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Anaplasma (formerly Ehrlichia) phagocytophilum, Ehrlichia chaffeensis, and Neorickettsia (formerly Ehrlichia) sennetsu are intracellular vector-borne pathogens that cause human ehrlichiosis, an emerging infectious disease. We present the complete genome sequences of these organisms along with comparisons to other organisms in the Rickettsiales order. Ehrlichia spp. and Anaplasma spp. display a unique large expansion of immunodominant outer membrane proteins facilitating antigenic variation. All Rickettsiales have a diminished ability to synthesize amino acids compared to their closest free-living relatives. Unlike members of the Rickettsiaceae family, these pathogenic Anaplasmataceae are capable of making all major vitamins, cofactors, and nucleotides, which could confer a beneficial role in the invertebrate vector or the vertebrate host. Further analysis identified proteins potentially involved in vacuole confinement of the Anaplasmataceae, a life cycle involving a hematophagous vector, vertebrate pathogenesis, human pathogenesis, and lack of transovarial transmission. These discoveries provide significant insights into the biology of these obligate intracellular pathogens. © 2006 Dunning Hotopp.

Mutualistic intracellular symbiosis between bacteria and insects is a widespread phenomenon that has contributed to the global success of insects. The symbionts, by provisioning nutrients lacking from diets, allow various insects to occupy or dominate ecological niches that might otherwise be unavailable. One such insect is the glassy-winged sharpshooter (Homalodisca coagulata), which feeds on xylem fluid, a diet exceptionally poor in organic nutrients. Phylogenetic studies based on rRNA have shown two types of bacterial symbionts to be coevolving with sharpshooters: the gamma-proteobacterium Baumannia cicadellinicola and the Bacteroidetes species Sulcia muelleri. We report here the sequencing and analysis of the 686,192-base pair genome of B. cicadellinicola and approximately 150 kilobase pairs of the small genome of S. muelleri, both isolated from H. coagulata. Our study, which to our knowledge is the first genomic analysis of an obligate symbiosis involving multiple partners, suggests striking complementarity in the biosynthetic capabilities of the two symbionts: B. cicadellinicola devotes a substantial portion of its genome to the biosynthesis of vitamins and cofactors required by animals and lacks most amino acid biosynthetic pathways, whereas S. muelleri apparently produces most or all of the essential amino acids needed by its host. This finding, along with other results of our genome analysis, suggests the existence of metabolic codependency among the two unrelated endosymbionts and their insect host. This dual symbiosis provides a model case for studying correlated genome evolution and genome reduction involving multiple organisms in an intimate, obligate mutualistic relationship. In addition, our analysis provides insight for the first time into the differences in symbionts between insects (e.g., aphids) that feed on phloem versus those like H. coagulata that feed on xylem. Finally, the genomes of these two symbionts provide potential targets for controlling plant pathogens such as Xylella fastidiosa, a major agroeconomic problem, for which H. coagulata and other sharpshooters serve as vectors of transmission. © 2006 Wu et al.

Saturated thalassic brines are among the most physically demanding habitats on Earth: few microbes survive in them. Salinibacter ruber is among these organisms and has been found repeatedly in significant numbers in climax saltern crystallizer communities. The phenotype of this bacterium is remarkably similar to that of the hyperhalophilic Archaea (Haloarchaea). The genome sequence suggests that this resemblance has arisen through convergence at the physiological level (different genes producing similar overall phenotype) and the molecular level (independent mutations yielding similar sequences or structures). Several genes and gene clusters also derive by lateral transfer from (or may have been laterally transferred to) haloarchaea. S. ruber encodes four rhodopsins. One resembles bacterial proteorhodopsins and three are of the haloarchaeal type, previously uncharacterized in a bacterial genome. The impact of these modular adaptive elements on the cell biology and ecology of S. ruber is substantial, affecting salt adaptation, bioenergetics, and photobiology. halophile | lateral gene transfer | convergence | prokaryotic evolution | rhodopsins

Research presents a comparison of the whole-genome of Mycobacterium tuberculosis clinical strain CDC1551 with the laboratory strain H37Rv. Data show extensive polymorphisms among M. tuberculosis strains conferring genetic variation, which play a role in their pathogenesis and immunity.

