The hippocampus is crucial for spatial navigation and episodic memory formation. Hippocampal place cells exhibit spatially selective activity within an environment and have been proposed to form the ...neural basis of a cognitive map of space that supports these mnemonic functions. However, the direct influence of place cell activity on spatial navigation behavior has not yet been demonstrated. Using an ‘all-optical’ combination of simultaneous two-photon calcium imaging and two-photon optogenetics, we identified and selectively activated place cells that encoded behaviorally relevant locations in a virtual reality environment. Targeted stimulation of a small number of place cells was sufficient to bias the behavior of animals during a spatial memory task, providing causal evidence that hippocampal place cells actively support spatial navigation and memory.
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•Two-photon optogenetics in VR enables targeted manipulation of place cell ensembles•Activating specific place cell ensembles drives their spatially associated behavior•Place cell stimulation inhibits endogenous place code expression and triggers remapping•Direct evidence for a causal role of place cells in spatial navigation
Selective stimulation of a small number of hippocampal place cells in mice provides causal evidence that hippocampal place cells actively support spatial navigation and memory.
Two-photon microscopy is widely used to investigate brain function across multiple spatial scales. However, measurements of neural activity are compromised by brain movement in behaving animals. ...Brain motion-induced artifacts are typically corrected using post hoc processing of two-dimensional images, but this approach is slow and does not correct for axial movements. Moreover, the deleterious effects of brain movement on high-speed imaging of small regions of interest and photostimulation cannot be corrected post hoc. To address this problem, we combined random-access three-dimensional (3D) laser scanning using an acousto-optic lens and rapid closed-loop field programmable gate array processing to track 3D brain movement and correct motion artifacts in real time at up to 1 kHz. Our recordings from synapses, dendrites and large neuronal populations in behaving mice and zebrafish demonstrate real-time movement-corrected 3D two-photon imaging with submicrometer precision.
•Regions such as the MLR were discovered using electrical stimulation.•Genetic and optogenetic techniques are now revealing functional heterogeneity within brainstem nuclei.•Specific neurotransmitter ...identity has been linked to distinct functional roles.•We review advances across vertebrate models in understanding supraspinal control of locomotion.
Electrical stimulation of various brainstem nuclei has revealed sites capable of initiating and modulating locomotion. However, subsequent experiments have revealed that these regions are functionally heterogeneous. Modern techniques including molecular-genetic methods to label cell types and optogenetic approaches to manipulate neural activity are now enabling functional examination at the cellular level. In this review, we will highlight recent work revealing distinct roles for neurons of defined neurotransmitter identity and show how comparisons across species can stimulate new experimental and analytical approaches to further our understanding of how supraspinal populations function at a cellular level to control precise aspects of behaviour.
Human parvovirus 4 (PARV4), a recently discovered parvovirus found exclusively in human plasma and liver tissue, was considered phylogenetically distinct from other parvoviruses. Here, we report the ...discovery of two novel parvoviruses closely related to PARV4, porcine hokovirus (PHoV) and bovine hokovirus (BHoV), from porcine and bovine samples in Hong Kong. Their nearly full-length sequences were also analysed. PARV4-like viruses were detected by PCR among 44.4 % (148/333) of porcine samples (including lymph nodes, liver, serum, nasopharyngeal and faecal samples), 13 % (4/32) of bovine spleen samples and 2 % (7/362) of human serum samples that were sent for human immunodeficiency virus and hepatitis C virus antibody tests. Three distinct parvoviruses were identified, including two novel parvoviruses, PHoV and BHoV, from porcine and bovine samples and PARV4 from humans, respectively. Analysis of genome sequences from seven PHoV strains, from three BHoV strains and from one PARV4 strain showed that the two animal parvoviruses were most similar to PARV4 with 61.5-63 % nt identities and, together with PARV4 (HHoV), formed a distinct cluster within the family Parvoviridae. The three parvoviruses also differed from other parvoviruses by their relatively large predicted VP1 protein and the presence of a small unique conserved putative protein. Based on these results, we propose a separate genus, Hokovirus, to describe these three parvoviruses. The co-detection of porcine reproductive and respiratory syndrome virus, the agent associated with the recent 'high fever' disease outbreaks in pigs in China, from our porcine samples warrants further investigation.
The pseudomalignant nature of the placenta prompted us to search for tumor suppressor gene hypermethylation, a phenomenon widely reported in cancer, in the human placenta. Nine tumor suppressor genes ...were studied. Hypermethylation of the Ras association domain family 1 A ( RASSF1A ) gene was found in human placentas from all three trimesters of pregnancy but was absent in other fetal tissues. Hypermethylation of Rassf1 was similarly observed in placentas from the rhesus monkey but not the mouse. An inverse relationship between RASSF1A promoter methylation and gene expression was demonstrated by bisulfite sequencing of microdissected placental cells and immunohistochemical staining of placental tissue sections using an anti-RASSF1A antibody. Treatment of choriocarcinoma cell lines, JAR and JEG3, by 5-aza-2′-deoxycytidine and trichostatin A led to reduction in RASSF1A methylation but increased expression. These observations extend the analogy between the primate placenta and malignant tumors to the epigenetic level.
We present constraints on cosmological parameters based on a sample of Sunyaev-Zel'dovich-selected (SZ-selected) galaxy clusters detected in a millimeter-wave survey by the Atacama Cosmology ...Telescope. The cluster sample used in this analysis consists of nine optically confirmed high-mass clusters comprising the high-significance end of the total cluster sample identified in 455 deg2 of sky surveyed during 2008 at 148 GHz. We focus on the most massive systems to reduce the degeneracy between unknown cluster astrophysics and cosmology derived from SZ surveys. We describe the scaling relation between cluster mass and SZ signal with a four-parameter fit. Marginalizing over the values of the parameters in this fit with conservative priors gives Delta *s8 = 0.851 ? 0.115 and w = --1.14 ? 0.35 for a spatially flat wCDM cosmological model with Wilkinson Microwave Anisotropy Probe (WMAP) seven-year priors on cosmological parameters. This gives a modest improvement in statistical uncertainty over WMAP seven-year constraints alone. Fixing the scaling relation between the cluster mass and SZ signal to a fiducial relation obtained from numerical simulations and calibrated by X-ray observations, we find Delta *s8 = 0.821 ? 0.044 and w = --1.05 ? 0.20. These results are consistent with constraints from WMAP7 plus baryon acoustic oscillations plus Type Ia supernova which give Delta *s8 = 0.802 ? 0.038 and w = --0.98 ? 0.053. A stacking analysis of the clusters in this sample compared to clusters simulated assuming the fiducial model also shows good agreement. These results suggest that, given the sample of clusters used here, both the astrophysics of massive clusters and the cosmological parameters derived from them are broadly consistent with current models.
In this randomized trial involving patients undergoing invasive ventilation, pantoprazole decreased the risk of upper gastrointestinal bleeding as compared with placebo but did not affect mortality.
Death-associated protein kinase (DAP-kinase) is a serine/threonine kinase and a positive mediator of apoptosis. Down-regulation of DAP-kinase was associated with increased metastatic potential of ...tumors. Gene promoter hypermethylation could lead to down-regulation of DAP-kinase. We aimed to investigate the frequency of gene promoter methylation of DAP-kinase in gastric carcinoma (GCA) and assessed its association with clinicopathological features. One hundred and seven cases of gastric carcinoma were examined. The relevant clinical and pathological features, including survival data were reviewed. Methylation status was assessed by methylation-specific PCR (MSP). Seventy-four cases (69.2%) of GCA demonstrated promoter methylation of DAP-kinase. Methylation of DAP-kinase was observed in intestinal, diffuse and mixed type of GCA. It also occurred in similar frequency among antral, body and cardiac gastric cancer. No association between methylation status and age or gender was demonstrated. However, the methylated cases correlated with the presence of nodal metastasis (p=0.041), advance stage of disease (p=0.029) and a poorer event-free survival (log-rank test p=0.0141). DAP-kinase promoter methylation as a potential prognostic marker for gastric cancer patients deserved further evaluation.
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