bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental improvement in the regularity and packing of mouse horizontal cells: Implications for mechanisms underlying mosaic pattern formation
Authors: RAVEN MARY A. , STAGG STEPHANIE B. , NASSAR HADI , REESE BENJAMIN E.
Published: April 2008

The present investigation has sought to determine whether the population of retinal horizontal cells undergoes an increase in the precision of its mosaic patterning during postnatal development, and if so, whether this increase is compatible with three different mechanistic accounts of retinal mosaic formation. Horizontal cells were labeled with antibodies to neurofilaments or calbindin at different developmental stages, and then visualized in retinal wholemounts. Multiple fields were sampled from each retina to determine horizontal cell density, while theX–Ycoordinates of each cell in a field were determined. An estimate of total horizontal cell number was calculated for each retina, while the Voronoi domain regularity index and the packing factor were computed for each field. Two strains of mice showing a two-fold difference in the size of their horizontal cell population in maturity were sampled, C57BL/6J and A/J. Horizontal cell number in C57BL/6J was approximately twice that observed in A/J at all postnatal stages, with neither strain showing an effect of age on horizontal cell number. In both strains, however, the Voronoi domain regularity index and the packing factor were significantly lower at P-1 relative to later developmental stages. These results show that accounts of mosaic formation proposing the selective death of irregularly positioned cells, or the periodic occurrence of fate-determining events, are insufficient to establish the final patterning achieved by horizontal cells. Rather, they support the hypothesis that tangential dispersion enhances mosaic patterning during postnatal development.
Mouse models of ocular diseases
Authors: CHANG B. , HAWES N.L. , HURD R.E. , WANG J. , HOWELL D. , DAVISSON M.T. , RODERICK T.H. , NUSINOWITZ S. , HECKENLIVELY J.R.
Published: April 2008

The Jackson Laboratory, having the world's largest collection of mouse mutant stocks and genetically diverse inbred strains, is an ideal place to discover genetically determined eye variations and disorders. In this paper, we list and describe mouse models for ocular research available from Mouse Eye Mutant Resource at The Jackson Laboratory. While screening mouse strains and stocks at The Jackson Laboratory (TJL) for genetic mouse models of human ocular disorders, we have identified numerous spontaneous or naturally occurring mutants. We characterized these mutants using serial indirect ophthalmoscopy, fundus photography, electroretinography (ERG) and histology, and performed genetic analysis including linkage studies and gene identification. Utilizing ophthalmoscopy, electroretinography, and histology, to date we have discovered 109 new disorders affecting all aspects of the eye including the lid, cornea, iris, lens, and retina, resulting in corneal disorders, glaucoma, cataracts, and retinal degenerations. The number of known serious or disabling eye diseases in humans is large and affects millions of people each year. Yet research on these diseases frequently is limited by the obvious restrictions on studying pathophysiologic processes in the human eye. Likewise, many human ocular diseases are genetic in origin, but appropriate families often are not readily available for genetic studies. Mouse models of inherited ocular disease provide powerful tools for rapid genetic analysis, characterization, and gene identification. Because of the great similarity among mammalian genomes, these findings in mice have direct relevance to the homologous human conditions.
The Tennessee Mouse Genome Consortium: Identification of ocular mutants
Authors: JABLONSKI MONICA M. , WANG XIAOFEI , LU LU , MILLER DARLA R. , RINCHIK EUGENE M. , WILLIAMS ROBERT W. , GOLDOWITZ DANIEL
Published: April 2008

The Tennessee Mouse Genome Consortium (TMGC) is in its fifth year of a ethylnitrosourea (ENU)-based mutagenesis screen to detect recessive mutations that affect the eye and brain. Each pedigree is tested by various phenotyping domains including the eye, neurohistology, behavior, aging, ethanol, drug, social behavior, auditory, and epilepsy domains. The utilization of a highly efficient breeding protocol and coordination of various universities across Tennessee makes it possible for mice with ENU-induced mutations to be evaluated by nine distinct phenotyping domains within this large-scale project known as the TMGC. Our goal is to create mutant lines that model human diseases and disease syndromes and to make the mutant mice available to the scientific research community. Within the eye domain, mice are screened for anterior and posterior segment abnormalities using slit-lamp biomicroscopy, indirect ophthalmoscopy, fundus photography, eye weight, histology, and immunohistochemistry. As of January 2005, we have screened 958 pedigrees and 4800 mice, excluding those used in mapping studies. We have thus far identified seven pedigrees with primary ocular abnormalities. Six of the mutant pedigrees have retinal or subretinal aberrations, while the remaining pedigree presents with an abnormal eye size. Continued characterization of these mutant mice should in most cases lead to the identification of the mutated gene, as well as provide insight into the function of each gene. Mice from each of these pedigrees of mutant mice are available for distribution to researchers for independent study.
Cochlin and glaucoma: A mini-review
Authors: BHATTACHARYA SANJOY K. , PEACHEY NEAL S. , CRABB JOHN W.
Published: April 2008

