The causes of impaired skeletal muscle mass and strength during aging are well-studied in healthy populations. Less is known on pathological age-related muscle wasting and weakness termed sarcopenia, which directly impacts physical autonomy and survival. Here, we compare genome-wide transcriptional changes of sarcopenia versus age-matched controls in muscle biopsies from 119 older men from Singapore, Hertfordshire UK and Jamaica. Individuals with sarcopenia reproducibly demonstrate a prominent transcriptional signature of mitochondrial bioenergetic dysfunction in skeletal muscle, with low PGC-1α/ERRα signalling, and downregulation of oxidative phosphorylation and mitochondrial proteostasis genes. These changes translate functionally into fewer mitochondria, reduced mitochondrial respiratory complex expression and activity, and low NAD+ levels through perturbed NAD+ biosynthesis and salvage in sarcopenic muscle. We provide an integrated molecular profile of human sarcopenia across ethnicities, demonstrating a fundamental role of altered mitochondrial metabolism in the pathological loss of skeletal muscle mass and function in older people.
Persistent organic pollutants, such as polychlorinated biphenyls (PCBs), are a global problem. We demonstrate enhanced depletion of PCBs using root-associated microbes, which can use plant secondary metabolites, such as phenylpropanoids. Using a "rhizosphere metabolomics" approach, we show that phenylpropanoids constitute 84% of the secondary metabolites exuded from Arabidopsis roots. Phenylpropanoid-utilizing microbes are more competitive and are able to grow at least 100-fold better than their auxotrophic mutants on roots of plants that are able to synthesize or overproduce phenylpropanoids, such as flavonoids. Better colonization of the phenylpropanoid-utilizing strain in a gnotobiotic system on the roots of flavonoid-producing plants leads to almost 90% removal of PCBs in a 28-d period. Our work complements previous approaches to engineer soil microbial populations based on opines produced by transgenic plants and used by microbes carrying opine metabolism genes. The current approach based on plant natural products can be applied to contaminated soils with pre-existing vegetation. This strategy is also likely to be applicable to improving the competitive abilities of biocontrol and biofertilization strains.The establishment of large numbers of metabolically active populations of beneficial soil microbes is critical for the success of several environmental remediation and agricultural practices (Metting, 1992). These microorganisms are successful in getting established in the soil ecosystem due to their high adaptability in a wide variety of environments, their faster growth rate, and their biochemical versatility to metabolize a variety of natural and xenobiotic chemicals. Majority of the microbial population found in the soil is associated with the plant roots, where their numbers can reach up to 10 9 to 10 12 per gram of soil (Whipps, 1990), leading to a biomass equivalent to 500 kg ha Ϫ1 (Metting, 1992). This abundance in vegetated soils is due to the availability of nutrients via plant root exudation (Brimecombe, 2001), which can stimulate microbial growth in the immediate vicinity of the roots (a region also known as the "rhizosphere"). Hence, the rhizosphere has been promoted as the ideal site to modify microbial populations ("rhizoengineering") to suite various applications in the soil (O'Connell, 1996).Rhizoengineering has been demonstrated successfully by devising strategies that favored the growth of the targeted microbes that possessed the ability to metabolize exotic nutrients exuded by plants . It was thus possible to create a nutritional bias that can be especially successful in identifying microbial populations due to the general nutrient-limiting conditions in the rhizosphere. One of the earliest successes in rhizoengineering was based on favorably partitioning the exotic nutrient, opines, which were produced by the transgenic plants (Oger, 1997;Savka and Farrand, 1997). This led to the improved and competitive growth of the metabolizing strains in comparison with the microbes unable to metab...
