Single-step deposition of high-mobility graphene at reduced temperatures.

Current methods of chemical vapour deposition (CVD) of graphene on copper are complicated by multiple processing steps and by high temperatures required in both preparing the copper and inducing subsequent film growth. Here we demonstrate a plasma-enhanced CVD chemistry that enables the entire process to take place in a single step, at reduced temperatures (<420 °C), and in a matter of minutes. Growth on copper foils is found to nucleate from arrays of well-aligned domains, and the ensuing films possess sub-nanometre smoothness, excellent crystalline quality, low strain, few defects and room-temperature electrical mobility up to (6.0±1.0) × 10(4) cm(2) V(-1) s(-1), better than that of large, single-crystalline graphene derived from thermal CVD growth. These results indicate that elevated temperatures and crystalline substrates are not necessary for synthesizing high-quality graphene.

Prevalence of undiagnosed diabetes mellitus and cardiovascular risk factors in Hong Kong professional drivers.

AIMS: To investigate the prevalence of undiagnosed diabetes mellitus (DM) and cardiovascular risk factors among professional drivers in Hong Kong. METHODS: Chinese professional drivers with no history of DM were invited to complete a questionnaire on their health status, followed by taking their body measurements, fasting blood glucose (FG) and lipids. 75g OGTT were performed when FG≥5.6 to <7.0mmol/L. RESULTS: Of these 3376 drivers (male 92.6%, mean age 50.9±7.6 years), the prevalence of undiagnosed DM, prediabetes, and metabolic syndrome was 8.1% (272/3376, 95% CI 7.1-9.0%), 10.0% (337/3376, 95% CI 9.0-11.0%) and 26.8% (904/3376, 95% CI 25.3-28.3%) respectively, while the corresponding WHO Standard Population age-standardized prevalence was 7.8%, 9.0% and 24.7% respectively. Many of them were obese (51.2%), had hypertension (57.0%) and high cholesterol (58.7%), and a third had hypertriglyceridaemia (34.9%) and low HDL-cholesterol (29.3%). Their median working hours were 60.0 (IQR 14)h. Majority had exercise <1h/week (56.0%) and ate out ≥6times/week (54.9%). CONCLUSIONS: Hong Kong professional drivers have higher prevalence of undiagnosed DM, cardiovascular risk factors and metabolic syndrome than the general population. Therefore, health care measures targeting against them should be taken to prevent and detect DM and cardiovascular diseases.

Complex, multimodal behavioral profile of the Homer1 knockout mouse.

Proteins of the Homer1 immediate early gene family have been associated with synaptogenesis and synaptic plasticity suggesting broad behavioral consequences of loss of function. This study examined the behavior of male Homer1 knockout (KO) mice compared with wild-type (WT) and heterozygous mice using a battery of 10 behavioral tests probing sensory, motor, social, emotional and learning/memory functions. KO mice showed mild somatic growth retardation, poor motor coordination, enhanced sensory reactivity and learning deficits. Heterozygous mice showed increased aggression in social interactions with conspecifics. The distribution of mGluR5 and N-methyl-D-aspartate receptors (NMDA) receptors appeared to be unaltered in the hippocampus (HIP) of Homer1 KO mice. The results indicate an extensive range of disrupted behaviors that should contribute to the understanding of the Homer1 gene in brain development and behavior.

Requirements of focal adhesions and calcium fluxes for interleukin-1-induced ERK kinase activation and c-fos expression in fibroblasts.

