Does the modern urbanized sleeping habitat pose a breast cancer risk?

Due to its disruptive effects on circadian rhythms and sleep deprivation at night, shiftworking is currently recognized as a risk factor for breast cancer (BC). As revealed by the present analysis based on a comparative case-control study of 1679 women, exposure to light-at-night (LAN) in the "sleeping habitat" is significantly associated with BC risk (odds ratio [OR]?=?1.220, 95% confidence interval [CI]?=?1.118-1.311; p?相似文献   

Acute and chronic effects of particles on hospital admissions in New-England

Background

Many studies have reported significant associations between exposure to PM_2.5 and hospital admissions, but all have focused on the effects of short-term exposure. In addition all these studies have relied on a limited number of PM_2.5 monitors in their study regions, which introduces exposure error, and excludes rural and suburban populations from locations in which monitors are not available, reducing generalizability and potentially creating selection bias.

Methods

Using our novel prediction models for exposure combining land use regression with physical measurements (satellite aerosol optical depth) we investigated both the long and short term effects of PM_2.5 exposures on hospital admissions across New-England for all residents aged 65 and older. We performed separate Poisson regression analysis for each admission type: all respiratory, cardiovascular disease (CVD), stroke and diabetes. Daily admission counts in each zip code were regressed against long and short-term PM_2.5 exposure, temperature, socio-economic data and a spline of time to control for seasonal trends in baseline risk.

Results

We observed associations between both short-term and long-term exposure to PM_2.5 and hospitalization for all of the outcomes examined. In example, for respiratory diseases, for every10-µg/m³ increase in short-term PM_2.5 exposure there is a 0.70 percent increase in admissions (CI = 0.35 to 0.52) while concurrently for every10-µg/m³ increase in long-term PM_2.5 exposure there is a 4.22 percent increase in admissions (CI = 1.06 to 4.75).

Conclusions

As with mortality studies, chronic exposure to particles is associated with substantially larger increases in hospital admissions than acute exposure and both can be detected simultaneously using our exposure models.     

Identifying functional links between genes using conserved chromosomal proximity

Conservation of proximity of a pair of genes across multiple genomes generally indicates that their functions could be linked. Here, we present a systematic evaluation using 42 complete microbial genomes from 25 phylogenetic groups to test the reliability of this observation in predicting function for genes. We find a relationship between the number of phylogenetic groups in which a gene pair is proximate and the probability that the pair belongs to a common pathway. Our method produces 1586 links between ortholog families substantiated by observed proximity in genomes representing at least three phylogenetic groups. Of the pairs annotated in the KEGG database, 80% are in the same biological pathway in KEGG.     

Mapping the depth dependence of shear properties in articular cartilage

Determining the depth dependence of the shear properties of articular cartilage is essential for understanding the structure-function relation in this tissue. Here, we measured spatial variations in the shear modulus G of bovine articular cartilage using a novel technique that combines shear testing, confocal imaging and force measurement. We found that G varied by up to two orders of magnitude across a single sample, exhibited a global minimum 50-250 microm below the articular surface in a region just below the superficial zone and was roughly constant at depths > 1000 microm (the "plateau region"). For plateau strains gamma(plateau) approximately 0.75% and overall compressive strains epsilon approximately 5%, G(min) and G(plateau) were approximately 70 and approximately 650 kPa, respectively. In addition, we found that the shear modulus profile depended strongly on the applied shear and axial strains. The greatest change in G occurred at the global minimum where the tissue was highly nonlinear, stiffening under increased shear strain, and weakening under increased compressive strain. Our results can be explained through a simple thought model describing the observed nonlinear behavior in terms of localized buckling of collagen fibers and suggest that compression may decrease the vulnerability of articular cartilage to shear-induced damage by lowering the effective strain on individual collagen fibrils.     

Identification and characterization of a novel molecular-recognition and self-assembly domain within the islet amyloid polypeptide

The islet amyloid polypeptide (hIAPP) is a 37 amino acid residue polypeptide that was found to accumulate as amyloid fibrils in the pancreas of individuals with type II diabetes. Previous studies identified various fragments of hIAPP that can form amyloid fibrils in vitro (e.g. hIAPP(8-20), hIAPP(23-27), and hIAPP(30-37)). However, no comparative and systematic information was available on the role of these structural domains (or others) in the process of molecular recognition that mediates fibrillization, in the context of the full-length polypeptide. To systematically map and compare potential recognition domains, we studied the ability of hIAPP to interact with an array of 28 membrane-spotted overlapping peptides that span the entire sequence of hIAPP (i.e. hIAPP(1-10), hIAPP(2-11...), hIAPP(28-37)). Our study clearly identified a major domain of molecular recognition within hIAPP, as the polypeptide was found to bind with high affinity to a defined linear group of peptides ranging from hIAPP(7-16) to hIAPP(12-21). The maximal binding of the full-length polypeptide was to the hIAPP(11-20) peptide fragment (with the sequence RLANFLVHSS). In order to define the minimal fragment, within this apparent recognition motif, that is capable of self-association and thus may serve as the core molecular recognition motif, we examined the ability of truncated analogs of the recognition sequence to self-assemble into amyloid fibrils. The shortest active fragments capable of self-assembly were found to be the pentapeptides FLVHS and NFLVH. The apparent role of this motif in the process of hIAPP self-assembly is consistent with the profile of the hIAAP-binding distribution to the peptide array. The identification of such short recognition motifs is extremely useful in the attempts to develop means to block amyloid fibril formation by hIAPP. It is worth mentioning that this is only the second time in which peptides as short as a pentapeptide were shown to form amyloid fibrils (the other pentapeptide is FGAIL).     

Bacillus thuringiensis Cry4Aa insecticidal protein: Functional importance of the intrinsic stability of the unique α4–α5 loop comprising the Pro-rich sequence

The long loop connecting transmembrane α4 and α5 of the Bacillus thuringiensis Cry4Aa toxin possesses a unique feature with Pro-rich sequence (Pro¹⁹³Pro¹⁹⁴_Pro¹⁹⁶) which was shown to be crucial for toxicity. Here, the structural role in the intrinsic stability of the Pro-rich sequence toward toxin activity was investigated. Three Val-substituted mutants (P193V, P194V and P196V) and one Phe-substituted mutant (P193F) were generated and over-expressed in Escherichia coli as inclusions at levels equal to the wild-type. Bioassays demonstrated that all mutants, particularly P193V and P193F whose inclusions were hardly soluble in carbonate buffer (pH 9.0), exhibited reduced toxicity, suggesting an essential role in toxin function by the specific cyclic structure of individual Pro residues. Analysis of the 65-kDa Cry4Aa structure from 10-ns molecular dynamics (MD) simulations revealed that the α4–α5 loop is substantially stable as it showed low structural fluctuation with a 1.2-Å RMSF value. When the flexibility of the α4–α5 loop was increased through P193G, P194G and P196G substitutions, decreased toxicity was also observed for all mutants, mostly for the P193G mutant with low alkali-solubility, suggesting a functional importance of loop-rigidity attributed by individual Pro-cyclic side-chains, particularly Pro¹⁹³. Further MD simulations revealed that the most critical residue−Pro¹⁹³ for which mutations vastly affect toxin solubility and larval toxicity is in close contact with several surrounding residues, thus playing an additional role in the structural arrangement of the Cry4Aa toxin molecule. Altogether, our data signify that the intrinsic stability of the unique Cry4Aa α4–α5 loop structure comprising the Pro-rich sequence plays an important role in toxin activity.