Coenzyme Q10 protects against β-cell toxicity induced by pravastatin treatment of hypercholesterolemia

New onset of diabetes is associated with the use of statins. We have recently demonstrated that pravastatin-treated hypercholesterolemic LDL receptor knockout (LDLr^−/−) mice exhibit reductions in insulin secretion and increased islet cell death and oxidative stress. Here, we hypothesized that these diabetogenic effects of pravastatin could be counteracted by treatment with the antioxidant coenzyme Q ₁₀ (CoQ ₁₀), an intermediate generated in the cholesterol synthesis pathway. LDLr ^−/− mice were treated with pravastatin and/or CoQ ₁₀ for 2 months. Pravastatin treatment resulted in a 75% decrease of liver CoQ ₁₀ content. Dietary CoQ ₁₀ supplementation of pravastatin-treated mice reversed fasting hyperglycemia, improved glucose tolerance (20%) and insulin sensitivity (>2-fold), and fully restored islet glucose-stimulated insulin secretion impaired by pravastatin (40%). Pravastatin had no effect on insulin secretion of wild-type mice. In vitro, insulin-secreting INS1E cells cotreated with CoQ ₁₀ were protected from cell death and oxidative stress induced by pravastatin. Simvastatin and atorvastatin were more potent in inducing dose-dependent INS1E cell death (10–15-fold), which were also attenuated by CoQ ₁₀ cotreatment. Together, these results demonstrate that statins impair β-cell redox balance, function and viability. However, CoQ ₁₀ supplementation can protect the statins detrimental effects on the endocrine pancreas.     

Lipid-Conjugated Rigidochromic Probe Discloses Membrane Alteration in Model Cells of Krabbe Disease

The plasma membrane of cells has a complex architecture based on the bidimensional liquid-crystalline bilayer arrangement of phospho- and sphingolipids, which in turn embeds several proteins and is connected to the cytoskeleton. Several studies highlight the spatial membrane organization into more ordered (L_o or lipid raft) and more disordered (L_d) domains. We here report on a fluorescent analog of the green fluorescent protein chromophore that, when conjugated to a phospholipid, enables the quantification of the L_o and L_d domains in living cells on account of its large fluorescence lifetime variation in the two phases. The domain composition is straightforwardly obtained by the phasor approach to confocal fluorescence lifetime imaging, a graphical method that does not require global fitting of the fluorescence decay in every spatial position of the sample. Our imaging strategy was applied to recover the domain composition in human oligodendrocytes at rest and under treatment with galactosylsphingosine (psychosine). Exogenous psychosine administration recapitulates many of the molecular fingerprints of a severe neurological disease, globoid cell leukodystrophy, better known as Krabbe disease. We found out that psychosine progressively destabilizes plasma membrane, as witnessed by a shrinking of the L_o fraction. The unchanged levels of galactosyl ceramidase, i.e., the enzyme lacking in Krabbe disease, upon psychosine treatment suggest that psychosine alters the plasma membrane structure by direct physical effect, as also recently demonstrated in model membranes.     

Introducing “best single template” models as reference baseline for the Continuous Automated Model Evaluation (CAMEO)

Critical blind assessment of structure prediction techniques is crucial for the scientific community to establish the state of the art, identify bottlenecks, and guide future developments. In Critical Assessment of Techniques in Structure Prediction (CASP), human experts assess the performance of participating methods in relation to the difficulty of the prediction task in a biennial experiment on approximately 100 targets. Yet, the development of automated computational modeling methods requires more frequent evaluation cycles and larger sets of data. The “Continuous Automated Model EvaluatiOn (CAMEO)” platform complements CASP by conducting fully automated blind prediction evaluations based on the weekly pre-release of sequences of those structures, which are going to be published in the next release of the Protein Data Bank (PDB). Each week, CAMEO publishes benchmarking results for predictions corresponding to a set of about 20 targets collected during a 4-day prediction window. CAMEO benchmarking data are generated consistently for all methods at the same point in time, enabling developers to cross-validate their method's performance, and referring to their results in publications. Many successful participants of CASP have used CAMEO—either by directly benchmarking their methods within the system or by comparing their own performance to CAMEO reference data. CAMEO offers a variety of scores reflecting different aspects of structure modeling, for example, binding site accuracy, homo-oligomer interface quality, or accuracy of local model confidence estimates. By introducing the "bestSingleTemplate" method based on structure superpositions as a reference for the accuracy of 3D modeling predictions, CAMEO facilitates objective comparison of techniques and fosters the development of advanced methods.     

