597 research outputs found

    Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

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    Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads. Furthermore, we address the challenge of reading out multichannel data with an application-specific integrated circuit (ASIC) performing signal amplification, band-pass filtering, and multiplexing functions. We demonstrate high spatial resolution extracellular measurements with a fully integrated, low noise 64-channel system weighing just 330 mg. The on-chip multiplexers make possible recordings with substantially fewer external wires than the number of input channels. By combining nanofabricated probes with ASICs we have implemented a system for performing large-scale, high-density electrophysiology in small, freely behaving animals that is both minimally invasive and highly scalable

    Phytoplankton dynamics in relation to seasonal variability and upwelling and relaxation patterns at the mouth of Ria de Aveiro (West Iberian Margin) over a four-year period

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    From June 2004 to December 2007, samples were weekly collected at a fixed station located at the mouth of Ria de Aveiro (West Iberian Margin). We examined the seasonal and inter-annual fluctuations in composition and community structure of the phytoplankton in relation to the main environmental drivers and assessed the influence of the oceano-graphic regime, namely changes in frequency and intensity of upwelling events, over the dynamics of the phytoplankton assemblage. The samples were consistently handled and a final subset of 136 OTUs (taxa with relative abundance > 0.01%) was subsequently submitted to various multivariate analyses. The phytoplankton assemblage showed significant changes at all temporal scales but with an overriding importance of seasonality over longer-(inter-annual) or shorter-term fluctuations (upwelling-related). Sea-surface temperature, salinity and maximum upwelling index were retrieved as the main driver of seasonal change. Seasonal signal was most evident in the fluctuations of chlorophyll a concentration and in the high turnover from the winter to spring phytoplankton assemblage. The seasonal cycle of production and succession was disturbed by upwelling events known to disrupt thermal stratification and induce changes in the phytoplankton assemblage. Our results indicate that both the frequency and intensity of physical forcing were important drivers of such variability, but the outcome in terms of species composition was highly dependent on the available local pool of species and the timing of those events in relation to the seasonal cycle. We conclude that duration, frequency and intensity of upwelling events, which vary seasonally and inter-annually, are paramount for maintaining long-term phytoplankton diversity likely by allowing unstable coexistence and incorporating species turnover at different scales. Our results contribute to the understanding of the complex mechanisms of coastal phytoplankton dynamics in relation to changing physical forcing which is fundamental to improve predictability of future prospects under climate change.Portuguese Foundation for Science and Technology (FCT, Portugal) [SFRH/BPD/ 94562/2013]; FEDER funds; national funds; CESAM [UID/AMB/50017]; FCT/MEC through national funds; FEDERinfo:eu-repo/semantics/publishedVersio

    Retrospective harm benefit analysis of pre-clinical animal research for six treatment interventions

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    The harm benefit analysis (HBA) is the cornerstone of animal research regulation and is considered to be a key ethical safeguard for animals. The HBA involves weighing the anticipated benefits of animal research against its predicted harms to animals but there are doubts about how objective and accountable this process is.i. To explore the harms to animals involved in pre-clinical animal studies and to assess these against the benefits for humans accruing from these studies; ii. To test the feasibility of conducting this type of retrospective HBA.Data on harms were systematically extracted from a sample of pre-clinical animal studies whose clinical relevance had already been investigated by comparing systematic reviews of the animal studies with systematic reviews of human studies for the same interventions (antifibrinolytics for haemorrhage, bisphosphonates for osteoporosis, corticosteroids for brain injury, Tirilazad for stroke, antenatal corticosteroids for neonatal respiratory distress and thrombolytics for stroke). Clinical relevance was also explored in terms of current clinical practice. Harms were categorised for severity using an expert panel. The quality of the research and its impact were considered. Bateson's Cube was used to conduct the HBA.The most common assessment of animal harms by the expert panel was 'severe'. Reported use of analgesia was rare and some animals (including most neonates) endured significant procedures with no, or only light, anaesthesia reported. Some animals suffered iatrogenic harms. Many were kept alive for long periods post-experimentally but only 1% of studies reported post-operative care. A third of studies reported that some animals died prior to endpoints. All the studies were of poor quality. Having weighed the actual harms to animals against the actual clinical benefits accruing from these studies, and taking into account the quality of the research and its impact, less than 7% of the studies were permissible according to Bateson's Cube: only the moderate bisphosphonate studies appeared to minimise harms to animals whilst being associated with benefit for humans.This is the first time the accountability of the HBA has been systematically explored across a range of pre-clinical animal studies. The regulatory systems in place when these studies were conducted failed to safeguard animals from severe suffering or to ensure that only beneficial, scientifically rigorous research was conducted. Our findings indicate a pressing need to: i. review regulations, particularly those that permit animals to suffer severe harms; ii. reform the processes of prospectively assessing pre-clinical animal studies to make them fit for purpose; and iii. systematically evaluate the benefits of pre-clinical animal research to permit a more realistic assessment of its likely future benefits

    Opposite polarities of ENSO drive distinct patterns of coral bleaching potentials in the southeast Indian Ocean.

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    Episodic anomalously warm sea surface temperature (SST) extremes, or marine heatwaves (MHWs), amplify ocean warming effects and may lead to severe impacts on marine ecosystems. MHW-induced coral bleaching events have been observed frequently in recent decades in the southeast Indian Ocean (SEIO), a region traditionally regarded to have resilience to global warming. In this study, we assess the contribution of El Niño-Southern Oscillation (ENSO) to MHWs across the mostly understudied reefs in the SEIO. We find that in extended summer months, the MHWs at tropical and subtropical reefs (divided at ~20°S) are driven by opposite ENSO polarities: MHWs are more likely to occur at the tropical reefs during eastern Pacific El Niño, driven by enhanced solar radiation and weaker Australian Monsoon, some likely alleviated by positive Indian Ocean Dipole events, and at the subtropical reefs during central Pacific La Niña, mainly caused by increased horizontal heat transport, and in some cases reinforced by local air-sea interactions. Madden-Julian Oscillations (MJO) also modulate the MHW occurrences. Projected future increases in ENSO and MJO intensity with greenhouse warming will enhance thermal stress across the SEIO. Implementing forecasting systems of MHWs can be used to anticipate future coral bleaching patterns and prepare management responses

    Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

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    The decay channel ψπ+πJ/ψ(J/ψγppˉ)\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) is studied using a sample of 1.06×1081.06\times 10^8 ψ\psi^\prime events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the ppˉp\bar{p} invariant mass spectrum. The enhancement can be fit with an SS-wave Breit-Wigner resonance function with a resulting peak mass of M=186113+6(stat)26+7(syst)MeV/c2M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2 and a narrow width that is Γ<38MeV/c2\Gamma<38 {\rm MeV/}c^2 at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics

    Knock-Down of Core Proteins Regulating MicroRNA Biogenesis Has No Effect on Sensitivity of Lung Cancer Cells to Ionizing Radiation

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    Recent studies underline the important role of microRNAs (miRNA) in the development of lung cancer. The main regulators of miRNA biogenesis are the ribonucleases Drosha, Dicer and Ago2. Here the role of core proteins of miRNA biogenesis machinery in the response of human non-small and small cell lung carcinoma cell lines to treatment with ionizing radiation was assessed. We found that Drosha and Dicer were expressed at higher levels in radioresistant but not in sensitive cell lines. However, down-regulation of either Dicer or Drosha had no effect on the sensitivity of cells to irradiation. Elimination of components of the RNA-induced silencing complex Ago2 and Tudor staphylococcal nuclease also did not sensitize cells to the same treatment. Thus, modulation of miRNA biogenesis machinery is not sufficient to increase the radiosensitivity of lung tumors and other strategies are required to combat lung cancer

    AMD, an Automated Motif Discovery Tool Using Stepwise Refinement of Gapped Consensuses

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    Motif discovery is essential for deciphering regulatory codes from high throughput genomic data, such as those from ChIP-chip/seq experiments. However, there remains a lack of effective and efficient methods for the identification of long and gapped motifs in many relevant tools reported to date. We describe here an automated tool that allows for de novo discovery of transcription factor binding sites, regardless of whether the motifs are long or short, gapped or contiguous

    Ret is essential to mediate GDNF’s neuroprotective and neuroregenerative effect in a Parkinson disease mouse model

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    Glial cell line-derived neurotrophic factor (GDNF) is a potent survival and regeneration-promoting factor for dopaminergic neurons in cell and animal models of Parkinson disease (PD). GDNF is currently tested in clinical trials on PD patients with so far inconclusive results. The receptor tyrosine kinase Ret is the canonical GDNF receptor, but several alternative GDNF receptors have been proposed, raising the question of which signaling receptor mediates here the beneficial GDNF effects. To address this question we overexpressed GDNF in the striatum of mice deficient for Ret in dopaminergic neurons and subsequently challenged these mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Strikingly, in this established PD mouse model, the absence of Ret completely abolished GDNF’s neuroprotective and regenerative effect on the midbrain dopaminergic system. This establishes Ret signaling as absolutely required for GDNF’s effects to prevent and compensate dopaminergic system degeneration and suggests Ret activation as the primary target of GDNF therapy in PD
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