Potential role of TBC1D4 in enhanced post-exercise insulin action in human skeletal muscle.

Aims/hypothesis: TBC1 domain family, member 4 (TBC1D4; also known as AS160) is a cellular signalling intermediate to glucose transport regulated by insulin-dependent and -independent mechanisms. Skeletal muscle insulin sensitivity is increased after acute exercise by an unknown mechanism that does not involve modulation at proximal insulin signalling intermediates. We hypothesised that signalling through TBC1D4 is involved in this effect of exercise as it is a common signalling element for insulin and exercise.

Deafness in TRbeta mutants is caused by malformation of the tectorial membrane.

Thyroid hormone receptor beta (TRbeta) dysfunction leads to deafness in humans and mice. Deafness in TRbeta(-/-) mutant mice has been attributed to TRbeta-mediated control of voltage- and Ca(2+)-activated K(+) (BK) channel expression in inner hair cells (IHCs). However, normal hearing in young constitutive BKalpha(-/-) mutants contradicts this hypothesis.

Reduced malonyl-CoA content in recovery from exercise correlates with improved insulin-stimulated glucose uptake in human skeletal muscle.

This study evaluated whether improved insulin-stimulated glucose uptake in recovery from acute exercise coincides with reduced malonyl-CoA (MCoA) content in human muscle. Furthermore, we investigated whether a high-fat diet [65 energy-% (Fat)] would alter the content of MCoA and insulin action compared with a high-carbohydrate diet [65 energy-% (CHO)]. After 4 days of isocaloric diet on two occasions (Fat/CHO), 12 male subjects performed 1 h of one-legged knee extensor exercise (approximately 80% peak workload).

Micro- and nanostructures inside sapphire by fs-laser irradiation and selective etching.

The fabrication of microchannels and self-assembled nanostructures in the volume of sapphire was performed by femtosecond laser irradiation followed by chemical etching with aqueous solution of HF acid. Depending on the focusing conditions self-organized nanostructures or elliptical microchannels are produced. While the dimensions in two directions are on a micro- respectively nanoscale, feature lengths of up to 1 mm are achieved.

B56beta, a regulatory subunit of protein phosphatase 2A, interacts with CALEB/NGC and inhibits CALEB/NGC-mediated dendritic branching.

The development of dendritic arbors is critical in neuronal circuit formation, as dendrites are the primary sites of synaptic input. Morphologically specialized dendritic protrusions called spines represent the main postsynaptic compartment for excitatory neurotransmission. Recently, we demonstrated that chicken acidic leucine-rich epidermal growth factor (EGF) -like domain-containing brain protein/neuroglycan C (CALEB/NGC), a neural member of the EGF family, mediates dendritic tree and spine complexity but that the signaling pathways in the respective processes differ.

First Report of Summer Patch of Kentucky Bluegrass Caused by Magnaporthe poae in Colorado.

The ectotrophic, root-infecting fungus Magnaporthe poae is the cause of summer patch of Kentucky bluegrass (Poa pratensis). The disease is widely distributed in the mid-Atlantic Region of the United States and west to central Nebraska and Kansas (2). It also has been found in certain locations of Washington and California (2) but has not been confirmed in the Rocky Mountain Region.

Persistence of Ca(v)1.3 Ca2+ channels in mature outer hair cells supports outer hair cell afferent signaling.

Outer hair cells (OHCs) are innervated by type II afferent fibers of as yet unknown function. It is still a matter of debate whether OHCs perform exocytosis. If so, they would require presynaptic Ca2+ channels at their basal poles where the type II fibers make contacts.

Exercise improves phosphatidylinositol-3,4,5-trisphosphate responsiveness of atypical protein kinase C and interacts with insulin signalling to peptide elongation in human skeletal muscle.

We investigated if acute endurance-type exercise interacts with insulin-stimulated activation of atypical protein kinase C (aPKC) and insulin signalling to peptide chain elongation in human skeletal muscle. Four hours after acute one-legged exercise, insulin-induced glucose uptake was approximately 80% higher (N = 12, P < 0.05) in previously exercised muscle, measured during a euglycaemic-hyperinsulinaemic clamp (100 microU ml(-1)).

