Efficient DNA packaging of bacteriophage PRD1 requires the unique vertex protein P6

The assembly of bacteriophage PRD1 proceeds via formation of empty procapsids containing an internal lipid membrane, into which the linear double-stranded DNA genome is subsequently packaged. The packaging ATPase P9 and other putative packaging proteins have been shown to be located at a unique vertex of the PRD1 capsid. Here, we describe the isolation and characterization of a suppressor-sensitive PRD1 mutant deficient in the unique vertex protein P6. Protein P6 was found to be an essential part of the PRD1 packaging machinery; its absence leads to greatly reduced packaging efficiency. Lack of P6 was not found to affect particle assembly, because in the P6-deficient mutant infection, wild-type (wt) amounts of particles were produced, although most were empty. P6 was determined not to be a specificity factor, as the few filled particles seen in the P6-deficient infection contained only PRD1-specific DNA. The presence of P6 was not necessary for retention of DNA in the capsid once packaging had occurred, and P6-deficient DNA-containing particles were found to be stable and infectious, albeit not as infectious as wt PRD1 virions. A packaging model for bacteriophage PRD1, based on previous results and those obtained in this study, is presented.     

Co-factors of LIM domains (Clims/Ldb/Nli) regulate corneal homeostasis and maintenance of hair follicle stem cells

The homeostasis of both cornea and hair follicles depends on a constant supply of progeny cells produced by populations of keratin (K) 14-expressing stem cells localized in specific niches. To investigate the potential role of Co-factors of LIM domains (Clims) in epithelial tissues, we generated transgenic mice expressing a dominant-negative Clim molecule (DN-Clim) under the control of the K14 promoter. As expected, the K14 promoter directed high level expression of the transgene to the basal cells of cornea and epidermis, as well as the outer root sheath of hair follicles. In corneal epithelium, the transgene expression causes decreased expression of adhesion molecule BP180 and defective hemidesmosomes, leading to detachment of corneal epithelium from the underlying stroma, which in turn causes blisters, wounds and an inflammatory response. After a period of epithelial thinning, the corneal epithelium undergoes differentiation to an epidermis-like structure. The K14-DN-Clim mice also develop progressive hair loss due to dysfunctional hair follicles that fail to generate hair shafts. The number of hair follicle stem cells is decreased by at least 60% in K14-DN-Clim mice, indicating that Clims are required for hair follicle stem cell maintenance. In addition, Clim2 interacts with Lhx2 in vivo, suggesting that Clim2 is an essential co-factor for the LIM homeodomain factor Lhx2, which was previously shown to play a role in hair follicle stem cell maintenance. Together, these data indicate that Clim proteins play important roles in the homeostasis of corneal epithelium and hair follicles.     

Environmental Risks at Finnish Shooting Ranges—A Case Study

We studied three Finnish shooting ranges in order to define the extent of the risks associated with elevated environmental concentrations of metals and PAHs. A scoring system revealed that lead, arsenic, and antimony were the most critical contaminants. On Site 3, the concentration of lead in groundwater exceeded the drinking water standard indicating evident health risks. For the remaining two sites we calculated Acceptable Daily Doses (ADD) based on the Reasonable Maximum Exposure (RME) approach and compared them with safe exposure levels. We also used a pharmacokinetic model to determine blood lead levels (PbBs). Risks to biota were assessed using ecological benchmarks and exposure and accumulation models. Prediction of leaching was based on laboratory tests and a distribution model. The health risk assessment for lead resulted in the maximum hazard quotient (HQ) of 1.2 whereas the HQs of As and Sb remained less than 1. Some exposure scenarios produced PbB estimates exceeding 10 μ g dl^?1 but based on the uncertainty analysis we expect the health risks to remain insignificant. However, leaching of contaminants presents a risk to groundwater quality. At site 1 the ecotoxicity-based HQs demonstrate high risks to soil biota, small mammals, terrestrial plants and aquatic organisms.     

