Single nucleotide substitution mutations and polymorphisms in ECM1 gene in lipoid proteinosis in siblings of a Pakistani family

A number of mutations in extracellular matrix protein 1 (ECM1) that is a glycoprotein and expressed in skin and other tissues are reported to cause a rare, autosomal recessive disorder called lipoid proteinosis (LP). The peculiar manifestation of LP is hoarseness of voice caused by laryngeal infiltration in infancy. Skin and mucous membrane changes clinically become apparent, and the disease typically follows a slowly progressive, yet often benign, course. About 300 cases of LP have been reported, but occurrence in siblings is rare. In this study, two siblings (18 and 24-year-old) of a Pakistani family were reported to have LP. This study presents two brothers with scaly itchy lesions on whole body, hoarse voice and macroglossia. Their deceased father had similar clinical manifestations but mother, younger brother and sister were unaffected. Blood from affected and clinically unaffected family members were collected with informed consent. The ECM1 gene containing 10 exons were amplified and sequenced. Both patients showed non-pathogenic missense and silent mutations in exon 6 and 8. In exon 6, a nucleotide C was substituted to T (C→T) at codon 2, in patient 1. This nonpathogenic missense mutation causes appearance of amino acid cysteine instead of arginine that is part of normal ECM1 protein. In patient 2, polymorphism of nucleotide C to T (C/T) was observed observed in exion 6 that may lead to the appearance of cysteine and/or arginine in the resulting gene product. In exon 8, a nucleotide G was substituted to A (G→A) at codon 53, in patient 1. This substitution leads to a silent mutation as serine is coded by both forms of codon. In patient 2, polymorphism of nucleotide G to A (G/A) was observed in exion 8 that do not cause any change in the coded amino acid. These findings represent a set of missense and silent mutations supporting an unusual function of ECM1 protein, broadening the spectrum of disease-linked mutations in rare cases of LP.Key words: Lipoid proteinosis, extracellular matrix protein 1 (ECM1), missense, silent mutation, single nucleotide polymorphism, exons 6 and 8, genodermatosis

Benign versus malignant hepatic nodules: MR imaging findings with pathologic correlation

According to the currently used nomenclature, there are only two types of hepatocellular nodular lesions: regenerative lesions and dysplastic or neoplastic lesions. Regenerative nodules include monoacinar regenerative nodules, multiacinar regenerative nodules, cirrhotic nodules, segmental or lobar hyperplasia, and focal nodular hyperplasia. Dysplastic or neoplastic nodules include hepatocellular adenoma, dysplastic foci, dysplastic nodules, and hepatocellular carcinoma (HCC). Many of these types of hepatic nodules play a role in the de novo and stepwise carcinogenesis of HCC, which comprises the following steps: regenerative nodule, low-grade dysplastic nodule, high-grade dysplastic nodule, small HCC, and large HCC. State-of-the-art magnetic resonance (MR) imaging facilitates detection and characterization in most cases of hepatic nodules. State-of-the-art MR imaging includes single-shot fast spin-echo imaging, in-phase and opposed-phase T1-weighted gradient-echo imaging, T2-weighted fast spin-echo imaging with fat saturation, and two-dimensional or three-dimensional dynamic multiphase contrast material-enhanced imaging

Correlation and path analysis for yield and yield components in sunflower (Helianthus annus. L)

Ten (10) sunflower genotypes were evaluated in a triplicated randomized complete blocked design in field for plant height, stem diameter at base, internodal length, head diameter, number of whorls head-1, achene weight head-1, 100-achene weight, achene oil and protein content. Association among various plant traits and direct and indirect effects of various traits on achene weight head-1 were estimated. Correlations of head diameter, 100-achene weight, stem diameter at base, internodal length and oil contents were positive and significant with achene weight head-1. Path analysis showed that direct effects of plant height, head diameter, 100-achene weight and oil contents were positive while direct effects of stem diameter at base, internodal length, number of fertile whorls head-1 and protein contents were negative on achene weight head-1. This shows that selection based on head diameter, 100-achene weight, plant height, internodal length and stem diameter at base will be more effective in improving yield.Keywords: Sunflower, correlation coefficient, path coefficient, yield componentsAfrican Journal of Biotechnology Vol. 12(16), pp. 1968-197

