Autophagy is a highly regulated process that has an important role in the control of a wide range of cellular functions, such as organelle recycling, nutrient availability and tissue differentiation. ...A recent study has shown an increased autophagic activity in the adipose tissue of obese subjects, and a role for autophagy in obesity-associated insulin resistance was proposed. Body mass reduction is the most efficient approach to tackle insulin resistance in over-weight subjects; however, the impact of weight loss in adipose tissue autophagy is unknown.
Adipose tissue autophagy was evaluated in mice and humans.
First, a mouse model of diet-induced obesity and diabetes was maintained on a 15-day, 40% caloric restriction. At baseline, markers of autophagy were increased in obese mice as compared with lean controls. Upon caloric restriction, autophagy increased in the lean mice, whereas it decreased in the obese mice. The reintroduction of ad libitum feeding was sufficient to rapidly reduce autophagy in the lean mice and increase autophagy in the obese mice. In the second part of the study, autophagy was evaluated in the subcutaneous adipose tissue of nine obese-non-diabetic and six obese-diabetic subjects undergoing bariatric surgery for body mass reduction. Specimens were collected during the surgery and approximately 1 year later. Markers of systemic inflammation, such as tumor necrosis factor-1α, interleukin (IL)-6 and IL-1β were evaluated. As in the mouse model, human obesity was associated with increased autophagy, and body mass reduction led to an attenuation of autophagy in the adipose tissue.
Obesity and caloric overfeeding are associated with the defective regulation of autophagy in the adipose tissue. The studies in obese-diabetic subjects undergoing improved metabolic control following calorie restriction suggest that autophagy and inflammation are regulated independently.
Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 ...December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.
Aquaculture production has been sharply increasing in Brazil in the last years. Many classes of antimicrobials are commonly used in aquaculture worldwide to treat infections caused by a variety of ...bacterial pathogens and they are also used as a growth promoter. However, these intense uses may cause environmental contamination and bacterial resistance. A method was developed and validated for simultaneous assessment of 12 drugs of different antimicrobial classes (chloramphenicol, florfenicol, oxytetracycline, tetracycline, chlortetracycline, sulfadimethoxine, sulfathiazole, sulfamethazine, enrofloxacin, ciprofloxacin, norfloxacin, and sarafloxacin) on the Nile tilapia's muscle (Oreochromis niloticus). This study presents the development of a rapid method using ultrafiltration by Captiva cartridges and liquid chromatography tandem mass spectrometry triple quadrupole (Agilent 6430 - Agilent Technologies) in a negative mode for florfenicol and a positive mode for the others. The sample pretreatment involves extraction with 5 g of muscle fish, 1mL of 0.1M Na2EDTA and 24mL of acetonitrile: water (0.1% formic acid; 70:30), and purification by Captiva cartridges, followed by the determination of all compounds in a single run. Sulfadimethoxine-d6 was used as an internal standard to obtain more reliable results. The developed method was validated based on Eurachem Guide: The fitness for purpose of analytical methods, with the calibration curves carried out at blank samples spiked, matrix-matched calibration (MMC). The limits of quantification were lower than 4.3μgkg−1 for all compounds; calibration curve showed linearity at the work range, recovery ranged from 83.8% to 110.1%, and accuracy was lower than 5.5%. The developed analytical method was successfully applied in 36 fish samples collected in 4 fish farms in the most important producing region of São Paulo State, Brazil.
•Efficient method for determination of antibiotic residues in tilapia muscle by LC–MS/MS.•The method allows the simultaneous analysis of 12 different antibiotics.•Simple sample preparation by ultrafiltration using Captiva cartridges.•The method was tested with tilapia samples collected from cage farms in Brazil.•The proposed method offers possibilities to be used in food safety monitoring research and quality control.
