Skin intrinsic fluorescence correlates with autonomic and distal symmetrical polyneuropathy in individuals with type 1 diabetes.

Objective: To determine whether skin intrinsic fluorescence (SIF) was associated with autonomic neuropathy and confirmed distal symmetrical polyneuropathy (CDSP) in 111 individuals with type 1 diabetes (mean age 49 years, mean diabetes duration 40 years).

Research Design And Methods: SIF was measured using the SCOUT DM device. Autonomic neuropathy was defined as an electrocardiographic abnormal heart rate response to deep breathing (expiration-to-inspiration ratio <1.

Reliability and sensitivity of the self-report of physician-diagnosed gout in the campaign against cancer and heart disease and the atherosclerosis risk in the community cohorts.

Objective: gout is often defined by self-report in epidemiologic studies. Yet the validity of self-reported gout is uncertain. We evaluated the reliability and sensitivity of the self-report of physician-diagnosed gout in the Campaign Against Cancer and Heart Disease (CLUE II) and the Atherosclerosis Risk in the Community (ARIC) cohorts.

Testicular pain followed by microscopic hematuria, a renal mass, palpable purpura, polyarthritis, and hematochezia.

We present the instructive case of a man who developed progressively severe testicular pain. He sought the medical care of several physicians, including general medicine, urology, and rheumatology. What began with focal testicular pain evolved over the ensuing weeks to a multisystem disorder affecting at least 3 additional organ systems beyond the genitourinary tract.

Speciation and distribution of vanadium in drinking water iron pipe corrosion by-products.

Vanadium (V) when ingested from drinking water in high concentrations (>15 μg L(-1)) is a potential health risk and is on track to becoming a regulated contaminant. High concentrations of V have been documented in lead corrosion by-products as Pb(5)(V(5+)O(4))(3)Cl (vanadinite) which, in natural deposits is associated with iron oxides/oxyhydroxides, phases common in iron pipe corrosion by-products. The extent of potential reservoirs of V in iron corrosion by-products, its speciation, and mechanism of inclusion however are unknown.

Widespread genomic breaks generated by activation-induced cytidine deaminase are prevented by homologous recombination.

Activation-induced cytidine deaminase (AID) is required for somatic hypermutation and immunoglobulin class switching in activated B cells. Because AID has no known target-site specificity, there have been efforts to identify non-immunoglobulin AID targets. We show here that AID acts promiscuously, generating widespread DNA double-strand breaks (DSBs), genomic instability and cytotoxicity in B cells with less homologous recombination ability.

Addition of adenoviral vector targeting of chemotherapy to the MUC-1/ecdCD40L VPPP vector prime protein boost vaccine prolongs survival of mice carrying growing subcutaneous deposits of Lewis lung cancer cells.

We studied the effect of adding chemotherapy or vector targeted chemotherapy to the administration of an Ad-sig-hMUC-1/ecdCD40L adenoviral vector prime-hMUC-1/ecdCD40L protein boost cancer vaccine (designated hMUC-1/ecdCD40L VPPP vaccine), which were administered to test mice 10 days following subcutaneous (s.c.) inoculation of 500,000 Lewis Lung Carcinoma cells, at a time when the average volume of the s.

Vitamin D treatment for the prevention of falls in older adults: systematic review and meta-analysis.

Objectives: To systematically review and quantitatively synthesize the effect of vitamin D therapy on fall prevention in older adults.

Design: Systematic review and meta-analysis.

Setting: MEDLINE, CINAHL, Web of Science, EMBASE, Cochrane Library, LILACS, bibliographies of selected articles, and previous systematic reviews through February 2009 were searched for eligible studies.

Sex-specific regulation of body size and bone slenderness by the acid labile subunit.

Insulin-like growth factor 1 (IGF-1) is a crucial mediator of body size and bone mass during growth and development. In serum, IGF-1 is stabilized by several IGF-1-binding proteins (IGFBPs) and the acid labile subunit (ALS). Previous research using ALS knockout (ALSKO) mice indicated a growth retardation phenotype, and clinical reports of humans have indicated short stature and low bone mineral density (BMD) in patients with ALS deficiency.

Annealing a magnetic cactus into phyllotaxis.