Primary open angle glaucoma (POAG) is a leading cause of late onset, progressive, irreversible blindness and, although its etiology is poorly understood, elevated intraocular pressure (IOP) often appears to be a contributory factor. Proteomic and Western analyses of trabecular meshwork (TM) from patients with POAG and age-matched controls originally implicated cochlin as possibly contributing to glaucoma pathogenesis. Cochlin deposits were subsequently detected in glaucomatous but not in control TM and older glaucomatous TM was found to contain higher levels of cochlin and significantly lower amounts of collagen type II. More recently, similar results were reported in DBA/2J mice, which at older ages develop elevated IOP, retinal ganglion cell degeneration, and optic nerve damage. Notably, cochlin was absent in TM from C57BL/6J, CD1, and BALBc/ByJ mice, which do not exhibit elevated IOP or glaucoma. Cochlin was found in the TM of very young DBA/2J mice, prior to elevated IOP, suggesting that over time the protein may contribute to the events leading to increased IOP and optic nerve damage. Here we review these findings and describe how future studies in DBA/2J mice can help resolve whether cochlin plays a causal role in mechanisms of POAG and elevated IOP.
Inherited glaucoma in DBA/2J mice: Pertinent disease features for studying the neurodegeneration
Authors: LIBBY RICHARD T. , ANDERSON MICHAEL G. , PANG IOK-HOU , ROBINSON ZACHARY H. , SAVINOVA OLGA V. , COSMA I. MIHAI , SNOW AMY , WILSON LAWRISTON A. , SMITH RICHARD S. , CLARK ABBOT F. , JOHN SIMON W.M.
Published: April 2008

The glaucomas are neurodegenerative diseases involving death of retinal ganglion cells and optic nerve head excavation. A major risk factor for this neurodegeneration is a harmfully elevated intraocular pressure (IOP). Human glaucomas are typically complex, progressive diseases that are prevalent in the elderly. Family history and genetic factors are clearly important in human glaucoma. Mouse studies have proven helpful for investigating the genetic and mechanistic basis of complex diseases. We previously reported inherited, age-related progressive glaucoma in DBA/2J mice. Here, we report our updated findings from studying the disease in a large number of DBA/2J mice. The period when mice have elevated IOP extends from 6 months to 16 months, with 8–9 months representing an important transition to high IOP for many mice. Optic nerve degeneration follows IOP elevation, with the majority of optic nerves being severely damaged by 12 months of age. This information should help with the design of experiments, and we present the data in a manner that will be useful for future studies of retinal ganglion cell degeneration and optic neuropathy.
Structural and functional composition of the developing retinogeniculate pathway in the mouse
Authors: JAUBERT-MIAZZA LISA , GREEN ERICK , LO FU-SUN , BUI KIM , MILLS JEREMY , GUIDO WILLIAM
Published: April 2008

