Multitaxonomic Diversity Patterns along a Desert Riparian–Upland Gradient

Riparian areas are noted for their high biodiversity, but this has rarely been tested across a wide range of taxonomic groups. We set out to describe species richness, species abundance, and community similarity patterns for 11 taxonomic groups (forbs & grasses, shrubs, trees, solpugids, spiders, scarab beetles, butterflies, lizards, birds, rodents, and mammalian carnivores) individually and for all groups combined along a riparian–upland gradient in semiarid southeastern Arizona, USA. Additionally, we assessed whether biological characteristics could explain variation in diversity along the gradient using five traits (trophic level, body size, life span, thermoregulatory mechanism, and taxonomic affiliation). At the level of individual groups diversity patterns varied along the gradient, with some having greater richness and/or abundance in riparian zones whereas others were more diverse and/or abundant in upland zones. Across all taxa combined, riparian zones contained significantly more species than the uplands. Community similarity between riparian and upland zones was low, and beta diversity was significantly greater than expected for most taxonomic groups, though biological traits explained little variance in diversity along the gradient. These results indicate heterogeneity amongst taxa in how they respond to the factors that structure ecological communities in riparian landscapes. Nevertheless, across taxonomic groups the overall pattern is one of greater species richness and abundance in riparian zones, coupled with a distinct suite of species

Canagliflozin inhibits interleukin-1β-stimulated cytokine and chemokine secretion in vascular endothelial cells by AMP-activated protein kinase-dependent and -independent mechanisms

YesRecent clinical trials of the hypoglycaemic sodium-glucose co-transporter-2 (SGLT2) inhibitors, which inhibit renal glucose reabsorption, have reported beneficial cardiovascular outcomes. Whether SGLT2 inhibitors directly affect cardiovascular tissues, however, remains unclear. We have previously reported that the SGLT2 inhibitor canagliflozin activates AMP-activated protein kinase (AMPK) in immortalised cell lines and murine hepatocytes. As AMPK has anti-inflammatory actions in vascular cells, we examined whether SGLT2 inhibitors attenuated inflammatory signalling in cultured human endothelial cells. Incubation with clinically-relevant concentrations of canagliflozin, but not empagliflozin or dapagliflozin activated AMPK and inhibited IL-1β-stimulated adhesion of pro-monocytic U937 cells and secretion of IL-6 and monocyte chemoattractant protein-1 (MCP-1). Inhibition of MCP-1 secretion was attenuated by expression of dominant-negative AMPK and was mimicked by the direct AMPK activator, A769662. Stimulation of cells with either canagliflozin or A769662 had no effect on IL-1β-stimulated cell surface levels of adhesion molecules or nuclear factor-κB signalling. Despite these identical effects of canagliflozin and A769662, IL-1β-stimulated IL-6/MCP-1 mRNA was inhibited by canagliflozin, but not A769662, whereas IL-1β-stimulated c-jun N-terminal kinase phosphorylation was inhibited by A769662, but not canagliflozin. These data indicate that clinically-relevant canagliflozin concentrations directly inhibit endothelial pro-inflammatory chemokine/cytokine secretion by AMPK-dependent and -independent mechanisms without affecting early IL-1β signalling.Project Grant (PG/13/82/30483 to IPS and TMP) and PhD studentships (FS/16/55/32731 and FS/14/61/31284 to DB and AS) from the British Heart Foundation and an equipment grant (BDA11/0004309 to IPS and TMP) from Diabetes UK. OJK was supported by a Scholarship from the Iraqi Ministry of Higher Education and Scientific Research. TAA was supported by a Libyan Ministry of Education PhD Studentship

The effect of forearm posture on wrist flexion in computer workers with chronic upper extremity musculoskeletal disorders

