Membrane Porters of ATP-Binding Cassette Transport Systems Are Polyphyletic

The ATP-binding cassette (ABC) superfamily consists of both importers and exporters. These transporters have, by tradition, been classified according to the ATP hydrolyzing constituents, which are monophyletic. The evolutionary origins of the transmembrane porter proteins/domains are not known. Using five distinct computer programs, we here provide convincing statistical data suggesting that the transmembrane domains of ABC exporters are polyphyletic, having arisen at least three times independently. ABC1 porters arose by intragenic triplication of a primordial two-transmembrane segment (TMS)-encoding genetic element, yielding six TMS proteins. ABC2 porters arose by intragenic duplication of a dissimilar primordial three-TMS-encoding genetic element, yielding a distinctive protein family, nonhomologous to the ABC1 proteins. ABC3 porters arose by duplication of a primordial four-TMS-encoding genetic element, yielding either eight- or 10-TMS proteins. We assign each of 48 of the 50 currently recognized families of ABC exporters to one of the three evolutionarily distinct ABC types. Currently available high-resolution structural data for ABC porters are fully consistent with our findings. These results provide guides for future structural and mechanistic studies of these important transport systems

Accelerating global left-ventricular function assessment in mice using reduced slice acquisition and three-dimensional guide-point modelling

<p>Abstract</p> <p>Background</p> <p>To investigate the utility of three-dimensional guide-point modeling (GPM) to reduce the time required for CMR evaluation of global cardiac function in mice, by reducing the number of image slices required for accurate quantification of left-ventricular (LV) mass and volumes.</p> <p>Methods</p> <p>Five female C57Bl/6 mice 8 weeks post myocardial infarction induced by permanent occlusion of the left coronary artery, and six male control (un-operated) C57Bl/6 mice, were subject to CMR examination under isoflurane anaesthesia. Contiguous short axis (SAX) slices (1 mm thick 7-9 slices) were obtained together with two long axis (LAX) slices in two chamber and four chamber orientations. Using a mathematical model of the heart to interpolate information between the available slices, GPM LV mass and volumes were determined using full slice (all SAX and two LAX), six slice (four SAX and two LAX) and four slice (two SAX and two LAX) analysis protocols. All results were compared with standard manual volumetric analysis using all SAX slices.</p> <p>Results</p> <p>Infarct size was 39.1 ± 5.1% of LV myocardium. No significant differences were found in left ventricular mass and volumes between the standard and GPM full and six slice protocols in infarcted mice (113 ± 10, 116 ± 11, and 117 ± 11 mg respectively for mass), or between the standard and GPM full, six and four slice protocols in control mice, (105 ± 14, 106 ± 10, 104 ± 12, and 105 ± 7 mg respectively for mass). Significant differences were found in LV mass (135 ± 18 mg) and EF using the GPM four slice protocol in infarcted mice (p < 0.05).</p> <p>Conclusion</p> <p>GPM enables accurate analysis of LV function in mice with relatively large infarcts using a reduced six slice acquisition protocol, and in mice with normal/symmetrical left-ventricular topology using a four slice protocol.</p

Defense Against Cannibalism: The SdpI Family of Bacterial Immunity/Signal Transduction Proteins

The SdpI family consists of putative bacterial toxin immunity and signal transduction proteins. One member of the family in Bacillus subtilis, SdpI, provides immunity to cells from cannibalism in times of nutrient limitation. SdpI family members are transmembrane proteins with 3, 4, 5, 6, 7, 8, or 12 putative transmembrane α-helical segments (TMSs). These varied topologies appear to be genuine rather than artifacts due to sequencing or annotation errors. The basic and most frequently occurring element of the SdpI family has 6 TMSs. Homologues of all topological types were aligned to determine the homologous TMSs and loop regions, and the positive-inside rule was used to determine sidedness. The two most conserved motifs were identified between TMSs 1 and 2 and TMSs 4 and 5 of the 6 TMS proteins. These showed significant sequence similarity, leading us to suggest that the primordial precursor of these proteins was a 3 TMS–encoding genetic element that underwent intragenic duplication. Various deletional and fusional events, as well as intragenic duplications and inversions, may have yielded SdpI homologues with topologies of varying numbers and positions of TMSs. We propose a specific evolutionary pathway that could have given rise to these distantly related bacterial immunity proteins. We further show that genes encoding SdpI homologues often appear in operons with genes for homologues of SdpR, SdpI’s autorepressor. Our analyses allow us to propose structure–function relationships that may be applicable to most family members

Characterisation of heart failure with normal ejection fraction in a tertiary hospital in Nigeria

<p>Abstract</p> <p>Background</p> <p>The study aimed to determine the frequency and characteristics of heart failure with normal EF in a native African population with heart failure.</p> <p>Methods</p> <p>It was a hospital cohort study. Subjects were 177 consecutive individuals with heart failure and ninety apparently normal control subjects. All the subjects underwent transthoracic echocardiography. The group with heart failure was further subdivided into heart failure with normal EF (EF ≥ 50) (HFNEF) and heart failure with low EF(EF <50)(HFLEF).</p> <p>Results</p> <p>The subjects with heart failure have a mean age of 52.3 ± 16.64 years vs 52.1 ± 11.84 years in the control subjects; p = 0.914. Other baseline characteristics except blood pressure parameters and height were comparable between the group with heart failure and the control subjects. The frequency of HFNEF was 39.5%. Compared with the HFLEF group, the HFNEF group have a smaller left ventricular diameter (in diastole and systole): (5.2 ± 1.22 cm vs 6.2 ± 1.39 cm; p < 0.0001 and 3.6 ± 1.24 cm vs 5.4 ± 1.35 cm;p < 0.0001) respectively, a higher relative wall thickness and deceleration time of the early mitral inflow velocity: (0.4 ± 0.12 vs 0.3 ± 0.14 p < 0.0001 and 149.6 ± 72.35 vs 110.9 ± 63.40 p = 0.001) respectively.</p> <p>The two groups with heart failure differed significantly from the control subjects in virtually all echocardiographic measurements except aortic root diameter, LV posterior wall thickness(HFLEF), and late mitral inflow velocity(HFNEF). HFNEF accounted for 70(39.5%) of cases of heart failure in this study.</p> <p>Hypertension is the underlying cardiovascular disease in 134(75.7%) of the combined heart failure population, 58 (82.9%) of the subjects with HFNEF group and 76(71%) of the HFLEF group. Females accounted for 44 (62.9%) of the subjects with HFNEF against 42(39.3%) in the HFLEF group (p = 0.002).</p> <p>Conclusion</p> <p>The frequency of heart failure with normal EF in this native African cohort with heart failure is comparable with the frequency in other populations. These groups of patients are more likely female, hypertensive with concentric pattern of left ventricular hypertrophy.</p