The appearance of mathematical regularities in the disposition of leaves on a stem, scales on a pine-cone, and spines on a cactus has puzzled scholars for millennia; similar so-called phyllotactic patterns are seen in self-organized growth, polypeptides, convection, magnetic flux lattices and ion beams. Levitov showed that a cylindrical lattice of repulsive particles can reproduce phyllotaxis under the (unproved) assumption that minimum of energy would be achieved by two-dimensional Bravais lattices. Here we provide experimental and numerical evidence that the Phyllotactic lattice is actually a ground state.

Skin fluorescence correlates strongly with coronary artery calcification severity in type 1 diabetes.

Background: Coronary artery calcification (CAC) is more severe and occurs at an earlier age in type 1 diabetes. Risk factors for this subclinical marker of atherosclerotic burden, like coronary artery disease (CAD) itself, are not fully identified. One postulated mechanism for the increased CAC observed in type 1 diabetes is the accumulation of advanced glycation end products (AGEs).

Secondary Sjogren's syndrome in systemic lupus erythematosus defines a distinct disease subset.

Objective: Sjögren's syndrome (SS) may occur in patients with systemic lupus erythematosus (SLE). We sought to determine whether the presence of SS in a large cohort of patients with SLE defines a subset with distinctive sociodemographic, clinical, and laboratory features.

Methods: The Johns Hopkins Lupus Cohort was divided into 2 groups, based on the presence or absence of SS, defined by the presence of an objective measure of sicca or an abnormal minor salivary gland biopsy in a patient with sicca symptoms.

Making a model meaningful to coral reef managers in a developing nation: a case study of overfishing and rock anchoring in Indonesia.

Most of the world's coral reefs line the coasts of developing nations, where impacts from intense and destructive fishing practices form critical conservation issues for managers. Overfishing of herbivorous fishes can cause phase shifts to macroalgal dominance, and fishers' use of rocks as anchors lowers coral cover, giving further competitive advantage to macroalgae. Overfishing and anchoring have been studied extensively, but the role of their interaction in lowering coral reef resilience has not been quantified formally.

Use of adenoviral vectors to target chemotherapy to tumor vascular endothelial cells suppresses growth of breast cancer and melanoma.

To target chemotherapy to tumor vascular endothelial cells (TVECs), we created the AdTie2RprCDFib(knob-RGD+) vector by inserting into an AdEasy adenoviral vector (Ad) backbone: (i) the cytosine deaminase (CD) gene driven by the Tie2 receptor promoter (Tie2Rpr) into the E1 region of Ad; (ii) mutations that reduce binding of the fiber knob to the Coxsackie adenovirus receptor (CAR); and (iii) the RGD peptide into the H1 loop of fiber for binding to the alpha(V)beta(3) integrin receptors on TVECs. To reduce uptake of the AdTie2RprCDFib(knob-RGD+) by reticuloendothelial (RE) and liver cells, we intravenously (i.v.

Noninvasive optical screening for diabetes.

Background: Advanced glycation end products (AGEs) are implicated in the complications of diabetes. Advanced glycation end products also accumulate in the skin and are sensitive biomarkers for the risk of developing diabetes and related complications. Some AGEs fluoresce and can be measured noninvasively by optical spectroscopy.

Oxidant conditioning protects cartilage from mechanically induced damage.

Articular cartilage degeneration in osteoarthritis has been linked to abnormal mechanical stresses that are known to cause chondrocyte apoptosis and metabolic derangement in in vitro models. Evidence implicating oxidative damage as the immediate cause of these harmful effects suggests that the antioxidant defenses of chondrocytes might influence their tolerance for mechanical injury. Based on evidence that antioxidant defenses in many cell types are stimulated by moderate oxidant exposure, we hypothesized that oxidant preconditioning would reduce acute chondrocyte death and proteoglycan depletion in cartilage explants after exposure to abnormal mechanical stresses.

Gp93, the Drosophila GRP94 ortholog, is required for gut epithelial homeostasis and nutrient assimilation-coupled growth control.