Controlled release of chlorhexidine from a HEMA-UDMA resin using a magnetic field

The authors thank Mr. Russell Bailey of Nanovision (QMUL) for help with SEM. Dong Luo thanks for the financial support from the China Scholarship Council during his PhD study. The authors would like to thank Adam Daykin and Queen Mary Innovation for providing funding via the Life Sciences Initiative Proof of Concept Fund

抗ヒスタミン薬ケトチフェンの連日投与による体内時計位相調節

富山大学・富生命博甲第90号・AHMAD ALSAWAF・2017/03/23Sleep and Biological Rhythms,2016.1,14(1),117-120,doi: 10.1007/s41105-015-0021-yに掲載。富山大学201

Randomised controlled trial of adjunctive triamcinolone acetonide in eyes undergoing vitreoretinal surgery following open globe trauma: the ASCOT study

BACKGROUND/AIMS: To investigate the clinical effectiveness of adjunctive triamcinolone acetonide (TA) given at the time of vitreoretinal surgery following open globe trauma (OGT). METHODS: A phase 3, multicentre, double-masked randomised controlled trial of patients undergoing vitrectomy following OGT comparing adjunctive TA (intravitreal and subtenons) against standard care (2014-2020). The primary outcome was the proportion of patients with at least 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letter improvement in corrected visual acuity (VA) at 6 months. Secondary outcomes included: change in ETDRS, retinal detachment (RD) secondary to PVR, retinal reattachment, macular reattachment, tractional RD, number of operations, hypotony, elevated intraocular pressure and quality of life. RESULTS: 280 patients were randomised over 75 months, of which 259 completed the study. 46.9% (n=61/130) of patients in the treatment group had a 10-letter improvement in VA compared with 43.4% (n=56/129) of the control group (difference 3.5% (95% CI -8.6% to 15.6%), OR=1.03 (95% CI 0.61 to 1.75), p=0.908)). Secondary outcome measures also failed to show any treatment benefit. For two of the secondary outcome measures, stable complete retinal and macular reattachment, outcomes were worse in the treatment group compared with controls, respectively, 51.6% (n=65/126) vs 64.2% (n=79/123), OR=0.59 (95% CI 0.36 to 0.99), and 54.0% (n=68/126) vs 66.7% (n=82/123), OR=0.59 (95% CI 0.35 to 0.98), for TA vs control. CONCLUSION: The use of combined intraocular and sub-Tenons capsule TA is not recommended as an adjunct to vitrectomy surgery following OGT. TRIAL REGISTRATION NUMBER: NCT02873026

Rising burden of Hepatitis C Virus in hemodialysis patients

<p>Abstract</p> <p>Aim</p> <p>High prevalence of Hepatitis C virus (HCV) has been reported among the dialysis patients throughout the world. No serious efforts were taken to investigate HCV in patients undergoing hemodialysis (HD) treatment who are at great increased risk to HCV. HCV genotypes are important in the study of epidemiology, pathogenesis and reaction to antiviral therapy. This study was performed to investigate the prevalence of active HCV infection, HCV genotypes and to assess risk factors associated with HCV genotype infection in HD patients of Khyber Pakhtunkhwa as well as comparing this prevalence data with past studies in Pakistan.</p> <p>Methods</p> <p>Polymerase chain reaction was performed for HCV RNA detection and genotyping in 384 HD patients. The data obtained was compared with available past studies from Pakistan.</p> <p>Results</p> <p>Anti HCV antibodies were observed in 112 (29.2%), of whom 90 (80.4%) were HCV RNA positive. In rest of the anti HCV negative patients, HCV RNA was detected in 16 (5.9%) patients. The dominant HCV genotypes in HCV infected HD patients were found to be 3a (n = 36), 3b (n = 20), 1a (n = 16), 2a (n = 10), 2b (n = 2), 1b (n = 4), 4a (n = 2), untypeable (n = 10) and mixed (n = 12) genotype.</p> <p>Conclusion</p> <p>This study suggesting that i) the prevalence of HCV does not differentiate between past and present infection and continued to be elevated ii) HD patients may be a risk for HCV due to the involvement of multiple routes of infections especially poor blood screening of transfused blood and low standard of dialysis procedures in Pakistan and iii) need to apply infection control practice.</p