A 5-drug regimen maximizing the dose of cyclophosphamide is effective therapy for adult Burkitt or Burkitt-like lymphomas.

Burkitt lymphoma (BL) and Burkitt-like lymphomas (BLL) are clinically and biologically aggressive B-cell malignancies. Brief-duration, high intensity multidrug regimens with central nervous system (CNS) prophylaxis have proven to be effective, with published series of adult patients documenting complete response (CR) rates of 80 to 100 percent and 2-year event-free survival (EFS) rates ranging from 60 to 90 percent. Based upon the known sensitivity of BL to cyclophosphamide and favorable results reported from the Dana Farber Cancer Center using high-dose CHOP in diffuse aggressive lymphomas, we tested a regimen designed to maximize the administered dose of cyclophosphamide while eliminating other agents commonly used in BL protocols.

The neural EGF family member CALEB/NGC mediates dendritic tree and spine complexity.

The development of dendritic arborizations and spines is essential for neuronal information processing, and abnormal dendritic structures and/or alterations in spine morphology are consistent features of neurons in patients with mental retardation. We identify the neural EGF family member CALEB/NGC as a critical mediator of dendritic tree complexity and spine formation. Overexpression of CALEB/NGC enhances dendritic branching and increases the complexity of dendritic spines and filopodia.

Thyroid hormone deficiency affects postnatal spiking activity and expression of Ca2+ and K+ channels in rodent inner hair cells.

Thyroid hormone (TH) is essential for the development of hearing. Lack of TH in a critical developmental period from embryonic day 17 to postnatal day 12 (P12) in rats and mice leads to morphological and functional deficits in the organ of Corti and the auditory pathway. We investigated the effects of TH on inner hair cells (IHCs) using patch-clamp recordings, capacitance measurements, and immunocytochemistry in hypothyroid rats and athyroid Pax8-/- mice.

Possible CaMKK-dependent regulation of AMPK phosphorylation and glucose uptake at the onset of mild tetanic skeletal muscle contraction.

The Ca(2+)/calmodulin (CaM) competitive inhibitor KN-93 has previously been used to evaluate 5'-AMP-activated protein kinase (AMPK)-independent Ca(2+)-signaling to contraction-stimulated glucose uptake in muscle during intense electrical stimulation ex vivo. With the use of low-intensity tetanic contraction of mouse soleus and extensor digitorum longus (EDL) muscles ex vivo, this study demonstrates that KN-93 can potently inhibit AMPK phosphorylation and activity after 2 min but not 10 min of contraction while strongly inhibiting contraction-stimulated 2-deoxyglucose uptake at both the 2- and 10-min time points. These data suggest inhibition of Ca(2+)/CaM-dependent signaling events upstream of AMPK, the most likely candidate being the novel AMPK kinase CaM-dependent protein kinase kinase (CaMKK).

Medication management assessment for older adults in the community.

Purpose: The purpose of this study was to describe the Medication Management Instrument for Deficiencies in the Elderly (MedMaIDE) and to provide results of reliability and validity testing.

Design And Methods: Participants were 50 older adults, aged 65 and older, who lived in the community, took at least one prescription medication, and were then self-medicating. Nonmedical study staff assessed participants in their homes at baseline and 1 week, and a study pharmacist conducted pill counts at baseline and 30 days.

Impact of second-generation antipsychotics on the use of antiparkinson agents in nursing homes and assisted-living facilities.

Background: It is not known whether the reduced risk of motor adverse effects with second-generation antipsychotics (SGAPs) translates into less use of antiparkinson drugs (APDs).

Objective: This study sought to estimate national rates of concomitant prescribing of APDs and antipsychotic drugs among elderly Medicare beneficiaries without Parkinson's disease (PD) who were residing in institutional settings from 1997 to 2000, a period during which the use of SGAPs increased greatly.

Methods: This was a retrospective, cross-sectional, descriptive analysis using the Medicare Current Beneficiary Survey database.

Optimization of the rolling-circle filter for Raman background subtraction.

A procedure is proposed to optimize a high-pass filter enabling one to subtract the broadband background signals inherent in Raman spectra. A spectral approach is used to analyze the characteristics of the filter and the distortions in the processed spectra. Examples of the processing of real spectra are presented.

Weight loss in the elderly: medications complicating the picture?

