The influence of colour and sound on neuronal activation during visual object naming

This paper investigates how neuronal activation for naming photographs of objects is influenced by the addition of appropriate colour or sound. Behaviourally, both colour and sound are known to facilitate object recognition from visual form. However, previous functional imaging studies have shown inconsistent effects. For example, the addition of appropriate colour has been shown to reduce antero-medial temporal activation whereas the addition of sound has been shown to increase posterior superior temporal activation. Here we compared the effect of adding colour or sound cues in the same experiment. We found that the addition of either the appropriate colour or sound increased activation for naming photographs of objects in bilateral occipital regions and the right anterior fusiform. Moreover, the addition of colour reduced left antero-medial temporal activation but this effect was not observed for the addition of object sound. We propose that activation in bilateral occipital and right fusiform areas precedes the integration of visual form with either its colour or associated sound. In contrast, left antero-medial temporal activation is reduced because object recognition is facilitated after colour and form have been integrated.

Fusiform activation to animals is driven by the process, not the stimulus

Previous studies have found that the lateral posterior fusiform gyri respond more robustly to pictures of animals than pictures of manmade objects and suggested that these regions encode the visual properties characteristic of animals. We suggest that such effects actually reflect processing demands arising when items with similar representations must be finely discriminated. In a positron emission tomography (PET) study of category verification with colored photographs of animals and vehicles, there was robust animal-specific activation in the lateral posterior fusiform gyri when stimuli were categorized at an intermediate level of specificity (e.g., dog or car). However, when the same photographs were categorized at a more specific level (e.g., Labrador or BMW), these regions responded equally strongly to animals and vehicles. We conclude that the lateral posterior fusiform does not encode domain-specific representations of animals or visual properties characteristic of animals. Instead, these regions are strongly activated whenever an item must be discriminated from many close visual or semantic competitors. Apparent category effects arise because, at an intermediate level of specificity, animals have more visual and semantic competitors than do artifacts.

Methane and nitrous oxide fluxes in annual and perennial land-use systems of the irrigated areas in the Aral Sea Basin

Land use and agricultural practices can result in important contributions to the global source strength of atmospheric nitrous oxide (N2O) and methane (CH4). However, knowledge of gas flux from irrigated agriculture is very limited. From April 2005 to October 2006, a study was conducted in the Aral Sea Basin, Uzbekistan, to quantify and compare emissions of N2O and CH4 in various annual and perennial land-use systems: irrigated cotton, winter wheat and rice crops, a poplar plantation and a natural Tugai (floodplain) forest. In the annual systems, average N2O emissions ranged from 10 to 150 μg N2O-N m−2 h−1 with highest N2O emissions in the cotton fields, covering a similar range of previous studies from irrigated cropping systems. Emission factors (uncorrected for background emission), used to determine the fertilizer-induced N2O emission as a percentage of N fertilizer applied, ranged from 0.2% to 2.6%. Seasonal variations in N2O emissions were principally controlled by fertilization and irrigation management. Pulses of N2O emissions occurred after concomitant N-fertilizer application and irrigation. The unfertilized poplar plantation showed high N2O emissions over the entire study period (30 μg N2O-N m−2 h−1), whereas only negligible fluxes of N2O (<2 μg N2O-N m−2 h−1) occurred in the Tugai. Significant CH4 fluxes only were determined from the flooded rice field: Fluxes were low with mean flux rates of 32 mg CH4 m−2 day−1 and a low seasonal total of 35.2 kg CH4 ha−1. The global warming potential (GWP) of the N2O and CH4 fluxes was highest under rice and cotton, with seasonal changes between 500 and 3000 kg CO2 eq. ha−1. The biennial cotton–wheat–rice crop rotation commonly practiced in the region would average a GWP of 2500 kg CO2 eq. ha−1 yr−1. The analyses point out opportunities for reducing the GWP of these irrigated agricultural systems by (i) optimization of fertilization and irrigation practices and (ii) conversion of annual cropping systems into perennial forest plantations, especially on less profitable, marginal lands.

