De novo protein sequence analysis of Macaca mulatta

<p>Abstract</p> <p>Background</p> <p><it>Macaca mulatta </it>is one of the most utilized non-human primate species in biomedical research offering unique behavioral, neuroanatomical, and neurobiochemcial similarities to humans. This makes it a unique organism to model various diseases such as psychiatric and neurodegenerative illnesses while also providing insight into the complexities of the primate brain. A major obstacle in utilizing rhesus monkey models for human disease is the paucity of protein annotations for this species (~42,000 protein annotations) compared to 330,210 protein annotations for humans. The lack of available information limits the use of rhesus monkey for proteomic scale studies which rely heavily on database searches for protein identification. While characterization of proteins of interest from <it>Macaca mulatta </it>using the standard database search engines (e.g., MASCOT) can be accomplished, searches must be performed using a 'broad species database' which does not provide optimal confidence in protein annotation. Therefore, it becomes necessary to determine partial or complete amino acid sequences using either manual or automated <it>de novo </it>peptide sequence analysis methods.</p> <p>Results</p> <p>The recently popularized MALDI-TOF-TOF mass spectrometer yields a complex MS/MS fragmentation pattern difficult to characterize by manual <it>de novo </it>sequencing method on a proteomics scale. Therefore, PEAKS assisted <it>de novo </it>sequencing was performed on nucleus accumbens cytosolic proteins from <it>Macaca mulatta</it>. The most abundant peptide fragments '<it>b-ions </it>and <it>y-ions</it>', the less abundant peptide fragments '<it>a-ions</it>' as well as the <it>immonium ions </it>were utilized to develop confident and complete peptide sequences <it>de novo </it>from MS/MS spectra. The generated sequences were used to perform homology searches to characterize the protein identification.</p> <p>Conclusion</p> <p>The current study validates a robust method to confidently characterize the proteins from an incomplete sequence database of <it>Macaca mulatta</it>, using the PEAKS <it>de novo </it>sequencing software, facilitating the use of this animal model in various neuroproteomics studies.</p

CommonMind Consortium provides transcriptomic and epigenomic data for Schizophrenia and Bipolar Disorder

Schizophrenia and bipolar disorder are serious mental illnesses that affect more than 2% of adults. While large-scale genetics studies have identified genomic regions associated with disease risk, less is known about the molecular mechanisms by which risk alleles with small effects lead to schizophrenia and bipolar disorder. In order to fill this gap between genetics and disease phenotype, we have undertaken a multi-cohort genomics study of postmortem brains from controls, individuals with schizophrenia and bipolar disorder. Here we present a public resource of functional genomic data from the dorsolateral prefrontal cortex (DLPFC; Brodmann areas 9 and 46) of 986 individuals from 4 separate brain banks, including 353 diagnosed with schizophrenia and 120 with bipolar disorder. The genomic data include RNA-seq and SNP genotypes on 980 individuals, and ATAC-seq on 269 individuals, of which 264 are a subset of individuals with RNA-seq. We have performed extensive preprocessing and quality control on these data so that the research community can take advantage of this public resource available on the Synapse platform at http://CommonMind.org

Dominance of Objects over Context in a Mediotemporal Lobe Model of Schizophrenia

Background: A large body of evidence suggests impaired context processing in schizophrenia. Here we propose that this impairment arises from defective integration of mediotemporal ‘what ’ and ‘where ’ routes, carrying object and spatial information to the hippocampus. Methodology and Findings: We have previously shown, in a mediotemporal lobe (MTL) model, that the abnormal connectivity between MTL regions observed in schizophrenia can explain the episodic memory deficits associated with the disorder. Here we show that the same neuropathology leads to several context processing deficits observed in patients with schizophrenia: 1) failure to choose subordinate stimuli over dominant ones when the former fit the context, 2) decreased contextual constraints in memory retrieval, as reflected in increased false alarm rates and 3) impaired retrieval of contextual information in source monitoring. Model analyses show that these deficits occur because the ‘schizophrenic MTL ’ forms fragmented episodic representations, in which objects are overrepresented at the expense of spatial contextual information. Conclusions and Significance: These findings highlight the importance of MTL neuropathology in schizophrenia, demonstrating that it may underlie a broad spectrum of deficits, including context processing and memory impairments. It is argued that these processing deficits may contribute to central schizophrenia symptoms such as contextuall

Task design and interaction in collaborative writing: the students’ story

This article investigates student behaviour on collaborative assignments, looking at the relationship between task type and interaction, and considers the implications for task design. Students reported on interactions in a year-long workplace-focussed group communication project, comparing these with interactions on other academy based group assignments. Differences were seen in the amount of brainstorming, the criteria for dividing up work, the intensity of editing, and how conflict was managed. Contributing factors to these differences included the presence or absence of a creative element, the instrumental nature of the task, and the need for a collective approach inherent in the task design