Patient-level interventions to reduce alcohol-related harms in low- and middle-income countries: A systematic review and meta-summary

BackgroundDisease and disability from alcohol use disproportionately impact people in low- and middle-income countries (LMICs). While varied interventions have been shown to reduce alcohol use in high-income countries, their efficacy in LMICs has not been assessed. This systematic review describes current published literature on patient-level alcohol interventions in LMICs and specifically describes clinical trials evaluating interventions to reduce alcohol use in LMICs.Methods and findingsIn accordance with PRISMA, we performed a systematic review using an electronic search strategy from January 1, 1995 to December 1, 2020. Title, abstract, as well as full-text screening and extraction were performed in duplicate. A meta-summary was performed on randomized controlled trials (RCTs) that evaluated alcohol-related outcomes. We searched the following electronic databases: PubMed, EMBASE, Scopus, Web of Science, Cochrane, WHO Global Health Library, and PsycINFO. Articles that evaluated patient-level interventions targeting alcohol use and alcohol-related harm in LMICs were eligible for inclusion. No studies were excluded based on language.After screening 5,036 articles, 117 articles fit our inclusion criteria, 75 of which were RCTs. Of these RCTs, 93% were performed in 13 middle-income countries, while 7% were from 2 low-income countries. These RCTs evaluated brief interventions (24, defined as any intervention ranging from advice to counseling, lasting less than 1 hour per session up to 4 sessions), psychotherapy or counseling (15, defined as an interaction with a counselor longer than a brief intervention or that included a psychotherapeutic component), health promotion and education (20, defined as an intervention encouraged individuals’ agency of taking care of their health), or biologic treatments (19, defined as interventions where the biological function of alcohol use disorder (AUD) as the main nexus of intervention) with 3 mixing categories of intervention types. Due to high heterogeneity of intervention types, outcome measures, and follow-up times, we did not conduct meta-analysis to compare and contrast studies, but created a meta-summary of all 75 RCT studies. The most commonly evaluated intervention with the most consistent positive effect was a brief intervention; similarly, motivational interviewing (MI) techniques were most commonly utilized among the diverse array of interventions evaluated.ConclusionsOur review demonstrated numerous patient-level interventions that have the potential to be effective in LMICs, but further research to standardize interventions, populations, and outcome measures is necessary to accurately assess their effectiveness. Brief interventions and MI techniques were the most commonly evaluated and had the most consistent positive effect on alcohol-related outcomes.Trial registrationProtocol Registry: PROSPERO CRD42017055549

Catherine Staton and co-workers report on evidence about interventions against harmful alcohol use in low- and middle-income countries.     

Prevalence rate and risk factors of human cystic echinococcosis: A cross-sectional,community-based,abdominal ultrasound study in rural and urban north-central Chile

BackgroundCystic echinococcosis (CE) caused by Echinococcus granulosus sensu lato (s.l.) is a neglected and underdiagnosed parasitic zoonosis that has a significant socioeconomic impact on rural communities relying on livestock farming. CE is endemic across Latin America, including Chile, where the Coquimbo region exhibits a relatively high record of hospital-based human cases and infected animals. However, the incidence of hospitalized CE cases may underestimate the real burden of infection in a population, since the majority of cases never reach medical attention or official disease records.Methodology/Principal findingsIn 2019, a cross-sectional, community-based study was conducted with the objectives of estimating for the first time the prevalence of human abdominal CE using abdominal ultrasound (US) screening in volunteers residing in urban and rural localities of the Monte Patria municipality located in Limarí province, Coquimbo region, Chile, and identifying the risk factors associated with human infection. Pre-screening activities included a 16-h lecture/hands-on training aimed at rural physicians that focused on the diagnosis of CE by US, based on current WHO recommendations. A total of 2,439 (~8% of municipality inhabitants) people from thirteen target localities were screened by abdominal US in June-July 2019. We found an overall CE prevalence of 1.6% (95% CI 1.1–2.2) with a significantly higher likelihood of infection in rural localities, older age classes and people drinking non-potable water; 84.6% of infected volunteers were newly diagnosed with CE. Cysts were either in active or inactive stages in equal proportions; active cysts were detected in all age classes, while 95.7% of inactive cysts occurred in >40 years-old subjects.Conclusions/SignificanceThis is the first US survey aimed at detecting human infection caused by Echinococcus granulosus s.l. in Chile. Our findings indicate a high CE prevalence in the area, and contribute to define the demographic and behavioral risk factors promoting the transmission of the parasitic infection within target communities. Our results support the implementation of cost-effective strategies for the diagnosis, treatment and control of CE, and the need to improve the epidemiological surveillance system in Chile.     

Structural and functional diversity of lectin repertoires in invertebrates, protochordates and ectothermic vertebrates

During the past few years, substantial progress has been accomplished in the elucidation of the structural diversity of the lectin repertoires of invertebrates, protochordates and ectothermic vertebrates, providing particularly valuable information on those groups that constitute the invertebrate/vertebrate 'boundary'. Although representatives of lectin families typical of mammals, such as C-type lectins, galectins and pentraxins, have been described in these taxa, the detailed study of selected model species has yielded either novel variants of the structures described for the mammalian lectin representatives or novel lectin families with unique sequence motifs, multidomain arrangements and a new structural fold. Along with the high structural diversity of the lectin repertoires in these taxa, a wide spectrum of biological roles is starting to emerge, underscoring the value of invertebrate and lower vertebrate models for gaining insight into structural, functional and evolutionary aspects of lectins.     