Nilotinib and MEK inhibitors induce synthetic lethality through paradoxical activation of RAF in drug-resistant chronic myeloid leukemia

We show that imatinib, nilotinib, and dasatinib possess weak off-target activity against RAF and, therefore, drive paradoxical activation of BRAF and CRAF in a RAS-dependent manner. Critically, because RAS is activated by BCR-ABL, in drug-resistant chronic myeloid leukemia (CML) cells, RAS activity persists in the presence of these drugs, driving paradoxical activation of BRAF, CRAF, MEK, and ERK, and leading to an unexpected dependency on the pathway. Consequently, nilotinib synergizes with MEK inhibitors to kill drug-resistant CML cells and block tumor growth in mice. Thus, we show that imatinib, nilotinib, and dasatinib drive paradoxical RAF/MEK/ERK pathway activation and have uncovered a synthetic lethal interaction that can be used to kill drug-resistant CML cells in vitro and in vivo.

Activation of forkhead box O transcription factors by oncogenic BRAF promotes p21cip1-dependent senescence

Oncogene-induced senescence (OIS) is a potent tumor-suppressive mechanism that is thought to come at the cost of aging. The Forkhead box O (FOXO) transcription factors are regulators of life span and tumor suppression. However, whether and how FOXOs function in OIS have been unclear. Here, we show a role for FOXO4 in mediating senescence by the human BRAFV600E oncogene, which arises commonly in melanoma. BRAFV600E signaling through mitogen-activated protein kinase/extracellular signal-regulated kinase kinase resulted in increased reactive oxygen species levels and c-Jun NH 2 terminal kinase-mediated activation of FOXO4 via its phosphorylation on Thr223, Ser226, Thr447, and Thr451. BRAFV600E-induced FOXO4 phosphorylation resulted in p21cip1-mediated cell senescence independent of p16 ink4a or p27kip1. Importantly, melanocyte-specific activation of BRAFV600E in vivo resulted in the formation of skin nevi expressing Thr223/Ser226-phosphorylated FOXO4 and elevated p21cip1. Together, these findings support a model in which FOXOs mediate a trade-off between cancer and aging.

Activation of toxic chemicals by cytochrome P450 enzymes : regio- and stereoselective oxidation of aflatoxin B1

Cytochrome P450 (P450) enzymes are involved in the oxidations of numerous steroids, eicosanoids, alkaloids, and other endogenous substrates. These enzymes are also the major ones involved in the oxidation of potential toxicants and carcinogens such as those encountered among pollutants, solvents, and pesticides, as well as many natural products. A proper understanding of the basic mechanisms by which the P450 enzymes oxidize such compounds is important in developing rational strategies for the evaluation of the risks of these compounds.

Mirror neuron activation is associated with facial emotion processing

Theoretical accounts suggest that mirror neurons play a crucial role in social cognition. The current study used transcranial-magnetic stimulation (TMS) to investigate the association between mirror neuron activation and facialemotion processing, a fundamental aspect of social cognition, among healthy adults (n = 20). Facial emotion processing of static (but not dynamic) images correlated significantly with an enhanced motor response, proposed to reflect mirror neuron activation. These correlations did not appear to reflect general facial processing or pattern recognition, and provide support to current theoretical accounts linking the mirror neuron system to aspects of social cognition. We discuss the mechanism by which mirror neurons might facilitate facial emotion recognition.

