Lead exposure and periodontitis in US adults

Lead is known to have significant effects on bone metabolism and the immune system. This study tested the hypothesis that lead exposure affects periodontitis in adults. Material and Methods:  This study used the data from the Third National Health and Nutrition Examination Survey (NHANES III, 1988–94). It analyzed data from 2500 men and 2399 women, 20–56 yr old, who received complete periodontal examination. Periodontitis was defined as the presence of > 20% of mesial sites with ≥ 4 mm of attachment loss. Lead exposure was grouped into three categories:  7 μg/dL. Covariates were cotinine levels, poverty ratio, race/ethnicity, education, bone mineral density, diabetes, calcium intake, dental visit, and menopause (for women). All analyses were performed separately for men and women and considering the effect design. Univariate, bivariate, and stratified analysis was followed by multivariable analysis by estimating prevalence ratios through poisson regression. Results:  After adjustment for confounders, the prevalence ratios, comparing those with a lead blood level of > 7 μg/dL to those with a lead blood level of < 3 μg/dL was 1.70 (95% confidence interval (CI): 1.02, 2.85) for men and 3.80 (95% CI: 1.66, 8.73) for women. Conclusion:  The lead blood level was positively and statistically associated with periodontitis for both men and women. Considering the public health importance of periodontitis and lead exposure, further studies are necessary to confirm this association.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65253/1/j.1600-0765.2006.00913.x.pd

CEERS Key Paper. V. Galaxies at 4 &lt; z &lt; 9 Are Bluer than They Appear-Characterizing Galaxy Stellar Populations from Rest-frame ∼1 μm Imaging

We present results from the Cosmic Evolution Early Release Survey on the stellar population parameters for 28 galaxies with redshifts 4 &lt; z &lt; 9 using imaging data from the James Webb Space Telescope (JWST) Mid-Infrared Instrument (MIRI) combined with data from the Hubble Space Telescope and the Spitzer Space Telescope. The JWST/MIRI 5.6 and 7.7 μm data extend the coverage of the rest-frame spectral energy distribution to nearly 1 μm for galaxies in this redshift range. By modeling the galaxies’ SEDs the MIRI data show that the galaxies have, on average, rest-frame UV (1600 Å)—I-band colors 0.4 mag bluer than derived when using photometry that lacks MIRI. Therefore, the galaxies have lower ratios of stellar mass to light. The MIRI data reduce the stellar masses by 〈 Δ log M * 〉 = 0.25 dex at 4 &lt; z &lt; 6 and 0.37 dex at 6 &lt; z &lt; 9. This also reduces the star formation rates (SFRs) by 〈ΔlogSFR〉 = 0.14 dex at 4 &lt; z &lt; 6 and 0.27 dex at 6 &lt; z &lt; 9. The MIRI data also improve constraints on the allowable stellar mass formed in early star formation. We model this using a star formation history that includes both a “burst” at z f = 100 and a slowly varying (“delayed-τ”) model. The MIRI data reduce the allowable stellar mass by 0.6 dex at 4 &lt; z &lt; 6 and by ≈1 dex at 6 &lt; z &lt; 9. Applying these results globally, this reduces the cosmic stellar-mass density by an order of magnitude in the early Universe (z ≈ 9). Therefore, observations of rest-frame ≳1 μm are paramount for constraining the stellar-mass buildup in galaxies at very high redshifts.</p

Inhibition of protein disulfide isomerase induces differentiation of acute myeloid leukemia cells