GRP94, the endoplasmic reticulum Hsp90, is a metazoan-restricted chaperone essential for early development in mammals, yet dispensable for mammalian cell viability. This dichotomy suggests that GRP94 is required for the functional expression of secretory and/or membrane proteins that enable the integration of cells into tissues. To explore this hypothesis, we have identified the Drosophila ortholog of GRP94, Gp93, and report that Gp93 is an essential gene in Drosophila.

A novel spontaneous mutation of Irs1 in mice results in hyperinsulinemia, reduced growth, low bone mass and impaired adipogenesis.

A spontaneous mouse mutant, designated 'small' (sml), was recognized by reduced body size suggesting a defect in the IGF1/GH axis. The mutation was mapped to the chromosome 1 region containing Irs1, a viable candidate gene whose sequence revealed a single nucleotide deletion resulting in a premature stop codon. Despite normal mRNA levels in mutant and control littermate livers, western blot analysis revealed no detectable protein in mutant liver lysates.

Surface plasmon resonance for high-throughput ligand screening of membrane-bound proteins.

Technologies based on surface plasmon resonance (SPR) have allowed rapid, label-free characterization of protein-protein and protein-small molecule interactions. SPR has become the gold standard in industrial and academic settings, in which the interaction between a pair of soluble binding partners is characterized in detail or a library of molecules is screened for binding against a single soluble protein. In spite of these successes, SPR is only beginning to be adapted to the needs of membrane-bound proteins which are difficult to study in situ but represent promising targets for drug and biomarker development.

Characterization of a key neutralizing epitope on pertussis toxin recognized by monoclonal antibody 1B7.

Despite more than five decades of research and vaccination, infection by Bordetella pertussis remains a serious disease with no specific treatments or validated correlates of protective immunity. Of the numerous monoclonal antibodies binding pertussis toxin (PTx) that have been produced and characterized, murine IgG2a monoclonal antibody 1B7 is uniquely neutralizing in all in vitro assays and in vivo murine models of infection. 1B7 binds an epitope on the enzymatically active S1 subunit of PTx (PTx-S1) with some linear elements, but previous work with S1 scanning peptides, phage-displayed peptide libraries, and S1 truncation/deletion variants was unable to more precisely define the epitope.

Efficient cross-priming of antiviral CD8+ T cells by antigen donor cells is GRP94 independent.

Cross-priming, the activation of naive CD8+ T cells by dendritic cells presenting Ags synthesized by other cells, is believed to play an important role in the generation of antiviral and antitumor responses. The molecular mechanism(s) underlying cross-priming remain poorly defined and highly controversial. GRP94 (gp96), an abundant endoplasmic reticulum chaperone with innate immune-activating capacity, has been widely reported to play a major role in cross-priming.

Vector prime protein boost vaccination in the setting of myeloablative-induced lymphopenia suppresses growth of leukemia and solid tumors.

We have developed a vaccine, which is designed to induce tumor-associated antigen (TAA)-specific T cells and antibodies in the setting of profound lymphopenia induced by myeloablative therapy and T-cell-depleted bone marrow transplantation. Test mice were injected subcutaneously (sc) with the 32DP210Bcr-Abl cell line, which is positive for the p210Bcr-Abl protein (Group 1). In Group 2, 7 days after injection of the 32DP210Bcr-Abl positive cell line, the mice received 900 cGy total body irradiation (TBI) followed in 1 h by the intravenous infusion of 10 million T-cell-depleted syngeneic bone marrow cells (TCDBMT) (Group 2).

Static and dynamical phyllotaxis in a magnetic cactus.

While the statics of many simple physical systems reproduce the striking number-theoretical patterns found in the phyllotaxis of living beings, their dynamics reveal unusual excitations: multiple classical rotons and a large family of interconverting topological solitons. As we introduce those, we also demonstrate experimentally for the first time Levitov's celebrated model for phyllotaxis. Applications at different scales and in different areas of physics are proposed and discussed.

A strategic framework for responding to coral bleaching events in a changing climate.

The frequency and severity of mass coral bleaching events are predicted to increase as sea temperatures continue to warm under a global regime of rising ocean temperatures. Bleaching events can be disastrous for coral reef ecosystems and, given the number of other stressors to reefs that result from human activities, there is widespread concern about their future. This article provides a strategic framework from the Great Barrier Reef to prepare for and respond to mass bleaching events.