PubMed Journal Database | Annals of general psychiatry 
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Showing PubMed Articles 1–25 of 430,000+ from annals of general psychiatry
Abstract Significance: Manganese superoxide dismutase (SOD2), encoded by the nuclear gene SOD2, is a critical mitochondrial antioxidant enzyme whose activity has broad implications in health and disease. Thirty years ago, Oberley and Buettner elegantly folded SOD2 into cancer biology with the free radical theory of cancer, which was built on the observation that many human cancers had reduced SOD2 activity. In the original formulation, the loss of SOD2 in tumor cells produced a state of perpetual oxidative...
A Bayesian statistical model and estimation methodology based on forward projection adaptive Markov chain Monte Carlo is developed in order to perform the calibration of a high-dimensional nonlinear system of ordinary differential equations representing an epidemic model for human papillomavirus types 6 and 11 (HPV-6, HPV-11). The model is compartmental and involves stratification by age, gender and sexual-activity group. Developing this model and a means to calibrate it efficiently is relevant because HP...
Effectively combining many classification instruments or diagnostic measurements together to improve the classification accuracy of individuals is a common idea in disease diagnosis or classification. These ensemble-type diagnostic methods can be constructed with respect to different kinds of performance criterions. Among them, the receiver operating characteristic (ROC) curve is the most popular criterion, which, together with some indexes derived from it, is commonly used to evaluate and summarize the per...
A simple decision analytic solution to the comparison of two binary diagnostic tests.
One of the most basic biostatistical problems is the comparison of two binary diagnostic tests. Commonly, one test will have greater sensitivity, and the other greater specificity. In this case, the choice of the optimal test generally requires a qualitative judgment as to whether gains in sensitivity are offset by losses in specificity. Here, we propose a simple decision analytic solution in which sensitivity and specificity are weighted by an intuitive parameter, the threshold probability of disease at wh...
Abstract Significance: Chronic obstructive pulmonary disease (COPD) is predominantly a tobacco smoke-triggered disease with features of chronic low-grade systemic inflammation and aging (inflammaging) of the lung associated with steroid resistance induced by cigarette smoke (CS)-mediated oxidative stress. Oxidative stress induces various kinase signaling pathways leading to chromatin modifications (histone acetylation/deacetylation and histone methylation/demethylation) in inflammation, senescence, and ster...
Establishing causality for dopamine in neural function and behavior with optogenetics.
Dopamine (DA) is known to play essential roles in neural function and behavior. Accordingly, DA neurons have been the focus of intense experimental investigation that has led to many important advances in our understanding of how DA influences these processes. However, it is becoming increasingly appreciated that delineating the precise contributions of DA neurons to cellular, circuit, and systems-level phenomena will require more sophisticated control over their patterns of activity than conventional techn...
Pharmacosynthetics: Reimagining the pharmacogenetic approach.
Pharmacology, in its broadest interpretation, is defined as the study of the interaction between physiological entities and drugs. In modern neuropsychopharmacology, this interaction is viewed as the drug itself on one side and signal transducer (receptor), the signal transduction cascade (effector proteins, second messengers), the cellular response (transcriptional regulation, activity modulation), the organ response (brain circuitry modulation), and, finally, the whole organism response (behavior) on the...
The lateral habenula (LHb) is part of the habenular complex in the dorsal diencephalon. The LHb is an important regulator of several neurotransmitter systems in the midbrain; disturbances in this regulation may contribute to mood disorders, abnormalities in cognition, drive, and addiction. Owing to the critical role this nucleus plays in modulating activity of midbrain nuclei, there has been a rapid increase in studies targeting the LHb in the recent years. In this review, we describe studies using traditio...
Abstract Aims: Mesenchymal stem cells (MSCs) with multilineage differentiation capacity and immunomodulatory properties are novel sources for cell therapy. However, in vitro expansion of these rare somatic stem cells leads to senescence, resulting in declines of differentiation and proliferative capacities. We therefore investigated the mechanisms mediating senescence in human fetal MSCs termed placenta-derived multipotent cells (PDMCs). Results: Long-term cultured PDMCs underwent senescence, with increased...
The physiology and circuitry associated with dorsal cochlear nucleus neurons (DCN) have been well described. The ability to remotely manipulate neuronal activity in these neurons would represent a step forward in the ability to understand the specific function of DCN neurons in hearing. Although, optogenetics has been used to study the function of pathways in other systems for several years, in the auditory system only neurons in the auditory cortex have been studied using this technique. Adeno-associated v...
The respiratory chemoreception conundrum: Light at the end of the tunnel?
Arterial PCO2 is tightly regulated via changes in breathing. A rise in PCO2 activates the carotid bodies and exerts additional effects on neurons located within the CNS, causing an increase in lung ventilation. Central respiratory chemoreception refers to the component of this homeostatic reflex that is triggered by activation of receptors located within the brain (central chemoreceptors). Throughout the body, CO2 generally operates via the proxy of pH. Since countless proteins, ion channels and neurons dis...
Transforming the Model T: random effects meta-analysis with stable weights.
Standard meta-analytic theory assumes that study outcomes are normally distributed with known variances. However, methods derived from this theory are often applied to effect sizes having skewed distributions with estimated variances. Both shortcomings can be largely overcome by first applying a variance stabilizing transformation. Here we concentrate on study outcomes with Student t-distributions and show that we can better estimate parameters of fixed or random effects models with confidence intervals usi...
Deciphering the epigenetic code: an overview of DNA methylation analysis methods.
