Transgenic overexpression of γ-cytoplasmic actin protects against eccentric contraction-induced force loss in mdx mice

<p>Abstract</p> <p>Background</p> <p>γ-cytoplasmic (γ-_cyto) actin levels are elevated in dystrophin-deficient <it>mdx </it>mouse skeletal muscle. The purpose of this study was to determine whether further elevation of γ-_cytoactin levels improve or exacerbate the dystrophic phenotype of <it>mdx </it>mice.</p> <p>Methods</p> <p>We transgenically overexpressed γ-_cytoactin, specifically in skeletal muscle of mdx mice (<it>mdx</it>-TG), and compared skeletal muscle pathology and force-generating capacity between <it>mdx </it>and <it>mdx</it>-TG mice at different ages. We investigated the mechanism by which γ-_cytoactin provides protection from force loss by studying the role of calcium channels and stretch-activated channels in isolated skeletal muscles and muscle fibers. Analysis of variance or independent <it>t</it>-tests were used to detect statistical differences between groups.</p> <p>Results</p> <p>Levels of γ-_cytoactin in <it>mdx</it>-TG skeletal muscle were elevated 200-fold compared to <it>mdx </it>skeletal muscle and incorporated into thin filaments. Overexpression of γ-_cytoactin had little effect on most parameters of <it>mdx </it>muscle pathology. However, γ-_cytoactin provided statistically significant protection against force loss during eccentric contractions. Store-operated calcium entry across the sarcolemma did not differ between <it>mdx </it>fibers compared to wild-type fibers. Additionally, the omission of extracellular calcium or the addition of streptomycin to block stretch-activated channels did not improve the force-generating capacity of isolated extensor digitorum longus muscles from <it>mdx </it>mice during eccentric contractions.</p> <p>Conclusions</p> <p>The data presented in this study indicate that upregulation of γ-_cytoactin in dystrophic skeletal muscle can attenuate force loss during eccentric contractions and that the mechanism is independent of activation of stretch-activated channels and the accumulation of extracellular calcium.</p

The chronology of adipose tissue appearance and distribution in the human fetus

Timing of first appearance and subsequent distribution of adipose tissue were assessed in 488 normal-for-age human fetuses. The sample represented each of the three trimesters of normal pregnancies. Light microscopy showed that adipose tissue first appears and progressively develops from the 14th to 24th week of gestation (100-216 mm crown-rump length) in those areas where it characteristically accumulates after birth. No significant sex differences were found in patterns of early fat deposition. It is suggested that the second trimester of gestation is the critical or key period in fat adipogenesis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24701/1/0000120.pd

CD27 Expression Promotes Long-Term Survival of Functional Effector–Memory CD8+Cytotoxic T Lymphocytes in HIV-infected Patients

Human immunodeficiency virus (HIV)-specific CD8+ T cells persist in high frequencies in HIV-infected patients despite impaired CD4+ T helper response to the virus, but, unlike other differentiated effector cytotoxic T lymphocytes, most continue to express the tumor necrosis factor receptor family member CD27. Because the ligand for CD27 (CD70) is also overexpressed in HIV-infected hosts, we examined the nature of expression and potential functional consequences of CD27 expression on HIV-specific CD8+ T cells. Analysis of CD27+ and CD27− T cells derived from the same HIV-specific clone revealed that retention of CD27 did not interfere with acquisition of effector functions, and that after T cell receptor stimulation, CD27+ cells that concurrently were triggered via CD27 exhibited more resistance to apoptosis, interleukin 2 production, and proliferation than CD27− T cells. After transfer back into an HIV-infected patient, autologous HIV-specific CD27− T cells rapidly disappeared, but CD27+ T cells derived from the same clone persisted at high frequency. Our findings suggest that the CD27–CD70 interaction in HIV infection may provide CD27+ CD8+ T cells with a survival advantage and compensate for limiting or absent CD4+ T help to maintain the CD8 response

The landscape of Saturn’s internal magnetic field from the Cassini Grand Finale

The Cassini mission entered the Grand Finale phase in April 2017 and executed 22.5 highly inclined, close-in orbits around Saturn before diving into the planet on September 15th 2017. Here we present our analysis of the Cassini Grand Finale magnetometer (MAG) dataset, focusing on Saturn’s internal magnetic field. These measurements demonstrate that Saturn’s internal magnetic field is exceptionally axisymmetric, with a dipole tilt less than 0.007 degrees (25.2 arcsecs). Saturn’s magnetic equator was directly measured to be shifted northward by ∼0.0468 ± 0.00043 (1σ) R_S, 2820 ± 26 km, at cylindrical radial distances between 1.034 and 1.069 R_S from the spin-axis. Although almost perfectly axisymmetric, Saturn’s internal magnetic field exhibits features on many characteristic length scales in the latitudinal direction. Examining B_r at the a = 0.75 R_S, c = 0.6993 R_S isobaric surface, the degree 4 to 11 contributions correspond to latitudinally banded magnetic perturbations with characteristic width ∼15∘, similar to that of the off-equatorial zonal jets observed in the atmosphere of Saturn. Saturn’s internal magnetic field beyond 60∘, in particular the small-scale features, are less well constrained by the available measurements, mainly due to incomplete spatial coverage in the polar region. Magnetic fields associated with the ionospheric Hall currents were estimated and found to contribute less than 2.5 nT to Gauss coefficients beyond degree 3. The magneto-disk field features orbit-to-orbit variations between 12 nT and 15.4 nT along the close-in part of Grand Finale orbits, offering an opportunity to measure the electromagnetic induction response from the interior of Saturn. A stably stratified layer thicker than 2500 km likely exists above Saturn’s deep dynamo to filter out the non-axisymmetric internal magnetic field. A heat transport mechanism other than pure conduction, e.g. double diffusive convection, must be operating within this layer to be compatible with Saturn’s observed luminosity. The latitudinally banded magnetic perturbations likely arise from a shallow secondary dynamo action with latitudinally banded differential rotation in the semi-conducting layer