Ibuprofen supplementation and its effects on NF-KB activation in skeletal muscle following resistance exercise

Resistance exercise triggers a subclinical inflammatory response that plays a pivotal role in skeletal muscle regeneration. Nuclear factor‐κB (NF‐κB) is a stress signalling transcription factor that regulates acute and chronic states of inflammation. The classical NF‐κB pathway regulates the early activation of post‐exercise inflammation; however there remains scope for this complex transcription factor to play a more detailed role in post‐exercise muscle recovery. Sixteen volunteers completed a bout of lower body resistance exercise with the ingestion of three 400 mg doses of ibuprofen or a placebo control. Muscle biopsy samples were obtained prior to exercise and at 0, 3 and 24 h post‐exercise and analysed for key markers of NF‐κB activity. Phosphorylated p65 protein expression and p65 inflammatory target genes were elevated immediately post‐exercise independent of the two treatments. These changes did not translate to an increase in p65 DNA binding activity. NF‐κB p50 protein expression and NF‐κB p50 binding activity were lower than pre‐exercise at 0 and 3 h post‐exercise, but were elevated at 24 h post‐exercise. These findings provide novel evidence that two distinct NF‐κB pathways are active in skeletal muscle after resistance exercise. The initial wave of activity involving p65 resembles the classical pathway and is associated with the onset of an acute inflammatory response. The second wave of NF‐κB activity comprises the p50 subunit, which has been previously shown to resolve an acute inflammatory program. The current study showed no effect of the ibuprofen treatment on markers of the NF‐κB pathway, however examination of the within group effects of the exercise protocol suggests that this pathway warrants further research.

Altering the redox state of skeletal muscle by glutathione depletion increases the exercise-activation of PGC-1α

We investigated the relationship between mitochondrial biogenesis, cell signalling and antioxidant enzymes by depleting skeletal muscle glutathione with diethyl maleate (DEM) which resulted in a demonstrable increase in oxidative stress during exercise. Animals were divided into six groups: (1) sedentary control rats; (2) sedentary rats treated with DEM; (3) exercise control rats euthanized immediately after exercise; (4) exercise rats + DEM; (5) exercise control rats euthanized 4 h after exercise, and; (6) exercise rats + DEM euthanized 4 h after exercise. Exercising animals ran on the treadmill at a 10% gradient at 20 m/min for the first 30 min. The speed was then increased every 10 min by 1.6 m/min until exhaustion. There was a reduction in total glutathione in the skeletal muscle of DEM treated animals compared to the control animals (P<0.05). Within the control group, total glutathione was higher in the sedentary group compared to after exercise (P<0.05). DEM treatment also significantly increased oxidative stress, as measured by increased plasma F2-isoprostanes (P<0.05). Exercising animals given DEM showed a significantly greater increase in peroxisome proliferator activated receptor γ coactivator-1α(PGC-1α) mRNA compared to the control animals that were exercised (P<0.05). This study provides novel evidence that by reducing the endogenous antioxidant glutathione in skeletal muscle and inducing oxidative stress through exercise, PGC-1α gene expression was augmented. These findings further highlight the important role of exercise induced oxidative stress in the regulation of mitochondrial biogenesis.

Activation of membrane-bound proteins and receptor systems: A link between tissue kallikrein and the KLK-related peptidases

The 15 members of the kallikrein-related serine peptidase (KLK) family have diverse tissue-specific expression profiles and roles in a range of cellular processes, including proliferation, migration, invasion, differentiation, inflammation and angiogenesis that are required in both normal physiology as well as pathological conditions. These roles require cleavage of a range of substrates, including extracellular matrix proteins, growth factors, cytokines as well as other proteinases. In addition, it has been clear since the earliest days of KLK research that cleavage of cell surface substrates is also essential in a range of KLK-mediated cellular processes where these peptidases are essentially acting as agonists and antagonists. In this review we focus on these KLK-regulated cell surface receptor systems including bradykinin receptors, proteinase-activated receptors, as well as the plasminogen activator, ephrins and their receptors, and hepatocyte growth factor/Met receptor systems and other plasma membrane proteins. From this analysis it is clear that in many physiological and pathological settings KLKs have the potential to regulate multiple receptor systems simultaneously; an important issue when these peptidases and substrates are targeted in disease.