Identification of multiple independent horizontal gene transfers into poxviruses using a comparative genomics approach

<p>Abstract</p> <p>Background</p> <p>Poxviruses are important pathogens of humans, livestock and wild animals. These large dsDNA viruses have a set of core orthologs whose gene order is extremely well conserved throughout poxvirus genera. They also contain many genes with sequence and functional similarity to host genes which were probably acquired by horizontal gene transfer.</p> <p>Although phylogenetic trees can indicate the occurrence of horizontal gene transfer and even uncover multiple events, their use may be hampered by uncertainties in both the topology and the rooting of the tree. We propose to use synteny conservation around the horizontally transferred gene (HTgene) to distinguish between single and multiple events.</p> <p>Results</p> <p>Here we devise a method that incorporates comparative genomic information into the investigation of horizontal gene transfer, and we apply this method to poxvirus genomes. We examined the synteny conservation around twenty four pox genes that we identified, or which were reported in the literature, as candidate HTgenes. We found support for multiple independent transfers into poxviruses for five HTgenes. Three of these genes are known to be important for the survival of the virus in or out of the host cell and one of them increases susceptibility to some antiviral drugs.</p> <p>Conclusion</p> <p>In related genomes conserved synteny information can provide convincing evidence for multiple independent horizontal gene transfer events even in the absence of a robust phylogenetic tree for the HTgene.</p

Does Current Diabetes Technology Improve Metabolic Control? A Cross-Sectional Study on the Use of Insulin Pumps and Continuous Glucose Monitoring Devices in a Nationwide Pediatric Population

Objective To examine the use of multiple daily injections (MDI), insulin pumps, self-measured blood glucose (SMBG), and continuous glucose monitoring (CGM) systems, and their association with glycated hemoglobin (HbA1c), diabetic ketoacidosis (DKA), and severe hypoglycemia. Methods In a pediatric population-based nationwide cross-sectional study, we analyzed data from 2623 participants up to 18 years of age with type 1 diabetes, using 2017 annual data from the Norwegian Childhood Diabetes Registry. HbA1c was adjusted for age, gender, and diabetes duration. Using a linear mixed-effects model, we assessed HbA1c and the incidence of DKA and severe hypoglycemia according to the use of MDI, insulin pumps, SMBG, and CGM. Results We observed that 74.7% of participants were using an insulin pump and 52.6% were using a CGM system. Mean HbA1c was 7.8% (62 mmol/mol). The HbA1c of pump users was 0.14 percentage points (pp) higher than that of MDI users. Fewer pump users than MDI users achieved an HbA1c of < 7.5% (38.3 vs. 41.6%). CGM users had a 0.18 pp lower HbA1c than SMBG users, with 40.5 and 38.0%, respectively, achieving an HbA1c of < 7.5%. The incidence of severe hypoglycemia or hospitalization due to DKA was not different in pump and CGM users compared with nonusers. Compared with other insulin pumps, patch pump use was associated with a significantly lower odds ratio for DKA. Conclusions Despite the broad use of diabetes technology, as many as 61% of our pediatric cohort did not reach the HbA1c target recommended by the International Society for Pediatric and Adolescent Diabetes (ISPAD). Lower HbA1c was associated with CGM use but not with insulin pump use. Acute complications were not less frequent in the groups using insulin pumps or CGM compared with those using MDI and SMBG. Further research is required to explore the lower incidence of DKA among patch pump users.publishedVersio

Single Photons on Pseudo-Demand from Stored Parametric Down-Conversion

We describe the results of a parametric down-conversion experiment in which the detection of one photon of a pair causes the other photon to be switched into a storage loop. The stored photon can then be switched out of the loop at a later time chosen by the user, providing a single photon for potential use in a variety of quantum information processing applications. Although the stored single photon is only available at periodic time intervals, those times can be chosen to match the cycle time of a quantum computer by using pulsed down-conversion. The potential use of the storage loop as a photonic quantum memory device is also discussed.Comment: 8 pages, 7 Figs., RevTe

Genotype- and sex-specific changes in vital parameters during isoflurane anesthesia in a mouse model of Alzheimer’s disease

