Continuous and Discontinuous Cigarette Smoke Exposure Differentially Affects Protective Th1 Immunity against Pulmonary Tuberculosis

Pulmonary tuberculosis (TB), caused by Mycobacterium tuberculosis, is the leading cause of death due to a bacterial pathogen. Emerging epidemiologic evidence suggests that the leading risk factor associated with TB mortality is cigarette smoke exposure. Despite this, it remains poorly understood what is the effect of cigarette smoke exposure on anti-TB immunity and whether its potential detrimental effect can be reversed by cigarette smoking cessation. In our current study, we have investigated the impact of both continuous and discontinuous cigarette smoke exposure on the development of anti-mycobacterial type 1 immunity in murine models. We find that while continuous cigarette smoke exposure severely impairs type 1 immunity in the lung, a short-term smoking cessation allows rapid restoration of anti-mycobacterial immunity. The ability of continuous cigarette smoke exposure to dampen type 1 protective immunity is attributed locally to its affects on innate immune cells in the lung. Continuous cigarette smoke exposure locally, by not systemically, impairs APC accumulation and their production of TNF, IL-12, and RANTES, blunts the recruitment of CD4+IFN-γ+ T cells to the lung, and weakens the formation of granuloma. On the other hand, smoking cessation was found to help restore type 1 immunity by rapidly improving the functionality of lung APCs, enhancing the recruitment of CD4+IFN-γ+ T cells to the lung, and promoting the formation of granuloma. Our study for the first time demonstrates that continuous, but not discontinuous, cigarette smoke exposure severely impedes the lung expression of anti-TB Th1 immunity via inhibiting innate immune activation and lung T cell recruitment. Our findings thus suggest cigarette smoking cessation to be beneficial to the control of pulmonary TB.     

Rapid chromosome territory relocation by nuclear motor activity in response to serum removal in primary human fibroblasts

Background  

Radial chromosome positioning in interphase nuclei is nonrandom and can alter according to developmental, differentiation, proliferation, or disease status. However, it is not yet clear when and how chromosome repositioning is elicited.     

Production of the Streptomyces scabies coronafacoyl phytotoxins involves a novel biosynthetic pathway with an F420‐dependent oxidoreductase and a short‐chain dehydrogenase/reductase

Coronafacoyl phytotoxins are secondary metabolites that are produced by various phytopathogenic bacteria, including several pathovars of the Gram‐negative bacterium Pseudomonas syringae as well as the Gram‐positive potato scab pathogen Streptomyces scabies. The phytotoxins are composed of the polyketide coronafacic acid (CFA) linked via an amide bond to amino acids or amino acid derivatives, and their biosynthesis involves the cfa and cfa‐like gene clusters that are found in P. syringae and S. scabies, respectively. The S. scabies cfa‐like gene cluster was previously reported to contain several genes that are absent from the P. syringae cfa gene cluster, including one (oxr) encoding a putative F₄₂₀—dependent oxidoreductase, and another (sdr) encoding a predicted short‐chain dehydrogenase/reductase. Using gene deletion analysis, we demonstrated that both oxr and sdr are required for normal production of the S. scabies coronafacoyl phytotoxins, and structural analysis of metabolites that accumulated in the Δsdr mutant cultures revealed that Sdr is directly involved in the biosynthesis of the CFA moiety. Our results suggest that S. scabies and P. syringae use distinct biosynthetic pathways for producing coronafacoyl phytotoxins, which are important mediators of host‐pathogen interactions in various plant pathosystems.     

