estuary. The internal copper concentration in nematodes was measured by applying micro X-ray fluorescence. The results showed that both internal and sediment copper concentrations were different between the two estuaries and among estuarine sections. The highest copper concentration in nematodes was found in the upstream section of Ba Lai estuary where the greatest accumulation of sedimentary copper was observed, while the dammed downstream part was lowest in internal copper accumulation. Moreover, there was more variation in the copper levels between the two sections within the dammed estuary compared to those in Ham Luong. These observations might point to the contribution of the Ba Lai dam to the increase of copper contaminants in the benthic environment leading to accumulation in nematodes.

Impact of a dam construction on the intertidal environment and free-living nematodes in the Ba Lai, Mekong Estuaries, Vietnam.

The impact of high siltation and accumulation of organic and waste material in the intertidal of the dammed Ba Lai River in Vietnam as part of the Mekong estuarine system was investigated by means of marine free-living nematodes. Nutrients content (nitrate, ammonium, total phosphorus, total nitrogen), total suspended solids, total organic carbon, coliform, bacteria E. coli, pH, dissolved oxygen, total dissolved solids, methane and hydrogen sulfide concentration, and the nematode communities were characterized in sediment at selected stations along the river above and below the dam. Our results found elevated methane concentrations at the upstream side of the dam while hydrogen sulfide concentrations found to be highest in the downstream side of the dam. Furthermore, methane and hydrogen sulfide concentrations were correlated to nematode community characteristics such as trophic composition densities and genera composition. There was a clear difference between the communities above and below the dam. The discontinuous nematode community distribution indicated that the Ba Lai River is impacted by dam construction. Potentially the high deposition and eutrophication could turn the area into a methane-rich area related to predicted impact on nematodes.

Genetic Determinants and Genotype-Phenotype Correlations in Vietnamese Patients With Dilated Cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is an important cause of heart failure and cardiac transplantation. This study determined the prevalence of DCM-associated genes and evaluated the genotype-phenotype correlation in Vietnamese patients.Methods and Results:This study analyzed 58 genes from 230 patients. The study cohort consisted of 64.3% men; age at diagnosis 47.9±13.7 years; familial (10.9%) and sporadic DCM (82.2%). The diagnostic yield was 23.5%, 44.0% in familial and 19.6% in sporadic DCM.TTNtruncating variants (TTNtv) were predominant (46.4%), followed byTPM1,DSP,LMNA,MYBPC3,MYH6,MYH7,DES,TNNT2,ACTC1,ACTN2,BAG3,DMD,FKTN,PLN,TBX5,RBM20,TCAP(2-6%). Familial DCM, genotype-positive andTTNtv-positive patients were younger than those with genotype-negative and sporadic DCM. Genotype-positive patients displayed a decreased systolic blood pressure and left ventricular wall thickness compared to genotype-negative patients. Genotype-positive patients, particularly those withTTNtv, had a family history of DCM, higher left atrial volume index and body mass index, and lower right ventricle-fractional area change than genotype-negative patients. Genotype-positive patients reached the combined outcomes more frequently and at a younger age than genotype-negative patients. Major cardiac events occurred more frequently in patients positive with genes other thanTTNtv. CONCLUSIONS: The study findings provided an overview of Vietnamese DCM patients' genetic profile and suggested that management of environmental factors may be beneficial for DCM patients.

Cytotoxic constituents from Isotrema tadungense.

In our search for cytotoxic constituents from Vietnamese plants, the methanolic extract of Isotrema tadungense was found to exhibit significant cytotoxic effect. Subsequent phytochemical investigation of ethyl acetate fractions of this plant led to isolation of 11 compounds including one new arylbenzofuran rhamnoside namely aristolochiaside (1), two aristololactams (2 and 3), three lignanamides (4-6) and five phenolic amides (7-11). Their structures were elucidated by 1 D and 2 D NMR and HR-QTOF-MS experiments. Among the isolated compounds, aristolochiaside (1), aristolactam AIIIa (2) and N-trans-sinapoyltyramine (10) exhibited strong and selective cytotoxicity on the HeLa human cancer cell line with IC50 values of 7.59 ± 1.03, 8.51 ± 1.73 and 9.77 ± 1.25 µM, respectively.[Formula: see text].

