Surname studies with genetics

Genetic studies of surnames are briefly reviewed. In particular, such DNA studies can sometimes provide clues to a surname's meaning. A few surnames are being found to include unusually large single families, which are far more populous than computer simulations for monogamous families predict, suggesting that they might best be explained by their getting off to a fast start through polygyny or concubines: Brehon Law in Ireland and medieval Welsh Law were relatively accepting of polygyny. The Plant surname in the Welsh Marches largely comprises an abnormally large single family and this favours the Welsh meaning '[many] children', though various other meanings for this surname have been suggested. The surnames Meates, Meats, Mates, Mate and Myatt in north Staffordshire and Ireland belong to a single family and appear to have derived from the female forename Maiot

Modern merthods and a controversial surname: Plant

In the past few years, DNA testing has begun to contribute to our understanding. It is currently emerging more clearly which surnames are multi-origin, originating with many different forefathers, and which descend from a single male ancestor. As a case study, I shall describe the application of modern, multidisciplinary methods to the surname Plant, which has been ascribed a different meaning each time an authority has written about it. The recent emergence of a different view anout this name's origins has prompted a reassessment of its meaning

The Tardy Adoption of the Plantagenet Surname

Accounts of the origins of Plantagenet have ignored a tradition of similar names, some of which had a bawdy insinuation. There could have been a mischievous interpretation of Plantagenet, building its currency amongst neighbouring commoners whilst delaying its acceptance for official royal purposes. This and other developments such as the spread of contemporary scholastic teachings can explain the slow but eventual adoption of the Plantagenet nickname as a hereditary royal surname despite the scarcity of its early mentions

Modern methods and a controversial surname: Plant

In the past few years, DNA testing has begun to contribute to our understanding. It is currently emerging more clearly which surnames are multi-origin, originating with many different forefathers, and which descend from a single male ancestor.\ud \ud As a case study, I shall describe the application of modern, multidisciplinary methods to the surname Plant, which has been ascribed a different meaning each time an authority has written about it. The recent emergence of a different view about this name's origins has prompted a reassessment of its meaning

Quantifying myosin light chain phosphorylation in single adherent cells with automated fluorescence microscopy

<p>Abstract</p> <p>Background</p> <p>In anchorage dependent cells, myosin generated contractile forces affect events closely associated with adhesion such as the formation of stress fibers and focal adhesions, and temporally distal events such as entry of the cell into S-phase. As occurs in many signaling pathways, a phosphorylation reaction (in this case, phosphorylation of myosin light chain) is directly responsible for cell response. Western blotting has been useful in measuring intracellular phosphorylation events, but cells are lysed in the process of sample preparation for western blotting, and spatial information such as morphology, localization of the phosphorylated species, and the distribution of individual cell responses across the population is lost. We report here a reliable automated microscopy method for quantitative measurement of myosin light chain phosphorylation in adherent cells. This method allows us to concurrently examine cell morphology, cell-cell contact, and myosin light chain diphosphorylation in vascular smooth muscle cells.</p> <p>Results</p> <p>Paraformaldehyde fixation and Triton X-100 permeabilization preserved cell morphology and myosin light chain phosphorylation better than the alternative fixation/permeabilization methods tested. We utilized automated microscopy methods to acquire three color images, determine cell spread area, and quantify the intensity of staining within each cell with anti-phospho-MLC antibody. Our results indicate that A10 rat aortic smooth muscle cells exhibit a re producible non-Gaussian distribution of MLC phosphorylation across a population of unsynchronized genetically identical cells. Adding an inhibitor of Rho kinase, Y27632, or plating cells on a low density of fibronectin, reduced phospho-myosin light chain signal as expected. On the other hand, adding calyculin A, an activator of contractility, increased myosin light chain phosphorylation. The IC₅₀for myosin light chain phosphorylation using Y27632 was determined to be 2.1 ± 0.6 micrometers. We observed a positive linear relationship between cell area and myosin light chain diphosphorylation, which is consistent with what has been reported in the literature using other methods.</p> <p>Conclusion</p> <p>Our results show that using proper specimen fixation techniques and background subtraction methods, imaging cytometry can be used to reliably measure relative myosin light chain phosphorylation in individual adherent cells. Importantly, the ability to make this measurement in adherent cells allows for simultaneous measurement of and correlation with other parameters of cellular topography such as morphology and cell-cell proximity. This assay has potential application in screening for drug development.</p

