The Vocascope - An Experimental Study in the Visual Measurement of Pitch and Quality

The project herein described is an experimental attempt to con- struct visual aids for the study of voice. Its purposes are: (1) to ako possible the visual perception of pitch change on a vertical scale; (2) to isolate certain overtones of the fundamental frequency in the hope of deriving some assistance to the improvement of quality. The principle of operation is the psychological phenomenon of stroboscopy, the illusion of stationary, constant light, as a result of synchronized interrupted vision. The Vocascope is composed of four essential parts: (1) the scanning drugs, (2) the light source, (3) the amplifier, (4) the filter

"Drinking in the Dark" (DID): a simple mouse model of binge-like alcohol intake

One of the greatest challenges that scientists face when studying the neurobiology and/or genetics of alcohol (ethanol) consumption is that most preclinical animal models do not voluntarily consume enough ethanol to achieve pharmacologically meaningful blood ethanol concentrations (BECs). Recent rodent models have been developed that promote binge-like levels of ethanol consumption associated with high BECs (i.e., ≥100 mg/dl). This unit describes procedures for an animal model of binge-like ethanol drinking which has come to be called "drinking in the dark" (DID). The "basic" variation of DID involves replacing the water bottle with a bottle containing 20% ethanol for 2 to 4 hr, beginning 3 hr into the dark cycle, on cages of singly-housed C57BL/6J mice. Using this procedure, mice typically consume enough ethanol to achieve BECs >100 mg/dl and to exhibit behavioral evidence of intoxication. An alternative two-bottle (ethanol and water) procedure is also described

Genetic relationship between predisposition for binge alcohol consumption and blunted sensitivity to adverse effects of alcohol in mice

BACKGROUND: Initial sensitivity to ethanol (EtOH) and the capacity to develop acute functional tolerance (AFT) to its adverse effects may influence the amount of alcohol consumed and may also predict future alcohol use patterns. The current study assessed sensitivity and AFT to the ataxic and hypnotic effects of EtOH in the first replicate of mice (HDID-1) selectively bred for high blood EtOH concentrations (BECs) following limited access to EtOH in the Drinking in the Dark (DID) paradigm. METHODS: Naïve male and female HDID-1 and HS/Npt mice from the progenitor stock were evaluated in 3 separate experiments. In Experiments 1 and 2, EtOH-induced ataxia was assessed using the static dowel task. In Experiment 3, EtOH-induced hypnosis was assessed by using modified restraint tubes to measure the loss of righting reflex (LORR). RESULTS: HDID-1 mice exhibited reduced initial sensitivity to both EtOH-induced ataxia (p < 0.001) and hypnosis (p < 0.05) relative to HS/Npt mice. AFT was calculated by subtracting the BEC at loss of function from the BEC at recovery (Experiments 1 and 3) or by subtracting BEC at an initial recovery from the BEC at a second recovery following an additional alcohol dose (Experiment 2). The dowel test yielded no line differences in AFT, but HS/Npt mice developed slightly greater AFT to EtOH-induced LORR than HDID-1 (p < 0.05). CONCLUSIONS: These results suggest that HDID-1 mice exhibit aspects of blunted ataxic and hypnotic sensitivity to EtOH which may influence their high EtOH intake via DID, but do not display widely different development of AFT. These findings differ from previous findings with the high alcohol-preferring (HAP) selected mouse lines, suggesting that genetic predisposition for binge, versus other forms of excessive alcohol consumption, is associated with unique responses to EtOH-induced motor incoordination

How Should Addiction-Related Research at the National Institutes of Health be Reorganized?