Yacon (Smallanthus sonchifolius), a perennial plant of the family Asteraceae native to the Andean regions of South America, is an abundant source of fructooligosaccharides (FOS). This comprehensive ...review of the literature addressed the role of yacon supplementation in promoting health and reducing the risk of chronic diseases. According to several preclinical and clinical trials, FOS intake favors the growth of health-promoting bacteria while reducing pathogenic bacteria populations. Moreover, the endproducts of FOS fermentation by the intestinal microbiota, short chain fatty acids (SCFA), act as substrates or signaling molecules in the regulation of the immune response, glucose homeostasis and lipid metabolism. As a result, glycemic levels, body weight and colon cancer risk can be reduced. Based on these findings, most studies reviewed concluded that due to their functional properties, yacon roots may be effectively used as a dietary supplement to prevent and treat chronic diseases.
In the past months, the use of the drug hydroxychloroquine has considerably increased in many countries, associated with a proposed treatment for the COVID-19 disease. Although there is no conclusive ...evidence about the efficacy of the drug for this purpose, surprisingly there are no conclusive studies in the literature concerning its mechanism of action inside cells, which is related to its interaction with nucleic acids. Here, we performed a robust characterization of the interaction between hydroxychloroquine and double-stranded DNA using single-molecule force spectroscopy and gel electrophoresis. Two different binding modes were identified, namely, minor groove binding for low drug concentrations and intercalation for high drug concentrations, and the sets of binding parameters were determined for each of these modes. Such results have unraveled in detail the molecular mechanism of action of the drug as a DNA ligand.
Background
Xeroderma pigmentosum (XP) patients present a high risk of developing skin cancer and other complications at an early age. This disease is characterized by mutations in the genes related ...to the DNA repair system.
Objectives
To describe the clinical and molecular findings in a cohort of 32 Brazilian individuals who received a clinical diagnosis of XP.
Methods
Twenty‐seven families were screened for germline variants in eight XP‐related genes.
Results
All patients (N = 32) were diagnosed with bi‐allelic germline pathogenic or potentially pathogenic variants, including nine variants previously undescribed. The c.2251‐1G>C XPC pathogenic variant, reported as the founder mutation in Comorian and Pakistani patients, was observed in 15 cases in homozygous or compound heterozygous. Seven homozygous patients for POLH/XPV variants developed their symptoms by an average age of 7.7 years. ERCC2/XPD, DDB2/XPE and ERCC5/XPG variants were found in a few patients. Aside from melanoma and non‐melanoma skin tumours, a set of patients developed skin sebaceous carcinoma, leiomyosarcoma, angiosarcoma, mucoepidermoid carcinoma, gastric adenocarcinoma and serous ovarian carcinoma.
Conclusions
We reported a high frequency of XPC variants in 32 XP Brazilian patients. Nine new variants in XP‐related genes, unexpected non‐skin cancer lesions and an anticipation of the clinical manifestation in POLH/XPV cases were also described.
The carbon gain in restored logged forest
There is currently great interest in the capacity of global forest to store carbon and hence contribute to the mitigation of climate change in the coming ...decades. In a study of Southeast Asian tropical forest, Philipson
et al.
show that active restoration of logged forests generates higher rates of carbon accumulation than naturally regenerating forest. To estimate the economic feasibility of restoration treatments, they modeled the carbon price required to offset the cost of restoration, finding that the highest prices seen in recent years would be needed to approach those that could offset restoration costs. These results are important for tropical forest policy, establishing the importance of restoration for the carbon recovery potential of tropical forests.
Science
, this issue p.
838
Restoration of logged tropical forests will be incentivized by carbon prices, consistent with the 2016 Paris climate agreement.
More than half of all tropical forests are degraded by human impacts, leaving them threatened with conversion to agricultural plantations and risking substantial biodiversity and carbon losses. Restoration could accelerate recovery of aboveground carbon density (ACD), but adoption of restoration is constrained by cost and uncertainties over effectiveness. We report a long-term comparison of ACD recovery rates between naturally regenerating and actively restored logged tropical forests. Restoration enhanced decadal ACD recovery by more than 50%, from 2.9 to 4.4 megagrams per hectare per year. This magnitude of response, coupled with modal values of restoration costs globally, would require higher carbon prices to justify investment in restoration. However, carbon prices required to fulfill the 2016 Paris climate agreement $40 to $80 (USD) per tonne carbon dioxide equivalent would provide an economic justification for tropical forest restoration.