Nationwide epidemiological study of severe gallstone disease in Taiwan

<p>Abstract</p> <p>Background</p> <p>Our study aimed to assess the nationwide trends in the incidence of severe gallstone disease in Taiwan among adults aged ≥20.</p> <p>Methods</p> <p>A retrospective longitudinal study was conducted using Taiwan National Health Insurance Research Database collected during 1997–2005. Patients with incident severe gallstone disease (acute cholecystitis, biliary pancreatitis, acute cholangitis) and gallstone-related procedures (elective and non-elective cholecystectomy, endoscopic retrograde cholangiopancreatography [ERCP]) that led to hospital admission were identified using ICD-9-CM diagnostic and procedure codes. Annual incidence rates of gallstone-related complications and procedures were calculated and their 95% confidence intervals (CI) were estimated assuming a Poisson distribution.</p> <p>Results</p> <p>The hospital admission rate for severe gallstone disease increased with advancing age and the age-standardized rate (95% CI) per 1000 population was 0.60 (0.59–0.60) for men and 0.59 (0.59–0.60) for women. Men had a higher rate of acute cholecystitis, probably due to the substantially lower rate of elective cholecystectomy among men than women. For those aged 20–39, hospital admissions for all gallstone-related complications and procedures increased significantly. For those aged ≥60, incidences of biliary pancreatitis, acute cholangitis, and hospital admission for gallstone receiving ERCP increased significantly without substantial change in the incidence of acute cholecystitis and despite a decreased rate of elective cholecystectomy.</p> <p>Conclusion</p> <p>This population-based study found a substantial increase in the rate of admission for severe gallstone disease among those aged 20–39. Concurrently, the incidences of biliary pancreatitis and acute cholangitis have risen among those aged ≥60.</p

Tau, prions and Aβ: the triad of neurodegeneration

This article highlights the features that connect prion diseases with other cerebral amyloidoses and how these relate to neurodegeneration, with focus on tau phosphorylation. It also discusses similarities between prion disease and Alzheimer’s disease: mechanisms of amyloid formation, neurotoxicity, pathways involved in triggering tau phosphorylation, links to cell cycle pathways and neuronal apoptosis. We review previous evidence of prion diseases triggering hyperphosphorylation of tau, and complement these findings with cases from our collection of genetic, sporadic and transmitted forms of prion diseases. This includes the novel finding that tau phosphorylation consistently occurs in sporadic CJD, in the absence of amyloid plaques

Actin Nemaline Myopathy Mouse Reproduces Disease, Suggests Other Actin Disease Phenotypes and Provides Cautionary Note on Muscle Transgene Expression

Mutations in the skeletal muscle α-actin gene (ACTA1) cause congenital myopathies including nemaline myopathy, actin aggregate myopathy and rod-core disease. The majority of patients with ACTA1 mutations have severe hypotonia and do not survive beyond the age of one. A transgenic mouse model was generated expressing an autosomal dominant mutant (D286G) of ACTA1 (identified in a severe nemaline myopathy patient) fused with EGFP. Nemaline bodies were observed in multiple skeletal muscles, with serial sections showing these correlated to aggregates of the mutant skeletal muscle α-actin-EGFP. Isolated extensor digitorum longus and soleus muscles were significantly weaker than wild-type (WT) muscle at 4 weeks of age, coinciding with the peak in structural lesions. These 4 week-old mice were ∼30% less active on voluntary running wheels than WT mice. The α-actin-EGFP protein clearly demonstrated that the transgene was expressed equally in all myosin heavy chain (MHC) fibre types during the early postnatal period, but subsequently became largely confined to MHCIIB fibres. Ringbinden fibres, internal nuclei and myofibrillar myopathy pathologies, not typical features in nemaline myopathy or patients with ACTA1 mutations, were frequently observed. Ringbinden were found in fast fibre predominant muscles of adult mice and were exclusively MHCIIB-positive fibres. Thus, this mouse model presents a reliable model for the investigation of the pathobiology of nemaline body formation and muscle weakness and for evaluation of potential therapeutic interventions. The occurrence of core-like regions, internal nuclei and ringbinden will allow analysis of the mechanisms underlying these lesions. The occurrence of ringbinden and features of myofibrillar myopathy in this mouse model of ACTA1 disease suggests that patients with these pathologies and no genetic explanation should be screened for ACTA1 mutations

THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Overview.

The Concise Guide to PHARMACOLOGY 2017/18 is the third in this series of biennial publications. This version provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13882/full. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are eight areas of focus: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2017, and supersedes data presented in the 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature Committee of the Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate

Getting the most from a surname study:\ud semantics, DNA and computer modelling\ud (third edition)

We here address such questions as: what does a surname\ud mean;is it single origin;and,why do some surnames grow abnormally large? Though most surnames are rare, most people have populous surnames. In this article, we consider in particular the evidence that some frequent surnames could be completely or nearly single origin; this would imply that the whole surname relates to a single family\ud that has grown abnormally large. Some populous surnames\ud have a geographical distribution that might be thought to be consistent with a single origin. As yet, such supposition generally lacks support from adequate DNA evidence.\ud \ud Guided by the empirical evidence, our computer simulations identify various possible reasons for a surname family’s unusually prolific growth. In particular, chance is a main factor. Also, overall population growth conditions vary widely between different counties. This can go a long way towards explaining the large population of Plant, which is apparently the second largest single-family contender in the favourable growing conditions of Staffordshire. This\ud surname shows relatively little evidence of a significant living population that stems from origins other than that of its dominant family. The initial semblance that Sykes could be the second largest single-family contender in West\ud Yorkshire is more open to debate, since there might be more\ud substantial other origins. To explain its dominant family, it seems necessary to invoke some exceptional characteristics such as more favourable growth factors for its homeland than those pertaining in the available data for the whole county. Also, for the computer modelling, we consider the effects of additional factors such as polygyny, resilience to plague,Y-chromosome linked fecundity, or an early start to an hereditary surname. Such factors can be beneficial in seeing a family through initial precarious times, sustaining its survival through to\ud a small but real chance of subsequent proliferation in more favourable Industrial Age growth conditions