The decades-old debate about the optimum organizational structure of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and National Institute on Drug Abuse (NIDA) has reached a crescendo with the recent deliberations of the Scientific Management Review Board, which, despite the lack of a crisis, proposed a structural reorganization that would dissolve the two institutes and create a new institute for substance use, abuse, and addiction, in hope of new scientific and public health advances (Collins, 2010). For a new institute to succeed, a multitude of potential challenges need to be negotiated effectivel

Preferential regulation of stably expressed genes in the human genome suggests a widespread expression buffering role of microRNAs

In this study, we comprehensively explored the stably expressed genes (SE genes) and fluctuant genes (FL genes) in the human genome by a meta-analysis of large scale microarray data. We found that these genes have distinct function distributions. miRNA targets are shown to be significantly enriched in SE genes by using propensity analysis of miRNA regulation, supporting the hypothesis that miRNAs can buffer whole genome expression fluctuation. The expression-buffering effect of miRNA is independent of the target site number within the 3'-untranslated region. In addition, we found that gene expression fluctuation is positively correlated with the number of transcription factor binding sites in the promoter region, which suggests that coordination between transcription factors and miRNAs leads to balanced responses to external perturbations

Integrative Analysis of Low- and High-Resolution eQTL

The study of expression quantitative trait loci (eQTL) is a powerful way of detecting transcriptional regulators at a genomic scale and for elucidating how natural genetic variation impacts gene expression. Power and genetic resolution are heavily affected by the study population: whereas recombinant inbred (RI) strains yield greater statistical power with low genetic resolution, using diverse inbred or outbred strains improves genetic resolution at the cost of lower power. In order to overcome the limitations of both individual approaches, we combine data from RI strains with genetically more diverse strains and analyze hippocampus eQTL data obtained from mouse RI strains (BXD) and from a panel of diverse inbred strains (Mouse Diversity Panel, MDP). We perform a systematic analysis of the consistency of eQTL independently obtained from these two populations and demonstrate that a significant fraction of eQTL can be replicated. Based on existing knowledge from pathway databases we assess different approaches for using the high-resolution MDP data for fine mapping BXD eQTL. Finally, we apply this framework to an eQTL hotspot on chromosome 1 (Qrr1), which has been implicated in a range of neurological traits. Here we present the first systematic examination of the consistency between eQTL obtained independently from the BXD and MDP populations. Our analysis of fine-mapping approaches is based on ‘real life’ data as opposed to simulated data and it allows us to propose a strategy for using MDP data to fine map BXD eQTL. Application of this framework to Qrr1 reveals that this eQTL hotspot is not caused by just one (or few) ‘master regulators’, but actually by a set of polymorphic genes specific to the central nervous system

DISC1 genetics, biology and psychiatric illness

Psychiatric disorders are highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points towards DISC1 being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain

The Vocascope - An Experimental Study in the Visual Measurement of Pitch and Quality

The project herein described is an experimental attempt to con- struct visual aids for the study of voice. Its purposes are: (1) to ako possible the visual perception of pitch change on a vertical scale; (2) to isolate certain overtones of the fundamental frequency in the hope of deriving some assistance to the improvement of quality. The principle of operation is the psychological phenomenon of stroboscopy, the illusion of stationary, constant light, as a result of synchronized interrupted vision. The Vocascope is composed of four essential parts: (1) the scanning drugs, (2) the light source, (3) the amplifier, (4) the filter

John C. Crabbe Papers

From 1937 to 1958, John C. Crabbe worked for the College of the Pacific, Stockton, California where he started the first broadcasting degree major west of the Mississippi River. There, he also worked for KUOP-FM as its station manager, having assisted in putting the station on the air in 1949. During World War II, while in Baltimore, Crabbe lobbied the Federal Communications Commission for reserved FM channels for educational use which was finally granted in April 1952. Meanwhile, from 1950 to 1953, he also served as President of the Association for Education by Radio-Television. In 1961, Crabbe worked as a regional consultant to a National Defense Education Act survey on the need for television channels in education. Other positions held throughout his career include: general manager of KVIE-TV of Stockton, California (1958-1969), vice-president of the Western Radio and Television Association's Western Educational Network (1967-1968) and then president (August 1968 to 1969), director of University of Southern Colorado Telecommunications Division (1981), and general manager of KTSC, Pueblo, Colorado. The collection consists of publications regarding instructional television in California, television in education as well as the interaction between children and television. It includes the 1952 FCC allocation report, Crabbe's personal recollections of KVIE's history and an audio cassette of a 1949 interview with "Death Valley Scotty" and a 1952 recording of an Institute for Education by Radio and Television featuring the cast of "Kukla, Fran & Ollie.