Role of microRNAs in translation regulation and cancer

MicroRNAs (miRNAs) are pervasively expressed and regulate most biological functions. They function by modulating transcriptional and translational programs and therefore they orchestrate both physiological and pathological processes, such as development, cell differentiation, proliferation, apoptosis and tumor growth. miRNAs work as small guide molecules in RNA silencing, by negatively regulating the expression of several genes both at mRNA and protein level, by degrading their mRNA target and/or by silencing translation. One of the most recent advances in the field is the comprehension of their role in oncogenesis. The number of miRNA genes is increasing and an alteration in the level of miRNAs is involved in the initiation, progression and metastases formation of several tumors. Some tumor types show a distinct miRNA signature that distinguishes them from normal tissues and from other cancer types. Genetic and biochemical evidence supports the essential role of miRNAs in tumor development. Although the abnormal expression of miRNAs in cancer cells is a widely accepted phenomenon, the cause of this dysregulation is still unknown. Here, we discuss the biogenesis of miRNAs, focusing on the mechanisms by which they regulate protein synthesis. In addition we debate on their role in cancer, highlighting their potential to become therapeutic targets

High levels of shading as a sustainable application for mitigating drought, in modern apple production

The sustainability of reducing light in apple orchards under well-watered (ww) and water stress (ws) conditions was evaluated for water relations, plant gas exchanges, fruit growth, yield determinants, and fruit quality over three years. A black (B) 28% shading net was compared with two different 50% shading nets: red (R) and white (W). Each net was combined with two irrigation regimes (ww and ws) based on plant water status. Under ww and ws conditions, increasing shade from 28% to 50% was not detrimental for plant gas exchanges, yield, or quality over three years. Higher shade improved plant water status regardless of irrigation regime. Higher shading could be considered sustainable in apple orchards over several seasons. Fruit quality was more sensitive to plant water status than to light reduction. ws increased fruit soluble solid content and relative dry matter, regardless of shading, and this was positively reflected in consumer’s preference. When water availability is limited, increasing shading to 50% can help save water and maintain high-quality yields associated with water stress. Given the likely reductions of water availability in agriculture, growers and consultants may consider shading apple orchards as a sustainable and safe horticultural technique to save water

Effects of the COVID-19 lockdown on glycaemic control in subjects with type 2 diabetes: the glycalock study

Aim: To assess the effect of the coronavirus disease 2019 (COVID-19) lockdown on glycaemic control in subjects with type 2 diabetes (T2D). Materials and Methods: In this observational, multicentre, retrospective study conducted in the Lazio region, Italy, we compared the differences in the HbA1c levels of 141 subjects with T2D exposed to lockdown with 123 matched controls with T2D who attended the study centres 1 year before. Basal data were collected from 9 December to 9 March and follow-up data from 3 June to 10 July in 2020 for the lockdown group, and during the same timeframes in 2019 for the control groups. Changes in HbA1c (ΔHbA1c) and body mass index (ΔBMI) during lockdown were compared among patients with different psychological well-being, as evaluated by tertiles of the Psychological General Well-Being Index (PGWBS). Results: No difference in ΔHbA1c was found between the lockdown and control groups (lockdown group −0.1% [−0.5%−0.3%] vs. control group −0.1% [−0.4%−0.2%]; p =.482). Also, no difference was found in ΔBMI (p =.316) or ΔGlucose (p =.538). In the lockdown group, subjects with worse PGWBS showed a worsening of HbA1c (p =.041 for the trend among PGWBS tertiles) and BMI (p =.022). Conclusions: The COVID-19 lockdown did not significantly impact glycaemic control in people with T2D. People with poor psychological well-being may experience a worsening a glycaemic control because of restrictions resulting from lockdown. These findings may aid healthcare providers in diabetes management once the second wave of COVID-19 has ended

Current evidence to propose different food supplements for weight loss: a comprehensive review

The use of food supplements for weight loss purposes has rapidly gained popularity as the prevalence of obesity increases. Navigating through the vast, often low quality, literature available is challenging, as is providing informed advice to those asking for it. Herein, we provide a comprehensive literature revision focusing on most currently marketed dietary supplements claimed to favor weight loss, classifying them by their purported mechanism of action. We conclude by proposing a combination of supplements most supported by current evidence, that leverages all mechanisms of action possibly leading to a synergistic effect and greater weight loss in the foreseen absence of adverse events. Further studies will be needed to confirm the weight loss and metabolic improvement that may be obtained through the use of the proposed combination

Discovery and Preliminary Characterization of Translational Modulators that Impair the Binding of eIF6 to 60S Ribosomal Subunits

Eukaryotic initiation factor 6 (eIF6) is necessary for the nucleolar biogenesis of 60S ribosomes. However, most of eIF6 resides in the cytoplasm, where it acts as an initiation factor. eIF6 is necessary for maximal protein synthesis downstream of growth factor stimulation. eIF6 is an antiassociation factor that binds 60S subunits, in turn preventing premature 40S joining and thus the formation of inactive 80S subunits. It is widely thought that eIF6 antiassociation activity is critical for its function. Here, we exploited and improved our assay for eIF6 binding to ribosomes (iRIA) in order to screen for modulators of eIF6 binding to the 60S. Three compounds, eIFsixty-1 (clofazimine), eIFsixty-4, and eIFsixty-6 were identified and characterized. All three inhibit the binding of eIF6 to the 60S in the micromolar range. eIFsixty-4 robustly inhibits cell growth, whereas eIFsixty-1 and eIFsixty-6 might have dose- and cell-specific effects. Puromycin labeling shows that eIF6ixty-4 is a strong global translational inhibitor, whereas the other two are mild modulators. Polysome profiling and RT-qPCR show that all three inhibitors reduce the specific translation of well-known eIF6 targets. In contrast, none of them affect the nucleolar localization of eIF6. These data provide proof of principle that the generation of eIF6 translational modulators is feasible

