Genetic diversity, infection prevalence, and possible transmission routes of Bartonella spp. in vampire bats

Bartonella spp. are globally distributed bacteria that cause endocarditis in humans and domestic animals. Recent work has suggested bats as zoonotic reservoirs of some human Bartonella infections; however, the ecological and spatiotemporal patterns of infection in bats remain largely unknown. Here we studied the genetic diversity, prevalence of infection across seasons and years, individual risk factors, and possible transmission routes of Bartonella in populations of common vampire bats (Desmodus rotundus) in Peru and Belize, for which high infection prevalence has previously been reported. Phylogenetic analysis of the gltA gene for a subset of PCR-positive blood samples revealed sequences that were related to Bartonella described from vampire bats from Mexico, other Neotropical bat species, and streblid bat flies. Sequences associated with vampire bats clustered significantly by country but commonly spanned Central and South America, implying limited spatial structure. Stable and nonzero Bartonella prevalence between years supported endemic transmission in all sites. The odds of Bartonella infection for individual bats was unrelated to the intensity of bat flies ectoparasitism, but nearly all infected bats were infested, which precluded conclusive assessment of support for vector-borne transmission. While metagenomic sequencing found no strong evidence of Bartonella DNA in pooled bat saliva and fecal samples, we detected PCR positivity in individual saliva and feces, suggesting the potential for bacterial transmission through both direct contact (i.e., biting) and environmental (i.e., fecal) exposures. Further investigating the relative contributions of direct contact, environmental, and vector-borne transmission for bat Bartonella is an important next step to predict infection dynamics within bats and the risks of human and livestock exposures

Effect of Gas Sparging in Mammalian Cell Bioreactors

One of the major problems in the operations of mammalian cell bioreactors is the detrimental effect of gas sparging. Since the most convenient way to oxygenate any bioreactor is by gas sparging, this adverse effect has often been one of the limiting oxygen transport problems in both laboratory and industrial mammalian cell bioreactors. When one examines the literature on the effect of gas sparging on the death of mammalian cells, a great deal of confusions has been reported. It is not clear from the published literature as to the leading cause for gas-sparged related cell death. These confusions prevent the rational design and operations of mammalian cell bioreactors. In our laboratory, we have attempted to address this problem both fundamentally as well as attempt to obtain a general understanding on the adverse effect of gas sparging. Our analyses first examined the fluid shear associated with the various sections that the gas bubbles encounter during entrance, passage through the bioreactor and the final exit of the gas bubbles. Our analyses showed that the major damage of the mammalian cells by gas bubbles is due to the burst of the bubbles when exiting the bioreactor. It was also our hypothesis that the entrained cells in the liquid boundary layer of the gas bubble upon bursting is the major cause for cell death. We have corroborated this hypothesis by correlating the liquid entrainment with the cell death rate using results from our laboratory as well as other studies. Pluonic F-68, a weak surfactant, has routinely been used in laboratory and industrial bioreactors. In the past, the protective effect of Pluronic F-68 has never been shown as to why it is effective. In our research, we have data using microphotography which clearly demonstrated and corroborated our entrainment hypothesis is the major reason for the effectiveness of Pluronic F-68 in protecting the cells from gas-sparged related cell death.Singapore-MIT Alliance (SMA

Effects of breaking up prolonged sitting following low and high glycaemic index breakfast consumption on glucose and insulin concentrations

