Genome wide association scan for chronic periodontitis implicates novel locus

Background: There is evidence for a genetic contribution to chronic periodontitis. In this study, we conducted a genome wide association study among 866 participants of the University of Pittsburgh Dental Registry and DNA Repository, whose periodontal diagnosis ranged from healthy (N = 767) to severe chronic periodontitis (N = 99).Methods: Genotypingi of over half-million single nucleotide polymorphisms was determined. Analyses were done twice, first in the complete dataset of all ethnicities, and second including only samples defined as self-reported Whites. From the top 100 results, twenty single nucleotide polymorphisms had consistent results in both analyses (borderline p-values ranging from 1E-05 to 1E-6) and were selected to be tested in two independent datasets derived from 1,460 individuals from Porto Alegre, and 359 from Rio de Janeiro, Brazil. Meta-analyses of the Single nucleotide polymorphisms showing a trend for association in the independent dataset were performed.Results: The rs1477403 marker located on 16q22.3 showed suggestive association in the discovery phase and in the Porto Alegre dataset (p = 0.05). The meta-analysis suggested the less common allele decreases the risk of chronic periodontitis.Conclusions: Our data offer a clear hypothesis to be independently tested regarding the contribution of the 16q22.3 locus to chronic periodontitis. © 2014 Feng et al.; licensee BioMed Central Ltd

Linking plant phenology to conservation biology

Phenology has achieved a prominent position in current scenarios of global change research given its role inmonitoring and predicting the timing of recurrent life cycle events. However, the implications of phenology to environmental conservation and management remain poorly explored. Here,we present the first explicit appraisal of howphenology-amultidisciplinary science encompassing biometeorology, ecology, and evolutionary biology- can make a key contribution to contemporary conservation biology. We focus on shifts in plant phenology induced by global change, their impacts on species diversity and plant-animal interactions in the tropics, and how conservation efforts could be enhanced in relation to plant resource organization. We identify the effects of phenological changes and mismatches in the maintenance and conservation of mutualistic interactions, and examine how phenological research can contribute to evaluate, manage and mitigate the consequences of land-use change and other natural and anthropogenic disturbances, such as fire, exotic and invasive species. Wealso identify cutting-edge tools that can improve the spatial and temporal coverage of phenological monitoring, from satellites to drones and digital cameras. We highlight the role of historical information in recovering long-term phenological time series, and track climate-related shifts in tropical systems. Finally, we propose a set of measures to boost the contribution of phenology to conservation science.Weadvocate the inclusion of phenology into predictive models integrating evolutionary history to identify species groups that are either resilient or sensitive to future climate-change scenarios, and understand how phenological m ismatches can affect community dynamics, ecosystem services, and conservation over time

Alkaline stress and iron deficiency regulate iron uptake and riboflavin synthesis gene expression differently in root and leaf tissue: implications for iron deficiency chlorosis

Iron (Fe) is an essential mineral that has low solubility in alkaline soils, where its deficiency results in chlorosis. Whether low Fe supply and alkaline pH stress are equivalent is unclear, as they have not been treated as separate variables in molecular physiological studies. Additionally, molecular responses to these stresses have not been studied in leaf and root tissues simultaneously. We tested how plants with the Strategy I Fe uptake system respond to Fe deficiency at mildly acidic and alkaline pH by measuring root ferric chelate reductase (FCR) activity and expression of selected Fe uptake genes and riboflavin synthesis genes. Alkaline pH increased cucumber (Cucumis sativus L.) root FCR activity at full Fe supply, but alkaline stress abolished FCR response to low Fe supply. Alkaline pH or low Fe supply resulted in increased expression of Fe uptake genes, but riboflavin synthesis genes responded to Fe deficiency but not alkalinity. Iron deficiency increased expression of some common genes in roots and leaves, but alkaline stress blocked up-regulation of these genes in Fe-deficient leaves. In roots of the melon (Cucumis melo L.) fefe mutant, in which Fe uptake responses are blocked upstream of Fe uptake genes, alkaline stress or Fe deficiency up-regulation of certain Fe uptake and riboflavin synthesis genes was inhibited, indicating a central role for the FeFe protein. These results suggest a model implicating shoot-to-root signaling of Fe status to induce Fe uptake gene expression in roots

Characteristics of European adults who dropped out from the Food4Me Internet-based personalised nutrition intervention

Objective To characterise participants who dropped out of the Food4Me Proof-of-Principle study. Design The Food4Me study was an Internet-based, 6-month, four-arm, randomised controlled trial. The control group received generalised dietary and lifestyle recommendations, whereas participants randomised to three different levels of personalised nutrition (PN) received advice based on dietary, phenotypic and/or genotypic data, respectively (with either more or less frequent feedback). Setting Seven recruitment sites: UK, Ireland, The Netherlands, Germany, Spain, Poland and Greece. Subjects Adults aged 18–79 years (n 1607). Results A total of 337 (21 %) participants dropped out during the intervention. At baseline, dropouts had higher BMI (0·5 kg/m2; P<0·001). Attrition did not differ significantly between individuals receiving generalised dietary guidelines (Control) and those randomised to PN. Participants were more likely to drop out (OR; 95 % CI) if they received more frequent feedback (1·81; 1·36, 2·41; P<0·001), were female (1·38; 1·06, 1·78; P=0·015), less than 45 years old (2·57; 1·95, 3·39; P<0·001) and obese (2·25; 1·47, 3·43; P<0·001). Attrition was more likely in participants who reported an interest in losing weight (1·53; 1·19, 1·97; P<0·001) or skipping meals (1·75; 1·16, 2·65; P=0·008), and less likely if participants claimed to eat healthily frequently (0·62; 0·45, 0·86; P=0·003). Conclusions Attrition did not differ between participants receiving generalised or PN advice but more frequent feedback was related to attrition for those randomised to PN interventions. Better strategies are required to minimise dropouts among younger and obese individuals participating in PN interventions and more frequent feedback may be an unnecessary burden