Yield sensing technologies for perennial and annual horticultural crops: a review

Yield maps provide a detailed account of crop production and potential revenue of a farm. This level of details enables a range of possibilities from improving input management, conducting on-farm experimentation, or generating profitability map, thus creating value for farmers. While this technology is widely available for field crops such as maize, soybean and grain, few yield sensing systems exist for horticultural crops such as berries, field vegetable or orchards. Nevertheless, a wide range of techniques and technologies have been investigated as potential means of sensing crop yield for horticultural crops. This paper reviews yield monitoring approaches that can be divided into proximal, either direct or indirect, and remote measurement principles. It reviews remote sensing as a way to estimate and forecast yield prior to harvest. For each approach, basic principles are explained as well as examples of application in horticultural crops and success rate. The different approaches provide whether a deterministic (direct measurement of weight for instance) or an empirical (capacitance measurements correlated to weight for instance) result, which may impact transferability. The discussion also covers the level of precision required for different tasks and the trend and future perspectives. This review demonstrated the need for more commercial solutions to map yield of horticultural crops. It also showed that several approaches have demonstrated high success rate and that combining technologies may be the best way to provide enough accuracy and robustness for future commercial systems

Aspirin for primary prevention of ST segment elevation myocardial infarction in persons with diabetes and multiple risk factors

Controversy exists as to whether low-dose aspirin use may give benefit in primary prevention of cardiovascular (CV) events. We hypothesized that the benefits of aspirin are underevaluated. We investigated 12,123 Caucasian patients presenting to hospital with acute coronary syndromes as first manifestation of CV disease from 2010 to 2019 in the ISACS-TC multicenter registry (ClinicalTrials.gov, NCT01218776). Individual risk of ST segment elevation myocardial infarction (STEMI) and its association with 30-day mortality was quantified using inverse probability of treatment weighting models matching for concomitant medications. Estimates were compared by test of interaction on the log scale. The risk of STEMI was lower in the aspirin users (absolute reduction: 6·8%; OR: 0·73; 95%CI: 0·65-0·82) regardless of sex (p for interaction=0·1962) or age (p for interaction=0·1209). Benefits of aspirin were seen in patients with hypertension, hypercholesterolemia, and in smokers. In contrast, aspirin failed to demonstrate a significant risk reduction in STEMI among diabetic patients (OR:1·10;95%CI:0·89-1·35) with a significant interaction (p: <0·0001) when compared with controls (OR:0·64,95%CI:0·56-0·73). Stratification of diabetes in risk categories revealed benefits (p interaction=0·0864) only in patients with concomitant hypertension and hypercholesterolemia (OR:0·87, 95% CI:0·65-1·15), but not in smokers. STEMI was strongly related to 30-day mortality (OR:1·93; 95%CI:1·59-2·35) Low-dose aspirin reduces the risk of STEMI as initial manifestation of CV disease with potential benefit in mortality. Patients with diabetes derive substantial benefit from aspirin only in the presence of multiple risk factors. In the era of precision medicine, a more tailored strategy is required

Understanding nanoscale temperature gradients in magnetic nanocontacts

We determine the temperature profile in magnetic nanocontacts submitted to the very large current densities that are commonly used for spin-torque oscillator behavior. Experimentally, the quadratic current-induced increase of the resistance through Joule heating is independent of the applied temperature from 6 K to 300 K. The modeling of the experimental rate of the current-induced nucleation of a vortex under the nanocontact, assuming a thermally-activated process, is consistent with a local temperature increase between 150 K and 220 K. Simulations of heat generation and diffusion for the actual tridimensional geometry were conducted. They indicate a temperature-independent efficiency of the heat sinking from the electrodes, combined with a localized heating source arising from a nanocontact resistance that is also essentially temperature-independent. For practical currents, we conclude that the local increase of temperature is typically 160 K and it extends 450 nm about the nanocontact. Our findings imply that taking into account the current-induced heating at the nanoscale is essential for the understanding of magnetization dynamics in nanocontact systems.Comment: 5 pages, 5 figure

Delayed Care and Mortality Among Women and Men with Myocardial Infarction

Background-Women with ST-segment-elevation myocardial infarction (STEMI) have higher mortality rates than men. We investigated whether sex-related differences in timely access to care among STEMI patients may be a factor associated with excess risk of early mortality in women. Methods and Results-We identified 6022 STEMI patients who had information on time of symptom onset to time of hospital presentation at 41 hospitals participating in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry (NCT01218776) from October 2010 through April 2016. Patients were stratified into time-delay cohorts. We estimated the 30-day risk of all-cause mortality in each cohort. Despite similar delays in seeking care, the overall time from symptom onset to hospital presentation was longer for women than men (median: 270 minutes [range: 130-776] versus 240 minutes [range: 120-600]). After adjustment for baseline variables, female sex was independently associated with greater risk of 30-day mortality (odds ratio: 1.58; 95% confidence interval, 1.27-1.97). Sex differences in mortality following STEMI were no longer observed for patients having delays from symptom onset to hospital presentation of (odds ratio: 0.77; 95% confidence interval, 0.29-2.02). Conclusions-Sex difference in mortality following STEMI persists and appears to be driven by prehospital delays in hospital presentation. Women appear to be more vulnerable to prolonged untreated ischemia

Incidence of Type 1 Diabetes Has Doubled in Rome and the Lazio Region in the 0- to 14-Year Age-Group: A 6-Year Prospective Study (2004-2009)

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