Mycobacterial Evolution Intersects With Host Tolerance

Over the past 200 years, tuberculosis (TB) has caused more deaths than any other infectious disease, likely infecting more people than it has at any other time in human history. Mycobacterium tuberculosis (Mtb), the etiologic agent of TB, is an obligate human pathogen that has evolved through the millennia to become an archetypal human-adapted pathogen. This review focuses on the evolutionary framework by which Mtb emerged as a specialized human pathogen and applies this perspective to the emergence of specific lineages that drive global TB burden. We consider how evolutionary pressures, including transmission dynamics, host tolerance, and human population patterns, may have shaped the evolution of diverse mycobacterial genomes

HOPS 383: An Outbursting Class 0 Protostar in Orion

We report the dramatic mid-infrared brightening between 2004 and 2006 of HOPS 383, a deeply embedded protostar adjacent to NGC 1977 in Orion. By 2008, the source became a factor of 35 brighter at 24 microns with a brightness increase also apparent at 4.5 microns. The outburst is also detected in the submillimeter by comparing APEX/SABOCA to SCUBA data, and a scattered-light nebula appeared in NEWFIRM K_s imaging. The post-outburst spectral energy distribution indicates a Class 0 source with a dense envelope and a luminosity between 6 and 14 L_sun. Post-outburst time-series mid- and far-infrared photometry shows no long-term fading and variability at the 18% level between 2009 and 2012. HOPS 383 is the first outbursting Class 0 object discovered, pointing to the importance of episodic accretion at early stages in the star formation process. Its dramatic rise and lack of fading over a six-year period hint that it may be similar to FU Ori outbursts, although the luminosity appears to be significantly smaller than the canonical luminosities of such objects.Comment: Accepted by ApJ Letters, 6 pages, 4 figures; v2 has an updated email address for the lead autho

Palaeontological evidence for an Oligocene divergence between Old World monkeys and apes

Apes and Old World monkeys are prominent components of modern African and Asian ecosystems, yet the earliest phases of their evolutionary history have remained largely undocumented(1). The absence of crown catarrhine fossils older than similar to 20 million years (Myr) has stood in stark contrast to molecular divergence estimates of similar to 25-30 Myr for the split between Cercopithecoidea (Old World monkeys) and Hominoidea (apes), implying long ghost lineages for both clades(2-4). Here we describe the oldest known fossil 'ape', represented by a partial mandible preserving dental features that place it with 'nyanzapithecine' stem hominoids. Additionally, we report the oldest stem member of the Old World monkey clade, represented by a lower third molar. Both specimens were recovered from a precisely dated 25.2-Myr-old stratum in the Rukwa Rift, a segment of the western branch of the East African Rift in Tanzania. These finds extend the fossil record of apes and Old World monkey swell into the Oligocene epoch of Africa, suggesting a possible link between diversification of crown catarrhines and changes in the African landscape brought about by previously unrecognized tectonic activity(5) in the East African rift system

Metabolic Characterization of Adults with Binge Eating in the General Population: The Framingham Heart Study

OBJECTIVE To describe the metabolic profile of individuals with objective binge eating (OBE) and to evaluate whether associations between OBE and metabolic risk factors are mediated by body mass index (BMI). DESIGN AND METHODS Participants from the Framingham Heart Study, Third Generation and Omni 2 cohorts (n = 3551, 53.1% women, mean age 46.4 years) were screened for binge eating. We used multivariable-adjusted regression models to examine the associations of OBE with metabolic risk factors. RESULTS The prevalence of OBE was 4.8% in women and 4.9% in men. Compared to non-binge eating, OBE was associated with higher odds of hypertension (OR 1.85, 95% CI 1.32–2.60), hypertriglyceridemia (OR 1.42, 95% CI 1.01–2.01), low HDL (OR 1.70, 95% CI 1.18–2.44), insulin resistance (OR 3.18, 95% CI 2.25–4.50) and metabolic syndrome (OR 2.75, 95% CI 1.94–3.90). Fasting glucose was 7.2 mg/dl higher in those with OBE (p=0.0001). Individuals with OBE had more visceral, subcutaneous and liver fat. Most of these associations were attenuated with adjustment for BMI, with the exception of fasting glucose. CONCLUSIONS Binge eating is associated with a high burden of metabolic risk factors. Much of the associated risk appears to be mediated by BMI, with the exception of fasting glucose

Aerothermal Ground Testing of Flexible Thermal Protection Systems for Hypersonic Inflatable Aerodynamic Decelerators

Flexible TPS development involves ground testing and analysis necessary to characterize performance of the FTPS candidates prior to flight testing. This paper provides an overview of the analysis and ground testing efforts performed over the last year at the NASA Langley Research Center and in the Boeing Large-Core Arc Tunnel (LCAT). In the LCAT test series, material layups were subjected to aerothermal loads commensurate with peak re-entry conditions enveloping a range of HIAD mission trajectories. The FTPS layups were tested over a heat flux range from 20 to 50 W/cm with associated surface pressures of 3 to 8 kPa. To support the testing effort a significant redesign of the existing shear (wedge) model holder from previous testing efforts was undertaken to develop a new test technique for supporting and evaluating the FTPS in the high-temperature, arc jet flow. Since the FTPS test samples typically experience a geometry change during testing, computational fluid dynamic (CFD) models of the arc jet flow field and test model were developed to support the testing effort. The CFD results were used to help determine the test conditions experienced by the test samples as the surface geometry changes. This paper includes an overview of the Boeing LCAT facility, the general approach for testing FTPS, CFD analysis methodology and results, model holder design and test methodology, and selected thermal results of several FTPS layups

Lysosomal Disorders Drive Susceptibility to Tuberculosis by Compromising Macrophage Migration.

