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Staphylococcus aureus (S. aureus) is an opportunistic pathogen causing diseases ranging from mild skin infections to life threatening conditions, including endocarditis, pneumonia, and sepsis. To identify host genes modulating this host-pathogen interaction, we infected 25 Collaborative Cross (CC) mouse strains with methicillin-resistant S. aureus (MRSA) and monitored disease progression for seven days using a surgically implanted telemetry system. CC strains varied widely in their response to intravenous MRSA infection. We identified eight 'susceptible' CC strains with high bacterial load, tissue damage, and reduced survival. Among the surviving strains, six with minimal colonization were classified as 'resistant', while the remaining six tolerated higher organ colonization ('tolerant'). The kidney was the most heavily colonized organ, but liver, spleen and lung colonization were better correlated with reduced survival. Resistant strains had higher pre-infection circulating neutrophils and lower post-infection tissue damage compared to susceptible and tolerant strains. We identified four CC strains with sexual dimorphism: all females survived the study period while all males met our euthanasia criteria earlier. In these CC strains, males had more baseline circulating monocytes and red blood cells. We identified several CC strains that may be useful as new models for endocarditis, myocarditis, pneumonia, and resistance to MRSA infection. Quantitative Trait Locus (QTL) analysis identified two significant loci, on Chromosomes 18 and 3, involved in early susceptibility and late survival after infection. We prioritized Npc1 and Ifi44l genes as the strongest candidates influencing survival using variant analysis and mRNA expression data from kidneys within these intervals. Author summary: Methicillin-resistant Staphylococcus aureus is a human opportunistic pathogen that can cause life-threatening diseases. To study the influence of host genetics on the outcome of MRSA infection, we infected a collection of genetically diverse mice. We identified different phenotypes for survival, organ colonization, and tissue damage, and classified CC strains into MRSA susceptible, tolerant, and resistant categories. We identified several parameters that correlated with these phenotypes. Four CC strains exhibited strong sexual dimorphism in infection outcome: females lived longer, and males had higher baseline circulating monocytes and red blood cells. Several of the CC strains we characterize may represent better animal models for diseases caused by MRSA. QTL analysis identified two genes, Npc1 and Ifi44l, as strong candidates for involvement in early susceptibility and late survival after MRSA infection. Our data suggests a strong involvement of host genetics in MRSA infection outcome. [ABSTRACT FROM AUTHOR]

The present work is on the linear and third order nonlinear optical properties of single walled carbon nanotubes functionalized noncovalently with free base porphyrin and a metalloporphyrin separately. The functionalized carbon nanotubes (CNTs) are soluble in dimethylformamide, and the microscopic images show that the porphyrin molecules are attached to the surface of the CNTs. The interaction between CNTs and porphyrins is noncovalent and probably due to π-π interaction as both CNTs and porphyrins have π-electron rich structures. The samples exhibit large ultrafast nonlinear absorption as evident from the open aperture z-scan studies performed using mode-locked Ti:Sapphire femtosecond pulses at 780 nm. The mechanisms of optical nonlinearity of the functionalized CNTs appear to be two photon absorption along with nonlinear scattering with a small contribution from saturable absorption, whereas nonfunctionalized CNTs are known to exhibit saturable absorption. The value of the nonlinear absorption coefficient for the CNTs functionalized with the free base porphyrin is one order smaller than that for CNTs functionalized with metalloporphyrin. Efficient low threshold ultrafast optical limiting is demonstrated for both types of functionalized CNTs. [ABSTRACT FROM AUTHOR]

