Minimizing Black Bear Problems at New York State Public Campgrounds

The black bear\u27s omnivorous foraging behavior has been both beneficial and detrimental to its coexistence with modern humans. The ability to feed on a variety of animal and vegetable matter, alive or dead, has been advantageous to the black bear\u27s survival as its range has diminished. Although black bears have an innate aversion to people, many have learned to tolerate humans to acquire easily obtainable high energy concentrated artificial foods. Human carelessness in the storage and disposal of foods within or near bear habit at has resulted in conflicts between campers and wild bears. Forest Preserve public campgrounds create a unique situation by concentrating people and food in remote forested environments frequented by black bears. The failure to effectively deal with this situation resulted in chronic bear-human problems at approximately one-third of New York\u27s Forest Preserve public campgrounds. In addition to loss of food, some people suffered property damage and a few sustained physical injuries. Alleviation of bear nuisance activity typically included attempts to capture and relocate bothersome bears. The high cost and ultimate failure of this approach led to the destruction of many bears while little long-term improvement was achieved

The drag on a microcantilever oscillating near a wall

Motivated by devices such as the atomic force microscope, we compute the drag experienced by a cylindrical body of circular or rectangular cross-section oscillating at small amplitude near a plane wall. The body lies parallel to the wall and oscillates normally to it; the body is assumed to be long enough for the dominant flow to be two-dimensional. The flow is parameterized by a frequency parameter γ² (a Strouhal number) and the wall–body separation Δ (scaled on body radius). Numerical solutions of the unsteady Stokes equations obtained using finite-difference computations in bipolar coordinates (for circular cross-sections) and boundary-element computations (for rectangular cross-sections) are used to determine the drag on the body. Numerical results are validated and extended using asymptotic predictions (for circular cylinders) obtained at all extremes of (γ, Δ)-parameter space. Regions in parameter space for which the wall has a significant effect on drag are identified.R. J. Clarke, S. M. Cox, P. M. Williams and O. E. Jense

CHANGES IN BALANCE AND JOINT POSITION SENSE DURING A 12-DAY HIGH ALTITUDE TREK

The purpose of this study was to investigate changes in postural control and knee joint position sense (KJPS) during a trek to high altitude. Postural control during standing balance and KJPS were measured in 12 participants at sea-level, 3619m, 4600m and 5140m. Total (p = 0.003, d=1.9) and anterior-posterior sway velocity (p= 0.001, d=1.9) during standing balance with eyes open velocity was significantly greater at altitudes of 3619m and 5140m when compared with sea level. Despite a gradual ascent profile, exposure to 3619 m was associated with impairments in postural control. Importantly, these impairments did not worsen at higher altitudes. The present findings should be considered during future trekking expeditions when considering specific strategies to manage impairments in postural control that occur with increasing altitude

A systematic review of biomarkers for disease progression in Parkinson's disease

Peer reviewedPublisher PD

Human candidate gene polymorphisms and risk of severe malaria in children in Kilifi, Kenya: a case-control association study

Background: Human genetic factors are important determinants of malaria risk. We investigated associations between multiple candidate polymorphisms—many related to the structure or function of red blood cells—and risk for severe Plasmodium falciparum malaria and its specific phenotypes, including cerebral malaria, severe malaria anaemia, and respiratory distress. Methods: We did a case-control study in Kilifi County, Kenya. We recruited as cases children presenting with severe malaria to the high-dependency ward of Kilifi County Hospital. We included as controls infants born in the local community between Aug 1, 2006, and Sept 30, 2010, who were part of a genetics study. We tested for associations between a range of candidate malaria-protective genes and risk for severe malaria and its specific phenotypes. We used a permutation approach to account for multiple comparisons between polymorphisms and severe malaria. We judged p values less than 0·005 significant for the primary analysis of the association between candidate genes and severe malaria. Findings: Between June 11, 1995, and June 12, 2008, 2244 children with severe malaria were recruited to the study, and 3949 infants were included as controls. Overall, 263 (12%) of 2244 children with severe malaria died in hospital, including 196 (16%) of 1233 with cerebral malaria. We investigated 121 polymorphisms in 70 candidate severe malaria-associated genes. We found significant associations between risk for severe malaria overall and polymorphisms in 15 genes or locations, of which most were related to red blood cells: ABO, ATP2B4, ARL14, CD40LG, FREM3, INPP4B, G6PD, HBA (both HBA1 and HBA2), HBB, IL10, LPHN2 (also known as ADGRL2), LOC727982, RPS6KL1, CAND1, and GNAS. Combined, these genetic associations accounted for 5·2% of the variance in risk for developing severe malaria among individuals in the general population. We confirmed established associations between severe malaria and sickle-cell trait (odds ratio [OR] 0·15, 95% CI 0·11–0·20; p=2·61 × 10−58), blood group O (0·74, 0·66–0·82; p=6·26 × 10−8), and –α3·7-thalassaemia (0·83, 0·76–0·90; p=2·06 × 10−6). We also found strong associations between overall risk of severe malaria and polymorphisms in both ATP2B4 (OR 0·76, 95% CI 0·63–0·92; p=0·001) and FREM3 (0·64, 0·53–0·79; p=3·18 × 10−14). The association with FREM3 could be accounted for by linkage disequilibrium with a complex structural mutation within the glycophorin gene region (comprising GYPA, GYPB, and GYPE) that encodes for the rare Dantu blood group antigen. Heterozygosity for Dantu was associated with risk for severe malaria (OR 0·57, 95% CI 0·49–0·68; p=3·22 × 10−11), as was homozygosity (0·26, 0·11–0·62; p=0·002). Interpretation: Both ATP2B4 and the Dantu blood group antigen are associated with the structure and function of red blood cells. ATP2B4 codes for plasma membrane calcium-transporting ATPase 4 (the major calcium pump on red blood cells) and the glycophorins are ligands for parasites to invade red blood cells. Future work should aim at uncovering the mechanisms by which these polymorphisms can result in severe malaria protection and investigate the implications of these associations for wider health. Funding: Wellcome Trust, UK Medical Research Council, European Union, and Foundation for the National Institutes of Health as part of the Bill & Melinda Gates Grand Challenges in Global Health Initiative