Interleukin-1 (IL-1) is an important inflammatory mediator and plays a central role in the destruction of connective tissue matrices in diseases such as arthritis and periodontitis. It is well established that IL-1 activation of the mitogen-activated protein (MAP) kinase pathway and induction of c-fos expression is a required step in the induction of matrix metalloproteinase expression involved in tissue degradation. Previous studies in our laboratory showed that IL-1-induced calcium flux is dependent on focal adhesion formation, suggesting a matrix-dependent restriction system for IL-1 signaling. Therefore, in the present study, we examined the consequences of this restriction on IL-1-mediated activation of the MAP kinase family and on c-fos expression. Treatment of human gingival fibroblasts with IL-1 activated extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinase (JNK), and p38 kinase activity and induced c-fos expression in a dose- and time-dependent fashion. Plating cells on poly-L-lysine prevented focal adhesion formation, eliminated IL-1-induced calcium influx, abolished ERK stimulation, and blocked c-fos expression. Cells in suspension and hence with no suitable substratum for focal adhesion formation also showed no ERK activation or enhanced c-fos expression in response to IL-1. In contrast, eliminating focal adhesion formation or calcium depletion in cells plated on fibronectin had no effect on IL-1 stimulation of JNK and p38 kinases, demonstrating that their activation was mediated through pathways independent of focal adhesions and calcium. Calcium depletion abolished IL-1-induced calcium uptake, ERK activation, and c-fos expression. The focal adhesion dependence of IL-1-induced ERK activation and c-fos expression could be circumvented in cells plated on poly-L-lysine by simultaneous incubation with IL-1 and the calcium ionophore ionomycin. In transfection studies, IL-1 stimulation of serum responsive element (SRE) transcriptional activity was dependent on the presence of extracellular calcium. This is consistent with a requirement for calcium in the activation of ERKs and their involvement in the induction of c-fos expression through the SRE site on the 5' promoter of the c-fos gene. Our results demonstrate that in cells attached to substrates by focal adhesions, IL-1-mediated calcium flux is required for ERK activation and c-fos expression but not for JNK or p38 activation. We conclude that cellular interactions with the extracellular matrix play an important role in restricting ERK and c-fos-dependent processes.

Interleukin-1 beta induction of c-fos and collagenase expression in articular chondrocytes: involvement of reactive oxygen species.

Interleukin-1 beta (IL-1) is implicated in cartilage destruction in arthritis through promotion of matrix metalloproteinase production. Upregulation of collagenase gene expression by IL-1 is known to require the transactivators Fos and Jun. Recently, reactive oxygen species (ROS) have been suggested to act as intracellular signaling molecules mediating the biological effects of cytokines. Here, we demonstrated ROS production by IL-1-stimulated bovine chondrocytes and that neutralizing ROS activity by the potent antioxidant, N-acetylcysteine, or inhibiting endogenous ROS production by diphenyleneiodonium (DPI), significantly attenuated IL-1-induced c-fos and collagenase gene expression. The inhibitory effect of DPI implicates enzymes such as NADPH oxidase in the endogenous production of ROS. Chondrocytes were also found to produce nitric oxide (NO) upon IL-1 stimulation. That NO may mediate part of the inducing effects of IL-1 was supported by the observation that L-NG-monomethylarginine, a NO synthase inhibitor, partially inhibited IL-1-regulated collagenase expression. Moreover, treatment of chondrocytes with the NO-producing agent, S-nitroso-N-acetylpenicillamine, was sufficient to induce collagenase mRNA levels. In summary, our results suggest that ROS released in response to IL-1 may function as second messengers transducing extracellular stimuli to their targets in the nucleus, leading to augmentation of gene expression.

Putaminal petechial haemorrhage as the cause of chorea: a neuroimaging study.

OBJECTIVES: A hyperintense putamen on either CT or MRI as a finding associated with chorea has occasionally been described and is almost always associated with non-ketotic hyperglycaemia. The cause of the hyperintensity of the striatum in these images is still controversial. Some reports have found that calcification was responsible whereas others have advocated petechial haemorrhage as the cause. The purpose of this study was to determine whether hyperintense striata are caused by petechial haemorrhage or calcification, with the sequential imaging changes. SUBJECTS AND METHODS: Five patients presenting with an acute onset of either hemichorea or generalised chorea and showed either unilateral or bilateral hyperdense striatum on the initial CT were assessed. Neuroimaging studies including sequential CT and MRI examinations and detailed biochemical tests were performed. RESULTS: Three patients had pronounced hyperglycaemia and the other two patients had no biochemical abnormalities. In all patients, the first CT scans, performed within two weeks of the onset of chorea, showed a high density over the striatum contralateral to the chorea, which diminished or disappeared two months later. T1 weighted imaging disclosed hypersignal intensities over the striatum contralateral to the chorea on admission which diminished two months later. T2 weighted imaging at two months showed hyposignal intensity changes corresponding to the area with hypersignal changes on T1 weighted images, implying haemosiderin deposition. CONCLUSION: Based on the evolution of clinical manifestations and the findings of neuroimaging, putaminal petechial haemorrhage might be a new entity causing either hemichorea or generalised chorea.

