Transcriptome in vivo analysis (TIVA) of spatially defined single cells in live tissue.

Transcriptome profiling of single cells resident in their natural microenvironment depends upon RNA capture methods that are both noninvasive and spatially precise. We engineered a transcriptome in vivo analysis (TIVA) tag, which upon photoactivation enables mRNA capture from single cells in live tissue. Using the TIVA tag in combination with RNA sequencing (RNA-seq), we analyzed transcriptome variance among single neurons in culture and in mouse and human tissue in vivo.

miR-199a-5p silencing regulates the unfolded protein response in chronic obstructive pulmonary disease and α1-antitrypsin deficiency.

Rationale: Retention of abnormal α1-antitrypsin (AAT) activates the unfolded protein response in AAT-deficient monocytes. The regulatory role of microRNAs (miRNAs) in unfolded protein responses and chronic obstructive pulmonary disease pathogenesis has not been investigated.

Objectives: To investigate miRNA expression and function in MM and ZZ monocytes and identify miRNA(s) regulating the unfolded protein response.

Serotonergic neuron regulation informed by in vivo single-cell transcriptomics.

Despite the recognized importance of the dorsal raphe (DR) serotonergic (5-HT) nuclei in the pathophysiology of depression and anxiety, the molecular components/putative drug targets expressed by these neurons are poorly characterized. Utilizing the promoter of an ETS domain transcription factor that is a stable marker of 5-HT neurons (Pet-1) to drive 5-HT neuronal expression of YFP, we identified 5-HT neurons in live acute slices. We isolated RNA from single 5-HT neurons in the ventromedial and lateral wings of the DR and performed single-cell RNA-Seq analysis identifying >500 G-protein coupled receptors (GPCRs) including receptors for classical transmitters, lipid signals, and peptides as well as dozens of orphan-GPCRs.

Cytoplasmic intron retention, function, splicing, and the sentinel RNA hypothesis.

Cytoplasmic splicing represents a newly emerging level of transcriptional regulation adding to the molecular diversity of mammalian cells. As examples of this noncanonical form of transcript processing are discovered, the evidence of its importance to normal cellular function grows. Work from a number of groups using a variety of cell types is steadily identifying a large number of transcripts (and soon to be even larger as genome-wide analyses of retained introns across a number of cellular phenotypes are currently underway) that undergo some level of regulated endogenous extranuclear splicing as part of their normal biosynthetic pathway.

Thermostable single domain antibody-maltose binding protein fusion for Bacillus anthracis spore protein BclA detection.

We constructed a genetic fusion of a single domain antibody (sdAb) with the thermal stable maltose binding protein from the thermophile Pyrococcus furiosus (PfuMBP). Produced in the Escherichia coli cytoplasm with high yield, it proved to be a rugged and effective immunoreagent. The sdAb-A5 binds BclA, a Bacillus anthracis spore protein, with high affinity (K(D) ∼ 50 pM).

Biomarkers in schizophrenia: a brief conceptual consideration.

Biomarkers have been sought after in the field of schizophrenia research for decades. In this paper, we discuss some of the concepts around developing biomarkers in an effort to understand why the use of biomarkers for schizophrenia has not been realized. In particular, we address the following 4 questions.

Subcellular RNA sequencing reveals broad presence of cytoplasmic intron-sequence retaining transcripts in mouse and rat neurons.

Recent findings have revealed the complexity of the transcriptional landscape in mammalian cells. One recently described class of novel transcripts are the Cytoplasmic Intron-sequence Retaining Transcripts (CIRTs), hypothesized to confer post-transcriptional regulatory function. For instance, the neuronal CIRT KCNMA1i16 contributes to the firing properties of hippocampal neurons.

A systematic, quantitative review of blood autoantibodies in schizophrenia.

Objective: Schizophrenia is associated with immune system dysfunction, including an increased prevalence of autoimmune disorders and autoantibodies. We performed a systematic, quantitative review of self-reacting blood antibodies in patients with schizophrenia.

Method: We identified articles by searching PubMed, PsychInfo, and ISI, and the reference lists of identified studies.

Lipidomics reveals early metabolic changes in subjects with schizophrenia: effects of atypical antipsychotics.

There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group), 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group), and 29 race-matched control subjects without schizophrenia.

What patients want: preferences regarding hospital pharmacy services.

