Vascular Contributions to Cognitive Impairment and Treatments with Traditional Chinese Medicine

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Tailoring the atomic structure of graphene nanoribbons by STM lithography

The practical realization of nano-scale electronics faces two major challenges: the precise engineering of the building blocks and their assembly into functional circuits. In spite of the exceptional electronic properties of carbon nanotubes only basic demonstration-devices have been realized by time-consuming processes. This is mainly due to the lack of selective growth and reliable assembly processes for nanotubes. However, graphene offers an attractive alternative. Here we report the patterning of graphene nanoribbons (GNRs) and bent junctions with nanometer precision, well-defined widths and predetermined crystallographic orientations allowing us to fully engineer their electronic structure using scanning tunneling microscope (STM) lithography. The atomic structure and electronic properties of the ribbons have been investigated by STM and tunneling spectroscopy measurements. Opening of confinement gaps up to 0.5 eV, allowing room temperature operation of GNR-based devices, is reported. This method avoids the difficulties of assembling nano-scale components and allows the realization of complete integrated circuits, operating as room temperature ballistic electronic devices.Comment: 8 pages text, 5 figures, Nature Nanotechnology, in pres

Understanding Sensory Nerve Mechanotransduction through Localized Elastomeric Matrix Control

BACKGROUND: While neural systems are known to respond to chemical and electrical stimulation, the effect of mechanics on these highly sensitive cells is still not well understood. The ability to examine the effects of mechanics on these cells is limited by existing approaches, although their overall response is intimately tied to cell-matrix interactions. Here, we offer a novel method, which we used to investigate stretch-activated mechanotransduction on nerve terminals of sensory neurons through an elastomeric interface. METHODOLOGY/PRINCIPAL FINDINGS: To apply mechanical force on neurites, we cultured dorsal root ganglion neurons on an elastic substrate, polydimethylsiloxane (PDMS), coated with extracellular matrices (ECM). We then implemented a controlled indentation scheme using a glass pipette to mechanically stimulate individual neurites that were adjacent to the pipette. We used whole-cell patch clamping to record the stretch-activated action potentials on the soma of the single neurites to determine the mechanotransduction-based response. When we imposed specific mechanical force through the ECM, we noted a significant neuronal action potential response. Furthermore, because the mechanotransduction cascade is known to be directly affected by the cytoskeleton, we investigated the cell structure and its effects. When we disrupted microtubules and actin filaments with nocodozale or cytochalasin-D, respectively, the mechanically induced action potential was abrogated. In contrast, when using blockers of channels such as TRP, ASIC, and stretch-activated channels while mechanically stimulating the cells, we observed almost no change in action potential signalling when compared with mechanical activation of unmodified cells. CONCLUSIONS/SIGNIFICANCE: These results suggest that sensory nerve terminals have a specific mechanosensitive response that is related to cell architecture

High motor variability in DYT1 dystonia is associated with impaired visuomotor adaptation.

For the healthy motor control system, an essential regulatory role is maintaining the equilibrium between keeping unwanted motor variability in check whilst allowing informative elements of motor variability. Kinematic studies in children with generalised dystonia (due to mixed aetiologies) show that movements are characterised by increased motor variability. In this study, the mechanisms by which high motor variability may influence movement generation in dystonia were investigated. Reaching movements in the symptomatic arm of 10 patients with DYT1 dystonia and 12 age-matched controls were captured using a robotic manipulandum and features of motor variability were extracted. Given that task-relevant variability and sensorimotor adaptation are related in health, markers of variability were then examined for any co-variance with performance indicators during an error-based learning visuomotor adaptation task. First, we confirmed that motor variability on a trial-by-trial basis was selectively increased in the homogenous and prototypical dystonic disorder DYT1 dystonia. Second, high baseline variability predicted poor performance in the subsequent visuomotor adaptation task offering insight into the rules which appear to govern dystonic motor control. The potential mechanisms behind increased motor variability and its corresponding implications for the rehabilitation of patients with DYT1 dystonia are highlighted

Hospitalizations for varicella in children and adolescents in a referral hospital in Hong Kong, 2004 to 2008: A time series study