The advent of transgenic mice has made the developing retinogeniculate pathway a model system for targeting potential mechanisms that underlie the refinement of sensory connections. However, a detailed characterization of the form and function of this pathway is lacking. Here we use a variety of anatomical and electrophysiological techniques to delineate the structural and functional changes occurring in the lateral geniculate nucleus (LGN) of dorsal thalamus of the C57/BL6 mouse. During the first two postnatal weeks there is an age-related recession in the amount of terminal space occupied by retinal axons arising from the two eyes. During the first postnatal week, crossed and uncrossed axons show substantial overlap throughout most of the LGN. Between the first and second week retinal arbors show significant pruning, so that by the time of natural eye opening (P12–14) segregation is complete and retinal projections are organized into distinct eye-specific domains. During this time of rapid anatomical rearrangement, LGN cells could be readily distinguished using immunocytochemical markers that stain for NMDA receptors, GABA receptors, L-type Ca2+channels, and the neurofilament protein SMI-32. Moreover, the membrane properties and synaptic responses of developing LGN cells are remarkably stable and resemble those of mature neurons. However, there are some notable developmental changes in synaptic connectivity. At early ages, LGN cells are binocularly responsive and receive input from as many as 11 different retinal ganglion cells. Optic tract stimulation also evokes plateau-like depolarizations that are mediated by the activation of L-type Ca2+channels. As retinal inputs from the two eyes segregate into nonoverlapping territories, there is a loss of binocular responsiveness, a decrease in retinal convergence, and a reduction in the incidence of plateau potentials. These data serve as a working framework for the assessment of phenotypes of genetically altered strains as well as provide some insight as to the molecular mechanisms underlying the refinement of retinogeniculate connections.
Optical imaging of the intrinsic signal as a measure of cortical
plasticity in the mouse
Authors: CANG JIANHUA , KALATSKY VALERY A. , LÖWEL SIEGRID , STRYKER MICHAEL P.
Published: April 2008

The responses of cells in the visual cortex to stimulation of the two
eyes changes dramatically following a period of monocular visual
deprivation (MD) during a critical period in early life. This phenomenon,
referred to as ocular dominance (OD) plasticity, is a widespread model for
understanding cortical plasticity. In this study, we designed stimulus
patterns and quantification methods to analyze OD in the mouse visual
cortex using optical imaging of intrinsic signals. Using periodically
drifting bars restricted to the binocular portion of the visual field, we
obtained cortical maps for both contralateral (C) and ipsilateral
(I) eyes and computed OD maps as (C −
I)/(C + I). We defined the OD index
(ODI) for individual animals as the mean of the OD map. The ODI
obtained from an imaging session of less than 30 min gives reliable
measures of OD for both normal and monocularly deprived mice under
Nembutal anesthesia. Surprisingly, urethane anesthesia, which yields
excellent topographic maps, did not produce consistent OD findings. Normal
Nembutal-anesthetized mice have positive ODI (0.22 ±
0.01), confirming a contralateral bias in the binocular zone. For mice
monocularly deprived during the critical period, the ODI of the
cortex contralateral to the deprived eye shifted negatively towards the
nondeprived, ipsilateral eye (ODI after 2-day MD: 0.12 ±
0.02, 4-day: 0.03 ± 0.03, and 6- to 7-day MD: −0.01 ±
0.04). The ODI shift induced by 4-day MD appeared to be near
maximal, consistent with previous findings using single-unit recordings.
We have thus established optical imaging of intrinsic signals as a fast
and reliable screening method to study OD plasticity in the mouse.
Horizontal cells in the retina of a diurnal rodent, the agouti (Dasyprocta aguti)
Authors: DE LIMA S.M.A. , AHNELT P.K. , CARVALHO T.O. , SILVEIRA J.S. , ROCHA F.A.F. , SAITO C.A. , SILVEIRA L.C.L.
Published: April 2008

The morphology and distribution of normally placed and displaced A horizontal cells were studied in the retina of a diurnal hystricomorph rodent, the agoutiDasyprocta aguti. Cells were labeled with anti-calbindin immunocytochemistry. Dendritic-field size reaches a minimum in the visual streak, of about 9000 μm2, and increases toward the retinal periphery both in the dorsal and ventral regions. There is a dorsoventral asymmetry, with dorsal cells being larger than ventral cells at equal distances from the streak. The peak value for cell density of 281 ± 28 cells/mm2occurs in the center of the visual streak, decreasing toward the dorsal and ventral retinal periphery, paralleling the increase in dendritic-field size. Along the visual streak, the decline in cell density is less pronounced, remaining between 100–200 cells/mm2in the temporal and nasal periphery. Displaced horizontal cells are rare and occur in the retinal periphery. They tend to be smaller than normally placed horizontal cells in the ventral region, whilst no systematic difference was observed between the two cell groups in the dorsal region. Mosaic regularity was studied using nearest-neighbor analysis and the Ripley function. When mosaic regularity was determined removing the displaced horizontal cells, there was a slight increase in the conformity ratio, but the bivariate Ripley function indicated some repulsive dependence between the two mosaics. Both results were near the level of significance. A similar analysis performed in the capybara retina, a closely related hystricomorph rodent bearing a higher density of displaced horizontal cells than found in the agouti, suggested spatial independence between the two mosaics, normally placedversusdisplaced horizontal cells.
Morphological characterization of the retinal degeneration in three
strains of mice carrying the rd-3 mutation
Authors: LINBERG KENNETH A. , FARISS ROBERT N. , HECKENLIVELY JOHN R. , FARBER DEBORA B. , FISHER STEVEN K.
Published: April 2008