The current COVID-19 pandemic is probably the worst the world has ever faced since the start of the new millennium. While the respiratory system is the most prominent target of SARS-CoV-2 (the contagion of COVID-19), extra-pulmonary involvement are emerging as important contributors of its morbidity and lethality. This article summarizes the impact of SARS-CoV and SARS-CoV-2 on the endocrine system to facilitate our understanding of the nature of coronavirus-associated endocrinopathy. Although new data are rapidly accumulating on this novel infection, many of the endocrine manifestations of COVID-19 remain incompletely elucidated. We hereby summarize various endocrine dysfunctions including coronavirus-induced new onset diabetes mellitus, hypocortisolism, thyroid hormone and reproductive system aberrations so that clinicians armed with such insights can potentially benefit COVID-19 patients at the bedside.
This study provides evidence that preoperative serum levels of haptoglobin could serve as an independent prognostic factor in patients presenting with epithelial ovarian cancer.
A natural shift is taking place in the approaches being adopted by plant scientists in response to the accessibility of systems-based technology platforms. Metabolomics is one such field, which involves a comprehensive non-biased analysis of metabolites in a given cell at a specific time. This review briefly introduces the emerging field and a range of analytical techniques that are most useful in metabolomics when combined with computational approaches in data analyses. Using cases from Arabidopsis and other selected plant systems, this review highlights how information can be integrated from metabolomics and other functional genomics platforms to obtain a global picture of plant cellular responses. We discuss how metabolomics is enabling large-scale and parallel interrogation of cell states under different stages of development and defined environmental conditions to uncover novel interactions among various pathways. Finally, we discuss selected applications of metabolomics.
Ovarian cancer (OC) is becoming the most common gynecological cancer in developed countries and the most lethal gynecological malignancy. It is also the fifth leading cause of all cancer-related deaths in women. The identification of diagnostic biomarkers and development of early detection techniques for OC largely depends on the understanding of the complex functionality and regulation of genes involved in this disease. Unfortunately, information about these OC genes is scattered throughout the literature and various databases making extraction of relevant functional information a complex task. To reduce this problem, we have developed a database dedicated to OC genes to support exploration of functional characterization and analysis of biological processes related to OC. The database contains general information about OC genes, enriched with the results of transcription regulation sequence analysis and with relevant text mining to provide insights into associations of the OC genes with other genes, metabolites, pathways and nuclear proteins. Overall, it enables exploration of relevant information for OC genes from multiple angles, making it a unique resource for OC and will serve as a useful complement to the existing public resources for those interested in OC genetics. Access is free for academic and non-profit users and database can be accessed at http://apps.sanbi.ac.za/ddoc/.
BackgroundBenign neutropenia often presents in certain populations without any genotype nor phenotype. Middle East countries are among the regions where endemic cases of chronic benign neutropenia are reported in the general population with an incidence of approximately between 10-15%. Not many studies have been performed to ascertain the cause or burden associated with this condition. The objective of the current study was to identify the frequency and characterize the consequences of chronic benign neutropenia in the country of Saudi Arabia.ResultsBenign neutropenia was found to be high in the Saudi Arabia general population (up to 20%), with an average neutrophil count of 1.48 (range 0.99 – 1.95 × 109cells/L), with Saudis having a higher incidence of chronic benign neutropenia compared to non-Saudis (p = <0.05). Complete blood count analyses showed significant difference in the total white cell count of neutrophils (p < 0.0001), WBC (p < 0.0001), lymphocytes (p < 0.001), monocytes (p < 0.001), eosinophils (p = 0.013) as well as the CD19 B cells (p = 0.008).ConclusionsOur study is the first to carefully quantitate benign neutropenia in Saudi Arabia. We identified that this condition is prevalent in the middle aged population (18 years to 55 years). These individuals not only had lower neutrophil counts, but also reduced peripheral blood cells types, especially the B-lymphocyte population (CD19 subset). As B-lymphocytes are involved in antibody production and antigen recognition, a decrease might easily predispose the individuals to infectious agents. As such more mechanistic studies need to be undertaken to understand the cause and potential long-term consequences of benign neutropenia.
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