The Swinfen Charitable Trust (SCT) provides an e-referral service for health practitioners in developing countries. Referral messages and responses are passed by email. We have developed a Web-based system to facilitate information retrieval from these messages and multimedia data mining. The system contains a search engine which implements full text searching, together with nearness-based retrieval. In pilot testing, cases with relatively high nearness ranking were reasonably near to the query cases. In addition, a Support Vector Machine (SVM) was used to classify cases into categories of gender and age. False positives did not increase significantly with the number of true positives, i.e. this represented very good classification performance. The system we have developed appears to be a promising way of storing and retrieving email-based medical correspondence. [ABSTRACT FROM AUTHOR]

Ketone bodies (acetoacetate and β-hydroxybutyrate) are oxidized in skeletal muscle mainly during fasting as an alternative source of energy to glucose. Previous studies suggest that there is a negative relationship between increased muscle ketolysis and muscle glucose metabolism in mice with obesity and/or type 2 diabetes. Therefore, we investigated the connection between increased ketone body exposure and muscle glucose metabolism by measuring the effect of a 3-h exposure to ketone bodies on glucose uptake in differentiated L6 myotubes. We showed that exposure to acetoacetate at a typical concentration (0.2 mM) resulted in increased basal glucose uptake in L6 myotubes, which was dependent on increased membrane glucose transporter type 4 (GLUT4) translocation. Basal and insulin-stimulated glucose uptake was also increased with a concentration of acetoacetate reflective of diabetic ketoacidosis or a ketogenic diet (1 mM). We found that β-hydroxybutyrate had a variable effect on basal glucose uptake: a racemic mixture of the two β-hydroxybutyrate enantiomers (d and l) appeared to decrease basal glucose uptake, while 3 mM d-β-hydroxybutyrate alone increased basal glucose uptake. However, the effects of the ketone bodies individually were not observed when acetoacetate was present in combination with β-hydroxybutyrate. These results provide insight that will help elucidate the effect of ketone bodies in the context of specific metabolic diseases and nutritional states (e.g., type 2 diabetes and ketogenic diets). NEW & NOTEWORTHY A limited number of studies investigate the effect of ketone bodies at concentrations reflective of both typical fasting and ketoacidosis. We tested a mix of physiologically relevant concentrations of ketone bodies, which allowed us to highlight the differential effects of d- and l-β-hydroxybutyrate and acetoacetate on skeletal muscle cell glucose uptake. Our findings will assist in better understanding the mechanisms that contribute to muscle insulin resistance and provide guidance on recommendations regarding ketogenic diets.

In recent years, ketogenic diets and ketone supplements have increased in popularity, particularly as a mechanism to improve exercise performance by modifying energetics. Since the skeletal muscle is a major metabolic and locomotory organ, it is important to take it into consideration when considering the effect of a dietary intervention, and the impact of physical activity on the body. The goal of this review is to summarize what is currently known and what still needs to be investigated concerning the relationship between ketone body metabolism and exercise, specifically in the skeletal muscle. Overall, it is clear that increased exposure to ketone bodies in combination with exercise can modify skeletal muscle metabolism, but whether this effect is beneficial or detrimental remains unclear and needs to be further interrogated before ketogenic diets or exogenous ketone supplementation can be recommended.