Photochemical efficiency of adult and young leaves of the neotropical understory shrub Psychotria limonensis (Rubiaceae) in response to changes in the light environment

We explored the short-term adjustment in photochemical efficiency (Fv/Fm) in adult and young leaves of the understory neotropical shrub Psychotria limonensis Krause (Rubiaceae) in response to rapid changes in the light environment. Leaves were collected from 20 individual plants growing under sun and shade conditions on Gigante Peninsula, Barro Colorado Natural Monument (Republic of Panama), during the wet season of 1996. Leaves were distributed in four sequences of light treatments (AB leaves were expanded under sun and were transferred to shade, BA leaves experienced the opposite transfer, and the controls AA and BB leaves that were expanded and maintained under sun or shade conditions). Adult and young leaves did not differ in overall photochemical efficiency. Instead, differences were found among light environments, for which leaves transferred from shade to sun showed the lowest Fv/Fm ratios. There was no relationship between photochemical efficiency and leaf temperature. In P. limonensis, understory plants are susceptible of photoinhibition independently of the leaf ontogenetic stage. The approach utilized in this experiment allowed the rapid exploration of this capacity, and could be applied to poorly studied understory species.     

Expression of ornithine decarboxylase of Coccidioides immitis in three Escherichia coli strains carrying the lambda DE3 lysogen and an E. coli EWH319 strain odc − null mutant

Ornithine decarboxylase from respiratory fungal pathogen, Coccidioides immitis, cloned in the pETCiODC plasmid under control of T7lac promoter, was produced in E. coli BL21(DE3), BL21(DE3)pLysS, BLR(DE3) and EWH319 transformant strains. E. coli BL21(DE3)pLysS-pETCiODC expressed the highest specific activity of ODC, suggesting that this strain could be successfully used for protein structure and drug testing studies.     

Description of two new species of Glypthelmins Stafford, 1905 (Digenea: Macroderoididae) in Rana spp. from Mexico, based on morphology and mtDNA and rDNA sequences

Glypthelmins Stafford, 1905 includes 29 putative species commonly found in the intestine and liver of anurans from all over the world but mainly in the Americas. Partial sequences of the cytochrome c oxidase subunit 1 ( cox 1), ribosomal internal transcribed spacer region 2 (ITS2) and the large subunit 28S rDNA gene were obtained and analysed using pairwise distance matrices and parsimony methods in order to characterise the interrelationships between 14 isolates of four nominal species of Glypthelmins recognised on morphological grounds. The highest intra-specific sequence divergence occurred in the cox 1 (18.53%) sequence, followed by that of the ITS2 (5.44%) and 28S (4.63%). Genetic variability was detected between the three isolates originally identified as G. facioi Brenes et al., 1959 from two localities in Mexico and one locality in Costa Rica. Sequence divergence exhibited among these isolates ranged from 10.70 to 11.22%, from 0.48 to 0.97% and from 1.33 to 1.88% for cox 1, ITS2 and 28S, respectively. Phylogenetic analysis combining all three data-sets generated a single most parsimonious tree. The three isolates of G. facioi form a clade, with an isolate collected from frogs in Veracruz State as the sister group to an isolate from Tabasco State + G. facioi from Costa Rica. The information derived from pairwise distance of independent data-sets plus the phylogenetic information indicate that each of the two isolates from Mexico, identified a priori as G. facioi, represent separate species. A re-examination of specimens was carried out and a re-evaluation made of the morphological characters to find reliable differences that had been overlooked. As a consequence, G. brownorumae n. sp. from Tabasco and G. tuxtlasensis n. sp. from Veracruz are described based on molecular and morphological differences.     

Lack of alterations on meiotic chromosomes and morphological characteristics of male germ cells in mice exposed to a 60 Hz and 2.0 mT magnetic field

The effect of in vivo exposure of mice to a 60 Hz sinusoidal magnetic field (MF) at 2.0 mT on male germ cells was studied. The cytological endpoints measured included meiotic chromosome aberrations in spermatocytes and sperm morphology. Three independent experiments were carried out: (a) animals exposed for 72 h, (b) 10 days/8 h daily, and (c) 72 h exposure to MF plus 5 mg/kg of Mitomycin-C. No statistically significant differences indicative of MF effects were observed between MF exposed and control animals. In addition, an opposite effect between MF exposure and Mitomycin-C treatment in terms of chromosomal aberrations and sperm morphology was observed.