On the chemical biology of the nitrite/sulfide interaction

The authors are grateful to the Susanne-Bunnenberg-Stiftung of the Düsseldorf Heart Center (to MK), the COST action BM1005 (European Network on Gasotransmitters), and the Faculty of Medicine, University of Southampton (to MF) for financial support.Sulfide (H2S/HS−) has been demonstrated to exert an astounding breadth of biological effects, some of which resemble those of nitric oxide (NO). While the chemistry, biochemistry and potential pathophysiology of the cross-talk between sulfide and NO have received considerable attention lately, a comparable assessment of the potential biological implications of an interaction between nitrite and sulfide is lacking. This is surprising inasmuch as nitrite is not only a known bioactive oxidation product of NO, but also efficiently converted to S-nitrosothiols in vivo; the latter have been shown to rapidly react with sulfide in vitro, leading to formation of S/N-hybrid species including thionitrite (SNO−) and nitrosopersulfide (SSNO−). Moreover, nitrite is used as a potent remedy against sulfide poisoning in the clinic. The chemistry of interaction between nitrite and sulfide or related bioactive metabolites including polysulfides and elemental sulfur has been extensively studied in the past, yet much of this information appears to have been forgotten. In this review, we focus on the potential chemical biology of the interaction between nitrite and sulfide or sulfane sulfur molecules, calling attention to the fundamental chemical properties and reactivities of either species and discuss their possible contribution to the biology, pharmacology and toxicology of both nitrite and sulfide.Publisher PDFPeer reviewe

A conserved and essential basic region mediates tRNA binding to the Elp1 subunit of the <em>Saccharomyces cerevisiae</em> Elongator complex

Elongator is a conserved, multi-protein complex discovered in Saccharomyces cerevisiae, loss of which confers a range of pleiotropic phenotypes. Elongator in higher eukaryotes is required for normal growth and development and a mutation in the largest subunit of human Elongator (Elp1) causes familial dysautonomia, a severe recessive neuropathy. Elongator promotes addition of mcm(5) and ncm(5) modifications to uridine in the tRNA anticodon ‘wobble’ position in both yeast and higher eukaryotes. Since these modifications are required for the tRNAs to function efficiently, a translation defect caused by hypomodified tRNAs may therefore underlie the variety of phenotypes associated with Elongator dysfunction. The Elp1 carboxy-terminal domain contains a highly conserved arginine/lysine-rich region that resembles a nuclear localization sequence (NLS). Using alanine substitution mutagenesis, we show that this region is essential for Elongator's function in tRNA wobble uridine modification. However, rather than acting to determine the nucleo-cytoplasmic distribution of Elongator, we find that the basic region plays a critical role in a novel interaction between tRNA and the Elp1 carboxy-terminal domain. Thus the conserved basic region in Elp1 may be essential for tRNA wobble uridine modification by acting as tRNA binding motif

Comment on Rishu et al. Time required to initiate outbreak and pandemic observational research

We applaud the work of Rishu and colleagues in tracking the timelines to initiation of outbreak and pandemic observational research. Through this work they highlight the challenges in being prepared with a clinical research response in the next pandemic. Pandemics are unpredictable but also recurrent. Recent experience of Ebola and Zika outbreaks highlight the devastating impact these outbreaks have on the health, economy and security of communities for generations to come

Constraints on Neutrino Parameters from Neutral-Current Solar Neutrino Measurements

We generalize the pull approach to define the $\chi^2$ function to the analysis of the data with correlated statistical errors. We apply this method to the analysis of the Sudbury Neutrino Collaboration data obtained in the salt-phase. In the global analysis of all the solar neutrino and KamLAND data we find the best fit (minimum $\chi^2$) values of neutrino parameters to be $\tan^2 \theta_{12} \sim 0.42$ and $\delta m_{12}^2 \sim 7.1 \times 10^{-5}$ eV$^2$. We confirm that the maximal mixing is strongly disfavored while the bounds on $\delta m_{12}^2$ are significantly strengthened.Comment: 6 figures. Some typos are corrected, figures are visually improve