Purpose: Breaking up prolonged sitting can attenuate the postprandial rise in glucose and insulin. Whether such effects are dependent of the glycaemic index (GI) of the consumed carbohydrate is unknown. This study examined the acute effects of breaking up prolonged sitting following a low GI and a high GI breakfast on postprandial glucose and insulin concentrations. Procedures: Fourteen adult males aged 22.1 ± 1.2 years completed four, 4 h experimental conditions: high GI breakfast followed by uninterrupted sitting (HGI-SIT), low GI breakfast followed by uninterrupted sitting (LGI-SIT), high GI breakfast followed by 2 min activity breaks every 20 min (HGI-ACT), and low GI breakfast followed by 2 min activity breaks every 20 min (LGI-ACT). Positive incremental area under the curve (iAUC) for glucose and insulin (mean [95% CI]) for each 4h experimental condition was calculated. Statistical analyses were completed using linear mixed models. Results: The sitting × breakfast GI interaction was not significant for glucose positive iAUC (P=0.119). Glucose positive iAUC (mmol/L4 h−1) was significantly lower in the activity breaks conditions than the uninterrupted sitting conditions (2.07 [2.24, 2.89] vs. 2.56 [1.74, 2.40], respectively, P=0.004) and significantly lower in the low GI conditions than the high GI conditions (2.13 [1.80, 2.45] vs. 2.51 [2.18, 2.84], respectively, P=0.022). Insulin concentrations did not differ between conditions (P ≥ 0.203). Conclusions: Breaking up prolonged sitting and lowering breakfast GI independently reduced postprandial glucose responses. This indicates that interrupting prolonged sitting and reducing dietary GI are beneficial approaches for reducing cardiometabolic disease risk

Photochemical enrichment of deuterium in Titan's atmosphere: new insights from Cassini-Huygens

Cassini-Huygens data are used to re-examine the potential sources of the D/H enhancement over solar, measured in methane, in Titan's atmosphere. Assuming that the system is closed with respect to carbon, the use of constraints from the Huygens probe for the determination of the current mass of atmospheric methane and the most up-to-date determination of D/H from Cassini/CIRS infrared spectra allow us to show that photochemical enrichment of deuterium is not sufficient to be the sole mechanism yielding the measured D/H value. A possible fractionation between CH3D and CH4 during the escape process may slightly enhance the deuterium enrichment, but is not sufficient to explain the observed D/H value over the range of escape values proposed in the literature. Hence, alternative mechanisms such as a primordial deuterium enrichment must be combined with the photochemical enrichment in Titan's atmosphere in order to explain its current D/H value.Comment: 4 pages, 3 figures, accepted in ApJ

Investigating intra-host and intra-herd sequence diversity of foot-and-mouth disease virus

Due to the poor-fidelity of the enzymes involved in RNA genome replication, foot-and-mouth disease (FMD) virus samples comprise of unique polymorphic populations. In this study, deep sequencing was utilised to characterise the diversity of FMD virus (FMDV) populations in 6 infected cattle present on a single farm during the series of outbreaks in the UK in 2007. A novel RT–PCR method was developed to amplify a 7.6 kb nucleotide fragment encompassing the polyprotein coding region of the FMDV genome. Illumina sequencing of each sample identified the fine polymorphic structures at each nucleotide position, from consensus level changes to variants present at a 0.24% frequency. These data were used to investigate population dynamics of FMDV at both herd and host levels, evaluate the impact of host on the viral swarm structure and to identify transmission links with viruses recovered from other farms in the same series of outbreaks. In 7 samples, from 6 different animals, a total of 5 consensus level variants were identified, in addition to 104 sub-consensus variants of which 22 were shared between 2 or more animals. Further analysis revealed differences in swarm structures from samples derived from the same animal suggesting the presence of distinct viral populations evolving independently at different lesion sites within the same infected animal

Distinguishing low frequency mutations from RT-PCR and sequence errors in viral deep sequencing data

There is a high prevalence of coronary artery disease (CAD) in patients with left bundle branch block (LBBB); however there are many other causes for this electrocardiographic abnormality. Non-invasive assessment of these patients remains difficult, and all commonly used modalities exhibit several drawbacks. This often leads to these patients undergoing invasive coronary angiography which may not have been necessary. In this review, we examine the uses and limitations of commonly performed non-invasive tests for diagnosis of CAD in patients with LBBB

Internal Universes in Models of Homotopy Type Theory

We begin by recalling the essentially global character of universes in various models of homotopy type theory, which prevents a straightforward axiomatization of their properties using the internal language of the presheaf toposes from which these model are constructed. We get around this problem by extending the internal language with a modal operator for expressing properties of global elements. In this setting we show how to construct a universe that classifies the Cohen-Coquand-Huber-Mörtberg (CCHM) notion of fibration from their cubical sets model, starting from the assumption that the interval is tiny - a property that the interval in cubical sets does indeed have. This leads to an elementary axiomatization of that and related models of homotopy type theory within what we call crisp type theory