The Influence of Dopant Concentration on Optical-Electrical Features of Quantum Dot-Sensitized Solar Cell.

In this study, TiO2/CdS/CdxCu1-xSe, TiO2/CdS/CdxMn1-xSe, and TiO2/CdS/CdxAg2-2xSe thin films were synthesized by chemical bath deposition for the fabrication of photoanode in quantum-dot-sensitized solar cells. As a result, the structural properties of the thin films have been studied by X-ray diffraction, which confirmed the zinc Blende structure in the samples. The optical films were researched by their experimental absorption spectra with different doping concentrations. Those results were combined with the Tauc correlation to estimate the absorption density, the band gap energy, valence band and conduction band positions, steepness parameter, and electron-phonon interaction. Furthermore, the electrical features, electrochemical impedance spectrum and photocurrent density curves were carried out. The result was used to explain the enhancing performance efficiency.

Phytochemical Screening and Evaluation of Antioxidant Properties and Antimicrobial Activity against Xanthomonas axonopodis of Euphorbia tirucalli Extracts in Binh Thuan Province, Vietnam.

Euphorbia tirucalli is a medicine plant possessing many bioactive properties. This paper focused on phytochemical screening (alkaloid, flavonoid, saponin, tannin, and anthraquinone), quantification of polyphenol and flavonoids, and activating evaluation of antioxidants and antimicrobial properties against Xanthomonas axonopodis of different extracts from Euphorbia tirucalli grown in Binh Thuan, Vietnam. The best activity fraction was used for purification and determining bioactive ingredients. The results showed that the phytochemical study revealed the presence of alkaloids, flavonoids, tannins, and terpenoids in the ethyl acetate fraction. Saponin and anthraquinone did not present in all extracts. The content of polyphenol and flavonoid of Euphorbia tirucalli stem was in the range of 16.65-106.32 mg EqAG/g and 97.97-450.83 µg QE/g. The ethyl acetate fraction showed higher amounts of polyphenol and flavonoids and antimicrobial activity against X. axonopodis than other fractions. The antioxidant (SC50) activity of Euphorbia tirucalli stem was in the range of 12.91 ± 0.70 and 528.33 ± 25.15 µg/mL. At concentrations of 5.0 and 7.5 mg/mL, the diameter of inhibition of the ethyl acetate fraction was 14.33 ± 0.76 mm and 17.87 ± 0.57 mm, respectively. The MIC (minimum inhibitory concentration) was 0.156 mg/mL. Scopoletin, gallic acid, and piperic acid got MICs corresponding to 78, 312, and 312 µg/mL, respectively. Scopoletin, gallic acid, and piperic acid were found in the ethyl acetate fraction of Euphorbia tirucalli and exhibited the treatment of citrus bacteria canker and plant diseases.

An Elite Hybrid Particle Swarm Optimization for Solving Minimal Exposure Path Problem in Mobile Wireless Sensor Networks.

Mobile wireless sensor networks (MWSNs), a sub-class of wireless sensor networks (WSNs), have recently been a growing concern among the academic community. MWSNs can improve network coverage quality which reflects how well a region of interest is monitored or tracked by sensors. To evaluate the coverage quality of WSNs, we frequently use the minimal exposure path (MEP) in the sensing field as an effective measurement. MEP refers to the worst covered path along which an intruder can go through the sensor network with the lowest possibility of being detected. It is greatly valuable for network designers to recognize the vulnerabilities of WSNs and to make necessary improvements. Most prior studies focused on this problem under a static sensor network, which may suffer from several drawbacks; i.e., failure in sensor position causes coverage holes in the network. This paper investigates the problem of finding the minimal exposure paths in MWSNs (hereinafter MMEP). First, we formulate the MMEP problem. Then the MMEP problem is converted into a numerical functional extreme problem with high dimensionality, non-differentiation and non-linearity. To efficiently cope with these characteristics, we propose HPSO-MMEP algorithm, which is an integration of genetic algorithm into particle swarm optimization. Besides, we also create a variety of custom-made topologies of MWSNs for experimental simulations. The experimental results indicate that HPSO-MMEP is suitable for the converted MMEP problem and performs much better than existing algorithms.