<p>Abstract</p> <p>Background</p> <p>Occupational computer use has been associated with upper extremity musculoskeletal disorders (UEMSDs), but the etiology and pathophysiology of some of these disorders are poorly understood. Various theories attribute the symptoms to biomechanical and/or psychosocial stressors. The results of several clinical studies suggest that elevated antagonist muscle tension may be a biomechanical stress factor. Affected computer users often exhibit limited wrist range of motion, particularly wrist flexion, which has been attributed to increased extensor muscle tension, rather than to pain symptoms. Recreational or domestic activities requiring extremes of wrist flexion may produce injurious stress on the wrist joint and muscles, the symptoms of which are then exacerbated by computer use. As these activities may involve a variety of forearm postures, we examined whether changes in forearm posture have an effect on pain reports during wrist flexion, or whether pain would have a limiting effect on flexion angle.</p> <p>Methods</p> <p>We measured maximum active wrist flexion using a goniometer with the forearm supported in the prone, neutral, and supine postures. Data was obtained from 5 subjects with UEMSDs attributed to computer use and from 13 control subjects.</p> <p>Results</p> <p>The UEMSD group exhibited significantly restricted wrist flexion compared to the control group in both wrists at all forearm postures with the exception of the non-dominant wrist with the forearm prone. In both groups, maximum active wrist flexion decreased at the supine forearm posture compared to the prone posture. No UEMSD subjects reported an increase in pain symptoms during testing.</p> <p>Conclusion</p> <p>The UEMSD group exhibited reduced wrist flexion compared to controls that did not appear to be pain related. A supine forearm posture reduced wrist flexion in both groups, but the reduction was approximately 100% greater in the UEMSD group. The effect of a supine forearm posture on wrist flexion is consistent with known biomechanical changes in the distal extensor carpi ulnaris tendon that occur with forearm supination. We infer from these results that wrist extensor muscle passive tension may be elevated in UEMSD subjects compared to controls, particularly in the extensor carpi ulnaris muscle. Measuring wrist flexion at the supine forearm posture may highlight flexion restrictions that are not otherwise apparent.</p

Notch and Prospero Repress Proliferation following Cyclin E Overexpression in the Drosophila Bristle Lineage

Understanding the mechanisms that coordinate cell proliferation, cell cycle arrest, and cell differentiation is essential to address the problem of how “normal” versus pathological developmental processes take place. In the bristle lineage of the adult fly, we have tested the capacity of post-mitotic cells to re-enter the cell cycle in response to the overexpression of cyclin E. We show that only terminal cells in which the identity is independent of Notch pathway undergo extra divisions after CycE overexpression. Our analysis shows that the responsiveness of cells to forced proliferation depends on both Prospero, a fate determinant, and on the level of Notch pathway activity. Our results demonstrate that the terminal quiescent state and differentiation are regulated by two parallel mechanisms acting simultaneously on fate acquisition and cell cycle progression

Decreased Mitochondrial DNA Mutagenesis in Human Colorectal Cancer

Genome instability is regarded as a hallmark of cancer. Human tumors frequently carry clonally expanded mutations in their mitochondrial DNA (mtDNA), some of which may drive cancer progression and metastasis. The high prevalence of clonal mutations in tumor mtDNA has commonly led to the assumption that the mitochondrial genome in cancer is genetically unstable, yet this hypothesis has not been experimentally tested. In this study, we directly measured the frequency of non-clonal (random) de novo single base substitutions in the mtDNA of human colorectal cancers. Remarkably, tumor tissue exhibited a decreased prevalence of these mutations relative to adjacent non-tumor tissue. The difference in mutation burden was attributable to a reduction in C∶G to T∶A transitions, which are associated with oxidative damage. We demonstrate that the lower random mutation frequency in tumor tissue was also coupled with a shift in glucose metabolism from oxidative phosphorylation to anaerobic glycolysis, as compared to non-neoplastic colon. Together these findings raise the intriguing possibility that fidelity of mitochondrial genome is, in fact, increased in cancer as a result of a decrease in reactive oxygen species-mediated mtDNA damage

Meta-Analysis of TNF 308 G/A Polymorphism and Type 2 Diabetes Mellitus

BACKGROUND AND OBJECTIVES: Many investigations have focused the association between TNF 308 G/A polymorphism and risk for type 2 diabetes mellitus (T2DM). However, the sample sizes of most of the studies were small. The aim of this study is to evaluate the precise association between this variant and risk for T2DM in a large-scale meta-analysis. METHODS: All publications were searched on the association between TNF 308 G/A polymorphism and T2DM. The key words were as follows: diabetes, tumor necrosis factor and polymorphism/variant/genotype. This meta-analysis was assessed by Review manager 5.0. RESULTS: There were 18 studies identified. The odds ratios (ORs) and 95% confidence intervals (CI) for GA+AA versus GG genotype of TNF 308 G/A polymorphism were 1.03 (0.95-1.12), 1.03 (0.94-1.13) and 1.03 (0.78-1.36) in overall, Caucasian and Asian populations, respectively. The sensitivity analysis further strengthened the validity of this association. No publication bias or heterogeneity was observed in this study. CONCLUSION: In summary, there was no significant association detected between the TNF 308 G/A polymorphism and risk for T2DM