Retinal development in 3 strains of rd-3/rd-3 mutant
mice, previously shown to have different rates of degeneration, was
studied using light, electron, and immunofluorescence microscopy. The time
course and phenotype of the degeneration as well as details on the
mechanism of massive photoreceptor cell loss are compared with other known
retinal degenerations in mice. Up until postnatal day (P) 10, the retinas
of all three strains (RBF, 4Bnr, In-30) develop similarly to those of
pigmented and nonpigmented controls. TUNEL-positive cells appear in the
outer nuclear layer (ONL) by P14, and reach a maximum in all three mutant
strains around P21. Scattered rods and cones form a loose, monolayered ONL
by 8 weeks in the albino RBF strain, by 10 weeks in the albino 4Bnr
strain, and by 16 weeks in the pigmented In-30 strain. Though the initial
degeneration begins in the central retina, there is no preferred gradient
of cell death between central and peripheral photoreceptors. Rods and
cones are present at all ages examined. During development, stacks of
outer segments (OS) form in all three strains though they never achieve
full adult lengths, and often have disorganized, atypical OS. Rod opsin is
expressed in the developing OS but is redistributed into plasma membrane
as OS degeneration proceeds. Retinal pigment epithelial (RPE) cells of all
mutant strains contain packets of phagocytosed OS, and their apical
processes associate with the distal ends of the OS. At their synaptic
sites, photoreceptor terminals contain ribbons apposed to apparently
normal postsynaptic triads. As photoreceptors are lost, Müller cells
fill in space in the ONL but they do not appear to undergo significant
hypertrophy or migration, though during the degeneration, glial fibrillary
acidic protein (GFAP) expression is gradually upregulated. Macrophage-like
cells are found frequently in the subretinal space after the onset of
photoreceptor apoptosis. As OS disappear, the RPE apical processes revert
to simple microvilli. Late in the degeneration, some RPE cells die and
neighboring cells appear to flatten as if to maintain confluence. In
regions of RPE cell loss that happen to lie above retina where the ONL is
gone, cells of the inner nuclear layer (INL), wrapped by Müller cell
processes, may front directly on Bruch's membrane.
Visual evoked potentials for red–green gratings reversing at
different temporal frequencies: Asymmetries with respect to
isoluminance
Authors: RUDVIN INGER , VALBERG ARNE
Published: April 2008

Human visual evoked potentials (VEPs) were recorded for abrupt
reversals of 2 cycles/deg (c/deg) square-wave gratings combining
high red–green contrast with different levels of luminance contrast.
Response characteristics—2nd harmonic amplitudes and peak latencies
as a function of luminance contrast—were compared for four different
reversal rates ranging from 6.25 Hz to 12.5 Hz. At every reversal
frequency, the VEP amplitude and latency plots were nonsymmetrical with
respect to isoluminance. The amplitude dropped to a minimum within a
region of rapid phase change, always at a red–green luminance
contrast for which the green color had the higher luminance, at about 40%
or 50% Michelson luminance contrast. The rapid phase shift around this
contrast suggested a sudden change in the relative impact of VEP
generators with different latencies, possibly dominated by parvocellular
or magnocellular input. The most prominent VEP waveform through most of
the luminance contrast range, P110, is interpreted in terms of a
parvo-mediated response that is attenuated with increasing reversal
frequency. Contrast-dependent changes in the P110 amplitude appear to be
responsible for the VEP asymmetries reported here.
Visual evoked potentials for reversals of red–green gratings with different chromatic contrasts: Asymmetries with respect to isoluminance
Authors: RUDVIN INGER
Published: April 2008