A prospective, open-label, single arm, multicentre study to evaluate efficacy, safety and acceptability of pericoital oral contraception using levonorgestrel 1.5 mg.

STUDY QUESTION: Will the use of levonorgestrel (LNG) 1.5 mg taken at each day of coitus by women who have relatively infrequent sex be an efficacious, safe and acceptable contraceptive method? SUMMARY ANSWER: Typical use of LNG 1.5 mg taken pericoitally, before or within 24 h of sexual intercourse, provides contraceptive efficacy of up to 11.0 pregnancies per 100 women-years (W-Y) in the primary evaluable population and 7.1 pregnancies per 100 W-Y in the evaluable population. WHAT IS KNOWN ALREADY: LNG 1.5 mg is an effective emergency contraception following unprotected intercourse. Some users take it repeatedly, as their means of regular contraception. STUDY DESIGN, SIZE, DURATION: This was a prospective, open-label, single-arm, multicentre Phase III trial study with women who have infrequent coitus (on up to 6 days a month). Each woman had a follow-up visit at 2.5, 4.5 and 6.5 months after admission or until pregnancy occurs if sooner, or she decided to interrupt participation. The study was conducted between 10 January 2012 and 15 November 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 330 healthy fertile women aged 18-45 years at risk of pregnancy who reported sexual intercourse on up to 6 days a month, were recruited from four university centres located in Bangkok, Thailand; Campinas, Brazil; Singapore and Szeged, Hungary to use LNG 1.5 mg pericoitally (24 h before or after coitus) as their primary method of contraception. The participants were instructed to take one tablet every day she had sex, without taking more than one tablet in any 24-h period, and to maintain a paper diary for recording date and time for every coital act and ingestion of the study tablet, use of other contraceptive methods and vaginal bleeding patterns. Anaemia was assessed by haemoglobin evaluation. Pregnancy tests were performed monthly and pregnancies occurring during product use were assessed by ultrasound. At the 2.5-month and final visit at 6.5 months, acceptability questions were administered. MAIN RESULTS AND THE ROLE OF CHANCE: There were 321 women included in the evaluable population (which includes all eligible women enrolled), with 141.9 woman-years (W-Y) of observation and with a rate (95% confidence interval [CI]) of 7.1 (3.8; 13.1) pregnancies per 100 W-Y of typical use (which reflects use of the study drug as main contraceptive method, but also includes possible use of other contraceptives from admission to end of study) and 7.5 (4.0; 13.9) pregnancies per 100 W-Y of sole use. In the primary evaluable population (which includes only eligible enrolled women <35 years old), the rate was 10.3 (5.4; 19.9) pregnancies per 100 W-Y of typical use, and 11.0 (5.7; 13.1) pregnancies per 100 W-Y of sole use. There were three reported severe adverse events and 102 other mild adverse events (most common were headache, nausea, abdominal and pelvic pain), with high recovery rate. The vaginal bleeding patterns showed a slight decrease in volume of bleeding and the number of bleeding-free days increased over time. There was only one case of severe anaemia, found at the final visit (0.4%). The method was considered acceptable, as over 90% of participants would choose to use it in the future or would recommend it to others. LIMITATIONS, REASONS FOR CAUTION: This was a single-arm study with small sample size, without a control group, designed as a proof of concept study to explore the feasibility of this type of contraception. WIDER IMPLICATIONS OF THE FINDINGS: A larger clinical study evaluating pericoital contraception with LNG is feasible and our data show that this method would be acceptable to many women. STUDY FUNDING/COMPETING INTERESTS: This study received partial financial support from the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research (RHR) and the World Health Organization. Gynuity and the Bill and Melinda Gates Foundation (BMGF) provided financial support for project monitoring. HRA Pharma donated the LNG product. N.K. was the initial project manager when she was with WHO/HRP and was employed by HRA Pharma, which distributes LNG for emergency contraception. The other authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: This study was registered on ANZCTR, Trial ID ACTRN12611001037998. TRIAL REGISTRATION DATE: 4 October 2011. DATE OF FIRST PATIENT'S ENROLMENT: 10 January 2012.

