Background Perivascular adipose tissue (PVAT) surrounds most vessels and shares common features with brown adipose tissue (BAT). Whereas adaptive thermogenesis in BAT increases energy expenditure and is beneficial for metabolic diseases, little is known on the role of PVAT in vascular diseases such as atherosclerosis. We hypothesize that the thermogenic function of PVAT regulates intravascular temperature and reduces atherosclerosis. Methods and Results PVAT shares similar structural and proteomics with BAT. We demonstrate that PVAT has thermogenic properties similar to BAT in response to cold stimuli in vivo. Proteomics analysis of the PVAT from mice housed in a cold environment identified differential expression in proteins highly related with cellular metabolic processes. In a mouse model deficient in PPARγ in smooth muscle cells (SMPG KO mice), we uncovered a complete absence of PVAT surrounding the vasculature likely due to PPARγ deletion also in the perivascular adipocyte precursor cells. Lack of PVAT, resulting in loss of its thermogenic activity, impairs vascular homeostasis causing temperature loss and endothelial dysfunction. We further show that cold exposure inhibits atherosclerosis and improves endothelial function in mice with intact PVAT, but not in SMPG KO mice, as a result of impaired lipid clearance. Pro-inflammatory cytokine expression in PVAT is not altered upon cold exposure. Finally, prostacyclin released from PVAT contributes to the vascular protection against endothelial dysfunction. Conclusions PVAT is a vasoactive organ with functional characteristics similar to BAT and is essential for intravascular thermoregulation upon cold acclimation. This thermogenic capacity of PVAT plays an important protective role in the pathogenesis of atherosclerosis.

Hyperpolarization-activated cyclic nucleotide-gated channels (HCN1-4) play a crucial role in the regulation of cell excitability. Importantly, they contribute to spontaneous rhythmic activity in brain and heart. HCN channels are principally activated by membrane hyperpolarization and binding of cAMP. Here, we identify tyrosine phosphorylation by Src kinase as another mechanism affecting channel gating. Inhibition of Src by specific blockers slowed down activation kinetics of native and heterologously expressed HCN channels. The same effect on HCN channel activation was observed in cells cotransfected with a dominant-negative Src mutant. Immunoprecipitation demonstrated that Src binds to and phosphorylates native and heterologously expressed HCN2. Src interacts via its SH3 domain with a sequence of HCN2 encompassing part of the C-linker and the cyclic nucleotide binding domain. We identified a highly conserved tyrosine residue in the C-linker of HCN channels (Tyr 476 in HCN2) that confers modulation by Src. Replacement of this tyrosine by phenylalanine in HCN2 or HCN4 abolished sensitivity to Src inhibitors. Mass spectrometry confirmed that Tyr 476 is phosphorylated by Src. Our results have functional implications for HCN channel gating. Furthermore, they indicate that tyrosine phosphorylation contributes in vivo to the fine tuning of HCN channel activity.

A simple but highly selective colorimetric and ratiometric fluorescent chemodosimeter was designed and synthesized to detect fluoride ions (F(-)) in aqueous solution and living cells by virtue of the strong affinity of F(-) toward silicon.

Abstract• The performance of ten commonly used taper equations for predicting both stem form and volume in balsam fir [Abies balsamea (L.) Mill], red spruce[Picea rubens (Sarg.)], and white pine[Pinus strobus (L.)] in the Acadian Region of North America was investigated.• Results show that the Kozak (2004) and Bi (2000) equations were superior to the other equations in predicting diameter inside bark for red spruce and white pine, while the Valentine and Gregoire (2000) performed well when those measurements were unavailable.• The incorporation of crown variables substantially improved stem volume predictions (mean absolute bias reduction of 7-15%; root mean square error reduction of 10-15%) for all three species, but had little impact on stem form predictions.• The best taper equation reduced the predicted root mean square error by 16, 39, and 45% compared to estimates from the widely used Honer (1965) regional stem volume equations for balsam fir, red spruce, and white pine, respectively.• When multiple taper equations exist for a certain species, the use of the geometric mean of all predictions is an attractive alternative to selecting the "best" equation. • L'incorporation de variables de couronne a amélioré sensiblement les prédictions du volume des troncs (réduction moyenne des biais absolu de 7-15 % ; réduction de l'erreur quadratique moyenne de 10-15 %) pour les trois espèces, mais avait peu d'impact sur les prédictions de la forme du tronc. Mots• La meilleure équation de décroissance a réduit l'estimation de l'erreur quadratique moyenne de 16, 39, et 45 % par rapport aux estimations largement utilisées avec les équations régionales d'Honer (1965) pour l'estimation du volume de la tige respectivement pour le sapin baumier, l'épinette rouge et le pin Weymouth.• Lorsque plusieurs équations de défilement existent pour certaines espèces, l'utilisation de la moyenne géométrique de toutes les prédictions est une alternative intéressante pour la sélection de la "meilleure" équation.

