Molecular Mechanisms of Resistance to Antifungals in <em>Candida albicans</em>

Invasive Candidiasis (IC) presents a global mortality rate greater than 40%, occupying the fourth place worldwide as the most frequent opportunistic nosocomial disease. Although the genus Candida consists of around 200 species, only 20 are reported as etiological agents of IC, being Candida albicans the most frequent causal agent. Even when there is a broad range of antifungals drugs for Candida infections, azoles, polyenes, and echinocandins are considered among the most effective treatment. However, there is some incidence for antifungal resistance among some Candida strains, limiting treatment options. Several molecular mechanisms with antifungal agents have been reported for C. albicans where insertions, deletions, and point mutations in genes codifying target proteins are frequently related to the antifungal drug resistance. Furthermore, gene overexpression is also frequently associated to antifungal resistance as well as an increase in the activity of proteins that reduce oxidative damage. This chapter summarizes the main molecular mechanisms to C. albicans antifungal drug resistance, besides offering an overview of new antifungal agents and new antifungal targets to combat fungal infections

Psychiatric Comorbidity in Mexican Adolescents with a Diagnosis of Eating Disorders Its Relationship with the Body Mass Index

The prevalence of comorbid psychiatric disorders among patients with eating disorders (ED) is higher than the general population. Individuals diagnosed with eating disorders have changes in their body mass index which could promote severe metabolic disruptions. This study aimed (1) to report the prevalence of comorbid psychiatric disorders among a Mexican adolescent sample diagnosed with eating disorders, (2) to compare our results with the prevalence of psychiatric disorders reported from a national survey of mental health of adolescents, (3) to compare the presence of psychiatric comorbidities between ED diagnoses, and (4) to explore the relationship of these comorbidities with the body mass index. In the study, we included 187 Mexican adolescents diagnosed with eating disorders. The psychiatric comorbidities were evaluated using the Mini International Neuropsychiatric Interview for children/adolescents, and a revised questionnaire on eating and weight patterns. We found that 89% of the Mexican adolescents diagnosed with ED had another psychiatric comorbidity. Major depressive disorder (52.40%) and suicide risk (40%) were the most prevalent comorbidities. Attention and deficit hyperactivity disorder (ADHD) prevalence was different between ED diagnosis, and adolescents with binge-eating disorder and ADHD had the higher body mass index. Our results showed that in this sample of Mexican adolescents, the presence of comorbidities could impact body mass index. This emphasizes the importance that clinicians take into consideration the presence of psychiatric comorbidities to achieve an integrative treatment for adolescents diagnosed with ED

Individuals Diagnosed with Binge-Eating Disorder Have DNA Hypomethylated Sites in Genes of the Metabolic System: A Pilot Study

Binge-eating disorder, recently accepted as a diagnostic category, is differentiated from bulimia nervosa in that the former shows the presence of binge-eating episodes and the absence of compensatory behavior. Epigenetics is a conjunct of mechanisms (like DNA methylation) that regulate gene expression, which are dependent on environmental changes. Analysis of DNA methylation in eating disorders shows that it is reduced. The present study aimed to analyze the genome-wide DNA methylation differences between individuals diagnosed with BED and BN. A total of 46 individuals were analyzed using the Infinium Methylation EPIC array. We found 11 differentially methylated sites between BED- and BN-diagnosed individuals, with genome-wide significance. Most of the associations were found in genes related to metabolic processes (ST3GAL4, PRKAG2, and FRK), which are hypomethylated genes in BED. Cg04781532, located in the body of the PRKAG2 gene (protein kinase AMP-activated non-catalytic subunit gamma 2), was hypomethylated in individuals with BED. Agonists of PRKAG2, which is the subunit of AMPK (AMP-activated protein kinase), are proposed to treat obesity, BED, and BN. The present study contributes important insights into the effect that BED could have on PRKAG2 activation

Early stage litter decomposition across biomes

Through litter decomposition enormous amounts of carbon is emitted to the atmosphere. Numerous large-scale decomposition experiments have been conducted focusing on this fundamental soil process in order to understand the controls on the terrestrial carbon transfer to the atmosphere. However, previous studies were mostly based on site-specific litter and methodologies, adding major uncertainty to syntheses, comparisons and meta-analyses across different experiments and sites. In the TeaComposition initiative, the potential litter decomposition is investigated by using standardized substrates (Rooibos and Green tea) for comparison of litter mass loss at 336 sites (ranging from −9 to +26 °C MAT and from 60 to 3113 mm MAP) across different ecosystems. In this study we tested the effect of climate (temperature and moisture), litter type and land-use on early stage decomposition (3 months) across nine biomes. We show that litter quality was the predominant controlling factor in early stage litter decomposition, which explained about 65% of the variability in litter decomposition at a global scale. The effect of climate, on the other hand, was not litter specific and explained <0.5% of the variation for Green tea and 5% for Rooibos tea, and was of significance only under unfavorable decomposition conditions (i.e. xeric versus mesic environments). When the data were aggregated at the biome scale, climate played a significant role on decomposition of both litter types (explaining 64% of the variation for Green tea and 72% for Rooibos tea). No significant effect of land-use on early stage litter decomposition was noted within the temperate biome. Our results indicate that multiple drivers are affecting early stage litter mass loss with litter quality being dominant. In order to be able to quantify the relative importance of the different drivers over time, long-term studies combined with experimental trials are needed.This work was performed within the TeaComposition initiative, carried out by 190 institutions worldwide. We thank Gabrielle Drozdowski for her help with the packaging and shipping of tea, Zora Wessely and Johannes Spiegel for the creative implementation of the acknowledgement card, Josip Dusper for creative implementation of the graphical abstract, Christine Brendle for the GIS editing, and Marianne Debue for her help with the data cleaning. Further acknowledgements go to Adriana Principe, Melanie Köbel, Pedro Pinho, Thomas Parker, Steve Unger, Jon Gewirtzman and Margot McKleeven for the implementation of the study at their respective sites. We are very grateful to UNILEVER for sponsoring the Lipton tea bags and to the COST action ClimMani for scientific discussions, adoption and support to the idea of TeaComposition as a common metric. The initiative was supported by the following grants: ILTER Initiative Grant, ClimMani Short-Term Scientific Missions Grant (COST action ES1308; COST-STSM-ES1308-36004; COST-STM-ES1308-39006; ES1308-231015-068365), INTERACT (EU H2020 Grant No. 730938), and Austrian Environment Agency (UBA). Franz Zehetner acknowledges the support granted by the Prometeo Project of Ecuador's Secretariat of Higher Education, Science, Technology and Innovation (SENESCYT) as well as Charles Darwin Foundation for the Galapagos Islands (2190). Ana I. Sousa, Ana I. Lillebø and Marta Lopes thanks for the financial support to CESAM (UID/AMB/50017), to FCT/MEC through national funds (PIDDAC), and the co-funding by the FEDER, within the PT2020 Partnership Agreement and Compete 2020. The research was also funded by the Portuguese Foundation for Science and Technology, FCT, through SFRH/BPD/107823/2015 (A.I. Sousa), co-funded by POPH/FSE. Thomas Mozdzer thanks US National Science Foundation NSF DEB-1557009. Helena C. Serrano thanks Fundação para a Ciência e Tecnologia (UID/BIA/00329/2013). Milan Barna acknowledges Scientific Grant Agency VEGA (2/0101/18). Anzar A Khuroo acknowledges financial support under HIMADRI project from SAC-ISRO, India