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

In vitro assessment of pacing as therapy for aortic regurgitation

Background and objective Clinical evaluation of pacing therapy in mitigating the aortic insufficiency after transchateter aortic valve implantation often gives contradictory outcomes. This study presents an in vitro investigation aimed at clarifying the effect of pacing on paravalvular leakage. Methods A series of in vitro tests reproducing the heart operating changes clinically obtained by pacing was carried out in a 26 mm Edwards Sapien XT prosthesis with mild paravalvular leakage. The effect of pacing on the regurgitant volumes per cycle and per minute was quantified, and the energy and power consumed by the left ventricle were calculated. Results Results indicate that though pacing results in some reduction in the total regurgitation per cycle, the volume of fluid regurgitating per minute increases substantially, causing overload of left ventricle. Conclusions Our tests indicate no effective haemodynamic benefit from pacing, suggesting a prudential clinical use of this therapy for the treatment of postoperative aortic regurgitation

In Vitro and Ex Vivo Hemodynamic Testing of an Innovative Occluder for Paravalvular Leak After Transcather Aortic Valve Implantation

This study aims at achieving a proof-of-concept for a novel device designed to occlude the orifices that may form between transcatheter valves and host tissues after TAVI. The device effect on the performance of a SAPIEN XT with a paravalvular gap was assessed into an in vitro and ex vivo pulse duplicator. The in vitro tests were performed complying with the standard international regulations, measuring the trasvalvular pressure and regurgitant volumes with and without the paravalvular gap, and with the occluder correctly positioned into the gap. In the second series of tests, the leakage reduction due to the presence of the occluder was assessed for the same setup, into a beating swine heart. The occluder implantation decreased the regurgitant fraction of about 50% for the in vitro assessment and 75% for the ex vivo test, under rest operating conditions. These results suggest that suitably designed occluders can lead to important benefit in the PVL treatment

Bax translocation to mitochondria subsequent to a rapid loss of mitochondrial membrane potential

Bax, a pro-apoptotic member of the Bcl-2 family, is a cytosolic protein that inserts into mitochondrial membranes upon induction of cell death. Using the green fluorescent protein fused to Bax (GFP-Bax) to quantitate mitochondrial binding in living cells we have investigated the cause of Bax association with mitochondria and the time course relative to endogenous and induced changes in mitochondrial membrane potential (Delta Psi (m)). We have found that staurosporine (STS) induces a loss in Delta Psi (m) before GFP-Bax translocation can be measured. the onset of the Delta Psi (m) loss is followed by a rapid and complete collapse of Delta Psi (m) which is followed by Bax association with mitochondria. the mitochondria uncoupler FCCP, in the presence of the F-1-F-0 ATPase inhibitor oligomycin, can trigger Bax translocation to mitochondria suggesting that when ATP levels are maintained a collapse of Delta Psi (m) induces Bax translocation. Neither FCCP nor oligomycin alone alters Bax location. Bax association with mitochondria is also triggered by inhibitors of the electron transport chain, antimycin and rotenone, compounds that collapse Delta Psi (m) without inducing rapid ATP hydrolysis that typically occurs with uncouplers such as FCCP. Taken together, our results suggest that alterations in mitochondrial energization associated with apoptosis can initiate Bax docking to mitochondria.NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USAUniversidade Federal de São Paulo, Dept Farmacol, São Paulo, BrazilNICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USAMed Univ S Carolina, Charleston, SC 29425 USAUniversidade Federal de São Paulo, Dept Farmacol, São Paulo, BrazilWeb of Scienc

Physiological vortices in the sinuses of Valsalva: An in vitro approach for bio-prosthetic valves

Purpose The physiological flow dynamics within the Valsalva sinuses, in terms of global and local parameters, are still not fully understood. This study attempts to identify the physiological conditions as closely as possible, and to give an explanation of the different and sometime contradictory results in literature. Methods An in vitro approach was implemented for testing porcine bio-prosthetic valves operating within different aortic root configurations. All tests were performed on a pulse duplicator, under physiological pressure and flow conditions. The fluid dynamics established in the various cases were analysed by means of 2D Particle Image Velocimetry, and related with the achieved hydrodynamic performance. Results Each configuration is associated with substantially different flow dynamics, which significantly affects the valve performance. The configuration most closely replicating healthy native anatomy was characterised by the best hemodynamic performance, and any mismatch in size and position between the valve and the root produced substantial modification of the fluid dynamics downstream of the valve, hindering the hydrodynamic performance of the system. The worst conditions were observed for a configuration characterised by the total absence of the Valsalva sinuses. Conclusion This study provides an explanation for the different vortical structures described in the literature downstream of bioprosthetic valves, enlightening the experimental complications in valve testing. Most importantly, the results clearly identify the fluid mechanisms promoted by the Valsalva sinuses to enhance the ejection and closing phases, and this study exposes the importance of an optimal integration of the valve and root, to operate as a single system