122 research outputs found

    A study of rheumatological manifestations of leprosy

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    BACKGROUND AND AIMS: Rheumatic manifestations are a common feature of leprosy. The present study was performed to assess the incidence of rheumatic manifestations in leprosy. METHODS: Seventy cases of leprosy attending the indoor and outdoor departments were studied. RESULTS: Out of the 70 cases studied, rheumatic manifestations were seen in 61.42% of cases: arthritis in 54.28% and soft tissue rheumatism in 17.14%. Enthesitis was seen in 2.84% of cases. The incidence of arthritis in lepra reactions was 57.57%. CONCLUSIONS: Musculoskeletal manifestations can occur at any time during the infection. Articular inflammation in leprosy usually occurs in reactive states, particularly erythema nodosum leprosum (ENL). Leprosy can present with arthritis as the first symptom

    Axial distribution of myosin binding protein-C is unaffected by mutations in human cardiac and skeletal muscle

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    Myosin binding protein-C (MyBP-C), a major thick filament associated sarcomeric protein, plays an important functional and structural role in regulating sarcomere assembly and crossbridge formation. Missing or aberrant MyBP-C proteins (both cardiac and skeletal) have been shown to cause both cardiac and skeletal myopathies, thereby emphasising its importance for the normal functioning of the sarcomere. Mutations in cardiac MyBP-C are a major cause of hypertrophic cardiomyopathy (HCM), while mutations in skeletal MyBP-C have been implicated in a disease of skeletal muscle—distal arthrogryposis type 1 (DA-1). Here we report the first detailed electron microscopy studies on human cardiac and skeletal tissues carrying MyBP-C gene mutations, using samples obtained from HCM and DA-1 patients. We have used established image averaging methods to identify and study the axial distribution of MyBP-C on the thick filament by averaging profile plots of the A-band of the sarcomere from electron micrographs of human cardiac and skeletal myopathy specimens. Due to the difficulty of obtaining normal human tissue, we compared the distribution to the A-band structure in normal frog skeletal, rat cardiac muscle and in cardiac muscle of MyBP-C-deficient mice. Very similar overall profile averages were obtained from the C-zones in cardiac HCM samples and skeletal DA-1 samples with MyBP-C gene mutations, suggesting that mutations in MyBP-C do not alter its mean axial distribution along the thick filament

    The vertebrate muscle Z-disc: sarcomere anchor for structure and signalling

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    The Z-disc, appearing as a fine dense line forming sarcomere boundaries in striated muscles, when studied in detail reveals crosslinked filament arrays that transmit tension and house myriads of proteins with diverse functions. At the Z-disc the barbed ends of the antiparallel actin filaments from adjoining sarcomeres interdigitate and are crosslinked primarily by layers of α-actinin. The Z-disc is therefore the site of polarity reversal of the actin filaments, as needed to interact with the bipolar myosin filaments in successive sarcomeres. The layers of α-actinin determine the Z-disc width: fast fibres have narrow (~30–50 nm) Z-discs and slow and cardiac fibres have wide (~100 nm) Z-discs. Comprehensive reviews on the roles of the numerous proteins located at the Z-disc in signalling and disease have been published; the aim here is different, namely to review the advances in structural aspects of the Z-disc

    Proportions of Convective and Stratiform Precipitation Revealed in Water Isotope Ratios

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    Tropical and midlatitude precipitation is fundamentally of two types, spatially-limited and high-intensity convective or widespread and lower-intensity stratiform, owing to differences in vertical air motions and microphysical processes governing rain formation. These processes are difficult to observe or model and precipitation partitioning into rain types is critical for understanding how the water cycle responds to climate changes. Here, we combine two independent data sets – convective and stratiform precipitation fractions, derived from the Tropical Rainfall Measuring Mission satellite or synoptic cloud observations, and stable isotope and tritium compositions of surface precipitation, derived from a global network – to show that isotope ratios reflect rain type proportions and are negatively correlated with stratiform fractions. Condensation and riming associated with boundary layer moisture produces higher isotope ratios in convective rain, along with higher tritium when riming in deep convection occurs with entrained air at higher altitudes. Based on our data, stable isotope ratios can be used to monitor changes in the character of precipitation in response to periodic variability or changes in climate. Our results also provide observational constraints for an improved simulation of convection in climate models and a better understanding of isotope variations in proxy archives, such as speleothems and tropical ice