Abstract Significance: Methylation of cytosine in DNA is linked with gene regulation, and this has profound implications in development, normal biology, and disease conditions in many eukaryotic organisms. A wide range of methods and approaches exist for its identification, quantification, and mapping within the genome. While the earliest approaches were nonspecific and were at best useful for quantification of total methylated cytosines in the chunk of DNA, this field has seen considerable progress and dev...
Balancing reactive oxygen species in the epigenome: NADPH oxidases as target and perpetrator.
Abstract Significance: NADPH oxidases are important sources for regulated generation of reactive oxygen species (ROS). The main ROS produced are superoxide and hydrogen peroxide, both of which are redox signaling molecules in the context of various cellular functions. Redox imbalance due to excessive or insufficient ROS is a hallmark of pathophysiological aspects, including cancer development and progression. Recent Advances: Epigenetic silencing of NADPH oxidases by hypermethylation of their promoter regio...
Statistical analysis of mixed recurrent event data with application to cancer survivor study.
Event history studies occur in many fields including economics, medical studies, and social science. In such studies concerning some recurrent events, two types of data have been extensively discussed in the literature. One is recurrent event data that arise if study subjects are monitored or observed continuously. In this case, the observed information provides the times of all occurrences of the recurrent events of interest. The other is panel count data, which occur if the subjects are monitored or obser...
Optogenetic dissection of neural circuits underlying emotional valence and motivated behaviors.
The neural circuits underlying emotional valence and motivated behaviors are several synapses away from both defined sensory inputs and quantifiable motor outputs. Electrophysiology has provided us with a suitable means for observing neural activity during behavior, but methods for controlling activity for the purpose of studying motivated behaviors have been inadequate: electrical stimulation lacks cellular specificity and pharmacological manipulation lacks temporal resolution. The recent emergence of opto...
G protein-coupled receptors (GPCRs) can activate simultaneously multiple signaling pathways upon agonist binding. The combined use of engineered GPCRs, such as the receptors activated solely by synthetic ligands (RASSLs), and of biased ligands that activate only one pathway at a time might help deciphering the physiological role of each G protein signaling. In order to find serotonin type 4 receptor (5-HT4R) biased ligands, we analyzed the ability of several compounds to activate the Gs and Gq/11 pathways i...
Abstract Aims: H2S, a third member of gasotransmitter family along with nitric oxide and carbon monoxide, exerts a wide range of cellular and molecular actions in our body. Cystathionine gamma-lyase (CSE) is a major H2S-generating enzyme in our body. Aging at the cellular level, known as cellular senescence, can result from increases in oxidative stress. The aim of this study was to investigate how H2S attenuates oxidative stress and delays cellular senescence. Results: Here we showed that mouse embryonic f...
Optogenetic identification of striatal projection neuron subtypes during in vivo recordings.
Optogenetics has revolutionized neuroscience over the past several years by allowing researchers to modulate the activity of specific cell types, both in vitro and in vivo. One promising application of optogenetics is to use channelrhodopsin-2 (ChR2) mediated spiking to identify distinct cell types in electrophysiological recordings from awake behaving animals. In this paper, we apply this approach to in vivo recordings of the two major projection cell types in the striatum: the direct- and indirect-pathway...
Post-translational control of protein function by disulfide bond cleavage.
Abstract Protein action in nature is largely controlled by the level of expression and by post-translational modifications. Post-translational modifications result in a proteome that is at least two orders of magnitude more diverse than the genome. There are three basic types of post-translational modifications: covalent modification of an amino acid side chain, hydrolytic cleavage or isomerization of a peptide bond, and reductive cleavage of a disulfide bond. This review addresses the modification of disul...
This study evaluated the role of cyclophilin A (CyPA) in early phase of atherosclerosis and also examined the atheroprotective effects of melatonin due to its antioxidant properties.
On estimating average effects for multiple treatment groups.
We propose to estimate average exposure (or treatment) effects from observational data for multiple exposure groups by fitting an approximation of the marginal sample distribution of the response variable in each exposure group to the data. The marginal sample distribution is a function of the true distribution of the response variable in the population and the assignment rule governing the allocation of the subjects to different exposure groups. The assignment rule can depend on the response variable in ad...
Egr2-neurons control the adult respiratory response to hypercapnia.
`The early growth response 2 transcription factor, Egr2, establishes a population of brainstem neurons essential for normal breathing at birth. Egr2-null mice die perinatally of respiratory insufficiency characterized by subnormal respiratory rate and severe apneas. Here we bypass this lethality using a noninvasive pharmacogenetic approach to inducibly perturb neuron activity postnatally, and ask if Egr2-neurons control respiration in adult mice. We found that the normal ventilatory increase in response to...
The main purpose of microarray studies is screening of differentially expressed genes as candidates for further investigation. Because of limited resources in this stage, prioritizing genes are relevant statistical tasks in microarray studies. For effective gene selections, parametric empirical Bayes methods for ranking and selection of genes with largest effect sizes have been proposed (Noma et al., 2010; Biostatistics 11: 281-289). The hierarchical mixture model incorporates the differential and non-diffe...
No one treatment is likely to affect all patients with a disorder in the same way. A treatment highly effective for some may be ineffective or even harmful for others. Statistically significant or not, the effect sizes of many treatments tend to be small. Consequently, emphasis in clinical research is gradually shifting (1) to increased focus on effect sizes and (2) to discovery and documentation of moderators of treatment effect on outcome in randomized clinical trials, that is, personalized medicine, in w...