Self-Rated Health in the Last 12 Years of Life Compared to Matched Surviving Controls: The Health and Retirement Study

Self-rated health (SRH) is a valid measure of health status and associated with mortality. Based on individual-level biannual repeat data on SRH we sought to characterize the natural history of poor SRH during the 12 years prior to death in men and women in different age groups. We conducted a retrospective analysis of the Health and Retirement Study participants who died between 1998 and 2010 and had at least two SRH measurements in the 12 years prior to death. We used a nested case-control design to compare SRH trajectories of deceased men and women aged 30–64, 65–79 and 80 years versus surviving participants. The cases comprised 3,350 deceased participants who were matched to surviving controls (n = 8,127). SRH was dichotomized into good vs. poor health. Men and women dying at age 65–79 and ≥80 years had 1.5 to 3 times higher prevalence of poor SRH already 11–12 years prior to death compared to surviving controls. The risk estimates remained statistically significant even after adjusting for life-style related risk factors and diagnosed diseases. Prevalence of poor SRH before death was lowest among those aged ≥80 years and highest in 30–64 year-olds. In conclusion, men and women who subsequently die perceive their health worse already 11–12 years prior to death compared to their surviving controls.     

Quantifying neighbourhood socioeconomic effects in clustering of behaviour-related risk factors: a multilevel analysis

Background

The extent to which neighbourhood characteristics explain accumulation of health behaviours is poorly understood. We examined whether neighbourhood disadvantage was associated with co-occurrence of behaviour-related risk factors, and how much of the neighbourhood differences in the co-occurrence can be explained by individual and neighbourhood level covariates.

Methods

The study population consisted of 60 694 Finnish Public Sector Study participants in 2004 and 2008. Neighbourhood disadvantage was determined using small-area level information on household income, education attainment, and unemployment rate, and linked with individual data using Global Positioning System-coordinates. Associations between neighbourhood disadvantage and co-occurrence of three behaviour-related risk factors (smoking, heavy alcohol use, and physical inactivity), and the extent to which individual and neighbourhood level covariates explain neighbourhood differences in co-occurrence of risk factors were determined with multilevel cumulative logistic regression.

Results

After adjusting for age, sex, marital status, and population density we found a dose-response relationship between neighbourhood disadvantage and co-occurrence of risk factors within each level of individual socioeconomic status. The cumulative odds ratios for the sum of health risks comparing the most to the least disadvantaged neighbourhoods ranged between 1.13 (95% confidence interval (CI): 1.03–1.24) and 1.75 (95% CI, 1.54–1.98). Individual socioeconomic characteristics explained 35%, and neighbourhood disadvantage and population density 17% of the neighbourhood differences in the co-occurrence of risk factors.

Conclusions

Co-occurrence of poor health behaviours associated with neighbourhood disadvantage over and above individual''s own socioeconomic status. Neighbourhood differences cannot be captured using individual socioeconomic factors alone, but neighbourhood level characteristics should also be considered.     

Leukocyte telomere length in the Finnish Diabetes Prevention Study

Leukocyte telomere length (TL) is considered a biomarker for biological aging. Shortened TL has been observed in many complex diseases, including type 2 diabetes (T2DM). Lifestyle intervention studies, e.g. the Diabetes Prevention Study (DPS), have shown a decrease in the incidence of T2DM by promoting healthy lifestyles in individuals with impaired glucose tolerance (IGT). Our aim was to study in the DPS the influence of the lifestyle intervention on TL. TL was measured by quantitative PCR-based method at two time points (N = 334 and 343) on average 4.5 years apart during the active intervention and post-intervention follow-up. TL inversely correlated with age. Our main finding was that TL increased in about two thirds of the individuals both in the intervention and in the control groups during follow-up; TL increased most in individuals with the shortest TL at the first measurement. TL was not associated with development of T2DM, nor did lifestyle intervention have an effect on TL. No association between insulin secretion or insulin resistance indices and TL was observed. We did not detect an association between TL and development of T2DM in the DPS participants. It could be due to all participants being overweight and having IGT at baseline, both of which have been found to be independently associated with shorter leukocyte TL in some earlier studies. TL had no substantial role in worsening of glucose tolerance in people with IGT. Our study confirms that leukocyte TL can increase with time even in obese people with impaired glucose metabolism.     

Prevalence, genotype distribution and persistence of human papillomavirus in oral mucosa of women: a six-year follow-up study

Background

Human papillomavirus (HPV) infections have been linked to a subset of oral and oropharyngeal cancers. However, little is known on the natural history of oral HPV infections. We designed the prospective Finnish HPV Family Study to assess the dynamics of HPV infections in parents and their infants. This study reports HPV genotype distribution and virus persistence in oral mucosa of the mothers.