Loss of ITM2A, a novel tumor suppressor of ovarian cancer through G2/M cell cycle arrest, is a poor prognostic factor of epithelial ovarian cancer.

OBJECTIVE: Integral membrane protein 2A (ITM2A) is a type 2 transmembrane protein of unknown function. The aim of this study was to investigate its expression pattern, clinical significance, and biological function in epithelial ovarian cancer. METHODS: ITM2A expression in 35 normal, 20 adenoma, 11 borderline and 90 cancerous ovarian tissues was measured by immunohistochemistry. Clinicopathological parameters were obtained from medical records. Survival data was analyzed using Kaplan-Meier estimates and multivariate analysis using the Cox-regression method. Anti-tumor activities of ITM2A were explored by cell proliferation and colony formation assays, flow cytometry, Western blots and animal studies using ovarian cancer cell lines. Chemoresponsiveness was evaluated by measuring IC50 and confirmed by animal studies using an intraperitoneal orthotropic model. RESULTS: ITM2A was significantly downregulated in invasive carcinomas compared to normal, adenoma and borderline tumor tissues. ITM2A loss occurred in 45.6% (41 of 90) of invasive carcinomas and was significantly associated with FIGO stage, type II tumors, suboptimal debulking operation, recurrence and chemoresistance. ITM2A loss and higher FIGO stage were independent factors for poor prognosis. Expression of ITM2A inhibited growth and induced G2/M cell cycle arrest by attenuating cdc2, cyclin B1, cdc25c and p-cdc2 (Thr 161). In vitro and in vivo experiments showed that ITM2A expression significantly reduced the paclitaxel and carboplatin IC50 and tumor mass after paclitaxel treatment. CONCLUSION: ITM2A is a new biomarker of poor prognosis in ovarian cancer. It is a novel tumor suppressor that induces cell cycle arrest, acts as a chemosensitizer, and has therapeutic potential for ovarian cancer.

Hypoxic culture conditions enhance the generation of regulatory T cells.

The generation of large amounts of induced CD4+  CD25+  Foxp3+ regulatory T (iTreg) cells is of great interest for several immunotherapy applications, therefore a better understanding of signals controlling iTreg cell differentiation and expansion is required. There is evidence that oxidative metabolism may regulate several key signalling pathways in T cells. This prompted us to investigate the effects of oxygenation on iTreg cell generation by comparing the effects of atmospheric (21%) or of low (5%) O2 concentrations on the phenotype of bead-stimulated murine splenic CD4+ T cells from Foxp3-KI-GFP T-cell receptor transgenic mice. The production of intracellular reactive oxygen species was shown to play a major role in the generation of iTreg cells, a process characterized by increased levels of Sirt1, PTEN and Glut1 on the committed cells, independently of the level of oxygenation. The suppressive function of iTreg cells generated either in atmospheric or low oxygen levels was equivalent. However, greater yields of iTreg cells were obtained under low oxygenation, resulting from a higher proliferative rate of the committed Treg cells and higher levels of Foxp3, suggesting a better stability of the differentiation process. Higher expression of Glut1 detected on iTreg cells generated under hypoxic culture conditions provides a likely explanation for the enhanced proliferation of these cells as compared to those cultured under ambient oxygen. Such results have important implications for understanding Treg cell homeostasis and developing in vitro protocols for the generation of Treg cells from naive T lymphocytes.

The first mouse mutants of D14Abb1e (Fam208a) show that it is critical for early development.

