Molecular analysis of the LDLR gene in coronary artery disease patients from the Indian population

BACKGROUND: Cardiovascular disease is a leading cause of mortality in Indian population. Mutations in LDLR, APOB and PCSK9 genes may lead to Familial Hypercholesterolemia, an autosomal dominant disorder which in turn leads to cardiovascular diseases. The primary objective of this study is to analyze these genes in CAD patients of Indian population. METHODS: A total of 30 patients were selected out of 300 CAD patients based on UK-Simon Broome criteria from South India. The gDNA was isolated by organic extraction method and the exons and exon-intron boundaries of LDLR gene, APOB (exon 26) and PCSK9 (exon 7) were screened by PCR-high resolution melt analysis. The amplicons showing shift in melting pattern were sequenced to find out the variation. RESULTS: This study reports three novel variations, an intronic deletion c.694+8_694+18del in intron 4, a synonymous variation c.966 C>T [p. (N322=)] in exon 7 and a deletion insertion c.1399_1340delinsTA [p. (T467Y)] in exon 10, two recurrent variations c.862G>A [p. (E288K)] in exon 6 and a splice site variation c.1845+2T>C in exon-intron junction of exon 12 in LDLR gene and PCSK9 gene had c.1180+17C>T change in intron 7. However there are no pathogenic variations in APOB and PCSK9 genes in Indian population. In silico analysis predicted all the variations as pathogenic except the synonymous variation. CONCLUSION: This report adds five new variations to the spectrum of LDLR variations in Indian population. This study also suggests that UK Simon Broom criteria can be followed to categorize FH patients in Indian population

Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive

Action selection in the basal ganglia is often described within the framework of a standard model, associating low dopaminergic drive with motor suppression. Whilst powerful, this model does not explain several clinical and experimental data, including varying therapeutic efficacy across movement disorders. We tested the predictions of this model in patients with Parkinson’s disease, on and off subthalamic deep brain stimulation (DBS), focussing on adaptive sensory-motor responses to a changing environment and maintenance of an action until it is no longer suitable. Surprisingly, we observed prolonged perseverance under on-stimulation, and high inter-individual variability in terms of the motor selections performed when comparing the two conditions. To account for these data, we revised the standard model exploring its space of parameters and associated motor functions and found that, depending on effective connectivity between external and internal parts of the globus pallidus and saliency of the sensory input, a low dopaminergic drive can result in increased, dysfunctional, motor switching, besides motor suppression. This new framework provides insight into the biophysical mechanisms underlying DBS, allowing a description in terms of alteration of the signal-to-baseline ratio in the indirect pathway, which better account of known electrophysiological data in comparison with the standard model

Nr2e3 is a Genetic Modifier That Rescues Retinal Degeneration and Promotes Homeostasis in Multiple Models of Retinitis Pigmentosa

Recent advances in viral vector engineering, as well as an increased understanding of the cellular and molecular mechanism of retinal diseases, have led to the development of novel gene therapy approaches. Furthermore, ease of accessibility and ocular immune privilege makes the retina an ideal target for gene therapies. In this study, the nuclear hormone receptor gene Nr2e3 was evaluated for efficacy as broad-spectrum therapy to attenuate early to intermediate stages of retinal degeneration in five unique mouse models of retinitis pigmentosa (RP). RP is a group of heterogenic inherited retinal diseases associated with over 150 gene mutations, affecting over 1.5 million individuals worldwide. RP varies in age of onset, severity, and rate of progression. In addition, ~40% of RP patients cannot be genetically diagnosed, confounding the ability to develop personalized RP therapies. Remarkably, Nr2e3 administered therapy resulted in reduced retinal degeneration as observed by increase in photoreceptor cells, improved electroretinogram, and a dramatic molecular reset of key transcription factors and associated gene networks. These therapeutic effects improved retinal homeostasis in diseased tissue. Results of this study provide evidence that Nr2e3 can serve as a broad-spectrum therapy to treat multiple forms of RP