Background: The role of hospital pharmacists has evolved over the past couple of decades from preparation and distribution of medications to active involvement in health care teams, through identification and resolution of patients' medication-related issues in an effort to improve patient outcomes. However, patients' preferences about pharmacy services are not well known.

Objective: To use content analysis of open-ended survey responses from recently discharged patients to determine desired pharmacy services.

An automated algorithm for consolidating dates of diagnosis from multiple sources.

Background: Multiple dates of diagnosis are often received from different reporting sources at a central cancer registry. Resolving these inconsistencies can be a labor-intensive task. To our knowledge, no algorithms for the consolidation of diagnosis dates have been published.

High-dose oral ziprasidone versus conventional dosing in schizophrenia patients with residual symptoms: the ZEBRAS study.

Uncontrolled studies have suggested that increasing the dose of ziprasidone above the standard maximum daily dose of 160 mg may be more effective for some patients with schizophrenia. To test this hypothesis, we conducted an 8-week, placebo-controlled, fixed-dose escalation trial comparing ziprasidone 160 versus 320 mg/d in individuals with schizophrenia or schizoaffective disorder who remained symptomatic despite treatment with ziprasidone 160 mg/d for at least 3 weeks. Of 75 randomized patients, 42 completed the study.

Does a latent class underlie schizotypal personality disorder? Implications for schizophrenia.

Despite growing enthusiasm for dimensional models of personality pathology, the taxonic versus dimensional status of schizotypal personality disorder (PD) remains a point of contention in modern psychiatry. The current study aimed to determine empirically the latent structure of schizotypal PD. We examined the latent structure of schizotypal PD in the Psychiatric Morbidity Survey in Great Britain and the second wave of the U.

Meta-analysis of oxidative stress in schizophrenia.

Background: Schizophrenia is associated with impaired antioxidant defense, including abnormal serum, plasma, and red blood cell (RBC) oxidative stress parameters. We performed a meta-analysis of these associations, considering the effect of clinical status and antipsychotic treatment after an acute exacerbation of psychosis.

Methods: We identified articles by searching PubMed, PsychInfo, and Institute for Scientific Information, and the reference lists of identified studies.

The genomic psychiatry cohort: partners in discovery.

The Genomic Psychiatry Cohort (GPC) is a longitudinal resource designed to provide the necessary population-based sample for large-scale genomic studies, studies focusing on Research Domain Criteria (RDoC) and/or other alternate phenotype constructs, clinical and interventional studies, nested case-control studies, long-term disease course studies, and genomic variant-to-phenotype studies. We provide and will continue to encourage access to the GPC as an international resource. DNA and other biological samples and diagnostic data are available through the National Institute of Mental Health (NIMH) Repository.

A prevalence study of urinary tract infections in acute relapse of schizophrenia.

Objective: Schizophrenia is associated with immune abnormalities and increased mortality from infectious diseases. The aim of this study was to examine whether acute relapse of schizophrenia was associated with urinary tract infection (UTI), in comparison with controls, after controlling for potential confounding factors.

Method: In a prevalence study conducted from January 2010 to April 2012 at Georgia Health Sciences University Medical Center, Augusta, we recruited 136 adult subjects (mean age = 42.

Pharmacological characterization of GSK573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases.

Activation of muscarinic subtype 3 (M3) muscarinic cholinergic receptors (mAChRs) increases airway tone, whereas its blockade improves lung function and quality of life in patients with pulmonary diseases. The present study evaluated the pharmacological properties of a novel mAChR antagonist, GSK573719 (4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.

Neuroimaging schizophrenia: a picture is worth a thousand words, but is it saying anything important?

Schizophrenia is characterized by neurostructural and neurofunctional aberrations that have now been demonstrated through neuroimaging research. The article reviews recent studies that have attempted to use neuroimaging to understand the relation between neurological abnormalities and aspects of the phenomenology of schizophrenia. Neuroimaging studies show that neurostructural and neurofunctional abnormalities are present in people with schizophrenia and their close relatives and may represent putative endophenotypes.

Misbehaviour in Pony Club horses: incidence and risk factors.

Reasons For Performing Study: Horse misbehaviour is an important cause of poor performance in Pony Club horses, is associated with horse-related rider injuries and has been implicated as a nonspecific presenting sign for musculoskeletal pain. Despite this, little is known about the incidence of and risk factors for misbehaviour in Pony Club horses.

Objective: This study aimed to describe the incidence and types of misbehaviour in a cohort of Pony Club horses and to identify risk factors for misbehaviour during riding.