Lipidomics analysis of juveniles' blue mussels (Mytilus edulis L. 1758), a key economic and ecological species

Blue mussels (Mytilus edulis L. 1758) are important components of coastal ecosystems and in the economy of rural and coastal areas. The understanding of their physiological processes at key life stages is important both within food production systems and in the management of wild populations. Lipids are crucial molecules for bivalve growth, but their diversity and roles have not been fully characterized. In this study, traditional lipid profiling techniques, such as fatty acid (FA) and lipid class analysis, are combined to un-targeted lipidomics to elucidate the lipid metabolism in newly settled spat fed on a range of diets. The evaluated diets included single strains treatments (Cylindrotheca fusiformis CCAP 1017/2 –CYL, Isochrysis galbana CCAP 927/1– ISO, Monodopsis subterranean CCAP 848/1 –MONO, Nannochloropsis oceanica CCAP 849/10– NANNO) and a commercial algae paste (SP). Spat growth was influenced by the diets, which, according to their efficacy were ranked as follows: ISO>NANNO/CYL>SP>MONO. A higher triacylglycerols (TG) content, ranging from 4.23±0.82 μg mgashfree Dry weight (DW)-1 at the beginning of the trial (T0) to 51±15.3 μg mgashfreeDW-1 in ISO, characterised significant growth in the spat, whereas, a reduction of TG (0.3±0.08 μg mgashfreeDW-1 in MONO), mono unsaturated FA–MUFA (from 8.52±1.02 μg mgFAashfreeDW-1 at T0 to 2.81±1.02 μg mgFAashfreeDW-1 in MONO) and polyunsaturated FA–PUFA (from 17.57±2.24 μg mgFAashfreeDW-1 at T0 to 6.19±2.49 μg mgFAashfreeDW-1 in MONO) content characterised poor performing groups. Untargeted lipidomics evidenced how the availability of dietary essential PUFA did not influence only neutral lipids but also the membrane lipids, with changes in lipid molecular species in relation to the essential PUFA provided via the diet. Such changes have the potential to affect spat production cycle and their ability to respond to the surrounding environment. This study evidenced the advantages of coupling different lipid analysis techniques, as each technique disclosed relevant information on nutritional requirements of M. edulis juveniles, expanding the existing knowledge on the physiology of this important species

Exploring the Chemical Space of Macro- and Micro-Algae Using Comparative Metabolomics

With more than 156,000 described species, eukaryotic algae (both macro- and micro-algae) are a rich source of biological diversity, however their chemical diversity remains largely unexplored. Specialised metabolites with promising biological activities have been widely reported for seaweeds, and more recently extracts from microalgae have exhibited activity in anticancer, antimicrobial, and antioxidant screens. However, we are still missing critical information on the distinction of chemical profiles between macro- and microalgae, as well as the chemical space these metabolites cover. This study has used an untargeted comparative metabolomics approach to explore the chemical diversity of seven seaweeds and 36 microalgal strains. A total of 1390 liquid chromatography-mass spectrometry (LC-MS) features were detected, representing small organic algal metabolites, with no overlap between the seaweeds and microalgae. An in-depth analysis of four Dunaliella tertiolecta strains shows that environmental factors may play a larger role than phylogeny when classifying their metabolomic profile

Pretransplant NT-proBNP, Dialysis Vintage, and Posttransplant Mortality in Kidney Transplant Recipients

Background. End-stage kidney disease and dialysis vintage are characterized by accelerated atherosclerosis, volume overload, and progressive left ventricular hypertrophy, leading to elevated N-terminal probrain natriuretic peptide (NT-proBNP) levels. Pretransplant dialysis vintage is associated with excess mortality after transplantation. We want to study whether pretransplant NT-proBNP is associated with posttransplantation mortality and if it explains the association of dialysis vintage with posttransplantation mortality in kidney transplant recipients (KTR). Methods. We measured plasma NT-proBNP on arrival at the hospital before kidney transplantation in 658 KTR between January 1995 and December 2005 in our center. Multivariable Cox regression analyses, adjusted for potential confounders, were used to prospectively study the associations of dialysis vintage and NT-proBNP with all-cause mortality. Results. During median 12.7 (7.8-15.6) years of follow-up after transplantation, 248 (37.7%) KTR died. Dialysis vintage was associated with an increased risk of posttransplant mortality in the fully adjusted model (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.03-1.43; P = 0.02), independent of potential confounders. The association weakened materially and lost significance after further adjustment for NT-proBNP (HR, 1.14; 0.96-1.34; P = 0.14). NT-proBNP was independently associated with all-cause mortality in the fully adjusted model (HR, 1.34; 1.16-1.55; P < 0.001). The association remained independent of adjustment for dialysis vintage (HR, 1.31; 1.13-1.52; P < 0.001). Conclusions. Our study shows that longer dialysis vintage is associated with a higher mortality risk in KTR, and this association might be explained for a considerable part by variation in pretransplant NT-proBNP at the time of transplantation