    Role of N-Terminal Amino Acids in the Potency of Anthrax Lethal Factor

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    Anthrax lethal factor (LF) is a Zn+2-dependent metalloprotease that cleaves several MAPK kinases and is responsible for the lethality of anthrax lethal toxin (LT). We observed that a recombinant LF (LF-HMA) which differs from wild type LF (LF-A) by the addition of two residues (His-Met) to the native Ala (A) terminus as a result of cloning manipulations has 3-fold lower potency toward cultured cells and experimental animals. We hypothesized that the “N-end rule”, which relates the half-life of proteins in cells to the identity of their N-terminal residue, might be operative in the case of LF, so that the N-terminal residue of LF would determine the cytosolic stability and thereby the potency of LF. Mutational studies that replaced the native N-terminal residue of LF with known N-end rule stabilizing or destabilizing residues confirmed that the N-terminal residue plays a significant role in determining the potency of LT for cultured cells and experimental animals. The fact that a commercially-available LF preparation (LF-HMA) that is widely used in basic research studies and for evaluation of vaccines and therapeutics is 3-fold less potent than native LF (LF-A) should be considered when comparing published studies and in the design of future experiments

    Formation of beads-on-a-string structures during break-up of viscoelastic filaments

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    Break-up of viscoelastic filaments is pervasive in both nature and technology. If a filament is formed by placing a drop of saliva between a thumb and forefinger and is stretched, the filament’s morphology close to break-up corresponds to beads of several sizes interconnected by slender threads. Although there is general agreement that formation of such beads-on-a-string (BOAS) structures occurs only for viscoelastic fluids, the underlying physics remains unclear and controversial. The physics leading to the formation of BOAS structures is probed by numerical simulation. Computations reveal that viscoelasticity alone does not give rise to a small, satellite bead between two much larger main beads but that inertia is required for its formation. Viscoelasticity, however, enhances the growth of the bead and delays pinch-off, which leads to a relatively long-lived beaded structure. We also show for the first time theoretically that yet smaller, sub-satellite beads can also form as seen in experiments.National Science Foundation (U.S.). ERC-SOPS (EEC-0540855)Nanoscale Interdisciplinary Research Thrust on 'Directed Self-assembly of Suspended Polymer Fibers' (NSF-DMS0506941

    Population Genetic Structure of the Grasshopper Eyprepocnemis plorans in the South and East of the Iberian Peninsula

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    The grasshopper Eyprepocnemis plorans subsp. plorans harbors a very widespread polymorphism for supernumerary (B) chromosomes which appear to have arisen recently. These chromosomes behave as genomic parasites because they are harmful for the individuals carrying them and show meiotic drive in the initial stages of population invasion. The rapid increase in B chromosome frequency at intrapopulation level is thus granted by meiotic drive, but its spread among populations most likely depends on interpopulation gene flow. We analyze here the population genetic structure in 10 natural populations from two regions (in the south and east) of the Iberian Peninsula. The southern populations were coastal whereas the eastern ones were inland populations located at 260–655 m altitude. The analysis of 97 ISSR markers revealed significant genetic differentiation among populations (average GST = 0.129), and the Structure software and AMOVA indicated a significant genetic differentiation between southern and eastern populations. There was also significant isolation by distance (IBD) between populations. Remarkably, these results were roughly similar to those found when only the markers showing low or no dropout were included, suggesting that allelic dropout had negligible effects on population genetic analysis. We conclude that high gene flow helped this parasitic B chromosome to spread through most of the geographical range of the subspecies E. plorans plorans.This study was supported by a grant from the Spanish Ministerio de Ciencia e Innovación (CGL2009-11917), and was partially performed by FEDER funds. MIMP was supported by a fellowship (FPU) from the Spanish Ministerio de Ciencia e Innovación
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