Key drivers of ozone change and its radiative forcing over the 21st century

Over the 21st century changes in both tropospheric and stratospheric ozone are likely to have important consequences for the Earth’s radiative balance. In this study, we investigate the radiative forcing from future ozone changes using the Community Earth System Model (CESM1), with the Whole Atmosphere Community Climate Model (WACCM), and including fully coupled radiation and chemistry schemes. Using year 2100 conditions from the Representative Concentration Pathway 8.5 (RCP8.5) scenario, we quantify the individual contributions to ozone radiative forcing of (1) climate change, (2) reduced concentrations of ozone depleting substances (ODSs), and (3) methane increases. We calculate future ozone radiative forcings and their standard error (SE; associated with inter-annual variability of ozone) relative to year 2000 of (1) 33 ± 104 m Wm−² , (2) 163 ± 109 m Wm−² , and (3) 238 ± 113 m Wm−² due to climate change, ODSs, and methane, respectively. Our best estimate of net ozone forcing in this set of simulations is 430 ± 130 m Wm−² relative to year 2000 and 760 ± 230 m Wm−² relative to year 1750, with the 95 % confidence interval given by ±30 %. We find that the overall long-term tropospheric ozone forcing from methane chemistry–climate feedbacks related to OH and methane lifetime is relatively small (46 m Wm−²). Ozone radiative forcing associated with climate change and stratospheric ozone recovery are robust with regard to background climate conditions, even though the ozone response is sensitive to both changes in atmospheric composition and climate. Changes in stratospheric-produced ozone account for ∼ 50 % of the overall radiative forcing for the 2000–2100 period in this set of simulations, highlighting the key role of the stratosphere in determining future ozone radiative forcing

A systematic review of methods for increasing vegetable consumption in early childhood

PURPOSE OF REVIEW: This study aims to synthesise the body of research investigating methods for increasing vegetable consumption in 2- to 5-year-old children, while offering advice for practitioners. RECENT FINDINGS: Repeated exposure is a well-supported method for increasing vegetable consumption in early childhood and may be enhanced with the inclusion of non-food rewards to incentivise tasting. Peer models appear particularly effective for increasing 2-5-year-olds' vegetable consumption. There is little evidence for the effectiveness of food adaptations (e.g. flavour-nutrient learning) for increasing general vegetable intake among this age group, although they show some promise with bitter vegetables. SUMMARY: This review suggests that practitioners may want to focus their advice to parents around strategies such as repeated exposure, as well as the potential benefits of modelling and incentivising tasting with non-food rewards. Intervention duration varies greatly, and considerations need to be made for how this impacts on success

Tandem quadruplication of HMA4 in the zinc (Zn) and cadmium (Cd) hyperaccumulator noccaea caerulescens

Zinc (Zn) and cadmium (Cd) hyperaccumulation may have evolved twice in the Brassicaceae, in Arabidopsis halleri and in the Noccaea genus. Tandem gene duplication and deregulated expression of the Zn transporter, HMA4, has previously been linked to Zn/Cd hyperaccumulation in A. halleri. Here, we tested the hypothesis that tandem duplication and deregulation of HMA4 expression also occurs in Noccaea. A Noccaea caerulescens genomic library was generated, containing 36,864 fosmid pCC1FOSTM clones with insert sizes ~20–40 kbp, and screened with a PCR-generated HMA4 genomic probe. Gene copy number within the genome was estimated through DNA fingerprinting and pooled fosmid pyrosequencing. Gene copy numbers within individual clones was determined by PCR analyses with novel locus specific primers. Entire fosmids were then sequenced individually and reads equivalent to 20-fold coverage were assembled to generate complete whole contigs. Four tandem HMA4 repeats were identified in a contiguous sequence of 101,480 bp based on sequence overlap identities. These were flanked by regions syntenous with up and downstream regions of AtHMA4 in Arabidopsis thaliana. Promoter-reporter b-glucuronidase (GUS) fusion analysis of a NcHMA4 in A. thaliana revealed deregulated expression in roots and shoots, analogous to AhHMA4 promoters, but distinct from AtHMA4 expression which localised to the root vascular tissue. This remarkable consistency in tandem duplication and deregulated expression of metal transport genes between N. caerulescens and A. halleri, which last shared a common ancestor >40 mya, provides intriguing evidence that parallel evolutionary pathways may underlie Zn/Cd hyperaccumulation in Brassicaceae