Development and assessment of a landscape-scale ecological threat index for the Lower Colorado River Basin

Anthropogenic disturbances impact freshwater biota but are rarely incorporated into conservation planning due to the difficulties in quantifying threats. There is currently no widely accepted method to quantify disturbances, and determining how to measure threats to upstream catchments using disturbance metrics can be time consuming and subjective. We compared four watershed-scale ecological threat indices for the Lower Colorado River Basin (LCRB) using landscape-level threats of land use (e.g., agricultural and urban lands), waterway development and diversions (e.g., number of canals, dams), and human development (e.g., road and railroads density, pollution sites). The LCRB is an ideal region to assess ecological threat indices because of the increasing need for conservation to ensure the persistence of native fishes in highly altered habitat. Each threat was measured for severity (i.e., level of influence on the upstream watershed) and frequency throughout each watershed; both severity and frequency were measured using two different methods. Severity values were based either on peer-reviewed literature and weighted in accordance to their published ecological impact, or assumed equal severity across stressors. Threat frequency was calculated according to either the presence/absence of each stressor, or on the relative density of each stressor in the watershed. Each measure of severity was combined with a measure of frequency, creating four ecological threat indices, and transformed to a 0–100 scale. Threat indices were highly correlated (slopes of 0.94–1.63; R² of 0.82–0.98), and were highest for watersheds close to urban centers, including Phoenix, Tucson, and Flagstaff, Arizona, and Las Vegas, Nevada. Road crossings and density appeared to be the most influential stressors in the index, but the removal of any individual stressor only changed the index by <5.1 units. Our results indicate that a simpler index with less subjectivity (i.e., presence/absence of a stressor in a watershed) provides similar results to the more subjective measure of threats (i.e., peer-reviewed threat severity). Because these threats have been linked to ecological health, the development of the index should be a useful tool to identify regions of greatest potential threat to aquatic biota and can aid in conservation planning for the Lower Colorado River Basin.     

INBREEDING DEPRESSION IN MORPHOLOGICAL AND PHYSIOLOGICAL TRAITS OF SCHIEDEA LYDGATEI (CARYOPHYLLACEAE) IN TWO ENVIRONMENTS

We compared inbreeding depression in hermaphroditic Schiedea lydgatei and its gynodioecious sister species, S. salicaria, to infer the level of inbreeding depression in their common ancestor. With measurements of selfing rates, this information can be used to assess the importance of inbreeding depression in the evolution of breeding systems in S. lydgatei and S. salicaria. Morphological and physiological characters related to fitness were compared for inbred and outcrossed S. lydgatei in high- and low-fertilizer environments in the greenhouse. Seed mass, number of seeds per capsule, germination, survival, biomass, number of flowers, and age at first flowering were compared for inbred versus outcrossed progeny. We also measured inbreeding depression in maximal rates of photosynthetic carbon assimilation and stomatal conductance to water vapor, traits that affect fitness through their influence on plant carbon balance and water-use efficiency (ratio of carbon gain to water loss). All traits except number of seeds per capsule in parents and survival showed inbreeding depression, with the magnitude depending on family and environment. High inbreeding depression is likely in the ancestor of S. lydgatei and S. salicaria, indicating that, with sufficiently high selfing rates, females could spread in populations. Hermaphroditism in S. lydgatei is probably favored by low selfing rates. In contrast, the evolution of gynodioecy in S. salicaria apparently has been favored by relatively high selfing rates in combination with high inbreeding depression.     

Superoxide dismutase is upregulated in <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> following protoporphyrin-mediated photodynamic inactivation and does not directly influence the response to photodynamic treatment

Background  

Staphylococcus aureus, a major human pathogen causes a wide range of disease syndromes. The most dangerous are methicillin-resistant S. aureus (MRSA) strains, resistant not only to all β-lactam antibiotics but also to other antimicrobials. An alarming increase in antibiotic resistance spreading among pathogenic bacteria inclines to search for alternative therapeutic options, for which resistance can not be developed easily. Among others, photodynamic inactivation (PDI) of S. aureus is a promising option. Photodynamic inactivation is based on a concept that a non toxic chemical, called a photosensitizer upon excitation with light of an appropriate wavelength is activated. As a consequence singlet oxygen and other reactive oxygen species (e.g. superoxide anion) are produced, which are responsible for the cytotoxic effect towards bacterial cells. As strain-dependence in photodynamic inactivation of S. aureus was observed, determination of the molecular marker(s) underlying the mechanism of the bacterial response to PDI treatment would be of great clinical importance. We examined the role of superoxide dismutases (Sod) in photodynamic inactivation of S. aureus as enzymes responsible for oxidative stress resistance.