Characteristics of offspring derived from conventional and X-sorted bovine sperm

peer-reviewedThe objective of this retrospective study was to compare survival during the first year of life and adult performance of offspring derived from artificial insemination (AI) with X-sorted or conventional sperm processed from the same ejaculates. We analyzed a data set that included AI of dairy heifers and lactating cows with fresh conventional sperm (3 × 106 sperm per straw), fresh X-sorted sperm (1 or 2 × 106 sperm per straw), or frozen X-sorted sperm (2 × 106 sperm per straw). The data set contained records of 5,179 offspring born on 396 farms. Offspring were classified as born from conventional sperm (CONV) if they were the product of an insemination with fresh conventional sperm, or born from X-sorted sperm (SS) if they were product of any of the 3 X-sorted sperm treatments. Generalized linear mixed models were used to evaluate the effect of sperm treatment on (1) survival during the first year of life; (2) reproductive performance, lactation performance, and survival of female offspring; and (3) slaughter characteristics of male offspring. Stillbirth rates and mortality rates during the first 2 mo of life were greater for male calves (2.8 and 5.0%, respectively) than for female calves (1.6 and 2.0%, respectively). No differences between offspring derived from SS and CONV were detected for incidences of stillbirth or mortality during the first 12 mo of life within sex of calf. Reproductive performance, milk volume, milk fat, milk protein yields during first; second; and third lactations, and survival to third lactation did not differ between female offspring derived from CONV and SS. Across all age groups, CONV steers had heavier carcasses than SS steers (325.3 vs. 318.3 kg), but there were no differences in weight between CONV and SS steers within any of the age groups (≤24, 25–27, 28–30, and >30 mo of age). The distribution of slaughter age did not differ between CONV and SS steers when the analysis was restricted to herds that reared steers derived from both types of sperm. Carcass conformation and fat scores of steers were not affected by sperm treatment. There was no difference in carcass weight between young bulls (≤2 yr) derived from CONV or SS. In conclusion, the results provide no evidence of differences in survival during the first year of life between offspring derived from CONV or SS, or for any of the reproductive and lactation performance characteristics studied between female offspring derived from CONV or SS. Modest differences in carcass weight between CONV and SS steers were detected, but this may reflect differences in management and husbandry in the rearing herds rather than the sex-sorting process. A controlled study using steers derived from conventional or X-sorted sperm from split ejaculates and reared under the same husbandry conditions is needed to clarify whether there is a true difference in body weight gain due to the sex-sorting process

Activation of the heat shock transcription factor Hsf1 is essential for the full virulence of the fungal pathogen Candida albicans

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Proteins and their peptide motifs in acellular apatite mineralization of scaffolds for tissue engineering

Many proteins in the inorganic=organic matrix of bone induce or modulate or inhibit mineralization of apatite in vivo. Many attempts have been made to mimic and understand this mechanism as part of bone formation, and ectopic mineralization and control thereof. Many attempts have also been made to use such proteins or protein fragments to harness their potential for improved mineralization. Such proteins and peptide motifs have also been the inspiration for attempts of making mimics of their structures and motifs using chemical or biological synthesis. The aim of this review is to highlight how proteins and (poly)peptides themselves impact mineralization in the human body, and how those could be used and have been used for improving apatite mineralization, for example, on or in materials that by themselves do not induce apatite mineralization but otherwise have interesting properties for use as bone tissue engineering scaffolds.J. Benesch wishes to acknowledge the financial support from FCT, postdoctoral fellowship scholarship SFRH/BPD/17584/2004. This work was carried out under the scope of the European Union NoE EXPERTISSUES (NMP3-CT-2004500283) and partially funded by the European Union FP6 STREP Project HIPPOCRATES (NMP3-CT-2003-505758) and FCT project ProteoLight (PTDC/FIS/68517/2006)