Predicting reservoir hosts and arthropod vectors from evolutionary signatures in RNA virus genomes

Identifying the animal origins of RNA viruses requires years of field and laboratory studies that stall responses to emerging infectious diseases. Using large genomic and ecological datasets, we demonstrate that animal reservoirs and the existence and identity of arthropod vectors can be predicted directly from viral genome sequences via machine learning. We illustrate the ability of these models to predict the epidemiology of diverse viruses across most human-infective families of single-stranded RNA viruses, including 69 viruses with previously elusive or never-investigated reservoirs or vectors. Models such as these, which capitalize on the proliferation of low-cost genomic sequencing, can narrow the time lag between virus discovery and targeted research, surveillance, and management

Vesivirus 2117 capsids more closely resemble sapovirus and lagovirus particles than other known vesivirus structures

Vesivirus 2117 is an adventitious agent that in 2009, was identified as a contaminant of CHO cells propagated in bioreactors at a pharmaceutical manufacturing plant belonging to Genzyme. The consequent interruption in supply of Fabrazyme and Cerezyme (drugs used to treat Fabry and Gaucher disease respectively), caused significant economic losses. Vesivirus 2117 is a member of the Caliciviridae; a family of small icosahedral viruses encoding a positive sense RNA genome. We have used cryo-electron microscopy and three dimensional image reconstruction to calculate a structure of vesivirus 2117 virus like particles as well as feline calicivirus and a chimeric sapovirus. We present a structural comparison of several members of the Caliciviridae, showing that the distal P domain of vesivirus 2117 is morphologically distinct from that seen in other known vesivirus structures. Furthermore, at intermediate resolutions we found a high level of structural similarity between vesivirus 2117 and Caliciviridae from other genera, such as sapovirus and rabbit haemorrhagic disease virus. Phylogenetic analysis confirms vesivirus 2117 as a vesivirus closely related to canine vesiviruses. We postulate that morphological differences in virion structure seen between vesivirus clades may reflect differences in receptor usage

Beneficial postprandial lipaemic effects of interrupting sedentary time with high-intensity physical activity versus a continuous moderate-intensity physical activity bout: a randomised crossover trial

Objectives To compare the postprandial cardiometabolic response to prolonged sitting, continuous moderate-intensity physical activity (PA) followed by prolonged sitting, and interrupting prolonged sitting with hourly high-intensity PA breaks. Design Three-condition randomised crossover trial. Methods Fourteen sedentary and inactive adults aged 29 ± 9 years took part in three, 8-h conditions: (1) prolonged sitting (SIT), (2) a continuous 30-min moderate-intensity PA bout followed by prolonged sitting (CONT-SIT), and (3) sitting interrupted hourly with 2 min 32 s high-intensity PA bouts (SIT-ACT). The treadmill PA in conditions 2 and 3 were matched for energy expenditure. Two standardised test meals were consumed during each condition. Incremental area under the curve (iAUC) for each 8-h condition was calculated for glucose, insulin, triglyceride, and high-density lipoprotein cholesterol (HDL-C) concentrations. Statistical analyses were completed using linear mixed models. Results Compared with SIT, SIT-ACT lowered triglyceride iAUC by 2.23 mmol/L ∙ 8 h (95% CI −4.33, −0.13) and raised HDL-C iAUC by 0.99 mmol/L ∙ 8 h (0.05, 1.93) (all p ≤ 0.038). There was no significant difference in triglyceride or HDL-C iAUC between CONT-SIT and SIT or SIT-ACT (p ≥ 0.211). There were no significant differences between conditions for glucose or insulin iAUC (p ≥ 0.504). Conclusions This study suggests that interrupting prolonged sitting with hourly high-intensity PA breaks acutely improves postprandial triglyceride and HDL-C concentrations compared with prolonged sitting, whereas a continuous moderate-intensity PA bout does not