Coevolved mutations reveal distinct architectures for two core proteins in the bacterial flagellar motor

Switching of bacterial flagellar rotation is caused by large domain movements of the FliG protein triggered by binding of the signal protein CheY to FliM. FliG and FliM form adjacent multi-subunit arrays within the basal body C-ring. The movements alter the interaction of the FliG C-terminal (FliGC) "torque" helix with the stator complexes. Atomic models based on the Salmonella entrovar C-ring electron microscopy reconstruction have implications for switching, but lack consensus on the relative locations of the FliG armadillo (ARM) domains (amino-terminal (FliGN), middle (FliGM) and FliGC) as well as changes during chemotaxis. The generality of the Salmonella model is challenged by the variation in motor morphology and response between species. We studied coevolved residue mutations to determine the unifying elements of switch architecture. Residue interactions, measured by their coevolution, were formalized as a network, guided by structural data. Our measurements reveal a common design with dedicated switch and motor modules. The FliM middle domain (FliMM) has extensive connectivity most simply explained by conserved intra and inter-subunit contacts. In contrast, FliG has patchy, complex architecture. Conserved structural motifs form interacting nodes in the coevolution network that wire FliMM to the FliGC C-terminal, four-helix motor module (C3-6). FliG C3-6 coevolution is organized around the torque helix, differently from other ARM domains. The nodes form separated, surface-proximal patches that are targeted by deleterious mutations as in other allosteric systems. The dominant node is formed by the EHPQ motif at the FliMMFliGM contact interface and adjacent helix residues at a central location within FliGM. The node interacts with nodes in the N-terminal FliGc α-helix triad (ARM-C) and FliGN. ARM-C, separated from C3-6 by the MFVF motif, has poor intra-network connectivity consistent with its variable orientation revealed by structural data. ARM-C could be the convertor element that provides mechanistic and species diversity.JK was supported by Medical Research Council grant U117581331. SK was supported by seed funds from Lahore University of Managment Sciences (LUMS) and the Molecular Biology Consortium

Transition of plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein pumilio

Many eukaryotic developmental and cell fate decisions that are effected post-transcriptionally involve RNA binding proteins as regulators of translation of key mRNAs. In malaria parasites (Plasmodium spp.), the development of round, non-motile and replicating exo-erythrocytic liver stage forms from slender, motile and cell-cycle arrested sporozoites is believed to depend on environmental changes experienced during the transmission of the parasite from the mosquito vector to the vertebrate host. Here we identify a Plasmodium member of the RNA binding protein family PUF as a key regulator of this transformation. In the absence of Pumilio-2 (Puf2) sporozoites initiate EEF development inside mosquito salivary glands independently of the normal transmission-associated environmental cues. Puf2- sporozoites exhibit genome-wide transcriptional changes that result in loss of gliding motility, cell traversal ability and reduction in infectivity, and, moreover, trigger metamorphosis typical of early Plasmodium intra-hepatic development. These data demonstrate that Puf2 is a key player in regulating sporozoite developmental control, and imply that transformation of salivary gland-resident sporozoites into liver stage-like parasites is regulated by a post-transcriptional mechanism