Metallo-dielectric diamond and zinc-blende photonic crystals

It is shown that small inclusions of a low absorbing metal can have a dramatic effect on the photonic band structure. In the case of diamond and zinc-blende photonic crystals, several complete photonic band gaps (CPBG's) can open in the spectrum, between the 2nd-3rd, 5th-6th, and 8th-9th bands. Unlike in the purely dielectric case, in the presence of small inclusions of a low absorbing metal the largest CPBG for a moderate dielectric constant (epsilon<=10) turns out to be the 2nd-3rd CPBG. The 2nd-3rd CPBG is the most important CPBG, because it is the most stable against disorder. For a diamond and zinc-blende structure of nonoverlapping dielectric and metallo-dielectric spheres, a CPBG begins to decrease with an increasing dielectric contrast roughly at the point where another CPBG starts to open--a kind of gap competition. A CPBG can even shrink to zero when the dielectric contrast increases further. Metal inclusions have the biggest effect for the dielectric constant 2<=epsilon<=12, which is a typical dielectric constant at near infrared and in the visible for many materials, including semiconductors and polymers. It is shown that one can create a sizeable and robust 2nd-3rd CPBG at near infrared and visible wavelengths even for a photonic crystal which is composed of more than 97% low refractive index materials (n<=1.45, i.e., that of silica glass or a polymer). These findings open the door for any semiconductor and polymer material to be used as genuine building blocks for the creation of photonic crystals with a CPBG and significantly increase the possibilities for experimentalists to realize a sizeable and robust CPBG in the near infrared and in the visible. One possibility is a construction method using optical tweezers, which is analyzed here.Comment: 25 pp, 23 figs, RevTex, to appear in Phys Rev B. For more information look at http://www.amolf.nl/research/photonic_materials_theory/moroz/moroz.htm

Weight regain and mental health outcomes following behavioural weight management programmes: a systematic review with meta‐analyses

Behavioural weight management programmes (BWMPs) lead to weight loss but subsequent weight regain may harm mental health outcomes. We searched for randomised trials of BWMPs in adults with overweight/obesity with follow-up ≥12 months from baseline that measured weight change both at and after programme-end. We included only studies reporting mental health at or after programme-end. We meta-analysed changes in various mental health outcomes using a random-effects model by nature of the comparator group and by time since programme end. Subgroup analysis explored heterogeneity. We used mixed models and meta-regression to analyse the association between change in weight and change in depression and/or anxiety over time, with higher scores indicating greater depression and/or anxiety. We included 47 studies. When comparing BWMPs (diet and/or exercise) to control, most estimates included the possibility of no difference, but pooled estimates for psychological wellbeing, self-esteem and mental-health composite scores at programme-end, anxiety at 1–6 months, and depression at 7–12 months after programme-end suggested improvements in intervention arms relative to control, with 95% CIs excluding no difference. Pooled estimates found no evidence that BWMPs harmed mental health at programme end or beyond. Mental health composite scores at programme-end favoured diet and exercise interventions over diet alone, with 95% CIs excluding no difference. All other measures and timepoints included the possibility of no difference or could not be meta-analysed due to high heterogeneity or a paucity of data. Mixed models and meta-regression of the association between change in depression and/or anxiety scores over time, and change in weight, were inconclusive. Despite weight regain after BWMPs, our meta-analyses found no evidence of mental health harm and some evidence that BWMPs may improve some dimensions of mental health at and after programme-end

Coexistence of 'alpha+ 208Pb' cluster structures and single-particle excitations in 212Po

Excited states in 212Po have been populated by alpha transfer using the 208Pb(18O,14C) reaction at 85MeV beam energy and studied with the EUROBALL IV gamma multidetector array. The level scheme has been extended up to ~ 3.2 MeV excitation energy from the triple gamma coincidence data. Spin and parity values of most of the observed states have been assigned from the gamma angular distributions and gamma -gamma angular correlations. Several gamma lines with E(gamma) < 1 MeV have been found to be shifted by the Doppler effect, allowing for the measurements of the associated lifetimes by the DSAM method. The values, found in the range [0.1-0.6] ps, lead to very enhanced E1 transitions. All the emitting states, which have non-natural parity values, are discussed in terms of alpha-208Pb structure. They are in the same excitation-energy range as the states issued from shell-model configurations.Comment: 21 pages, 19 figures, corrected typos, revised arguments in Sect. III