Reactive oxygen species mediate cytokine activation of c-Jun NH2-terminal kinases.

Interleukin 1 (IL-1) and tumor necrosis factor alpha (TNFalpha) are known to induce production of reactive oxygen species (ROS), which have been suggested to act as second messengers. Here we demonstrate that ROS production by bovine chondrocytes upon cytokine stimulation induces c-jun expression. Since c-jun expression is regulated by its own gene product via phosphorylation by c-Jun NH2-terminal kinases (JNKs), we investigated if cytokines and ROS could modulate JNK activity in chondrocyte monolayer cultures. Treatment of bovine chondrocytes with both IL-1 and TNFalpha leads to rapid induction of JNK activity, stimulating JNK activity 7- and 20-fold, respectively. Importantly, the observation that antioxidant treatment antagonizes IL-1 and TNFalpha activation of JNK provides strong evidence that ROS can act as mediators of JNK activity. Moreover, potent activation of JNK is also observed by direct addition of the ROS hydrogen peroxide (H2O2) to the chondrocyte cultures. Nitric oxide (NO), a multifunctional ROS, also appears to simulate JNK, albeit to a lesser extent. These findings identify JNK as another molecular target for the actions of NO and H2O2. In addition, the inhibitory effect of diphenyleneiodonium on JNK activation implicates the involvement of flavonoid-containing enzymes in the ROS-mediated signaling process. Overstimulation of JNK activity by excessive production of ROS may, therefore, underlie pathological conditions such as arthritis and cancer.

Involvement of reactive oxygen species in cytokine and growth factor induction of c-fos expression in chondrocytes.

The cytokine tumor necrosis factor alpha (TNF alpha) and the growth factor basic fibroblast growth factor (bFGF) are known to induce early response genes such as c-fos and c-jun in various cell types. Activation of AP-1, a heterodimeric complex of Fos and Jun proteins, is required for matrix metalloproteinase production and cell proliferation. However, the signaling pathways by which these two factors influence the expression and activities of AP-1 remain currently poorly characterized. Several studies have shown that cytokines induce reactive oxygen species (ROS) production, but growth factor induction of ROS has not been reported. In the present study we demonstrate that both TNF alpha and bFGF induce ROS production, and that this is a common signaling event involved in the stimulation of c-fos gene expression in chondrocytes. To our knowledge, this is the first report directly demonstrating ROS production upon stimulation with a growth factor. TNF alpha and bFGF induction of ROS production is mediated through flavonoid-containing enzymes such as NADPH oxidase. Moreover, the ROS nitric oxide is not responsible for the induction of c-fos expression by TNF alpha and bFGF. In addition, the inhibitory effects of antioxidants on c-fos expression may account for their protective roles against proliferative and inflammatory diseases such as cancer, cardiovascular diseases, and arthritis.

Control of preweaning diarrhea in piglets by acupuncture and Chinese medicine.

Preweaning diarrhea in piglets is a very common disease. Even thought vaccination and antibiotics are used widely for controlling the disease nowadays, it is still a serious production problem. Therefore, the search for a new medication that is both cheaper and more effective is of major importance. During the last year, acupuncture and Chinese medicine have been evaluated for this purpose. The results are summarized as follows: 1) Oral administration of 0.5 g of Ko-ken-huang-lien-huang-chin-tang (pueraria, coptis, scute and licorice combination) to piglets at 1 day old was effective in reducing incidence of infection (P less than 0.1) and increasing the body weight gain (P less than 0.05) during the first 10 days of life. Gentamycin or aqua-acupuncture at day 1 of life had no prophylactic value. 2) Piglets with preweaning diarrhea were treated by aqua-acupuncture at Chang-Chiang point (VG 1, or so called Chiao-Chao in traditional pig charts) with 0.2 ml of 3% saline, or by oral administration of 0.5 g of Ko-ken-huang-lien-huang-chin-tang or by injection of gentamycin (10 mg/piglet) twice a day for 1-3 days. These treatments significantly reduced the duration of illness (P less than 0.01) when compared with the control groups which received 0.5 g lactose orally. These results indicate that both acupuncture treatment and Chinese medicine have a high clinical value for controlling piglet diarrhea.