Nitrate enhances skeletal muscle fatty acid oxidation via a nitric oxide-cGMP-PPAR-mediated mechanism.

BACKGROUND: Insulin sensitivity in skeletal muscle is associated with metabolic flexibility, including a high capacity to increase fatty acid (FA) oxidation in response to increased lipid supply. Lipid overload, however, can result in incomplete FA oxidation and accumulation of potentially harmful intermediates where mitochondrial tricarboxylic acid cycle capacity cannot keep pace with rates of β-oxidation. Enhancement of muscle FA oxidation in combination with mitochondrial biogenesis is therefore emerging as a strategy to treat metabolic disease. Dietary inorganic nitrate was recently shown to reverse aspects of the metabolic syndrome in rodents by as yet incompletely defined mechanisms. RESULTS: Herein, we report that nitrate enhances skeletal muscle FA oxidation in rodents in a dose-dependent manner. We show that nitrate induces FA oxidation through a soluble guanylate cyclase (sGC)/cGMP-mediated PPARβ/δ- and PPARα-dependent mechanism. Enhanced PPARβ/δ and PPARα expression and DNA binding induces expression of FA oxidation enzymes, increasing muscle carnitine and lowering tissue malonyl-CoA concentrations, thereby supporting intra-mitochondrial pathways of FA oxidation and enhancing mitochondrial respiration. At higher doses, nitrate induces mitochondrial biogenesis, further increasing FA oxidation and lowering long-chain FA concentrations. Meanwhile, nitrate did not affect mitochondrial FA oxidation in PPARα(-/-) mice. In C2C12 myotubes, nitrate increased expression of the PPARα targets Cpt1b, Acadl, Hadh and Ucp3, and enhanced oxidative phosphorylation rates with palmitoyl-carnitine; however, these changes in gene expression and respiration were prevented by inhibition of either sGC or protein kinase G. Elevation of cGMP, via the inhibition of phosphodiesterase 5 by sildenafil, also increased expression of Cpt1b, Acadl and Ucp3, as well as CPT1B protein levels, and further enhanced the effect of nitrate supplementation. CONCLUSIONS: Nitrate may therefore be effective in the treatment of metabolic disease by inducing FA oxidation in muscle.This work was kindly supported by a British Heart Foundation studentship to TA (FS/09/050). AJMu thanks the Research Councils UK for supporting his academic fellowship. LDR is supported by the Medical Research Council-Human Nutrition Research Elsie Widdowson Fellowship. AJMo thanks the Natural Sciences and Engineering Research Council for supporting her postdoctoral fellowship. MF acknowledges support from the Medical Research Council (G1001536). JLG thanks the Medical Research Council (MC_UP_A090_1006), the Biotechnology and Biological Sciences Research Council (BB/H013539/2) and British Heart Foundation for supporting work in his laboratory

Breast cancer prognosis predicted by nuclear receptor-coregulator networks

Although molecular signatures based on transcript expression in breast cancer samples have provided new insights into breast cancer classification and prognosis, there are acknowledged limitations in current signatures. To provide rational, pathway-based signatures of disrupted physiology in cancer tissues that may be relevant to prognosis, this study has directly quantitated changed gene expression, between normal breast and cancer tissue, as a basis for signature development. The nuclear receptor (NR) family of transcription factors, and their coregulators, are fundamental regulators of every aspect of metazoan life, and were rigorously quantified in normal breast tissues and ERα positive and ERα negative breast cancers. Coregulator expression was highly correlated with that of selected NR in normal breast, particularly from postmenopausal women. These associations were markedly decreased in breast cancer, and the expression of the majority of coregulators was down-regulated in cancer tissues compared with normal. While in cancer the loss of NR-coregulator associations observed in normal breast was common, a small number of NR (Rev-ERBβ, GR, NOR1, LRH-1 and PGR) acquired new associations with coregulators in cancer tissues. Elevated expression of these NR in cancers was associated with poorer outcome in large clinical cohorts, as well as suggesting the activation of ERα -related, but ERα-independent, pathways in ERα negative cancers. In addition, the combined expression of small numbers of NR and coregulators in breast cancer was identified as a signature predicting outcome in ERα negative breast cancer patients, not linked to proliferation and with predictive power superior to existing signatures containing many more genes. These findings highlight the power of predictive signatures derived from the quantitative determination of altered gene expression between normal breast and breast cancers. Taken together, the findings of this study identify networks of NR-coregulator associations active in normal breast but disrupted in breast cancer, and moreover provide evidence that signatures based on NR networks disrupted in cancer can provide important prognostic information in breast cancer patients