The AMPK β2 subunit is required for energy homeostasis during metabolic stress.

AMP activated protein kinase (AMPK) plays a key role in the regulatory network responsible for maintaining systemic energy homeostasis during exercise or nutrient deprivation. To understand the function of the regulatory β2 subunit of AMPK in systemic energy metabolism, we characterized β2 subunit-deficient mice. Using these mutant mice, we demonstrated that the β2 subunit plays an important role in regulating glucose, glycogen, and lipid metabolism during metabolic stress.

Autonomic symptoms are common and are associated with overall symptom burden and disease activity in primary Sjogren's syndrome.

Objectives: To determine the prevalence of autonomic dysfunction (dysautonomia) among patients with primary Sjögren's syndrome (PSS) and the relationships between dysautonomia and other clinical features of PSS.

Methods: Multicentre, prospective, cross-sectional study of a UK cohort of 317 patients with clinically well-characterised PSS. Symptoms of autonomic dysfunction were assessed using a validated instrument, the Composite Autonomic Symptom Scale (COMPASS).

Computationally efficient measure of topological redundancy of biological and social networks.

It is well known that biological and social interaction networks have a varying degree of redundancy, though a consensus of the precise cause of this is so far lacking. In this paper, we introduce a topological redundancy measure for labeled directed networks that is formal, computationally efficient, and applicable to a variety of directed networks such as cellular signaling, and metabolic and social interaction networks. We demonstrate the computational efficiency of our measure by computing its value and statistical significance on a number of biological and social networks with up to several thousands of nodes and edges.

Spectral bidirectional reflectance distribution function measurements on well-defined textured surfaces: direct observation of shadowing, masking, inter-reflection, and transparency effects.

We present results for the bidirectional reflectance distribution function (BRDF) for samples of uniform rectangular and triangular grooves constructed from polydimethylsilicone replicas. The measurements are performed with the detector in the plane of incidence, but with varying groove orientations with respect to that plane. The samples are opaque in some cases and semitransparent in others.

Ischaemic manifestations in giant cell arteritis are associated with area level socio-economic deprivation, but not cardiovascular risk factors.

Objectives: To determine whether ischaemic manifestations of GCA are associated with pre-existing hypertension, atherosclerosis or area-level socio-economic deprivation.

Methods: We conducted an observational study of rheumatologist/ophthalmologist-diagnosed GCA in eight UK centres. The main outcome measure was ischaemic manifestations observed during active GCA: visual loss/blurring, aura, diplopia, jaw/tongue/limb claudication, cerebral/myocardial ischaemia or scalp necrosis.

Distinct roles of overlapping and non-overlapping regions of hub protein interfaces in recognition of multiple partners.

Cellular functions of an organism are maintained by protein-protein interactions. Those proteins that bind multiple partners asynchronously (date hub proteins) are important to make the interaction network coordinated. It is known that many date hub proteins bind different partners at overlapping (OV) interfaces.

Sprengel's deformity of the shoulder: Current perspectives in management.

Sprengel's deformity or congenital elevation of scapula is a complex deformity of the pectoral girdle, and results in symptomatic cosmetic and functional disability. Several studies have attempted to analyze the three-dimensional aspects of this deformity; optimal methodologies of quantification and surgical correction techniques have been debated since the condition was first described. This article presents a concise review of the exact pathoanatomy, clinical presentation, imaging techniques, and surgical procedures described in the management of this condition.

Definition of remission and relapse in polymyalgia rheumatica: data from a literature search compared with a Delphi-based expert consensus.

Objective: To compare current definitions of remission and relapse in polymyalgia rheumatica (PMR) with items resulting from a Delphi-based expert consensus.

Methods: Relevant studies including definitions of PMR remission and relapse were identified by literature search in PubMed. The questionnaire used for the Delphi survey included clinical (n=33), laboratory (n=54) and imaging (n=7) parameters retrieved from a literature search.

Delays in recognition and management of giant cell arteritis: results from a retrospective audit.

Prompt institution of corticosteroids (CS) can prevent devastating neuro-ophthalmic complications (NOC) in patients with giant cell arteritis (GCA). Guidelines on managing GCA place emphasis on early recognition of symptoms and prompt treatment of the disease where there is a high index of clinical suspicion. The aims of this study are to review the clinical findings in patients with GCA, evaluate the baseline practice in diagnosis and treatment and to identify delays in treating patients with NOC.