Objective To evaluate the safety of co-administering tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) and influenza vaccines during pregnancy by comparing adverse events after concomitant and sequential vaccination. Methods We conducted a retrospective cohort study of pregnant women aged 14–49 years in the Vaccine Safety Datalink from January 1, 2007 to November 15, 2013. We compared medically attended acute events (fever, any acute reaction) and adverse birth outcomes (preterm delivery, low birth weight, small for gestational age) in women receiving concomitant Tdap and influenza vaccination and women receiving sequential vaccination. Results Among 36,844 pregnancies in which Tdap and influenza vaccines were administered, the vaccines were administered concomitantly in 8,464 (23%) pregnancies, and sequentially in 28,380 (77%) pregnancies. Acute adverse events after vaccination were rare. We found no statistically significant increased risk of fever or any medically attended acute adverse event in pregnant women vaccinated concomitantly compared to sequentially. When analyzing women at 20 weeks of gestation or greater during periods of influenza vaccine administration, there were no differences in preterm delivery, low birth weight or small-for-gestational-age infants between women vaccinated concomitantly compared with sequentially in pregnancy. Conclusion Concomitant administration of Tdap and influenza vaccines during pregnancy was not associated with a higher risk of medically attended adverse acute outcomes or birth outcomes compared to sequential vaccination.

We created a site-directed UAS-ORF library of 655 growth-regulating genes in Drosophila. This library represents a large collection of genes regulating cell cycle, cell size, and proliferation and will be a valuable resource for studying growth regulation in vivo. By using misexpression of genes, we prevent problems arising from genetic redundancy and can uncover novel gene functions. To validate the usefulness of this library, we screened for Wingless (Wg) pathway components. We used a combination of experimental and bioinformatic approaches to predict candidates and identified three serine/threonine kinases as regulators of Wg signaling. We show that one of these, Nek2, optimizes pathway response by direct phosphorylation of Dishevelled. In addition, we describe functional relations for roughly 5% of all Drosophila genes and identify a large number of genes that regulate cell size, proliferation, and final organ size upon misexpression.

Background The Vaccine Safety Datalink (VSD) is a collaboration between CDC and 9 integrated health care systems that serves as a cornerstone of US post-licensure vaccine safety monitoring. Given concerns that potential differences between the insured VSD population and the US population could limit the generalizability of VSD study findings, we performed a comparison of the demographic characteristics between the two populations. Methods We collected data from medical records and administrative files at VSD sites in 2010 to compare sex, age, race, ethnicity, income, and educational attainment to the 2010 US Census population. We also compared data on the 2012 VSD Medicaid population to 2012 US Medicaid data. Results The VSD population included over 8 million individuals in 2010, which represented 2.6% of the total US population. All major demographic groups were represented in the VSD. We found no major differences in comparing sex, race, ethnicity and educational attainment between the VSD and the US population. Middle income populations were comparable between the VSD and the US. While the percentage of lower income populations was less in the VSD compared to the US, the VSD had over 2 million individuals in this group. Additionally, there were over 600,000 Medicaid members in the VSD in 2012, which represented 1.1% of the US Medicaid population. Conclusions We found that the VSD population is representative of the general US population on several key demographic and socioeconomic variables. Despite a few specific groups being underrepresented in the VSD compared to the US, the absolute number of VSD members is large enough to ensure significant representation of these groups in vaccine safety studies that use VSD data.

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