Tropical Stratospheric Circulation and Ozone Coupled to Pacific Multi-Decadal Variability

Observational and modeling evidence suggest a recent acceleration of the stratospheric Brewer-Dobson circulation (BDC), driven by climate change and stratospheric ozone depletion. However, slowly varying natural variability can compromise our ability to detect such forced changes over the relatively short observational record. Using observations and chemistry-climate model simulations, we demonstrate a link between multi-decadal variability in the strength of the BDC and the Interdecadal Pacific Oscillation (IPO), with knock-on impacts for composition in the stratosphere. After accounting for the IPO-like variability in the BDC, the modeled trend is approximately 7%–10% dec−1 over 1979–2010. Furthermore, we find that sea surface temperatures explain up to 50% of the simulated decadal variability in tropical mid-stratospheric ozone. Our findings demonstrate strong links between low-frequency variability in the oceans, troposphere and stratosphere, as well as their potential importance in detecting structural changes in the BDC and future ozone recovery

In-depth investigation of the molecular pathogenesis of bladder cancer in a unique 26-year old patient with extensive multifocal disease: A case report

Background. The molecular characteristics and the clinical disease course of bladder cancer (BC) in young patients remain largely unresolved. All patients are monitored according to an intensive surveillance protocol and we aim to gain more insight into the molecular pathways of bladder tumors in young patients that could ultimately contribute to patient stratification, improve patient quality of life and reduce associated costs. We also determined whether a biomarker-based surveillance could be feasible. Case Presentation. We report a unique case of a 26-year-old Caucasian male with recurrent non-muscle invasive bladder tumors occurring at a high frequency and analyzed multiple tumors (maximal pTaG2) and urine samples of this patient. Analysis included FGFR3 mutation detection, FGFR3 and TP53 immunohistochemistry, mircosatellite analysis of markers on chromosomes 8, 9, 10, 11 and 17 and a genome wide single nucleotide polymorphism-array (SNP). All analyzed tumors contained a mutation in FGFR3 and were associated with FGFR3 overexpression. None of the tumors showed overexpression of TP53. We found a deletion on chromosome 9 in the primary tumor and this was confirmed by the SNP-array that showed regions of loss on chromosome 9. Detection of all recurrences was possible by urinary FGFR3 mutation analysis. Conclusions. Our findings would suggest that the BC disease course is determined by not only a patient's age, but also by the molecular characteristics of a tumor. This young patient contained typical genetic changes found in tumors of older patients and implies a clinical disease course comparable to older patients. We demonstrate that FGFR3 mutation analysis on voided urine is a simple non-invasive method and could serve as a feasible follow-up approach for this young patient presenting with an FGFR3 mutant tumor

Prevalence of diabetes mellitus and the performance of a risk score among Hindustani Surinamese, African Surinamese and ethnic Dutch: a cross-sectional population-based study

<p>Abstract</p> <p>Background</p> <p>While the prevalence of type 2 diabetes mellitus (DM) is high, tailored risk scores for screening among South Asian and African origin populations are lacking. The aim of this study was, first, to compare the prevalence of (known and newly detected) DM among Hindustani Surinamese, African Surinamese and ethnic Dutch (Dutch). Second, to develop a new risk score for DM. Third, to evaluate the performance of the risk score and to compare it to criteria derived from current guidelines.</p> <p>Methods</p> <p>We conducted a cross-sectional population based study among 336 Hindustani Surinamese, 593 African Surinamese and 486 Dutch, aged 35–60 years, in Amsterdam. Logistic regressing analyses were used to derive a risk score based on non-invasively determined characteristics. The diagnostic accuracy was assessed by the area under the Receiver-Operator Characteristic curve (AUC).</p> <p>Results</p> <p>Hindustani Surinamese had the highest prevalence of DM, followed by African Surinamese and Dutch: 16.7, 8.1, 4.2% (age 35–44) and 35.0, 19.0, 8.2% (age 45–60), respectively. The risk score included ethnicity, body mass index, waist circumference, resting heart rate, first-degree relative with DM, hypertension and history of cardiovascular disease. Selection based on age alone showed the lowest AUC: between 0.57–0.62. The AUC of our score (0.74–0.80) was higher than that of criteria from guidelines based solely on age and BMI and as high as criteria that required invasive specimen collection.</p> <p>Conclusion</p> <p>In Hindustani Surinamese and African Surinamese populations, screening for DM should not be limited to those over 45 years, as is advocated in several guidelines. If selective screening is indicated, our ethnicity based risk score performs well as a screening test for DM among these groups, particularly compared to the criteria based on age and/or body mass index derived from current guidelines.</p