Background: Varicella accounts for significant morbidities and remains a public health issue worldwide. Climatic factors have been shown to associate with the incidence and transmission of various infectious diseases. We describe the epidemiology of varicella in paediatric patients hospitalized at a tertiary referral hospital in Hong Kong from 2004 to 2008, and to explore the possible association between the occurrence of varicella infection and various climatic factors. Methods. The hospital discharge database of Princess Margaret Hospital was retrospectively analyzed for admissions associated with varicella from 2004 to 2008. Meteorological data were obtained from the monthly meteorological reports from the Hong Kong Observatory website. Time series analysis was performed with Poisson regression using a Generalized Estimating Equation (GEE) approach. Results: During the study period, 598 children were hospitalized for varicella. The mean age on admission was 57.6 months, and the mean duration of hospitalization was 3.7 days. The overall complication rate was 47%. The mean monthly relative humidity, especially in cool seasons, was inversely correlated with the monthly varicella cases of the same month. Conclusions: Varicella can lead to serious complications and prolonged hospitalization, even in previously healthy children. Lower relative humidity in cool seasons is associated with higher number of paediatric varicella hospital admissions. These findings are useful for a better understanding of the pattern of paediatric varicella hospitalization in Hong Kong. © 2011 Chan et al; licensee BioMed Central Ltd.link_to_subscribed_fulltex

Lysine-Rich Extracellular Rings Formed by hβ2 Subunits Confer the Outward Rectification of BK Channels

The auxiliary β subunits of large-conductance Ca2+-activated K+ (BK) channels greatly contribute to the diversity of BK (mSlo1 α) channels, which is fundamental to the adequate function in many tissues. Here we describe a functional element of the extracellular segment of hβ2 auxiliary subunits that acts as the positively charged rings to modify the BK channel conductance. Four consecutive lysines of the hβ2 extracellular loop, which reside sufficiently close to the extracellular entryway of the pore, constitute three positively charged rings. These rings can decrease the extracellular K+ concentration and prevent the Charybdotoxin (ChTX) from approaching the extracellular entrance of channels through electrostatic mechanism, leading to the reduction of K+ inflow or the outward rectification of BK channels. Our results demonstrate that the lysine rings formed by the hβ2 auxiliary subunits influences the inward current of BK channels, providing a mechanism by which current can be rapidly diminished during cellular repolarization. Furthermore, this study will be helpful to understand the functional diversity of BK channels contributed by different auxiliary β subunits

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Transcriptome-scale similarities between mouse and human skeletal muscles with normal and myopathic phenotypes

BACKGROUND: Mouse and human skeletal muscle transcriptome profiles vary by muscle type, raising the question of which mouse muscle groups have the greatest molecular similarities to human skeletal muscle. METHODS: Orthologous (whole, sub-) transcriptome profiles were compared among four mouse-human transcriptome datasets: (M) six muscle groups obtained from three mouse strains (wildtype, mdx, mdx(5cv)); (H1) biopsied human quadriceps from controls and Duchenne muscular dystrophy patients; (H2) four different control human muscle types obtained at autopsy; and (H3) 12 different control human tissues (ten non-muscle). RESULTS: Of the six mouse muscles examined, mouse soleus bore the greatest molecular similarities to human skeletal muscles, independent of the latters' anatomic location/muscle type, disease state, age and sampling method (autopsy versus biopsy). Significant similarity to any one mouse muscle group was not observed for non-muscle human tissues (dataset H3), indicating this finding to be muscle specific. CONCLUSION: This observation may be partly explained by the higher type I fiber content of soleus relative to the other mouse muscles sampled

Visuomotor adaptive improvement and aftereffects are impaired differentially following cerebellar lesions in SCA and PICA territory

The aim of the present study was to elucidate the contribution of the superior and posterior inferior cerebellum to adaptive improvement and aftereffects in a visuomotor adaptation task. Nine patients with ischemic lesions within the territory of the posterior inferior cerebellar artery (PICA), six patients with ischemic lesions within the territory of the superior cerebellar artery (SCA) and 17 age-matched controls participated. All subjects performed center-out reaching movements under 60° rotation of visual feedback. For the assessment of aftereffects, we tested retention of adaptation and de-adaptation under 0° visual rotation. From this data we also quantified five measures of motor performance. Cerebellar lesion-symptom mapping was performed using magnetic resonance imaging subtraction analysis. Adaptive improvement during 60° rotation was significantly degraded in PICA patients and even more in SCA patients. Subtraction analysis revealed that posterior (Crus I) as well as anterior cerebellar regions (lobule V) showed a common overlap related to deficits in adaptive improvement. However, for aftereffect measures as well as for motor performance variables only SCA patients, but not PICA patients showed significant differences to control subjects. Subtraction analysis showed that affection of lobules V and VI were more common in patients with impaired retention and de-adaptation, respectively. Data shows that areas both within the superior and posterior inferior cerebellum are involved in adaptive improvement. However, only the superior cerebellum including lobules V and VI appears to be important for aftereffects and therefore true adaptive ability