An ENU mutagenesis screen to identify novel epigenetic modifiers was established in mice carrying a multi-copy GFP transgene, which is expressed in a variegated manner in erythrocytes and is highly sensitive to epigenetic silencing. The screen has produced mouse mutants of both known modifiers of epigenetic state, such as Dnmt1 and Smarca5, and novel modifiers, such as Smchd1 and Rlf. Here we report two mouse lines generated from the screen, MommeD6 and MommeD20, with point mutations in D14Abb1e. These are the first mouse mutants of D14Abb1e (also known as Fam208a), a gene about which little is known. Heterozygous intercrosses show that homozygous mutants from both the MommeD6 and MommeD20 lines are not viable beyond gastrulation, demonstrating an important role for D14Abb1e in development. We demonstrate that haploinsufficiency for D14Abb1e effects transgene expression at the RNA level. Analysis of the predicted D14Abb1e protein sequence reveals that it contains putative nuclear localisation signals and a domain of unknown function, DUF3715. Our studies reveal that D14Abb1e is localised to the nucleus and is expressed in skin and testes.

Quantification of the effects of architectural traits on dry mass production and light interception of tomato canopy under different temperature regimes using a dynamic functional-structural plant model.

There is increasing interest in evaluating the environmental effects on crop architectural traits and yield improvement. However, crop models describing the dynamic changes in canopy structure with environmental conditions and the complex interactions between canopy structure, light interception, and dry mass production are only gradually emerging. Using tomato (Solanum lycopersicum L.) as a model crop, a dynamic functional-structural plant model (FSPM) was constructed, parameterized, and evaluated to analyse the effects of temperature on architectural traits, which strongly influence canopy light interception and shoot dry mass. The FSPM predicted the organ growth, organ size, and shoot dry mass over time with high accuracy (>85%). Analyses of this FSPM showed that, in comparison with the reference canopy, shoot dry mass may be affected by leaf angle by as much as 20%, leaf curvature by up to 7%, the leaf length:width ratio by up to 5%, internode length by up to 9%, and curvature ratios and leaf arrangement by up to 6%. Tomato canopies at low temperature had higher canopy density and were more clumped due to higher leaf area and shorter internodes. Interestingly, dry mass production and light interception of the clumped canopy were more sensitive to changes in architectural traits. The complex interactions between architectural traits, canopy light interception, dry mass production, and environmental conditions can be studied by the dynamic FSPM, which may serve as a tool for designing a canopy structure which is 'ideal' in a given environment.

What are validated self-report adherence scales really measuring?: a systematic review.

AIMS: Medication non-adherence is a significant health problem. There are numerous methods for measuring adherence, but no single method performs well on all criteria. The purpose of this systematic review is to (i) identify self-report medication adherence scales that have been correlated with comparison measures of medication-taking behaviour, (ii) assess how these scales measure adherence and (iii) explore how these adherence scales have been validated. METHODS: Cinahl and PubMed databases were used to search articles written in English on the development or validation of medication adherence scales dating to August 2012. The search terms used were medication adherence, medication non-adherence, medication compliance and names of each scale. Data such as barriers identified and validation comparison measures were extracted and compared. RESULTS: Sixty articles were included in the review, which consisted of 43 adherence scales. Adherence scales include items that either elicit information regarding the patient's medication-taking behaviour and/or attempts to identify barriers to good medication-taking behaviour or beliefs associated with adherence. The validation strategies employed depended on whether the focus of the scale was to measure medication-taking behaviour or identify barriers or beliefs. CONCLUSIONS: Supporting patients to be adherent requires information on their medication-taking behaviour, barriers to adherence and beliefs about medicines. Adherence scales have the potential to explore these aspects of adherence, but currently there has been a greater focus on measuring medication-taking behaviour. Selecting the 'right' adherence scale(s) requires consideration of what needs to be measured and how (and in whom) the scale has been validated.

Optogenetically engineered calcium oscillations promote autophagy-mediated cell death via AMPK activation.