Materials and Methods

Totally, 324 pregnant women were enrolled at the 3^rd trimester of pregnancy and followed-up for 6 years. Oral scrapings taken with a brush were collected and HPV-genotyping was performed with nested PCR and Multimetrix® test (Progen, Heidelberg, Germany). The predictors of persistent oral HPV species 7/9 infections were analyzed using generalized estimating equation models.

Results

The point prevalence of oral HPV varied from 15% to 24% during the 6-year follow-up. Altogether, 18 HPV genotypes were identified either as single or multiple-type oral infections. HPV16 was the most prevalent type at 9.7%–18.4%, followed by HPV18, HPV6, and multiple infections. Altogether, 74 women had persistent oral HPV infection determined as at least two consecutive samples positive with the same HPV genotype. HPV16 and HPV6 were the two most frequent types to persist (76% and 9%) for a mean of 18.6 and 20.2 months, respectively, followed by multiple infections (8%) for 18.3 months. An increased risk for persistent oral HPV infection with species 7/9 was associated with being seropositive for low-risk (LR)-HPV-types at baseline, whereas the use of oral contraceptives and a second pregnancy during follow-up were protective. Clinical oral lesions were detected in 17% of these women, one-third of whom had persistent oral HPV-infections.

Conclusion

HPV16 and HPV6 were the most common genotypes in oral HPV-infections and were also most likely to persist. Use of oral contraceptives and a second pregnancy protected against oral HPV persistence.     

Association between the ABO blood group and the human intestinal microbiota composition

ABSTRACT: BACKGROUND: The mucus layer covering the human intestinal epithelium forms a dynamic surface for host-microbial interactions. In addition to the environmental factors affecting the intestinal equilibrium, such as diet, it is well established that the microbiota composition is individually driven, but the host factors determining the composition have remained unresolved. RESULTS: In this study, we show that ABO blood group is involved in differences in relative proportion and overall profiles of intestinal microbiota. Specifically, the microbiota from the individuals harbouring the B antigen (secretor B and AB) differed from the non-B antigen groups and also showed higher diversity of the Eubacterium rectale-Clostridium coccoides (EREC) and Clostridium leptum (CLEPT) -groups in comparison with other blood groups. CONCLUSIONS: Our novel finding indicates that the ABO blood group is one of the genetically determined host factors modulating the composition of the human intestinal microbiota, thus enabling new applications in the field of personalized nutrition and medicine.     

Molecular Characterization of a Variant of Bacillus anthracis-Specific Phage AP50 with Improved Bacteriolytic Activity

The genome sequence of a Bacillus anthracis-specific clear plaque mutant phage, AP50c, contains 31 open reading frames spanning 14,398 bp, has two mutations compared to wild-type AP50t, and has a colinear genome architecture highly similar to that of gram-positive Tectiviridae phages. Spontaneous AP50c-resistant B. anthracis mutants exhibit a mucoid colony phenotype.     

Greenhouse gas fluxes from the eutrophic Temmesjoki River and its Estuary in the Liminganlahti Bay (the Baltic Sea)

We studied concentrations of carbon dioxide (CO₂), methane (CH₄) and nitrous oxide (N₂O) in the eutrophic Temmesjoki River and Estuary in the Liminganlahti Bay in 2003–2004 and evaluated the atmospheric fluxes of the gases based on measured concentrations, wind speeds and water current velocities. The Temmesjoki River was a source of CO₂, CH₄ and N₂O to the atmosphere, whereas the Liminganlahti Bay was a minor source of CH₄ and a minor source or a sink of CO₂ and N₂O. The results show that the fluxes of greenhouse gases in river ecosystems are highly related to the land use in its catchment areas. The most upstream river site, surrounded by forests and drained peatlands, released significant amounts of CO₂ and CH₄, with average fluxes of 5,400 mg CO₂–C m⁻² d⁻¹ and 66 mg CH₄–C m⁻² d⁻¹, and concentrations of 210 μM and 345 nM, respectively, but N₂O concentrations, at an average of 17 nM, were close to the atmospheric equilibrium concentration. The downstream river sites surrounded by agricultural soils released significant amounts of N₂O (with an average emission of 650 μg N₂O–N m⁻² d⁻¹ and concentration of 22 nM), whereas the CO₂ and CH₄ concentrations were low compared to the upstream site (55 μM and 350 nM). In boreal regions, rivers are partly ice-covered in wintertime (approximately 5 months). A large part of the gases, i.e. 58% of CO₂, 55% of CH₄ and 36% of N₂O emissions, were found to be released during wintertime from unfrozen parts of the river.