Animal Ca2+ release-activated Ca2+ (CRAC) channels appear to be homologous to and derived from the ubiquitous cation diffusion facilitators

<p>Abstract</p> <p>Background</p> <p>Antigen stimulation of immune cells triggers Ca²⁺entry through Ca²⁺release-activated Ca²⁺(CRAC) channels, promoting an immune response to pathogens. Defects in a CRAC (Orai) channel in humans gives rise to the hereditary Severe Combined Immune Deficiency (SCID) syndrome. We here report results that define the evolutionary relationship of the CRAC channel proteins of animals, and the ubiquitous Cation Diffusion Facilitator (CDF) carrier proteins.</p> <p>Findings</p> <p>CDF antiporters derived from a primordial 2 transmembrane spanner (TMS) hairpin structure by intragenic triplication to yield 6 TMS proteins. Four programs (IC/GAP, GGSEARCH, HMMER and SAM) were evaluated for identifying sequence similarity and establishing homology using statistical means. Overall, the order of sensitivity (similarity detection) was IC/GAP = GGSEARCH > HMMER > SAM, but the use of all four programs was superior to the use of any two or three of them. Members of the CDF family appeared to be homologous to members of the 4 TMS Orai channel proteins.</p> <p>Conclusions</p> <p>CRAC channels derived from CDF carriers by loss of the first two TMSs of the latter. Based on statistical analyses with multiple programs, TMSs 3-6 in CDF carriers are homologous to TMSs 1-4 in CRAC channels, and the former was the precursor of the latter. This is an unusual example of how a functionally and structurally more complex protein may have predated a simpler one.</p

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

Variability of NT-proBNP and Its Relationship with Inflammatory Status in Patients with Stable Essential Hypertension: A 2-Year Follow-Up Study

The variability of NT-proBNP levels has been studied in heart failure, yet no data exist on these changes over time in hypertensive patients. Furthermore, studies on the relationship between natriuretic peptides and inflammatory status are limited.220 clinically and functionally asymptomatic stable patients (age 59 ± 13, 120 male) out of 252 patients with essential hypertension were followed up, and NT-proBNP was measured at baseline, 12 and 24 months. No differences in NT-proBNP were found with respect to the basal stage in the hypertrophic group, but significant changes were found in non-hypertrophic subjects. The reproducibility of NT-proBNP measurements was better in patients with hypertrophy than in the non-hypertrophic group for the three intervals (stage I-basal; stage II-stage I; stage II-basal) with a reference change value of 34%, 35% and 41%, respectively, in the hypertrophic group. A more elevated coefficient of correlation was obtained in the hypertrophic group than in patients without hypertrophy: basal versus stage I (r = 0.79, p < 0.0001 and r = 0.59, p < 0.0001) and stage I versus stage II (r = 0.86, p < 0.0001 and r = 0.56, p < 0.0001). Finally, levels of NT-proBNP significantly correlated with sTNF-R1 (p < 0.0001) and IL-6 (p < 0.01) during follow-up. A multivariate linear regression analysis showed that sTNF-R1 is an independent factor of NT-proBNP.This work shows that there is good stability in NT-proBNP levels in a follow-up study of asymptomatic patients with stable hypertension and left ventricular hypertrophy. As a consequence, assessment of NT-proBNP concentrations may be a useful tool for monitoring the follow-up of hypertensive patients with hypertrophy. Measured variations in peptide levels, exceeding 35% in a 12-month follow-up and 41% in a 24-month follow-up, may indicate an increase in cardiovascular risk, and therefore implies adjustment in the medical treatment. In addition, this study shows a link between neurohormonal and inflammatory activation in these patients

Evidence and perceptions of rainfall change in Malawi: Do maize cultivar choices enhance climate change adaptation in sub-Saharan Africa?

Getting farmers to adopt new cultivars with greater tolerance for coping with climatic extremes and variability is considered as one way of adapting agricultural production to climate change. However, for successful adaptation to occur, an accurate recognition and understanding of the climate signal by key stakeholders (farmers, seed suppliers and agricultural extension services) is an essential precursor. This paper presents evidence based on fieldwork with smallholder maize producers and national seed network stakeholders in Malawi from 2010 to 2011, assessing understandings of rainfall changes and decision-making about maize cultivar choices. Our findings show that preferences for short-season maize cultivars are increasing based on perceptions that season lengths are growing shorter due to climate change and the assumption that growing shorter-season crops represents a good strategy for adapting to drought. However, meteorological records for the two study areas present no evidence for shortening seasons (or any significant change to rainfall characteristics), suggesting that short-season cultivars may not be the most suitable adaptation option for these areas. This demonstrates the dangers of oversimplified climate information in guiding changes in farmer decision-making about cultivar choice