Autophagy is a double-edged sword for cells; it can lead to both cell survival and death. Calcium (Ca2+) signalling plays a crucial role in regulating various cellular behaviours, including cell migration, proliferation and death. In this study, we investigated the effects of modulating cytosolic Ca2+ levels on autophagy using chemical and optogenetic methods. Our findings revealed that ionomycin and thapsigargin induce Ca2+ influx to promote autophagy, whereas the Ca2+ chelator BAPTA-AM induces Ca2+ depletion and inhibits autophagy. Furthermore, the optogenetic platform allows the manipulation of illumination parameters, including density, frequency, duty cycle and duration, to create different patterns of Ca2+ oscillations. We used the optogenetic tool Ca2+-translocating channelrhodopsin, which is activated and opened by 470 nm blue light to induce Ca2+ influx. These results demonstrated that high-frequency Ca2+ oscillations induce autophagy. In addition, autophagy induction may involve Ca2+-activated adenosine monophosphate (AMP)-activated protein kinases. In conclusion, high-frequency optogenetic Ca2+ oscillations led to cell death mediated by AMP-activated protein kinase-induced autophagy.

Heterologous expression of pediocin PA-1 in Pichia pastoris: cloning, expression, characterization, and application in pork bologna preservation.

OBJECTIVE: Pediocin PA-1, an antimicrobial peptide derived from Pediococcus acidilactici PAC1.0, has a potential application as a food preservative thanks to its strong inhibitory activity against the foodborne pathogen L. monocytogenes. This study aimed to produce Pediocin PA-1 from the yeast P. pastoris and evaluate its characteristics. METHODS: Gene encoding Pediocin PA-1 was integrated into P. pastoris X33 genome to establish the strain X33::ped, which could produce and secrete this peptide into culture medium. The antimicrobial activity of Pediocin PA-1 was examined using agar diffusion assay. The stability of pediocin PA-1 was determined based on its remaining antibacterial activity after exposure to proteases and extreme pH and temperatures. The potential use of this bacteriocin in food preservation was demonstrated using the L. monocytogenes infected pork bologna. The anticancer activity of Pediocin PA-1 was also investigated on some cancer cells using MTT assay. RESULTS: We established the yeast P. pastoris X33::ped capable of producing pediocin PA-1 with antimicrobial activity against L. monocytogenes and some other harmful bacteria. Pediocin PA-1 was stable at 100˚C and resistant against pH 1-12 for 1 h, but susceptible to trypsin, α-chymotrypsin, and proteinase K. This peptide could reduce the number of L. monocytogenes in pork bologna by 3.59 log CFU/g after 7 days of storage at 4˚C. Finally, Pediocin PA-1 (25 µg/ml) inhibited the proliferation of A549 and Hela cancer cells. CONCLUSION: We succeeded in producing active Pediocin PA-1 from P. pastoris and demonstrated its potential use in food preservation and pharmaceutical industry.

Store-operated calcium entry inhibits primary ciliogenesis via the activation of Aurora A.

The primary cilium is an antenna-like organelle protruding from the cell surface that can detect physical and chemical stimuli in the extracellular space to activate specific signaling pathways and downstream gene expressions. Calcium ion (Ca2+ ) signaling regulates a wide spectrum of cellular processes, including fertilization, proliferation, differentiation, muscle contraction, migration, and death. This study investigated the effects of the regulation of cytosolic Ca2+ levels on ciliogenesis using chemical, genetic, and optogenetic approaches. We found that ionomycin-induced Ca2+ influx inhibited ciliogenesis and Ca2+ chelator BATPA-AM-induced Ca2+ depletion promoted ciliogenesis. In addition, store-operated Ca2+ entry and the endoplasmic reticulum Ca2+ sensor stromal interaction molecule 1 (STIM1) negatively regulated ciliogenesis. Moreover, an optogenetic platform was used to create different Ca2+ oscillation patterns by manipulating lighting parameters, including density, frequency, exposure time, and duration. Light-activated Ca2+ -translocating channelrhodopsin (CatCh) is activated by 470-nm blue light to induce Ca2+ influx. Our results show that high-frequency Ca2+ oscillations decrease ciliogenesis. Furthermore, the inhibition of cilia formation induced by Ca2+ may occur via the activation of Aurora kinase A. Cilia not only induce Ca2+ signaling but also regulate cilia formation by Ca2+ signaling.