On method, theory, and the classification of complex disorders

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72867/1/j.1360-0443.1997.tb02886.x.pd

The N-terminal domain of human GATA1 prevents dyserythropoietic anemia and megakaryocyte dysplasia in vivo

We describe a child with dyserythropoietic anemia, thrombocytosis, functional platelet defect, and megakaryocyte dysplasia. We show that (i) this constellation of hematopoietic abnormalities was due to a germline mutation within the 5′ untranslated region (5′UTR) of globin transcription factor 1 (GATA1); (ii) the mutation impaired a 5′UTR GATA1 splicing site, with promoted production of the shortened GATA1 isoform lacking the N-terminus; and (iii) expression of the GATA1 N-terminus is restricted to erythroblasts and megakaryocytes in normal marrow, consistent with the patient's abnormal erythropoiesis and megakaryopoiesis. Our findings provide insights into the clinically relevant in vivo function of the N-terminal domain of GATA1 in human hematopoiesis

Parsing the Undercontrol–Disinhibition Pathway to Substance Use Disorders: A Multilevel Developmental Problem

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88062/1/j.1750-8606.2011.00172.x.pd

Feasibility of Using Interactive Voice Response to Monitor Daily Drinking, Moods, and Relationship Processes on a Daily Basis in Alcoholic Couples

Daily process research on alcohol involvement has used paper-and-pencil and electronic data collection methods, but no studies have yet tested the feasibility of using Interactive Voice Response (IVR) technology to monitor drinking, affective, and social interactional processes among alcoholic (ALC) couples. This study tested the feasibility of using IVR with n  = 54 ALC couples.Participants were n  = 54 couples (probands who met criteria for a past 1-year alcohol use disorder and their partners) recruited from a substance abuse treatment center and the local community. Probands and their partners reported on their daily drinking, marital interactions, and moods once a day for 14 consecutive days using an IVR system. Probands and partners were on average 43.4 and 43.0 years old, respectively.Participants completed a total of 1,418 out of a possible 1,512 diary days for an overall compliance rate of 93.8%. ALC probands completed an average of 13.3 (1.0) diary reports, and partners completed an average of 13.2 (1.0) diary reports. On average, daily IVR calls lasted 7.8 (3.0) minutes for ALC probands and 7.6 (3.0) minutes for partners. Compliance was significantly lower on weekend days (Fridays and Saturdays) compared to other weekdays for probands and spouses. Although today’s intoxication predicted tomorrow’s noncompliance for probands but not spouses, the strongest predictor of proband’s compliance was their spouse’s compliance. Daily anxiety and marital conflict were associated with daily IVR nonresponse, which triggered automated reminder calls.Findings supported that IVR is a useful method for collecting daily drinking, mood, and relationship process data from alcoholic couples. Probands’ compliance is strongly associated with their partners’ compliance, and automated IVR calls may facilitate compliance on high anxiety, high conflict days.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79396/1/j.1530-0277.2009.01115.x.pd

Fishing for complementarities : competitive research funding and research productivity

This paper empirically investigates complementarities between different sources of research funding with regard to academic publishing. We find for a sample of UK engineering academics that competitive funding is associated with an increase in ex-post publications but that industry funding decreases the marginal utility of public funding by lowering the publication and citation rate increases associated with public grants. However, when holding all other explanatory variables at their mean, the negative effect of the interaction does not translate into an effective decrease in publication and citation numbers. The paper also shows that the positive effect of public funding is driven by UK research council and charity grants and that EU funding has no significant effect on publication outcomes

Family History of Alcoholism and Childhood Adversity: Joint Effects on Alcohol Consumption and Dependence

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65494/1/j.1530-0277.1994.tb00085.x.pd

Flow cytometry as a rapid analytical tool to determine physiological responses to changing O2 and iron concentration by Magnetospirillum gryphiswaldense strain MSR-1

