Antagomir-mediated suppression of microRNA-134 reduces kainic acid-induced seizures in immature mice

MicroRNAs are short non-coding RNAs that negatively regulate protein levels and perform important roles in establishing and maintaining neuronal network function. Previous studies in adult rodents have detected upregulation of microRNA-134 after prolonged seizures (status epilepticus) and demonstrated that silencing microRNA-134 using antisense oligonucleotides, termed antagomirs, has potent and long-lasting seizure-suppressive effects. Here we investigated whether targeting microRNA-134 can reduce or delay acute seizures in the immature brain. Status epilepticus was induced in 21 day-old (P21) male mice by systemic injection of 5 mg/kg kainic acid. This triggered prolonged electrographic seizures and select bilateral neuronal death within the CA3 subfield of the hippocampus. Expression of microRNA-134 and functional loading to Argonaute-2 was not significantly changed in the hippocampus after seizures in the model. Nevertheless, when levels of microRNA-134 were reduced by prior intracerebroventricular injection of an antagomir, kainic acid-induced seizures were delayed and less severe and mice displayed reduced neuronal death in the hippocampus. These studies demonstrate targeting microRNA-134 may have therapeutic applications for the treatment of seizures in children

Single-Atom Gating of Quantum State Superpositions

The ultimate miniaturization of electronic devices will likely require local and coherent control of single electronic wavefunctions. Wavefunctions exist within both physical real space and an abstract state space with a simple geometric interpretation: this state space--or Hilbert space--is spanned by mutually orthogonal state vectors corresponding to the quantized degrees of freedom of the real-space system. Measurement of superpositions is akin to accessing the direction of a vector in Hilbert space, determining an angle of rotation equivalent to quantum phase. Here we show that an individual atom inside a designed quantum corral can control this angle, producing arbitrary coherent superpositions of spatial quantum states. Using scanning tunnelling microscopy and nanostructures assembled atom-by-atom we demonstrate how single spins and quantum mirages can be harnessed to image the superposition of two electronic states. We also present a straightforward method to determine the atom path enacting phase rotations between any desired state vectors. A single atom thus becomes a real space handle for an abstract Hilbert space, providing a simple technique for coherent quantum state manipulation at the spatial limit of condensed matter.Comment: Published online 6 April 2008 in Nature Physics; 17 page manuscript (including 4 figures) + 3 page supplement (including 2 figures); supplementary movies available at http://mota.stanford.ed

Prospecting environmental mycobacteria: combined molecular approaches reveal unprecedented diversity

Background: Environmental mycobacteria (EM) include species commonly found in various terrestrial and aquatic environments, encompassing animal and human pathogens in addition to saprophytes. Approximately 150 EM species can be separated into fast and slow growers based on sequence and copy number differences of their 16S rRNA genes. Cultivation methods are not appropriate for diversity studies; few studies have investigated EM diversity in soil despite their importance as potential reservoirs of pathogens and their hypothesized role in masking or blocking M. bovis BCG vaccine. Methods: We report here the development, optimization and validation of molecular assays targeting the 16S rRNA gene to assess diversity and prevalence of fast and slow growing EM in representative soils from semi tropical and temperate areas. New primer sets were designed also to target uniquely slow growing mycobacteria and used with PCR-DGGE, tag-encoded Titanium amplicon pyrosequencing and quantitative PCR. Results: PCR-DGGE and pyrosequencing provided a consensus of EM diversity; for example, a high abundance of pyrosequencing reads and DGGE bands corresponded to M. moriokaense, M. colombiense and M. riyadhense. As expected pyrosequencing provided more comprehensive information; additional prevalent species included M. chlorophenolicum, M. neglectum, M. gordonae, M. aemonae. Prevalence of the total Mycobacterium genus in the soil samples ranged from 2.3×107 to 2.7×108 gene targets g−1; slow growers prevalence from 2.9×105 to 1.2×107 cells g−1. Conclusions: This combined molecular approach enabled an unprecedented qualitative and quantitative assessment of EM across soil samples. Good concordance was found between methods and the bioinformatics analysis was validated by random resampling. Sequences from most pathogenic groups associated with slow growth were identified in extenso in all soils tested with a specific assay, allowing to unmask them from the Mycobacterium whole genus, in which, as minority members, they would have remained undetected

Expression analysis of Clavata1-like and Nodulin21-like genes from Pinus sylvestris during ectomycorrhiza formation

The ecology and physiology of ectomycorrhizal (EcM) symbiosis with conifer trees are well documented. In comparison, however, very little is known about the molecular regulation of these associations. In an earlier study, we identified three EcM-regulated Pinus expressed sequence tags (EST), two of which were identified as homologous to the Medicago truncatula nodulin MtN21. The third EST was a homologue to the receptor-like kinase Clavata1. We have characterized the expression patterns of these genes and of auxin- and mycorrhiza-regulated genes after induction with indole-3-butyric acid in Pinus sylvestris and in a time course experiment during ectomycorrhizal initiation with the co-inoculation of 2,3,5-triiodobenzoic acid, an auxin transport inhibitor. Our results suggest that different P. sylvestris nodulin homologues are associated with diverse processes in the root. The results also suggest a potential role of the Clv1-like gene in lateral root initiation by the ectomycorrhizal fungus

Strengthening field-based training in low and middle-income countries to build public health capacity: Lessons from Australia's Master of Applied Epidemiology program

BACKGROUND: The International Health Regulations (2005) and the emergence and global spread of infectious diseases have triggered a re-assessment of how rich countries should support capacity development for communicable disease control in low and medium income countries (LMIC). In LMIC, three types of public health training have been tried: the university-based model; streamed training for specialised workers; and field-based programs. The first has low rates of production and teaching may not always be based on the needs and priorities of the host country. The second model is efficient, but does not accord the workers sufficient status to enable them to impact on policy. The third has the most potential as a capacity development measure for LMIC, but in practice faces challenges which may limit its ability to promote capacity development. DISCUSSION: We describe Australia's first Master of Applied Epidemiology (MAE) model (established in 1991), which uses field-based training to strengthen the control of communicable diseases. A central attribute of this model is the way it partners and complements health department initiatives to enhance workforce skills, health system performance and the evidence-base for policies, programs and practice. SUMMARY: The MAE experience throws light on ways Australia could collaborate in regional capacity development initiatives. Key needs are a shared vision for a regional approach to integrate training with initiatives that strengthen service and research, and the pooling of human, financial and technical resources. We focus on communicable diseases, but our findings and recommendations are generalisable to other areas of public health

Alertness and visuospatial attention in clinical depression

<p>Abstract</p> <p>Background</p> <p>Cognitive deficits are a substantial burden in clinical depression. The present study considered dysfunction in the right-hemispheric attention network in depression, examining alertness and visuospatial attention.</p> <p>Methods</p> <p>Three computerized visuospatial attention tests and an alertness test were administered to 16 depressive patients and 16 matched healthy controls.</p> <p>Results</p> <p>Although no significant group effect was observed, alertness predicted reduced visuospatial performance in the left hemifield. Furthermore, sad mood showed a trend towards predicting left visual field omissions.</p> <p>Conclusions</p> <p>Decreased alertness may lead to lower left hemifield visuospatial attention; this mechanism may be responsible for a spatial bias to the right side in depression, even though treatment of depression and anxiety may reduce this cognitive deficit.</p

The effect of antecedent hypoglycaemia on β2-adrenergic sensitivity in healthy participants with the Arg16Gly polymorphism of the β2-adrenergic receptor

Contains fulltext : 96423.pdf (publisher's version ) (Closed access)AIMS/HYPOTHESIS: Homozygosity for glycine at codon 16 (GlyGly) of the beta(2)-adrenergic receptor may alter receptor sensitivity upon chronic stimulation and has been implicated in the pathogenesis of hypoglycaemia unawareness. We compared the effect of antecedent hypoglycaemia on beta(2)-adrenergic receptor sensitivity between GlyGly participants and those with arginine 16 homozygosity (ArgArg) for the beta(2)-adrenergic receptor. METHODS: We enrolled 16 healthy participants, who were either GlyGly (n = 8) or ArgArg (n = 8). They participated randomly in two 2 day experiments. Day 1 consisted of two 2-h hyperinsulinaemic hypoglycaemic (2.8 mmol/l) or euglycaemic (4.8 mmol/l) glucose clamps. On day 2, we measured the forearm vasodilator response to the beta(2)-adrenergic receptor agonist salbutamol and the dose of isoprenaline required to increase the heart rate by 25 bpm (IC(25)). RESULTS: The vasodilator response to salbutamol tended to be greater after antecedent hypoglycaemia than after euglycaemia (p = 0.078), consistent with increased beta(2)-adrenergic receptor sensitivity. This effect was driven by a significant increase in beta(2)-adrenergic receptor sensitivity following hypoglycaemia compared with euglycaemia in ArgArg participants (p = 0.019), whereas no such effect was observed in the GlyGly participants. Antecedent hypoglycaemia tended to decrease the IC(25) in ArgArg participants, whereas the reverse occurred in the GlyGly participants (GlyGly vs ArgArg group p = 0.047). CONCLUSION/INTERPRETATION: Antecedent hypoglycaemia did not affect beta(2)-adrenergic receptor sensitivity in healthy GlyGly participants, but increased it in ArgArg participants. If these results also hold for participants with type 1 diabetes, such an increase in beta(2)-adrenergic receptor sensitivity may potentially reduce the risk of repeated hypoglycaemia and the subsequent development of hypoglycaemia unawareness in ArgArg diabetic participants. TRIAL REGISTRATION: ClinicalTrials.gov NCT00160056

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Chemical Basis of Prey Recognition in Thamnophiine Snakes: The Unexpected New Roles of Parvalbumins

Detecting and locating prey are key to predatory success within trophic chains. Predators use various signals through specialized visual, olfactory, auditory or tactile sensory systems to pinpoint their prey. Snakes chemically sense their prey through a highly developed auxiliary olfactory sense organ, the vomeronasal organ (VNO). In natricine snakes that are able to feed on land and water, the VNO plays a critical role in predatory behavior by detecting cues, known as vomodors, which are produced by their potential prey. However, the chemical nature of these cues remains unclear. Recently, we demonstrated that specific proteins–parvalbumins–present in the cutaneous mucus of the common frog (Rana temporaria) may be natural chemoattractive proteins for these snakes. Here, we show that parvalbumins and parvalbumin-like proteins, which are mainly intracellular, are physiologically present in the epidermal mucous cells and mucus of several frog and fish genera from both fresh and salt water. These proteins are located in many tissues and function as Ca2+ buffers. In addition, we clarified the intrinsic role of parvalbumins present in the cutaneous mucus of amphibians and fishes. We demonstrate that these Ca2+-binding proteins participate in innate bacterial defense mechanisms by means of calcium chelation. We show that these parvalbumins are chemoattractive for three different thamnophiine snakes, suggesting that these chemicals play a key role in their prey-recognition mechanism. Therefore, we suggest that recognition of parvalbumin-like proteins or other calcium-binding proteins by the VNO could be a generalized prey-recognition process in snakes. Detecting innate prey defense mechanism compounds may have driven the evolution of this predator-prey interaction