Acute myeloid leukemia is a malignant disease of immature myeloid cells. Despite significant therapeutic effects of differentiation-inducing agents in some acute myeloid leukemia subtypes, the disease remains incurable in a large fraction of patients. Here we show that SK053, a thioredoxin inhibitor, induces differentiation and cell death of acute myeloid leukemia cells. Considering that thioredoxin knock-down with short hairpin RNA failed to exert antiproliferative effects in one of the acute myeloid leukemia cell lines, we used a biotin affinity probe-labeling approach to identify potential molecular targets for the effects of SK053. Mass spectrometry of proteins precipitated from acute myeloid leukemia cells incubated with biotinylated SK053 used as a bait revealed protein disulfide isomerase as a potential binding partner for the compound. Biochemical, enzymatic and functional assays using fluorescence lifetime imaging confirmed that SK053 binds to and inhibits the activity of protein disulfide isomerase. Protein disulfide isomerase knockdown with short hairpin RNA was associated with inhibition of cell growth, increased CCAAT enhancer-binding protein α levels, and induction of differentiation of HL-60 cells. Molecular dynamics simulation followed by the covalent docking indicated that SK053 binds to the fourth thioredoxin-like domain of protein disulfide isomerase. Differentiation of myeloid precursor cells requires the activity of CCAAT enhancer-binding protein α, the function of which is impaired in acute myeloid leukemia cells through various mechanisms, including translational block by protein disulfide isomerase. SK053 increased the levels of CCAAT enhancer-binding protein α and upregulated mRNA levels for differentiation-associated genes. Finally, SK053 decreased the survival of blasts and increased the percentage of cells expressing the maturation-associated CD11b marker in primary cells isolated from bone marrow or peripheral blood of patients with acute myeloid leukemia. Collectively, these results provide a proof-of-concept that protein disulfide isomerase inhibition has potential as a therapeutic strategy for the treatment of acute myeloid leukemia and for the development of small-molecule inhibitors of protein disulfide isomerase

CEERS Key Paper IV: Galaxies at 4<z<94 < z < 9 are Bluer than They Appear -- Characterizing Galaxy Stellar Populations from Rest-Frame ∼1\sim 1 micron Imaging

We present results from the Cosmic Evolution Early Release Survey (CEERS) on the stellar-population parameters for 28 galaxies with redshifts $4<z<9$ using imaging data from the James Webb Space Telescope (JWST) Mid-Infrared Instrument (MIRI) combined with data from the Hubble Space Telescope and the Spitzer Space Telescope. The JWST/MIRI 5.6 and 7.7 $\mu$m data extend the coverage of the rest-frame spectral-energy distribution (SED) to nearly 1 micron for galaxies in this redshift range. By modeling the galaxies' SEDs the MIRI data show that the galaxies have, on average, rest-frame UV (1600 \r{A}) $-$ $I$-band colors 0.4 mag bluer than derived when using photometry that lacks MIRI. Therefore, the galaxies have lower (stellar)-mass-to-light ratios. The MIRI data reduce the stellar masses by $\langle \Delta\log M_\ast\rangle=0.25$ dex at $4<z<6$ (a factor of 1.8) and 0.37 dex at $6<z<9$ (a factor of 2.3). This also reduces the star-formation rates (SFRs) by $\langle \Delta\log\mathrm{SFR} \rangle=0.14$ dex at $4<z<6$ and 0.27 dex at $6<z<9$. The MIRI data also improve constraints on the allowable stellar mass formed in early star-formation. We model this using a star-formation history that includes both a "burst' at $z_f=100$ and a slowly varying ("delayed-$\tau$") model. The MIRI data reduce the allowable stellar mass by 0.6 dex at $4<z< 6$ and by $\approx$1 dex at $6<z<9$. Applying these results globally, this reduces the cosmic stellar-mass density by an order of magnitude in the early universe ($z\approx9$). Therefore, observations of rest-frame $\gtrsim$1 $\mu$m are paramount for constraining the stellar-mass build-up in galaxies at very high-redshifts.Comment: Updated with accepted ApJ version. Part of the CEERS Focus Issue. 27 pages, many figures (4 Figure Sets, available upon reasonable request

Insights into the Transposable Mobilome of Paracoccus spp. (Alphaproteobacteria)