Magnetotactic bacteria (MTB) are a diverse group of bacteria that synthesise magnetosomes, magnetic membrane-bound nanoparticles that have a variety of diagnostic, clinical and biotechnological applications. We present the development of rapid methods using flow cytometry to characterize several aspects of the physiology of the commonly-used MTB Magnetospirillum gryphiswaldense MSR-1. Flow cytometry is an optical technique that rapidly measures characteristics of individual bacteria within a culture, thereby allowing determination of population heterogeneity and also permitting direct analysis of bacteria. Scatter measurements were used to measure and compare bacterial size, shape and morphology. Membrane permeability and polarization were measured using the dyes propidium iodide and bis-(1,3-dibutylbarbituric acid) trimethine oxonol to determine the viability and ‘health’ of bacteria. Dyes were also used to determine changes in concentration of intracellular free iron and polyhydroxylakanoate (PHA), a bacterial energy storage polymer. These tools were then used to characterize the responses of MTB to different O2 concentrations and iron-sufficient or iron-limited growth. Rapid analysis of MTB physiology will allow development of bioprocesses for the production of magnetosomes, and will increase understanding of this fascinating and useful group of bacteria

Organization of sensory feature selectivity in the whisker system

Our sensory receptors are faced with an onslaught of different environmental inputs. Each sensory event or encounter with an object involves a distinct combination of physical energy sources impinging upon receptors. In the rodent whisker system, each primary afferent neuron located in the trigeminal ganglion innervates and responds to a single whisker and encodes a distinct set of physical stimulus properties – features – corresponding to changes in whisker angle and shape and the consequent forces acting on the whisker follicle. Here we review the nature of the features encoded by successive stages of processing along the whisker pathway. At each stage different neurons respond to distinct features, such that the population as a whole represents diverse properties. Different neuronal types also have distinct feature selectivity. Thus, neurons at the same stage of processing and responding to the same whisker nevertheless play different roles in representing objects contacted by the whisker. This diversity, combined with the precise timing and high reliability of responses, enables populations at each stage to represent a wide range of stimuli. Cortical neurons respond to more complex stimulus properties – such as correlated motion across whiskers – than those at early subcortical stages. Temporal integration along the pathway is comparatively weak: neurons up to barrel cortex are sensitive mainly to fast (tens of milliseconds) fluctuations in whisker motion. The topographic organization of whisker sensitivity is paralleled by systematic organization of neuronal selectivity to certain other physical features, but selectivity to touch and to dynamic stimulus properties is distributed in “salt-and-pepper” fashion

A tale of two stories: astrocyte regulation of synaptic depression and facilitation

Short-term presynaptic plasticity designates variations of the amplitude of synaptic information transfer whereby the amount of neurotransmitter released upon presynaptic stimulation changes over seconds as a function of the neuronal firing activity. While a consensus has emerged that changes of the synapse strength are crucial to neuronal computations, their modes of expression in vivo remain unclear. Recent experimental studies have reported that glial cells, particularly astrocytes in the hippocampus, are able to modulate short-term plasticity but the underlying mechanism is poorly understood. Here, we investigate the characteristics of short-term plasticity modulation by astrocytes using a biophysically realistic computational model. Mean-field analysis of the model unravels that astrocytes may mediate counterintuitive effects. Depending on the expressed presynaptic signaling pathways, astrocytes may globally inhibit or potentiate the synapse: the amount of released neurotransmitter in the presence of the astrocyte is transiently smaller or larger than in its absence. But this global effect usually coexists with the opposite local effect on paired pulses: with release-decreasing astrocytes most paired pulses become facilitated, while paired-pulse depression becomes prominent under release-increasing astrocytes. Moreover, we show that the frequency of astrocytic intracellular Ca2+ oscillations controls the effects of the astrocyte on short-term synaptic plasticity. Our model explains several experimental observations yet unsolved, and uncovers astrocytic gliotransmission as a possible transient switch between short-term paired-pulse depression and facilitation. This possibility has deep implications on the processing of neuronal spikes and resulting information transfer at synapses.Comment: 93 pages, manuscript+supplementary text, 10 main figures, 11 supplementary figures, 1 tabl