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Structures of SRP54 and SRP19, the Two Proteins that Organize the Ribonucleic Core of the Signal Recognition Particle from Pyrococcus furiosus

In all organisms the Signal Recognition Particle (SRP), binds to signal sequences of proteins destined for secretion or membrane insertion as they emerge from translating ribosomes. In Archaea and Eucarya, the conserved ribonucleoproteic core is composed of two proteins, the accessory protein SRP19, the essential GTPase SRP54, and an evolutionarily conserved and essential SRP RNA. Through the GTP-dependent interaction between the SRP and its cognate receptor SR, ribosomes harboring nascent polypeptidic chains destined for secretion are dynamically transferred to the protein translocation apparatus at the membrane. We present here high-resolution X-ray structures of SRP54 and SRP19, the two RNA binding components forming the core of the signal recognition particle from the hyper-thermophilic archaeon Pyrococcus furiosus (Pfu). The 2.5 Å resolution structure of free Pfu-SRP54 is the first showing the complete domain organization of a GDP bound full-length SRP54 subunit. In its ras-like GTPase domain, GDP is found tightly associated with the protein. The flexible linker that separates the GTPase core from the hydrophobic signal sequence binding M domain, adopts a purely α-helical structure and acts as an articulated arm allowing the M domain to explore multiple regions as it scans for signal peptides as they emerge from the ribosomal tunnel. This linker is structurally coupled to the GTPase catalytic site and likely to propagate conformational changes occurring in the M domain through the SRP RNA upon signal sequence binding. Two different 1.8 Å resolution crystal structures of free Pfu-SRP19 reveal a compact, rigid and well-folded protein even in absence of its obligate SRP RNA partner. Comparison with other SRP19•SRP RNA structures suggests the rearrangement of a disordered loop upon binding with the RNA through a reciprocal induced-fit mechanism and supports the idea that SRP19 acts as a molecular scaffold and a chaperone, assisting the SRP RNA in adopting the conformation required for its optimal interaction with the essential subunit SRP54, and proper assembly of a functional SRP

DiAlert: a lifestyle education programme aimed at people with a positive family history of type 2 diabetes and overweight, study protocol of a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Family history is a known risk factor for type 2 diabetes (T2DM), and more so in the presence of overweight. This study aims to develop and evaluate the effectiveness of a new lifestyle education programme 'DiAlert' targeted at 1st degree relatives of people with T2DM and overweight. In view of the high risk for diabetes and cardiovascular disease in immigrants from Turkish origin living in Western Europe, a culturally appropriate Turkish version of DiAlert will be developed and tested.</p> <p>Methods/design</p> <p>In this RCT, 268 (134 Dutch and 134 Turkish) overweight 1st degree relatives of patients with T2DM will be allocated to either the intervention or control group (leaflet). The intervention DiAlert aims to promote intrinsic motivation to change lifestyle, and sustain achieved behaviour changes during follow-up. Primary outcome is weight loss. Secondary outcomes include biological, behavioural and psychological indices, along with process indicators. Measurements will take place at baseline and after 3 and 9 months. Changes in outcomes are tested between intervention and control group at 3 months; effects over time are tested within and between both ethnic groups at 3 and 9 months.</p> <p>Discussion</p> <p>The DiAlert intervention is expected to be more effective than the control condition in achieving significant weight loss at 3 months, in both Dutch and Turkish Dutch participants.</p> <p>Trial registration</p> <p>Netherlands National Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2036">NTR2036</a></p