An 81-year-old female presented with weight loss as a result of her multiple comorbidities, including a history of congestive heart failure (CHF), coronary artery disease, paroxysmal atrial fibrillation, myocardial infarction, pulmonary embolism, and stroke. She has experienced deep-venous thrombosis in her right leg, severe depression, and dementia and also has suffered a right tibial and fibular fracture. All of these comorbidites and her medication regimen complicated the issue of weight loss.

The impact of drug coverage on COX-2 inhibitor use in Medicare.

Passage of the Medicare drug benefit legislation has renewed attention to the relationship between drug coverage and medication use. This study assesses the impact of drug coverage on COX-2 inhibitor use among elderly people with osteoarthritis, taking into account risk for adverse gastrointestinal events. COX-2 use among aged beneficiaries with the most generous coverage was twice that of those with no third-party coverage.

The EDNAP mitochondrial DNA population database (EMPOP) collaborative exercises: organisation, results and perspectives.

This paper presents an overview of the organisation and the results of the collaborative exercises (CE) of the European DNA Profiling (EDNAP) Group's mitochondrial DNA population database project (EMPOP). The aim of the collaborative exercises was to determine whether uniformity of mtDNA sequencing results could be achieved among different laboratories. These were asked to sequence either the complete mtDNA control region or the two hypervariable regions HVI (16024-16365) and HVII (73-340) from DNA extracts, buccal swabs or bloodstains, proceeding in accordance with the protocol and strategies used in each individual laboratory.

Rett syndrome: clinical manifestations in males with MECP2 mutations.

Rett syndrome is a neurodevelopmental disorder characterized by cognitive and adaptive regression with autistic features, loss of acquired skills, and stereotypic hand movements that almost exclusively affects females. It is an X-linked dominant disorder, with presumed lethality in males. Nonetheless, there are a few descriptions of males suspected of having Rett syndrome.

Membrane topography of cardiac triadin.

Fusion constructs of partial sequences of triadin that contain green fluorescent protein at the N-terminus and glutathione transferase at the C-terminus have been expressed in human embryonic kidney -293 cells. A comparison of the subcellular disposition of a range of triadin fusion peptides indicates localization either to a few large organelles as a default target or to endoplasmic reticulum when amino acids 68-98 are present and structurally intact. Fluorescence from the conjugate of monochlorobimane with glutathione identifies whether the C-terminus has a cytoplasmic or luminal location.

The use of hirudin as universal anticoagulant in haematology, clinical chemistry and blood grouping.

Undesirable interactions between anticoagulants and diagnostic test kit procedures so far have prevented the development of a single uniform blood sampling tube. Contrary to K2-EDTA, heparin and other anticoagulants, hirudin only minimally alters blood cells and dissolved blood constituents, thus qualifying as a universal anticoagulant for diagnostic purposes. Automated complete blood counts, automated analyses of clinical chemistry analytes and immunohaematology were performed from hirudinised and routinely processed blood obtained from healthy volunteers (n=35) and hospitalised patients (n=45).

Measurement of hematological, clinical chemistry, and infection parameters from hirudinized blood collected in universal blood sampling tubes.

Hirudin, the anticoagulatory polypeptide of the leech Hirudo medicinalis, strongly inhibits thrombus formation by specifically interacting with thrombin. For diagnostic purposes, hirudin should be superior to other anticlotting compounds because it only minimally alters the mineral, protein, and cellular blood constituents. To test this hypothesis, hirudinized and routinely processed venous blood from 80 healthy volunteers and patients was subjected to a variety of automated blood tests.

Neonatal screening for galactosemia by quantitative analysis of hexose monophosphates using tandem mass spectrometry: a retrospective study.

Background: Classic galactosemia (OMIM 230400) is an inherited disorder in the metabolism of galactose caused by deficiency of the enzyme galactose 1-phosphate uridyl transferase (EC 2.7.7.

Design of a pilot study to evaluate tandem mass spectrometry for neonatal screening.

In recent years, tandem mass spectrometry has generated great interest as a method for neonatal screening. The basic principle is electronically controlled separation of analytes by their mass-to-charge ratio. The advantage of this detection system is speed, the capability to analyze for many different compounds in a single analysis, and a minimal need for auxilliary assay reagents.