Prototypical antipsychotic drugs protect hippocampal neuronal cultures against cell death induced by growth medium deprivation

BACKGROUND: Several clinical studies suggested that antipsychotic-based medications could ameliorate cognitive functions impaired in certain schizophrenic patients. Accordingly, we investigated the effects of various dopaminergic receptor antagonists – including atypical antipsychotics that are prescribed for the treatment of schizophrenia – in a model of toxicity using cultured hippocampal neurons, the hippocampus being a region of particular relevance to cognition. RESULTS: Hippocampal cell death induced by deprivation of growth medium constituents was strongly blocked by drugs including antipsychotics (10(-10)-10(-6 )M) that display nM affinities for D(2 )and/or D(4 )receptors (clozapine, haloperidol, (±)-sulpiride, domperidone, clozapine, risperidone, chlorpromazine, (+)-butaclamol and L-741,742). These effects were shared by some caspases inhibitors and were not accompanied by inhibition of reactive oxygen species. In contrast, (-)-raclopride and remoxipride, two drugs that preferentially bind D(2 )over D(4 )receptors were ineffective, as well as the selective D(3 )receptor antagonist U 99194. Interestingly, (-)-raclopride (10(-6 )M) was able to block the neuroprotective effect of the atypical antipsychotic clozapine (10(-6 )M). CONCLUSION: Taken together, these data suggest that D2-like receptors, particularly the D(4 )subtype, mediate the neuroprotective effects of antipsychotic drugs possibly through a ROS-independent, caspase-dependent mechanism

Parvalbumin Interneurons of Hippocampus Tune Population Activity at Theta Frequency

SummaryHippocampal theta rhythm arises from a combination of recently described intrinsic theta oscillators and inputs from multiple brain areas. Interneurons expressing the markers parvalbumin (PV) and somatostatin (SOM) are leading candidates to participate in intrinsic rhythm generation and principal cell (PC) coordination in distal CA1 and subiculum. We tested their involvement by optogenetically activating and silencing PV or SOM interneurons in an intact hippocampus preparation that preserves intrinsic connections and oscillates spontaneously at theta frequencies. Despite evidence suggesting that SOM interneurons are crucial for theta, optogenetic manipulation of these interneurons modestly influenced theta rhythm. However, SOM interneurons were able to strongly modulate temporoammonic inputs. In contrast, activation of PV interneurons powerfully controlled PC network and rhythm generation optimally at 8 Hz, while continuously silencing them disrupted theta. Our results thus demonstrate a pivotal role of PV but not SOM interneurons for PC synchronization and the emergence of intrinsic hippocampal theta

Editorial: Adaptation to psychological stress in sport

First paragraph: Psychological stress is ubiquitous in sport. Unsurprisingly then, research that examines the antecedents, correlates, consequences, and interventions pertaining to psychological stress in sport is sizable and broad. With this Research Topic we aimed to capture the breadth and depth of work taking place around the theme of adaptation to psychological stress in sport. Pleasingly, 111 authors responded to our call for papers, contributing 25 papers between them. In this Editorial we undertake the difficult task of synthesizing these contributions, and highlight important implications that could influence future research and practice

Integrating behavioural, imaging and transcriptional profiling to discover the impact of midlife stress in Alzheimer\u27s disease

We will be integrating this cognitive assessment with imaging of brain structure and function to understand the mechanisms by which a risk factor, in this case modifiable life stress, influences Alzheimer\u27s disease-related decline. The resultant data will be integrated and disseminated using a new open-access neuroinformatics platform developed at Western (MouseBytes.ca), which will become a unique resource for open science investigations and set the standard for sharing of behavioural data across the world.https://ir.lib.uwo.ca/brainscanprojectsummaries/1028/thumbnail.jp

An Untranslated cis-Element Regulates the Accumulation of Multiple C4 Enzymes in Gynandropsis gynandra Mesophyll Cells.