Several trap plasmids (enabling positive selection of transposition events) were used to identify a pool of functional transposable elements (TEs) residing in bacteria of the genus Paracoccus (Alphaproteobacteria). Complex analysis of 25 strains representing 20 species of this genus led to the capture and characterization of (i) 37 insertion sequences (ISs) representing 9 IS families (IS3, IS5, IS6, IS21, IS66, IS256, IS1182, IS1380 and IS1634), (ii) a composite transposon Tn6097 generated by two copies of the ISPfe2 (IS1634 family) containing two predicted genetic modules, involved in the arginine deiminase pathway and daunorubicin/doxorubicin resistance, (iii) 3 non-composite transposons of the Tn3 family, including Tn5393 carrying streptomycin resistance and (iv) a transposable genomic island TnPpa1 (45 kb). Some of the elements (e.g. Tn5393, Tn6097 and ISs of the IS903 group of the IS5 family) were shown to contain strong promoters able to drive transcription of genes placed downstream of the target site of transposition. Through the application of trap plasmid pCM132TC, containing a promoterless tetracycline resistance reporter gene, we identified five ways in which transposition can supply promoters to transcriptionally silent genes. Besides highlighting the diversity and specific features of several TEs, the analyses performed in this study have provided novel and interesting information on (i) the dynamics of the process of transposition (e.g. the unusually high frequency of transposition of TnPpa1) and (ii) structural changes in DNA mediated by transposition (e.g. the generation of large deletions in the recipient molecule upon transposition of ISPve1 of the IS21 family). We also demonstrated the great potential of TEs and transposition in the generation of diverse phenotypes as well as in the natural amplification and dissemination of genetic information (of adaptative value) by horizontal gene transfer, which is considered the driving force of bacterial evolution

DYNC2H1 hypomorphic or retina-predominant variants cause nonsyndromic retinal degeneration

Purpose: Determining the role of DYNC2H1 variants in nonsyndromic inherited retinal disease (IRD). Methods: Genome and exome sequencing were performed for five unrelated cases of IRD with no identified variant. In vitro assays were developed to validate the variants identified (fibroblast assay, induced pluripotent stem cell [iPSC] derived retinal organoids, and a dynein motility assay). Results: Four novel DYNC2H1 variants (V1, g.103327020_103327021dup; V2, g.103055779A>T; V3, g.103112272C>G; V4, g.103070104A>C) and one previously reported variant (V5, g.103339363T>G) were identified. In proband 1 (V1/V2), V1 was predicted to introduce a premature termination codon (PTC), whereas V2 disrupted the exon 41 splice donor site causing incomplete skipping of exon 41. V1 and V2 impaired dynein-2 motility in vitro and perturbed IFT88 distribution within cilia. V3, homozygous in probands 2–4, is predicted to cause a PTC in a retina-predominant transcript. Analysis of retinal organoids showed that this new transcript expression increased with organoid differentiation. V4, a novel missense variant, was in trans with V5, previously associated with Jeune asphyxiating thoracic dystrophy (JATD). Conclusion: The DYNC2H1 variants discussed herein were either hypomorphic or affecting a retina-predominant transcript and caused nonsyndromic IRD. Dynein variants, specifically DYNC2H1 variants are reported as a cause of non syndromic IRD

Utility of cardiac computed tomography for inflow cannula patency assessment and prediction of clinical outcome in patients with the HeartMate II left ventricular assist device

OBJECTIVES: Proper inflow cannula orientation during implantation of the HeartMate II (HMII) left ventricular assist device (LVAD) is important for optimal pump function. This article describes our experience with cardiac computed tomography (CCT) to evaluate inflow cannula patency and predict future adverse outcomes (AE) after HMII LVAD implantation. METHODS: Ninety-three patients underwent HMII LVAD implantation for end-stage cardiomyopathy from January 2010 until March 2014. A total of 25 consecutive patients had CCT after the implantation; 3 patients were excluded from the analysis due to associated abnormality of the outflow graft. The 22 patients with CCT after HMII LVAD were censored for adverse events related to LVAD malfunction after HMII LVAD implantation. The maximum percentage of inflow cannula obstruction on CCT was recorded. We analysed the predictive value of CCT in addition to other clinical and diagnostic variables for future AEs. RESULTS: Seven of the 22 patients (32%) experienced AEs after HMII LVAD implantation. The degree of inflow cannula obstruction was higher in the group of patients who experienced an AE (70 vs 14%; P &lt; 0.001). Inflow cannula obstruction &gt;30% showed excellent correlation with AE longitudinally based on receiver operating curve (0.829). The group with AEs more frequently experienced CHF symptoms (P = 0.054). CONCLUSIONS: Inflow cannula obstruction &gt;30% on CCT predicts future adverse events in patients with HMII LVAD; the need for surgical intervention in terms of LVAD exchange or urgent listing for heart transplantation should be considered in good surgical risk patients. Cardiac computed tomography should be considered routinely postoperatively in patients with HMII LVAD. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved