Mitochondrial damage and ageing using skin as a model organ.

Ageing describes the progressive functional decline of an organism over time, leading to an increase in susceptibility to age-related diseases and eventually to death, and it is a phenomenon observed across a wide range of organisms. Despite a vast repertoire of ageing studies performed over the past century, the exact causes of ageing remain unknown. For over 50 years it has been speculated that mitochondria play a key role in the ageing process, due mainly to correlative data showing an increase in mitochondrial dysfunction, mitochondrial DNA (mtDNA) damage, and reactive oxygen species (ROS) with age.

Giant Chondroid Syringoma of the Lower Eyelid.

Chondroid syringoma is a benign mixed tumor characterized by sweat gland elements in a cartilaginous stroma. This rare tumor accounts for only 0.01% of all primary skin tumors and occurs only rarely in the periorbital region.

Downscaling land-use data to provide global 30″ estimates of five land-use classes.

Land-use change is one of the biggest threats to biodiversity globally. The effects of land use on biodiversity manifest primarily at local scales which are not captured by the coarse spatial grain of current global land-use mapping. Assessments of land-use impacts on biodiversity across large spatial extents require data at a similar spatial grain to the ecological processes they are assessing.

Characterization of the Probiotic Yeast Saccharomyces boulardii in the Healthy Mucosal Immune System.

The probiotic yeast Saccharomyces boulardii has been shown to ameliorate disease severity in the context of many infectious and inflammatory conditions. However, use of S. boulardii as a prophylactic agent or therapeutic delivery vector would require delivery of S.

Constrained inference of protein interaction networks for invadopodium formation in cancer.

Integrating prior molecular network knowledge into interpretation of new experimental data is routine practice in biology research. However, a dilemma for deciphering interactome using Bayes' rule is the demotion of novel interactions with low prior probabilities. Here the authors present constrained generalised logical network (CGLN) inference to predict novel interactions in dynamic networks, respecting previously known interactions and observed temporal coherence.

A Genomic Signature of Influenza Infection Shows Potential for Presymptomatic Detection, Guiding Early Therapy, and Monitoring Clinical Responses.

Early, presymptomatic intervention with oseltamivir (corresponding to the onset of a published host-based genomic signature of influenza infection) resulted in decreased overall influenza symptoms (aggregate symptom scores of 23.5 vs 46.3), more rapid resolution of clinical disease (20 hours earlier), reduced viral shedding (total median tissue culture infectious dose [TCID50] 7.

Environmentally relevant concentrations of arsenite and monomethylarsonous acid inhibit IL-7/STAT5 cytokine signaling pathways in mouse CD3+CD4-CD8- double negative thymus cells.

Environmental arsenic exposure is a public health issue. Immunotoxicity induced by arsenic has been reported in humans and animal models. The purpose of this study was to evaluate mechanisms of As(+3) and MMA(+3) toxicity in mouse thymus cells.

Transformation of Probiotic Yeast and Their Recovery from Gastrointestinal Immune Tissues Following Oral Gavage in Mice.

Development of recombinant oral therapy would allow for more direct targeting of the mucosal immune system and improve the ability to combat gastrointestinal disorders. Adapting probiotic yeast in particular for this approach carries several advantages. These strains have not only the potential to synthesize a wide variety of complex heterologous proteins but are also capable of surviving and protecting those proteins during transit through the intestine.

Refeeding Low Weight Hospitalized Adolescents With Anorexia Nervosa: A Multicenter Randomized Controlled Trial.

Background: Refeeding patients with anorexia nervosa (AN) is associated with high morbidity and mortality. A lack of evidence from interventional studies has hindered refeeding practice and led to worldwide disparities in management recommendations. In the first randomized controlled trial in this area, we tested the hypothesis that refeeding adolescents with AN with a higher energy intake than what many guidelines recommend improved anthropometric outcomes without adversely affecting cardiac and biochemical markers associated with refeeding.

A Supervised Learning Process to Validate Online Disease Reports for Use in Predictive Models.

Pathogen distribution models that predict spatial variation in disease occurrence require data from a large number of geographic locations to generate disease risk maps. Traditionally, this process has used data from public health reporting systems; however, using online reports of new infections could speed up the process dramatically. Data from both public health systems and online sources must be validated before they can be used, but no mechanisms exist to validate data from online media reports.

Role of the Slug Transcription Factor in Chemically-Induced Skin Cancer.

The Slug transcription factor plays an important role in ultraviolet radiation (UVR)-induced skin carcinogenesis, particularly in the epithelial-mesenchymal transition (EMT) occurring during tumor progression. In the present studies, we investigated the role of Slug in two-stage chemical skin carcinogenesis. Slug and the related transcription factor Snail were expressed at high levels in skin tumors induced by 7,12-dimethylbenz[α]anthracene application followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment.

Host gene expression classifiers diagnose acute respiratory illness etiology.

Acute respiratory infections caused by bacterial or viral pathogens are among the most common reasons for seeking medical care. Despite improvements in pathogen-based diagnostics, most patients receive inappropriate antibiotics. Host response biomarkers offer an alternative diagnostic approach to direct antimicrobial use.

Adaptation to AI Therapy in Breast Cancer Can Induce Dynamic Alterations in ER Activity Resulting in Estrogen-Independent Metastatic Tumors.

Purpose: Acquired resistance to aromatase inhibitor (AI) therapy is a major clinical problem in the treatment of breast cancer. The detailed mechanisms of how tumor cells develop this resistance remain unclear. Here, the adapted function of estrogen receptor (ER) to an estrogen-depleted environment following AI treatment is reported.

Temporal and latitudinal trends of p,p'-DDE in eggs and carcasses of North American birds from 1980 to 2005.

The use of 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane (DDT) in agriculture in the United States and Canada was prohibited in the early 1970s; however, it continued to be used restrictively in Mexico until 2000. Forty years later, 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE), continues to be detected in eggs and bird carcasses in North America. The use of DDE has been associated with reproductive failure of several avian species, primarily through eggshell thinning.

Energetic electrons driven in the polarization direction of an intense laser beam incident normal to a solid target.

Experiments were performed at the LLNL Titan laser to measure the propagation direction of the energetic electrons that were generated during the interaction of the polarized laser beam with solid targets in the case of normal incidence. The energetic electrons propagated through vacuum to spectator metal wires in the polarization direction and in the perpendicular direction, and the K shell spectra from the different wire materials were recorded as functions of the distance from the laser focal spot. It was found that the fluence of the energetic electrons driven into the spectator wires in the polarization direction compared to the perpendicular direction was larger and increased with the distance from the focal spot.

Potential Cost-effectiveness of Early Identification of Hospital-acquired Infection in Critically Ill Patients.

Rationale: Limitations in methods for the rapid diagnosis of hospital-acquired infections often delay initiation of effective antimicrobial therapy. New diagnostic approaches offer potential clinical and cost-related improvements in the management of these infections.

Objectives: We developed a decision modeling framework to assess the potential cost-effectiveness of a rapid biomarker assay to identify hospital-acquired infection in high-risk patients earlier than standard diagnostic testing.

Inhibition of poly(ADP-ribose)polymerase-1 and DNA repair by uranium.

Uranium has radiological and non-radiological effects within biological systems and there is increasing evidence for genotoxic and carcinogenic properties attributable to uranium through its heavy metal properties. In this study, we report that low concentrations of uranium (as uranyl acetate; <10 μM) is not cytotoxic to human embryonic kidney cells or normal human keratinocytes; however, uranium exacerbates DNA damage and cytotoxicity induced by hydrogen peroxide, suggesting that uranium may inhibit DNA repair processes. Concentrations of uranyl acetate in the low micromolar range inhibited the zinc finger DNA repair protein poly(ADP-ribose) polymerase (PARP)-1 and caused zinc loss from PARP-1 protein.

Probable primary polydipsia in a domestic shorthair cat.

Case Summary: A 10-month-old neutered male domestic shorthair cat presented with a 4 month history of polyuria and polydipsia. After a thorough diagnostic work-up the only abnormal findings were hyposthenuria and an elevated random plasma osmolality level. Trial therapy with the oral and ophthalmic forms of desmopressin failed to concentrate urine.

Inselect: Automating the Digitization of Natural History Collections.

The world's natural history collections constitute an enormous evidence base for scientific research on the natural world. To facilitate these studies and improve access to collections, many organisations are embarking on major programmes of digitization. This requires automated approaches to mass-digitization that support rapid imaging of specimens and associated data capture, in order to process the tens of millions of specimens common to most natural history collections.

Novel Activities of Select NSAID R-Enantiomers against Rac1 and Cdc42 GTPases.

Rho family GTPases (including Rac, Rho and Cdc42) collectively control cell proliferation, adhesion and migration and are of interest as functional therapeutic targets in numerous epithelial cancers. Based on high throughput screening of the Prestwick Chemical Library® and cheminformatics we identified the R-enantiomers of two approved drugs (naproxen and ketorolac) as inhibitors of Rac1 and Cdc42. The corresponding S-enantiomers are considered the active component in racemic drug formulations, acting as non-steroidal anti-inflammatory drugs (NSAIDs) with selective activity against cyclooxygenases.

A modular and compact portable mini-endstation for high-precision, high-speed fixed target serial crystallography at FEL and synchrotron sources.

The design and implementation of a compact and portable sample alignment system suitable for use at both synchrotron and free-electron laser (FEL) sources and its performance are described. The system provides the ability to quickly and reliably deliver large numbers of samples using the minimum amount of sample possible, through positioning of fixed target arrays into the X-ray beam. The combination of high-precision stages, high-quality sample viewing, a fast controller and a software layer overcome many of the challenges associated with sample alignment.

Monomethylarsonous acid (MMA+3) Inhibits IL-7 Signaling in Mouse Pre-B Cells.

Our previously published data show that As(+3) in vivo and in vitro, at very low concentrations, inhibits lymphoid, but not myeloid stem cell development in mouse bone marrow. We also showed that the As(+3) metabolite, monomethylarsonous acid (MMA(+3)), was responsible for the observed pre-B cell toxicity caused by As(+3). Interleukin-7 (IL-7) is the primary growth factor responsible for pre-lymphoid development in mouse and human bone marrow, and Signal Transducer and Activator of Transcription 5 (STAT5) is a transcriptional factor in the IL-7 signaling pathway.

Differential evolution of peripheral cytokine levels in symptomatic and asymptomatic responses to experimental influenza virus challenge.

Exposure to influenza virus triggers a complex cascade of events in the human host. In order to understand more clearly the evolution of this intricate response over time, human volunteers were inoculated with influenza A/Wisconsin/67/2005 (H3N2), and then had serial peripheral blood samples drawn and tested for the presence of 25 major human cytokines. Nine of 17 (53%) inoculated subjects developed symptomatic influenza infection.

Environmentally Relevant Concentrations of Arsenite Induce Dose-Dependent Differential Genotoxicity Through Poly(ADP-Ribose) Polymerase Inhibition and Oxidative Stress in Mouse Thymus Cells.

Inhibition of DNA repair and oxidative stress are 2 common mechanisms associated with arsenic-induced genotoxicity. The purpose of this study was to examine mechanisms of genotoxicity induced by environmentally relevant doses of arsenite (As(+3)) in mouse thymus cells. An increase in DNA damage and a decrease in poly(ADP-ribose) polymerase (PARP) activity were seen in vitro following exposure to 50 nM As(+3) in primary mouse thymus cells and a murine thymus pre-T cell line, D1.

Expression of the Receptor Tyrosine Kinase EphB2 on Dendritic Cells Is Modulated by Toll-Like Receptor Ligation but Is Not Required for T Cell Activation.

The Eph receptor tyrosine kinases interact with their ephrin ligands on adjacent cells to facilitate contact-dependent cell communication. Ephrin B ligands are expressed on T cells and have been suggested to act as co-stimulatory molecules during T cell activation. There are no detailed reports of the expression and modulation of EphB receptors on dendritic cells, the main antigen presenting cells that interact with T cells.