C4 photosynthesis is a complex phenotype that allows more efficient carbon capture than the ancestral C3 pathway. In leaves of C4 species, hundreds of transcripts increase in abundance compared with C3 relatives and become restricted to mesophyll (M) or bundle sheath (BS) cells. However, no mechanism has been reported that regulates the compartmentation of multiple enzymes in M or BS cells. We examined mechanisms regulating CARBONIC ANHYDRASE4 (CA4) in C4 Gynandropsis gynandra. Increased abundance is directed by both the promoter region and introns of the G. gynandra gene. A nine-nucleotide motif located in the 5' untranslated region (UTR) is required for preferential accumulation of GUS in M cells. This element is present and functional in three additional 5' UTRs and six 3' UTRs where it determines accumulation of two isoforms of CA and pyruvate,orthophosphate dikinase in M cells. Although the GgCA4 5' UTR is sufficient to direct GUS accumulation in M cells, transcripts encoding GUS are abundant in both M and BS. Mutating the GgCA4 5' UTR abolishes enrichment of protein in M cells without affecting transcript abundance. The work identifies a mechanism that directs cell-preferential accumulation of multiple enzymes required for C4 photosynthesis.We would like to thank the BBSRC for funding.This is the author accepted manuscript. The final version is available from the American Society of Plant Biologists via http://dx.doi.org/10.​1105/​tpc.​15.​0057

Finding and counting vertex-colored subtrees

The problems studied in this article originate from the Graph Motif problem introduced by Lacroix et al. in the context of biological networks. The problem is to decide if a vertex-colored graph has a connected subgraph whose colors equal a given multiset of colors $M$. It is a graph pattern-matching problem variant, where the structure of the occurrence of the pattern is not of interest but the only requirement is the connectedness. Using an algebraic framework recently introduced by Koutis et al., we obtain new FPT algorithms for Graph Motif and variants, with improved running times. We also obtain results on the counting versions of this problem, proving that the counting problem is FPT if M is a set, but becomes W[1]-hard if M is a multiset with two colors. Finally, we present an experimental evaluation of this approach on real datasets, showing that its performance compares favorably with existing software.Comment: Conference version in International Symposium on Mathematical Foundations of Computer Science (MFCS), Brno : Czech Republic (2010) Journal Version in Algorithmic

Arabidopsis uses two gluconeogenic gateways for organic acids to fuel seedling establishment.

Gluconeogenesis is a fundamental metabolic process that allows organisms to make sugars from non-carbohydrate stores such as lipids and protein. In eukaryotes only one gluconeogenic route has been described from organic acid intermediates and this relies on the enzyme phosphoenolpyruvate carboxykinase (PCK). Here we show that two routes exist in Arabidopsis, and that the second uses pyruvate, orthophosphate dikinase (PPDK). Gluconeogenesis is critical to fuel the transition from seed to seedling. Arabidopsis pck1 and ppdk mutants are compromised in seed-storage reserve mobilization and seedling establishment. Radiolabelling studies show that PCK predominantly allows sugars to be made from dicarboxylic acids, which are products of lipid breakdown. However, PPDK also allows sugars to be made from pyruvate, which is a major product of protein breakdown. We propose that both routes have been evolutionarily conserved in plants because, while PCK expends less energy, PPDK is twice as efficient at recovering carbon from pyruvate.We thank the Biotechnology and Biology Sciences Research Council for funding J.M.H. (P18931 and a studentship to B.P.W.) and P.J.E. (BB/G009724/1 and BB/K002147/1), the Isaac Newton Trust and the Max-Planck Gesellschaft for funding and ATC for a CASE studentship to H.M.A.This is the final published version. It first appeared at http://www.nature.com/ncomms/2015/150410/ncomms7659/full/ncomms7659.html

An inter­molecular dative B←N bond in 5-(4,4,5,5-tetra­methyl-1,3,2-dioxa­borolan-2-yl)-1,3-thia­zole

The title compound, C9H14BNO2S, is in an unusual bend conformation and the B atom of one mol­ecule within the crystal forms an inter­molecular dative bond with the N atom of a neighbouring mol­ecule, an infrequent phenomenon in boronic derivative crystals

Bubbles and jackets: new scaling bounds in topological group field theories

We use a reformulation of topological group field theories in 3 and 4 dimensions in terms of variables associated to vertices, in 3d, and edges, in 4d, to obtain new scaling bounds for their Feynman amplitudes. In both 3 and 4 dimensions, we obtain a bubble bound proving the suppression of singular topologies with respect to the first terms in the perturbative expansion (in the cut-off). We also prove a new, stronger jacket bound than the one currently available in the literature. We expect these results to be relevant for other tensorial field theories of this type, as well as for group field theory models for 4d quantum gravity.Comment: v2: Minor modifications to match published versio