Introduction: Immunometabolism examines the links between immune cell function and metabolism. Dysregulation of immune cell metabolism is now an established feature of innate immune cell activation. Advances in liquid chromatography mass spectrometry (LC-MS) technologies have allowed discovery of unique insights into cellular metabolomics. Here we have studied and compared different sample preparation techniques and data normalisation methods described in the literature when applied to metabolomic profiling of human monocytes., Methods: Primary monocytes stimulated with lipopolysaccharide (LPS) for four hours was used as a study model. Monocytes (n=24) were freshly isolated from whole blood and stimulated for four hours with lipopolysaccharide (LPS). A methanol-based extraction protocol was developed and metabolomic profiling carried out using a Hydrophilic Interaction Liquid Chromatography (HILIC) LC-MS method. Data analysis pipelines used both targeted and untargeted approaches, and over 40 different data normalisation techniques to account for technical and biological variation were examined. Cytokine levels in supernatants were measured by ELISA., Results: This method provided broad coverage of the monocyte metabolome. The most efficient and consistent normalisation method was measurement of residual protein in the metabolite fraction, which was further validated and optimised using a commercial kit. Alterations to the monocyte metabolome in response to LPS can be detected as early as four hours post stimulation. Broad and profound changes in monocyte metabolism were seen, in line with increased cytokine production. Elevated levels of amino acids and Krebs cycle metabolites were noted and decreases in aspartate and β-alanine are also reported for the first time. In the untargeted analysis, 154 metabolite entities were significantly altered compared to unstimulated cells. Pathway analysis revealed the most prominent changes occurred to (phospho-) inositol metabolism, glycolysis, and the pentose phosphate pathway., Discussion: These data report the emergent changes to monocyte metabolism in response to LPS, in line with reports from later time points. A number of these metabolites are reported to alter inflammatory gene expression, which may facilitate the increases in cytokine production. Further validation is needed to confirm the link between metabolic activation and upregulation of inflammatory responses., Competing Interests: Author HK was employed by Agilent Technologies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Leacy, Batten, Sanelli, McElheron, Brady, Little and Khouri.)

Compelling evidence supports the health benefits of physical exercise on the immune system, possibly through the molecules secreted by the skeletal muscles known as myokines. Herein, we assessed the impact of exercise interventions on plasma Heat shock protein 90 (Hsp90) levels in 27 patients with idiopathic inflammatory myopathies (IIM) compared with 23 IIM patients treated with standard-of-care immunosuppressive therapy only, and in 18 healthy subjects undergoing strenuous eccentric exercise, and their associations with the traditional serum markers of muscle damage and inflammation. In contrast to IIM patients treated with pharmacotherapy only, in whom we demonstrated a significant decrease in Hsp90 over 24 weeks, the 24-week exercise program resulted in a stabilization of Hsp90 levels. These changes in Hsp90 levels were associated with changes in several inflammatory cytokines/chemokines involved in the pathogenesis of IIM or muscle regeneration in general. Strenuous eccentric exercise in healthy volunteers induced a brief increase in Hsp90 levels with a subsequent return to baseline levels at 14 days after the exercise, with less pronounced correlations to systemic inflammation. In this study, we identified Hsp90 as a potential myokine and mediator for exercise-induced immune response and as a potential biomarker predicting improvement after physiotherapy in muscle endurance in IIM.