Oncogene Activation Induces Metabolic Transformation Resulting in Insulin-Independence in Human Breast Cancer Cells

Normal breast epithelial cells require insulin and EGF for growth in serum-free media. We previously demonstrated that over expression of breast cancer oncogenes transforms MCF10A cells to an insulin-independent phenotype. Additionally, most breast cancer cell lines are insulin-independent for growth. In this study, we investigated the mechanism by which oncogene over expression transforms MCF10A cells to an insulin-independent phenotype. Analysis of the effects of various concentrations of insulin and/or IGF-I on proliferation of MCF10A cells demonstrated that some of the effects of insulin were independent from those of IGF-I, suggesting that oncogene over expression drives a true insulin-independent proliferative phenotype. To test this hypothesis, we examined metabolic functions of insulin signaling in insulin-dependent and insulin-independent cells. HER2 over expression in MCF10A cells resulted in glucose uptake in the absence of insulin at a rate equal to insulin-induced glucose uptake in non-transduced cells. We found that a diverse set of oncogenes induced the same result. To gain insight into how HER2 oncogene signaling affected increased insulin-independent glucose uptake we compared HER2-regulated gene expression signatures in MCF10A and HER2 over expressing MCF10A cells by differential analysis of time series gene expression data from cells treated with a HER2 inhibitor. This analysis identified genes specifically regulated by the HER2 oncogene, including VAMP8 and PHGDH, which have known functions in glucose uptake and processing of glycolytic intermediates, respectively. Moreover, these genes specifically implicated in HER2 oncogene-driven transformation are commonly altered in human breast cancer cells. These results highlight the diversity of oncogene effects on cell regulatory pathways and the importance of oncogene-driven metabolic transformation in breast cancer

Spared unconscious influences of spatial memory in diencephalic amnesia

Spatial memory is crucial to our daily lives and in part strongly depends on automatic, implicit memory processes. This study investigates the neurocognitive basis of conscious and unconscious influences of object–location memory in amnesic patients with Korsakoff’s syndrome (N = 23) and healthy controls (N = 18) using a process-dissociation procedure in a computerized spatial memory task. As expected, the patients performed substantially worse on the conscious memory measures but showed even slightly stronger effects of unconscious influences than the controls. Moreover, a delayed test administered after 1 week revealed a strong decline in conscious influences in the patients, while unconscious influences were not affected. The presented results suggest that conscious and unconscious influences of spatial memory can be clearly dissociated in Korsakoff’s syndrome

Muscle Dystroglycan Organizes the Postsynapse and Regulates Presynaptic Neurotransmitter Release at the Drosophila Neuromuscular Junction

International audienceBACKGROUND: The Dystrophin-glycoprotein complex (DGC) comprises dystrophin, dystroglycan, sarcoglycan, dystrobrevin and syntrophin subunits. In muscle fibers, it is thought to provide an essential mechanical link between the intracellular cytoskeleton and the extracellular matrix and to protect the sarcolemma during muscle contraction. Mutations affecting the DGC cause muscular dystrophies. Most members of the DGC are also concentrated at the neuromuscular junction (NMJ), where their deficiency is often associated with NMJ structural defects. Hence, synaptic dysfunction may also intervene in the pathology of dystrophic muscles. Dystroglycan is a central component of the DGC because it establishes a link between the extracellular matrix and Dystrophin. In this study, we focused on the synaptic role of Dystroglycan (Dg) in Drosophila. METHODOLOGY/PRINCIPAL FINDINGS: We show that Dg was concentrated postsynaptically at the glutamatergic NMJ, where, like in vertebrates, it controls the concentration of synaptic Laminin and Dystrophin homologues. We also found that synaptic Dg controlled the amount of postsynaptic 4.1 protein Coracle and alpha-Spectrin, as well as the relative subunit composition of glutamate receptors. In addition, both Dystrophin and Coracle were required for normal Dg concentration at the synapse. In electrophysiological recordings, loss of postsynaptic Dg did not affect postsynaptic response, but, surprisingly, led to a decrease in glutamate release from the presynaptic site. CONCLUSION/SIGNIFICANCE: Altogether, our study illustrates a conservation of DGC composition and interactions between Drosophila and vertebrates at the synapse, highlights new proteins associated with this complex and suggests an unsuspected trans-synaptic function of Dg