Placenta percreta is the most severe form of abnormal placental attachment. It is a variant of placenta accreta in which chorionic villi penetrate the entire thickness of the myometrium through the uterine serosa and may involve the adjacent structures. Literature review shows very few cases encountered during the first trimester of pregnancy. A-20-year-old woman with previous one cesarean section presented with continuous vaginal bleeding beginning after incomplete abortion at seven weeks and six days period of gestation for which she underwent dilatation and curettage. MRI revealed irregular heterogeneous signal intensity mass with large area of hemorrhage in lower anterior wall extending towards the endometrial cavity suggestive of morbid adherent placenta. Following continuous bleeding after repeated curettage for retained, adherent placenta her coagulation profile got deranged and DIC developed. Correction of coagulopathy and emergency hysterectomy as a life saving measure for placenta percreta was done in our case. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To study the role of α 1 AT and TIMP-1 gene polymorphisms in development of COPD. Design and methods: Blood samples from total 408 subjects (217 COPD patients and 191 controls) were used for genotyping and estimating biolevels of α1AT, TIMP-1 and inflammatory cytokines. Data was analyzed to determine the role of interaction of TIMP-1 and α 1 AT genes; and interplay between various genotypes and biolevels of α1AT, TIMP-1 and inflammatory cytokines in development of COPD. Results: Significantly low levels of α1AT and TIMP-1 were observed in COPD patients as compared to controls (P=0.001), where as the inflammatory cytokines were found to be increased in patients. PIM3 allele of α 1 AT gene in COPD patients was found to be associated with low levels of α1AT (P=0.001), the effect being more pronounced when PIM3 combined with rs6609533 of TIMP-1 gene (P=0.0001). Combination of genotypes rs6609533 of TIMP-1 and PIM3 of α 1 AT containing the risk alleles was over-represented in patients (P=0.005). Conclusion: The SNP rs6609533 of TIMP-1 gene interacted with PIM3 of α 1 AT to make a possible risk combination for development of COPD. [Copyright &y& Elsevier]

Abstract: Transmissible spongiform encephalopathies (TSEs) depend on misfolding of a normal cellular protein (PrPC) to an infectious conformation (PrPSc). Targeting PrPSc may represent an effective strategy for immunotherapy while avoiding consequences associated with immune responses to self-proteins. A weakly immunogenic epitope of PrPC (YYR), which induces PrPSc-specific antibodies, is used as a starting point for vaccine development. Through optimization of epitope, as well as formulation/delivery, we enhance immunogenicity while retaining PrPSc specificity. In particular, QVYYRPVDQYSNQN, presented by a leukotoxin carrier protein, emerges as a strong vaccine candidate. A vaccine representing this construct induces consistent and sustained serum PrPSc-specific IgG antibody responses following two vaccinations. Antigen specific antibodies are also present within cerebral spinal fluid and mucosal secretions. These characteristics provide a foundation for development of a TSE vaccine. [Copyright &y& Elsevier]

Understanding the molecular mechanisms underlying resistance and tolerance to pathogen infection may present the opportunity to develop novel interventions. Resistance is the absence of clinical disease with a low pathogen burden, while tolerance is minimal clinical disease with a high pathogen burden. Salmonella is a worldwide health concern. We studied 18 strains of collaborative cross mice that survive acute Salmonella Typhimurium (STm) infections. We infected these strains orally and monitored them for 3 weeks. Five strains cleared STm (resistant), six strains maintained a bacterial load and survived (tolerant), while seven strains survived >7 days but succumbed to infection within the study period and were called "delayed susceptible." Tolerant strains were colonized in the Peyer's patches, mesenteric lymph node, spleen, and liver, while resistant strains had significantly reduced bacterial colonization. Tolerant strains had lower preinfection core body temperatures and had disrupted circadian patterns of body temperature postinfection sooner than other strains. Tolerant strains had higher circulating total white blood cells than resistant strains, driven by increased numbers of neutrophils. Tolerant strains had more severe tissue damage and higher circulating levels of monocyte chemoattractant protein 1 (MCP-1) and interferon gamma (IFN-γ), but lower levels of epithelial neutrophil-activating protein 78 (ENA-78) than resistant strains. Quantitative trait locus (QTL) analysis revealed one significant association and six suggestive associations. Gene expression analysis identified 22 genes that are differentially regulated in tolerant versus resistant animals that overlapped these QTLs. Fibrinogen genes ( Fga , Fgb , and Fgg ) were found across the QTL, RNA, and top canonical pathways, making them the best candidate genes for differentiating tolerance and resistance. IMPORTANCE To survive a bacterial infection, an infected host can display resistance or tolerance. Resistance is indicated by a decrease in pathogen load, while for tolerance a high pathogen load is accompanied by minimal disease. We infected genetically diverse mice with Salmonella Typhimurium for 21 days and discovered new phenotypes for disease outcome (delayed susceptible, tolerant, and resistant). Tolerant strains showed the lowest preinfection core body temperatures and the most rapid disruption in circadian patterns of body temperature postinfection. Tolerant strains had higher circulating neutrophils and higher circulating levels of MCP-1 and IFN-γ, but lower levels of ENA-78 than did resistant strains, in addition to more severe tissue damage. QTL analysis revealed multiple associated regions, and gene expression analysis identified 22 genes that are differentially regulated in tolerant versus resistant animals in these regions. Fibrinogen genes ( Fga , Fgb , and Fgg ) were found across the QTL, RNA, and the top canonical pathways, suggesting a role in tolerance.