Obesity-induced insulin resistance in human skeletal muscle is characterised by defective activation of p42/p44 MAP kinase

Insulin resistance (IR), an impaired cellular, tissue and whole body response to insulin, is a major pathophysiological defect of type 2 diabetes mellitus. Although IR is closely associated with obesity, the identity of the molecular defect(s) underlying obesity-induced IR in skeletal muscle remains controversial; reduced post-receptor signalling of the insulin receptor substrate 1 (IRS1) adaptor protein and downstream effectors such as protein kinase B (PKB) have previously been implicated. We examined expression and/or activation of a number of components of the insulin-signalling cascade in skeletal muscle of 22 healthy young men (with body mass index (BMI) range, 20–37 kg/m2). Whole body insulin sensitivity (M value) and body composition was determined by the hyperinsulinaemic (40 mU. min−1.m−2.), euglycaemic clamp and by dual energy X-ray absorptiometry (DEXA) respectively. Skeletal muscle (vastus lateralis) biopsies were taken before and after one hour of hyperinsulinaemia and the muscle insulin signalling proteins examined by western blot and immunoprecipitation assay. There was a strong inverse relationship between M-value and BMI. The most striking abnormality was significantly reduced insulin-induced activation of p42/44 MAP kinase, measured by specific assay, in the volunteers with poor insulin sensitivity. However, there was no relationship between individuals' BMI or M-value and protein expression/phosphorylation of IRS1, PKB, or p42/44 MAP kinase protein, under basal or hyperinsulinaemic conditions. In the few individuals with poor insulin sensitivity but preserved p42/44 MAP kinase activation, other signalling defects were evident. These findings implicate defective p42/44 MAP kinase signalling as a potential contributor to obesity-related IR in a non-diabetic population, although clearly multiple signalling defects underlie obesity associated IR

Site-specific incorporation of phosphotyrosine using an expanded genetic code.

Access to phosphoproteins with stoichiometric and site-specific phosphorylation status is key to understanding the role of protein phosphorylation. Here we report an efficient method to generate pure, active phosphotyrosine-containing proteins by genetically encoding a stable phosphotyrosine analog that is convertible to native phosphotyrosine. We demonstrate its general compatibility with proteins of various sizes, phosphotyrosine sites and functions, and reveal a possible role of tyrosine phosphorylation in negative regulation of ubiquitination

Hearing the voices of older adult patients: processes and findings to inform health services research

Background Clinical academic research and service improvement is planned using Patient and Public Involvement and Engagement (PPIE) but older PPIE participants are consulted less often due to the perception that they are vulnerable or hard to engage. Objectives To consult frail older adults about a recently adopted service, discharge to assess (D2A), and to prioritise services improvements and research topics associated with the design and delivery of discharge from hospital. To use successive PPIE processes to enable a permanent PPIE panel to be established. Participants Following guidance from an established hospital PPI panel 27 older adult participants were recruited. Participants from Black, Asian and Minority Ethnic (BAME) communities, affluent and non-affluent areas and varied social circumstances were included. Methods Focus groups and individual interviews were conducted in participants own homes or nearby social venues. Results Priorities for discharge included remaining independent despite often feeling lonely at home; to remain in hospital if needed; and for services to ensure effective communication with families. The main research priority identified was facilitating independence, whilst establishing a permanent PPIE panel involving older adults was viewed favourably. Conclusions Taking a structured approach to PPIE enabled varied older peoples’ voices to express their priorities and concerns into early discharge from hospital, as well as enabling the development of health services research into hospital discharge planning and management. Older people as participants identified research priorities after reflecting on their experiences. Listening and reflection enabled researchers to develop a new “Community PPIE Elders Panel” to create an enduring PPIE infrastructure for frail older housebound people to engage in research design, development and dissemination

Prevalence Rates of Mental Disorders in Chilean Prisons

PMCID: PMC371883

Description of a New Species of Slave-making Ant in the \u3ci\u3eFormica Sanguinea\u3c/i\u3e Group (Hymenoptera: Formicidae)

The new species, Formica gynocrates, is described and illustrated from all the castes. This slave-making species is a member of the sanguinea group and is most similar to F. pergandei. The type locality is the E. S. George Reserve, Livingston County, Michigan. Specimens were also examined from North Dakota, Wyoming, and Colorado. A key is provided for the separation of the described North American members of the sanguinea group. The most commonly associated slave species is F. vinculans Wheeler, a member of the neogagates group. It is our opinion that F. vinculans is a valid species and not a synonym of F. neogagates, as has been previously supposed

The Epidemiology of Stargardt Disease in the United Kingdom

The authors thank the British Ophthalmological Surveillance Unit (BOSU) for the support received, as well as Mr Barnaby Foot, research coordinator for BOSU, for his help and advice on this project. The authors thank the following ophthalmologists who assisted with data collection for this study: N. Acharya, S. Anwar, V. Bansal, P.N. Bishop, D. Byles, J.S. Chawla, A. Churchill, M. Clarke, B. Dhillon, M. Ekstein, S. George, J. Gillian, J.T. Gillow, D. Gilmour, R. Gray, P.T.S. Gregory, R. Gupta, S.P. Kelly, I.C. Lloyd, A. Lotery, M. McKibbin, R. MacLaren, G. Menon, A.T. Moore, A. Mulvihill, Y. Osoba, R. Pilling, H. Porooshani, A. Raghu Ram, T. Rimmer, I. Russell-Eggitt, M. Sarhan, R. Savides, S. Shafquat, A. Smith, A. Tekriwal, P. Tesha, P. Watts.Peer reviewedPublisher PD

Some statistical and computational challenges, and opportunities in astronomy

The data complexity and volume of astronomical findings have increased in recent decades due to major technological improvements in instrumentation and data collection methods. The contemporary astronomer is flooded with terabytes of raw data that produce enormous multidimensional catalogs of objects (stars, galaxies, quasars, etc.) numbering in the billions, with hundreds of measured numbers for each object. The astronomical community thus faces a key task: to enable efficient and objective scientific exploitation of enormous multifaceted data sets and the complex links between data and astrophysical theory. In recognition of this task, the National Virtual Observatory (NVO) initiative recently emerged to federate numerous large digital sky archives, and to develop tools to explore and understand these vast volumes of data. The effective use of such integrated massive data sets presents a variety of new challenging statistical and algorithmic problems that require methodological advances. An interdisciplinary team of statisticians, astronomers and computer scientists from The Pennsylvania State University, California Institute of Technology and Carnegie Mellon University is developing statistical methodology for the NVO. A brief glimpse into the Virtual Observatory and the work of the Penn State-led team is provided here

Celebre centuria que consagro la ilustre y real villa de Alcoy a honor, y culto del Soberano Sacramento del Altar (que sea por siempre alabado) en el ano 1668

Palau, 43.734Anadense las historias de S. George y los sucesos de los terremoto