Current understanding and management of giant cell arteritis and polymyalgia rheumatica.

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are linked conditions that occur in the elderly. GCA is a vasculitis of large- and medium-sized vessels causing critical ischemia. It is a medical emergency owing to the high incidence of neuro-ophthalmic complications.

Concise guidance: diagnosis and management of giant cell arteritis.

Giant cell arteritis (GCA) or temporal arteritis (TA) with polymyalgia rheumatica (PMR) is among the most common reasons for long-term steroid prescription. GCA is a critically ischaemic disease, the most common form of vasculitis and should be treated as a medical emergency. Visual loss occurs in up to a fifth of patients, which may be preventable by prompt recognition and treatment.

Inference of signal transduction networks from double causal evidence.

Here, we present a novel computational method, and related software, to synthesize signal transduction networks from single and double causal evidences. This is a significant and topical problem because there are currently no high-throughput experimental methods for constructing signal transduction networks, and because the understanding of many signaling processes is limited to the knowledge of the signal(s) and of key mediators' positive or negative effects on the whole process. Our software NET-SYNTHESIS is freely downloadable from http://www.

Clinical observations on the significance of raised cardiac troponin-T in patients with myositis of varying etiologies seen in rheumatology practice.

To study the source and clinical relevance of elevated cardiac troponin-T (cTnT) in patients with inflammatory myositis of varying etiology is the objective of this study. Patients with new-onset myositis of varying etiologies and raised serum cTnT and creatine kinase (CK) were identified. Clinical myocardial disease was ruled out on the basis of history, examination, ECG, and 2D-echocardiography.

Discovery of 6-chloro-2-trifluoromethyl-7-aryl-7H-imidazo[1,2-a]imidazol-3-ylmethylamines, a novel class of corticotropin-releasing factor receptor type 1 (CRF1R) antagonists.

A novel series of [6-chloro-2-trifluoromethyl-7-aryl-7H-imidazo[1,2-a]imidazol-3-ylmethyl]-dialkylamines was discovered as potent CRF(1)R antagonists. The optimization of binding affinity in the series by the parallel reaction approach is discussed herein.

Combinatorial reconstruction of half-sibling groups from microsatellite data.

While full-sibling group reconstruction from microsatellite data is a well-studied problem, reconstruction of half-sibling groups is much less studied, theoretically challenging, and computationally demanding. In this paper, we present a formulation of the half-sibling reconstruction problem and prove its APX-hardness. We also present exact solutions for this formulation and develop heuristics.

Design, synthesis and evaluation of constrained tetrahydroimidazopyrimidine derivatives as antagonists of corticotropin-releasing factor type 1 receptor (CRF1R).

Several tetrahydroimidazopyrimidines were prepared using silver assisted cyclization as the key step. The binding affinities of compounds thus prepared were evaluated in vitro toward hCRF(1)R. Initial lead compound 16 (K(i)=32 nM) demonstrated modest putative anxiolytic effects in the mouse canopy test.

Reliability exercise for the polymyalgia rheumatica classification criteria study: the oranjewoud ultrasound substudy.

Objective. A study supported by the EULAR and the ACR being conducted to establish classification criteria for polymyalgia rheumatica (PMR) will include ultrasound examination of the shoulders and hips. Ultrasound (US) depicts glenohumeral joint effusion, biceps tenosynovitis, subdeltoid bursitis, hip joint synovitis, and trochanteric bursitis in PMR.

Blocking platelet/endothelial cell adhesion molecule 1 (PECAM) inhibits disease progression and prevents joint erosion in established collagen antibody-induced arthritis.

Collagen antibody-induced arthritis is a robust murine model of arthritis that histologically recapitulates the inflammatory characteristics of rheumatoid arthritis including pannus formation and destruction of articular cartilage and bone. PECAM is a molecule expressed by both leukocytes and endothelial cells that has been shown to play a major role in the extravasation of leukocytes into sites of inflammation. Genetic deletion of many molecules will blunt the onset and progression of arthritis in murine models, as will administration of various anti-inflammatory therapies given prior to the onset of disease.