Queen mandibular pheromone: questions that remain to be resolved

The discovery of ‘queen substance’, and the subsequent identification and synthesis of keycomponents of queen mandibular pheromone, has been of significant importance to beekeepers and to thebeekeeping industry. Fifty years on, there is greater appreciation of the importance and complexity of queenpheromones, but many mysteries remain about the mechanisms through which pheromones operate. Thediscovery of sex pheromone communication in moths occurred within the same time period, but in this case,intense pressure to find better means of pest management resulted in a remarkable focusing of research activityon understanding pheromone detection mechanisms and the central processing of pheromone signals in themoth. We can benefit from this work and here, studies on moths are used to highlight some of the gaps in ourknowledge of pheromone communication in bees. A better understanding of pheromone communication inhoney bees promises improved strategies for the successful management of these extraordinary animals

Stable Isotope Evidence for Dietary Overlap between Alien and Native Gastropods in Coastal Lakes of Northern KwaZulu-Natal, South Africa

Tarebia granifera (Lamarck, 1822) is originally from South-East Asia, but has been introduced and become invasive in many tropical and subtropical parts of the world. In South Africa, T. granifera is rapidly invading an increasing number of coastal lakes and estuaries, often reaching very high population densities and dominating shallow water benthic invertebrate assemblages. An assessment of the feeding dynamics of T. granifera has raised questions about potential ecological impacts, specifically in terms of its dietary overlap with native gastropods.A stable isotope mixing model was used together with gut content analysis to estimate the diet of T. granifera and native gastropod populations in three different coastal lakes. Population density, available biomass of food and salinity were measured along transects placed over T. granifera patches. An index of isotopic (stable isotopes) dietary overlap (IDO, %) aided in interpreting interactions between gastropods. The diet of T. granifera was variable, including contributions from microphytobenthos, filamentous algae (Cladophora sp.), detritus and sedimentary organic matter. IDO was significant (>60%) between T. granifera and each of the following gastropods: Haminoea natalensis (Krauss, 1848), Bulinus natalensis (Küster, 1841) and Melanoides tuberculata (Müller, 1774). However, food did not appear to be limiting. Salinity influenced gastropod spatial overlap. Tarebia granifera may only displace native gastropods, such as Assiminea cf. ovata (Krauss, 1848), under salinity conditions below 20. Ecosystem-level impacts are also discussed.The generalist diet of T. granifera may certainly contribute to its successful establishment. However, although competition for resources may take place under certain salinity conditions and if food is limiting, there appear to be other mechanisms at work, through which T. granifera displaces native gastropods. Complementary stable isotope and gut content analysis can provide helpful ecological insights, contributing to monitoring efforts and guiding further invasive species research

Diving into the vertical dimension of elasmobranch movement ecology

This is the final version. Available on open access from the American Association for the Advancement of Science via the DOI in this recordData and materials availability: Processed data and code used in the analysis are accessible from the Zenodo Repository: 10.5281/zenodo.6885455Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements.Bertarelli FoundationResearch EnglandMoore FoundationPackard FoundationInstituto Politecnico NacionalDarwin InitiativeGeorgia AquariumRolex Awards for EnterpriseWhitley Fund for Natur

Colour Doppler ultrasound of the lumbar arteries: A novel application and reproducibility study in healthy subjects

Lumbar arteries are important because they are the main source of blood supply to the lumbar spine structures. However, these vessels and their flow characteristics have received little attention and their role in conditions such as low back pain remains unclear. The present study 1. describes the application of duplex ultrasonography in the assessment of lumbar artery blood flow and 2. evaluates the interobserver and intraobserver reproducibility of lumbar artery Doppler velocimetry. A total of 13 healthy volunteers were evaluated by two different examiners successively on the same day and measurements repeated by the same examiners I week later. Peak systolic velocities of lumbar arteries were recorded at an optimal angle below 60 degrees. Overall mean peak systolic velocity (+/- SD) for lumbar arteries was 0.158 +/- 0.051 m/s, and mean Doppler angle (+/- SD) was 24.6 +/- 14.5 degrees. For interobserver variability, the coefficient of variation was 23.4% and SD of differences 0.037 m/s. Reliable results of lumbar artery Doppler velocimetry demonstrate its applicability in future clinical investigations in patients with low back disorders. (E-mail: [email protected]) (C) 2006 World Federation for Ultrasound in Medicine & Biology