BackgroundThe prevalence of neurodegenerative diseases is increasing as is life expectancy with Alzheimer’s disease accounting for two-thirds of dementia cases globally. Whether general anesthesia and surgery worsen cognitive decline is still a matter of debate and most likely depending on the interplay of various influencing factors. In order to account for this complexity, Alzheimer’s disease animal models have been developed. The Tg2576 model of Alzheimer’s disease is a well-established mouse model exhibiting amyloidopathy and age-dependent sex-specific differences in Alzheimer’s disease symptomology. Yet, data on anesthesia in this mouse model is scarce and a systematic comparison of vital parameters during anesthesia with wild-type animals is missing. In order to investigate the safety of general anesthesia and changes in vital parameters during general anesthesia in Tg2576 mice, we did a secondary analysis of vital parameters collected during general anesthesia in aged Tg2576 mice.MethodsAfter governmental approval (General Administration of the Free State of Bavaria, file number: 55.2-1-54-2532-149-11) 60 mice at 10-12 months of age were exposed to isoflurane (1.6 Vol%) for 120 min, data of 58 mice was analyzed. During general anesthesia, heart rate, respiratory rate, temperature, isoflurane concentration and fraction of inspired oxygen were monitored and collected. Data were analyzed using univariate and multivariate linear mixed regression models.ResultsDuring general anesthesia, heart rate decreased in a sex-specific manner. Respiratory rate decreased and body temperature increased dependent on genotype. However, the changes were limited and all vital parameters stayed within physiological limits.ConclusionIsoflurane anesthesia in the Tg2576 mouse model is safe and does not seem to influence experimental results by interacting with vital parameters. The present study provides information on appropriate anesthesia in order to advance research on anesthesia and AD and could contribute to improving laboratory animal welfare

Fish Granzyme A Shows a Greater Role Than Granzyme B in Fish Innate Cell-Mediated Cytotoxicity

Granzymes (Gzm) are serine proteases, contained into the secretory granules of cytotoxic cells, responsible for the cell-mediated cytotoxicity (CMC) against tumor cells and intracellular pathogens such as virus and bacteria. In fish, they have received little attention to their existence, classification or functional characterization. Therefore, we aimed to identify and evaluate their functional and transcriptomic relevance in the innate CMC activity of two relevant teleost fish species, gilthead seabream and European sea bass. Afterwards, we wanted to focus on their regulation upon nodavirus (NNV) infection, a virus that causes great mortalities to sea bass specimens while seabream is resistant. In this study, we have identified genes encoding GzmA and GzmB in both seabream and sea bass, as well as GzmM in seabream, which showed good phylogenetic relation to their mammalian orthologs. In addition, we found enzymatic activity related to tryptase (GzmA and/or GzmK), aspartase (GzmB), metase (GzmM), or chymase (GzmH) in resting head-kidney leucocytes (HKLs), with the following order of activity: GzmA/K∼GzmM>> GzmH >>> GzmB. In addition, during innate CMC assays consisting on HKLs exposed to either mock- or NNV-infected target cells, though all the granzyme transcripts were increased only the tryptase activity did. Thus, our data suggest a high functional activity of GzmA/K in the innate CMC and a marginal one for GzmB. Moreover, GzmB activity was detected into target cells during the CMC assays. However, the percentage of target cells with GzmB activity after the CMC assays was about 10-fold lower than the death target cells, demonstrating that GzmB is not the main inductor of cell death. Moreover, in in vivo infection with NNV, gzm transcription is differently regulated depending on the fish species, genes and tissues. However, the immunohistochemistry study revealed an increased number of GzmB stained cells and areas in the brain of seabream after NNV infection, which was mainly associated with the lesions detected. Further studies are needed to ascertain the molecular nature, biological function and implication of fish granzymes in the CMC activity, and in the antiviral defense in particular. Keywords:Versión del edito

Mycobacterium tuberculosis promotes Th17 expansion via regulation of human dendritic cells toward a high CD14 and low IL-12p70 phenotype that reprograms upon exogenous IFN-γ.

Item does not contain fulltextThe capacity to develop protective immunity against mycobacteria is heterogeneously distributed among human beings, and it is currently unknown why the initial immune response induced against Mycobacterium tuberculosis (Mtb) does not provide proper clearance of this pathogen. Dendritic cells (DCs) are some of the first cells to interact with Mtb and they play an essential role in development of protective immunity against Mtb. Given that Mtb-infected macrophages have difficulties in degrading Mtb, they need help from IFN-gamma-producing CD4+ T cells propagated via IL-12p70-producing DCs. Here we report that Mtb modifies human DC plasticity by expanding a CD14+ DC subset with weak IL-12p70-producing capacity. The CD14+ Mtb-promoted subset was furthermore poor inducers of IFN-gamma by naive CD4+ T cells, but instead prompted IL-17A-producing RORgammaT+ CD4+ T cells. Mtb-derived peptidoglycan and mannosylated lipoarabinomannan partly recapitulated the subset partition induced by Mtb. Addition of IFN-gamma, but neither IL-17A nor IL-22, which are potentially produced by Mtb-exposed gamma/delta-T cells in mucosal linings, inhibited the differentiation toward CD14+ DCs and promoted high-level IL-12p70 in Mtb-challenged DCs. We conclude that Mtb exploits DC plasticity to reduce production of IL-12p70, and that this process is entirely divertible by exogenous IFN-gamma. These data suggest that strategies to increase local IFN-gamma production in the lungs of tuberculosis patients may boost host immunity toward Mtb