A zebrafish genetic screen for determinants of susceptibility to Mycobacterium marinum identified a hypersusceptible mutant deficient in lysosomal cysteine cathepsins that manifests hallmarks of human lysosomal storage diseases. Under homeostatic conditions, mutant macrophages accumulate undigested lysosomal material, which disrupts endocytic recycling and impairs their migration to, and thus engulfment of, dying cells. This causes a buildup of unengulfed cell debris. During mycobacterial infection, macrophages with lysosomal storage cannot migrate toward infected macrophages undergoing apoptosis in the tuberculous granuloma. The unengulfed apoptotic macrophages undergo secondary necrosis, causing granuloma breakdown and increased mycobacterial growth. Macrophage lysosomal storage similarly impairs migration to newly infecting mycobacteria. This phenotype is recapitulated in human smokers, who are at increased risk for tuberculosis. A majority of their alveolar macrophages exhibit lysosomal accumulations of tobacco smoke particulates and do not migrate to Mycobacterium tuberculosis. The incapacitation of highly microbicidal first-responding macrophages may contribute to smokers' susceptibility to tuberculosis.This work was supported by the National Institutes of Health (R37AI054503, LR, R01NS082567, CBM, 5F30HL110455, RB, 1DP2-OD008614, DMT), the Wellcome Trust (LR), the National Institute of Health Research Cambridge Biomedical Research Centre (LR), the Health Research Board of Ireland (HRA_POR/2013/387, MO’S and CSA/2012/16, JK), and The Royal City of Dublin Hospital Trust (Grant 146, JK).This is the final version of the article. It first appeared from Cell Press via http://dx.doi.org/10.1016/j.cell.2016.02.034

Agricultural intensification heightens food safety risks posed by wild birds

Agricultural intensification and simplification are key drivers of recent declines in wild bird populations, heightening the need to better balance conservation with food production. This is hindered, however, by perceptions that birds threaten food safety. While birds are known reservoirs of foodborne pathogens, there remains uncertainty about the links between landscape context, farming practices, and actual crop contamination by birds. Here, we examine relationships between landscape context, farming practices, and pathogen contamination by birds using a barrier-to-spillover approach. First, we censused bird communities using point count surveys. Second, we collected 2,024 faecal samples from captured birds alongside 1,215 faecal samples from brassica fields and food processing areas across 50 farms spanning the USA West Coast. We then estimated the prevalence of three foodborne pathogens across landscape and livestock intensification gradients. Finally, we quantified the number of plants with faeces. Campylobacterspp. were detected in 10.2% of faeces from captured birds and 13.1% of faeces from production areas. Non-native birds were 4.1 times more likely to haveCampylobacterspp. than native birds.Salmonellaspp. were detected in 0.2% of faeces from production areas and were never detected in captured birds. We detected evidence of Shiga toxigenicE. coliin one sample across the >3,200 tested. Campylobacterspp. prevalence in faeces from production areas increased with increasing mammalian livestock densities in the landscape but decreased with increasing amounts of natural habitat. We encountered bird faeces on 3.3% of plants examined. Despite the impact on pathogen prevalence, amount of natural habitat in the landscape did not increase the number of plants with bird faeces, although on-farm mammalian livestock density slightly did. Synthesis and applications. Food safety and wildlife conservation are often thought to be in conflict. However, our findings suggest that natural habitat around farms may reduce crop contamination rates by birds. This is perhaps because natural habitat can promote native birds that are less likely to harbour foodborne pathogens or because it decreases contact with livestock waste. Our results suggest that preservation of natural habitats around farms could benefit both conservation and food safety, contrary to current standards for 'best practices'

Zebrafish: A See-Through Host and a Fluorescent Toolbox to Probe Host–Pathogen Interaction

In many ways, the zebrafish represents a hybrid between mouse and invertebrate infection models. Powerful forwardgenetic tools that have made invertebrates justifiably famous are not only relatively accessible in the zebrafish, but have been exploited to yield new insights into human infectious diseases, including leprosy and tuberculosis [1]. Transgenic technologies have enabled detailed, non-invasive in vivo visualization of macrophages and neutrophils in pitched battle with bacteria and fungi [2,3]. Reverse genetics with morpholinos, vivo-morpholinos, and zinc-finger nucleases (but unfortunately not homologous recombination, which for the moment remains out of reach in this organism) enable examination of the roles of specific genes during infection. Flexible genetic systems such as Gal4-UAS and Cre-Lox permit tissue-specific transformation and ablation ([3]; Figure 1)