wtV5α associates with DPC micelles (DPCm) and acquires partial α-helical structure.

<p>(<b>A</b>) Overlay of the ¹⁵N-¹H HSQC spectra of wtV5α (black) and wtV5α/DPCm (red). HS673 stands for homoserine lactone, which is the C-terminal residue generated upon CNBr cleavage of the (His)₆-tag from V5α. (<b>B</b>) Chemical shift perturbation analysis of the wtV5α/DPCm and wtV5α pair. Residues having an incomplete set of chemical shifts are listed in Section S4 of the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0065699#pone.0065699.s005" target="_blank">File S1</a>. (<b>C</b>) SSP scores plotted as a function of the primary structure. (<b>D</b>) Circular dichroism spectra of wtV5α domains in the presence (red) and absence (black) of DPC micelles. (<b>E</b>) Proposed model of PKCα maturation, in which V5 serves as a membrane anchor. Reg and Kin are the regulatory and kinase domains, respectively. The regulatory domain comprises the tandem C1A and C1B domains, commonly referred to as C1, and the C2 domain. PS stands for the pseudo-substrate region. V5α is shown in red.</p

V5 domain is a variable C-terminal region of PKCs.

<p>(<b>A</b>) Linear diagram of conventional PKC isoforms illustrating the multi-modular structure of the enzyme. (<b>B</b>) Alignment of V5 primary structures of PKC isoforms from <i>M. musculus</i>. The conserved NFD motif is highlighted in gray; HM and TM motifs are boxed. The Ser/Thr residue of the HM is a Glu residue (blue) in atypical isoforms. (<b>C</b>) Catalytic domain (residues 339–679) taken from the crystal structure of the PKCβII “intermediate”, PDB ID 3PFQ. The B-factors of backbone atoms are mapped onto the structure as a color gradient. The N−/C-lobes of the kinase domain and V5 are shown with transparent and opaque representations, respectively. (<b>D</b>) Circular dichroism spectra of micelle-free wtV5α and dmV5α domains.</p

Cis-trans isomerization of Pro residues modulates the conformation of V5α.

<p>(<b>A</b>) The C(CO)NH strip plots of the F614 and V636 ¹H-¹⁵N amide planes showing the characteristic spectroscopic pattern of cis- and trans- Pro⁶¹²-Pro⁶¹³ and Gln⁶³⁴-Pro⁶³⁵ peptide bonds. The differences between the Cβ and Cγ chemical shifts are marked with vertical dashed lines. Horizontal blue lines indicate the positions of the Cβ and Cγ cross-peaks corresponding to the most abundant trans Pro⁶¹²-Pro⁶¹³ conformer. (<b>B</b>)–(<b>D</b>) Fractional populations of the V5α species having one Xaa-Pro bond in cis-conformation. Isomerizing Pro residues are highlighted in orange. The wtV5α and dmV5α data are shown in black and green, respectively. The position of Pro residues is indicated with arrows. Residues with quantifiable populations are underlined. In (<b>C</b>), the mutation site T638E is highlighted in red. The data for the turn motif Thr(Glu)⁶³⁸-Pro⁶³⁹-Pro⁶⁴⁰ are shown with filled bars.</p

Conformational preferences and sub-nanosecond dynamics of wtV5α and dmV5α.

<p>(<b>A</b>) Overlay of the ¹⁵N-¹H HSQC spectra of wtV5α (black) and dmV5α (green). The asterisks indicate the mutation sites, Thr638 (TM) and Ser657 (HM). HS673 stands for homoserine lactone, which is the C-terminal residue generated upon CNBr cleavage of the (His)₆-tag from V5α. (<b>B</b>) Chemical shift perturbation analysis of the dmV5α-wtV5α pair. Purple vertical lines mark the mutation sites; the NFD motif is shaded. (<b>C</b>) SSP scores plotted as a function of the primary structure. The secondary structure elements of the V5 domain in the structure of the catalytic domain from PKCα (PDB ID 3IW4) are shown for comparison. (<b>D</b>) Comparison of the hetero-nuclear {¹H}-¹⁵N NOE values obtained for wtV5α (black) and dmV5α (green). The NOE values and their difference are plotted against the V5 primary structure in the top and bottom panels, respectively.</p

Relationship between cytokine level in patients with major depressive disorder and depression and anxiety scores.

<p>Relationship between cytokine level in patients with major depressive disorder and depression and anxiety scores.</p

Relationships between interleukin (IL)-1β, IL-8, and tumor necrosis factor (TNF)-α levels, and Hamilton Depression Rating Scale (HAMD) scores.

<p>Relationships between interleukin (IL)-1β, IL-8, and tumor necrosis factor (TNF)-α levels, and Hamilton Depression Rating Scale (HAMD) scores.</p

Baseline characteristics.

<p>Baseline characteristics.</p

Relationships between interleukin (IL)-8 levels and Hamilton Anxiety Rating Scale (HAMA) scores.

<p>Relationships between interleukin (IL)-8 levels and Hamilton Anxiety Rating Scale (HAMA) scores.</p

Multiple linear regression analyses of Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA) scores.

<p>Multiple linear regression analyses of Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA) scores.</p

Lack of an Association between Passive Smoking and Incidence of Female Breast Cancer in Non-Smokers: Evidence from 10 Prospective Cohort Studies

<div><p>Background</p><p>Several case-control studies have suggested that passive smoking may increase the incidence of female breast cancer. However, the results of cohort studies have been inconsistent in establishing an association. The present study evaluated the association between passive smoking and incidence of female breast cancer through a meta-analysis of prospective cohort studies.</p><p>Methods</p><p>Relevant articles published before August 2012 were identified by searching the electronic databases PubMed, Embase, and Web of Science. Pooled relative risks (RRs) were determined with either a fixed or random effects model and were used to assess the strength of the association. Sensitivity and subgroup analyses according to ethnicity, menopausal status, and the period and place of exposure to passive smoking were also performed.</p><p>Results</p><p>Ten prospective cohort studies involving 782 534 female non-smokers were included in the meta-analysis and 14 831 breast cancer cases were detected. Compared with the women without exposure to passive smoking, the overall combined RR of breast cancer was 1.01 (95% confidence interval: 0.96 to 1.06, P = 0.73) among women with exposure to passive smoking. Similar results were achieved through the subgroup analyses. No evidence of publication bias was observed.</p><p>Conclusion</p><p>The results suggest that passive smoking may not be associated with increased incidence of breast cancer. However, the present conclusion should be considered carefully and confirmed with further studies.</p></div