Under insulin-stimulated conditions, skeletal muscle is the largest glucose consumer in the body. Mitochondrial dysfunction and damage to this tissue from oxidative stress are linked to the pathogenesis of type 2 diabetes. Environmental exposure to dichlorodiphenyltrichloroethane (DDT) and its metabolite, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), has been associated with the incidence of type 2 diabetes as well as altered oxidative stress and mitochondrial dysfunction in non-muscle tissues. We hypothesized that energy metabolism and insulin sensitivity in skeletal muscle will be altered with exposure to DDT and DDE. In this pilot study, mitochondrial function was measured in permeabilized muscle fibers from Sprague-Dawley rats after one week of exposure to a single injection of DDT (40 μg/kg), a dose comparable to DDT levels in the diets of the Inuit of Northern Canada. The levels of oxidative phosphorylation chain complexes and ROS detoxification enzymes were measured in muscle tissue from these specimens. This acute in vivo exposure to DDT decreased muscle mitochondrial function by 45% without affecting the levels of mitochondrial oxidative phosphorylation chain complexes nor levels of ROS detoxification enzymes. To isolate the effects of DDT and DDE exposure on muscle, L6 myotubes were exposed to DDT or DDE (0, 10, 100, 1000, 10 000 nM) for 24 h. Only very high concentrations of DDT and DDE (1 000 - 10 000 nM) altered maximal respiration with only DDT altering basal glucose uptake in L6 myotubes. This did not alter levels of ROS detoxification enzymes or malondialdehyde (MDA) in L6 myotubes. Altogether, acute exposure to environmentally relevant doses of DDT resulted in muscle mitochondrial dysfunction in vivo in rats, but not when muscle cells were directly exposed to the pollutant or its metabolite., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Introduction: Conjoined twins are an infrequent occurrence in obstetric practice. Live-conjoined twins on a late preterm triplet pregnancy is an even rarer event., Objective: The objective of this study is to emphasize the critical importance of perinatal palliative care and non-directive parental counseling, informed decision making and respect for autonomy following full disclosure of findings, fetal life-limiting diagnosis, treatment alternatives, maternal-fetal potential complications, and most likely perinatal outcomes., Methods: Early surprise prenatal diagnosis, comprehensive parental counseling, palliative care, and perinatal care of a set of conjoined twins and a singleton., Results: Cesarean delivery of a set of conjoined twins and a singleton at 34 weeks' gestation. Immediate neonatal death of the conjoined twins, intact survival, and discharge of the singleton. Review of the database on previously reported similar cases. It is very important to utilize simple and direct language for parents to understand the grave prognosis to the pregnancy. Care alternatives in view of the maternal physical risks and psychological impact of carrying a high order abnormal multiple pregnancy, along with the possible side effects on the singleton.

Here we present the draft genome of Synergistes jonesii 78-1, ATCC 49833, a member of the Synergistes phylum. This organism was isolated from the rumen of a Hawaiian goat and ferments pyridinediols. The assembly contains 2,747,397 bp in 61 contigs., (Copyright © 2014 Holland-Moritz et al.)

Background: Haloferax volcanii is an easily culturable moderate halophile that grows on simple defined media, is readily transformable, and has a relatively stable genome. This, in combination with its biochemical and genetic tractability, has made Hfx. volcanii a key model organism, not only for the study of halophilicity, but also for archaeal biology in general., Methodology/principal Findings: We report here the sequencing and analysis of the genome of Hfx. volcanii DS2, the type strain of this species. The genome contains a main 2.848 Mb chromosome, three smaller chromosomes pHV1, 3, 4 (85, 438, 636 kb, respectively) and the pHV2 plasmid (6.4 kb)., Conclusions/significance: The completed genome sequence, presented here, provides an invaluable tool for further in vivo and in vitro studies of Hfx. volcanii.

The complete genomes of three strains from the phylum Acidobacteria were compared. Phylogenetic analysis placed them as a unique phylum. They share genomic traits with members of the Proteobacteria, the Cyanobacteria, and the Fungi. The three strains appear to be versatile heterotrophs. Genomic and culture traits indicate the use of carbon sources that span simple sugars to more complex substrates such as hemicellulose, cellulose, and chitin. The genomes encode low-specificity major facilitator superfamily transporters and high-affinity ABC transporters for sugars, suggesting that they are best suited to low-nutrient conditions. They appear capable of nitrate and nitrite reduction but not N(2) fixation or denitrification. The genomes contained numerous genes that encode siderophore receptors, but no evidence of siderophore production was found, suggesting that they may obtain iron via interaction with other microorganisms. The presence of cellulose synthesis genes and a large class of novel high-molecular-weight excreted proteins suggests potential traits for desiccation resistance, biofilm formation, and/or contribution to soil structure. Polyketide synthase and macrolide glycosylation genes suggest the production of novel antimicrobial compounds. Genes that encode a variety of novel proteins were also identified. The abundance of acidobacteria in soils worldwide and the breadth of potential carbon use by the sequenced strains suggest significant and previously unrecognized contributions to the terrestrial carbon cycle. Combining our genomic evidence with available culture traits, we postulate that cells of these isolates are long-lived, divide slowly, exhibit slow metabolic rates under low-nutrient conditions, and are well equipped to tolerate fluctuations in soil hydration.