Exposure to heat stress (HS) in utero was postulated to trigger an adaptive molecular response that can be transmitted to the next generation. Hence, this study assessed the impact of HS exposure at ...different stages of the gestational period of mice on the female F1 population and their offspring. Heat stress exposure (41°C and 65% relative humidity—RH) occurred during the first half (FP), the second half (SP), or the entire pregnancy (TP). A control group (C) was maintained in normothermic conditions (25°C, 45% RH) throughout the experiment. Heat stress had a significant negative effect on intrauterine development, mainly when HS exposure occurred in the first half of pregnancy (FP and TP groups). Postnatal growth of FP and TP mice was hindered until 4 weeks of age. The total number of follicles per ovary did not vary (P > 0.05) between the control and HS-exposed groups. Mean numbers of primordial follicles were lower (P < 0.05) in the sexually mature FP than those in SP and TP F1 females. However, the mean number of viable embryos after superovulation was lower (P < 0.05) in TP compared with C group. The expression of genes associated with physiological and cellular response to HS, autophagy, and apoptosis was significantly affected in the ovarian tissue of F1 females and F2 in vivo-derived blastocysts in all HS-exposed groups. In conclusion, exposure to HS during pregnancy compromised somatic development and reproductive parameters as well as altered gene expression profile that was then transmitted to the next generation of mice. Graphical Abstract
In professional soccer, increasing amounts of data are collected that harness great potential when it comes to analysing tactical behaviour. Unlocking this potential is difficult as big data ...challenges the data management and analytics methods commonly employed in sports. By joining forces with computer science, solutions to these challenges could be achieved, helping sports science to find new insights, as is happening in other scientific domains. We aim to bring multiple domains together in the context of analysing tactical behaviour in soccer using position tracking data. A systematic literature search for studies employing position tracking data to study tactical behaviour in soccer was conducted in seven electronic databases, resulting in 2338 identified studies and finally the inclusion of 73 papers. Each domain clearly contributes to the analysis of tactical behaviour, albeit in - sometimes radically - different ways. Accordingly, we present a multidisciplinary framework where each domain's contributions to feature construction, modelling and interpretation can be situated. We discuss a set of key challenges concerning the data analytics process, specifically feature construction, spatial and temporal aggregation. Moreover, we discuss how these challenges could be resolved through multidisciplinary collaboration, which is pivotal in unlocking the potential of position tracking data in sports analytics.
The study aimed to investigate the impact of HLA‐DPB1 allelic and molecular mismatches on the occurrence of acute rejection (AR) and low 5‐year graft function (5Y‐GF) in first kidney transplant (KT) ...recipients. This is a single center retrospective study of 130 deceased donor KT recipients transplanted between 2014 and 2016. HLA‐DPB1 allelic MM and the following molecular MM (mMM) were analyzed: expression MM with the high expression G allele in the donor; T cell epitope MM (TCE MM); epitope MM (EMM), considering all six hypervariable regions (EMM‐ABCDEF HVR), or only ABEF regions (EMM‐ABEF HVR); eplet MM (EpMM); antibody‐verified eplet MM (AbVer EpMM); and solvent accessible amino acid MM (SAMM). There was no association of allelic MM with AR or 5Y‐GF. The variables independently associated (Cox regression analyses) with AR were high donor final creatinine, nonpermissive TCE MM, ABCDEF EMM load ≥6, EpMM load ≥6; SAMM load ≥5, and AbVer EpMM load ≥3. No association between any HLA‐DPB1 mMM and 5Y‐GF was observed when all 130 transplant recipients were considered. However, when transplants from expanded criteria donors were excluded, independent associations were detected (logistic regression analyses) with AbVerEpMM load ≥2, SAMM load ≥7, cerebro‐vascular death, donor age, and AR. To our knowledge, this is the first study that shows that some HLA‐DPB1 mMM are associated with AR and low 5Y‐GF in a population of exclusively first kidney transplant recipients.
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