Human visual evoked potentials (VEPs) were recorded for abrupt 6.25-Hz reversals of 2 c/deg square-wave gratings combining red–green contrast with different levels of luminance contrast. Response characteristics— amplitudes and peak latencies as a function of luminance contrast—were compared for four different pairs of red–green colors and an isochromatic yellow grating. For each of the red–green color pairs, the plots of VEP amplitudes and latencies were nonsymmetrical with respect to isoluminance. The amplitude dropped to a minimum within a region of rapid phase change, at a different contrast for each color pair but always at a luminance contrast for which the greener color had the higher luminance. When the contrast-response curve for each of the four red–green pairs was modeled by a simple |CL− CM| opponency of L- and M-cone contrast using a fixed CL/CMweighting ratio of about two, there was a close correspondence between the contrast giving a null in the modeled response and that giving a minimum in the VEP amplitude. So for the stimulus parameters applied here, the reversal VEP appeared to be dominated by L/M-opponent response contributions for which the signed CL/CM-cone weighting ratio was close to a value of minus two rather than to a value of minus one, which is characteristic of the psychophysical red–green detection mechanism and representative of CL/CMweighting ratios for precortical cells in the parvocellular pathway.
Glycine- and GABA-activated inhibitory currents on axon terminals of rabbit cone bipolar cells
Authors: ZHOU CHENGWEN , DACHEUX RAMON F.
Published: April 2008

Glycine- and GABA-activated currents were examined in the axon terminals of 12 types of rabbit cone bipolar cells. In the superfused retinal slice, a cell was voltage clamped at 0 mV in the presence of cobalt; then glycine or GABA was puffed onto the axon terminal. Types CBa1, CBa2, and a few CBa1-2 cells demonstrated larger glycine-activated currents than GABA-activated ones. However, some OFF cells (CBa2n, CBa1-2n, CBa1w), most CBa1-2, and most ON cells (CBb3, CBb3-4, CBb3n, and CBb4) displayed larger GABA-activated currents. The ON cell, CBb5, possessed only a GABA-activated current. The predominance of glycinergic currents in CBa1, CBa2, and a few CBa1-2 cells suggests a major input from the glycinergic AII amacrine cell and thus a key role for these cells in the rod bipolar pathway. Certain OFF cells (most CBa1-2) expressed larger GABA-activated currents. All types expressed both GABAAand GABACcurrents about equally, although most OFF types (CBa1, CB a2n, CBa1-2, and CBa2n) displayed a slightly greater GABAAcomponent.
Characteristics of period doubling in the human cone flicker electroretinogram
Authors: ALEXANDER KENNETH R. , LEVINE MICHAEL W. , SUPER BOAZ J.
Published: April 2008

Electroretinogram (ERG) responses of the cone system to a flickering stimulus can exhibit a cyclic variation in amplitude. This phenomenon of synchronous period doubling has been attributed to a nonlinear feedback mechanism within the retina that alters response gain. The aim of the present study was to investigate intersubject variability in period doubling in the ERG of the human cone system, and to assess the implications of this variability for signal processing within the retina. Period doubling was examined in a group of 12 visually normal subjects, using sinusoidal full-field flicker and harmonic analysis of the ERG waveforms. For all subjects, the ERG responses to 32-Hz flicker (a frequency commonly used clinically) were characterized by a harmonic component at the stimulus frequency and at higher harmonics that were integral multiples of the stimulus frequency, as expected. In addition, six of the subjects showed period doubling at 32 Hz, characterized by harmonic components at integer multiples of a frequency that was half the stimulus frequency (the subharmonic). However, the subharmonic itself did not exceed the noise level. These findings suggest that the subharmonic is generated prior to or at the site that produces the nonlinear higher harmonics of the ERG response, and that a subsequent band-pass filter attenuates this subharmonic. Examination of harmonic components of the subjects' ERG waveforms at other stimulus frequencies, as well as a cycle-by-cycle analysis of the ERG waveforms, suggested that individual differences in period doubling may be due to intersubject variation in the strength of the hypothesized feedback signal and/or the time constant of its decay.
Gycine and GABA interact to regulate the nitric oxide/cGMP
signaling pathway in the turtle retina
Authors: YU DOU , ELDRED WILLIAM D.
Published: April 2008

Nitric oxide (NO) is a free radical that is important in retinal
signal transduction and cyclic guanosine monophosphate (cGMP) is a
critical downstream messenger of NO. The NO/cGMP signaling pathway has
been shown to modulate neurotransmitter release and gap junction coupling
in horizontal cells and amacrine cells, and increase the gain of the light
response in photoreceptors. However, many of the mechanisms controlling
the production of NO and cGMP remain unclear. Previous studies have shown
activation of NO/cGMP production in response to stimulation with
N-methyl-d-aspartate (NMDA) or nicotine, and the differential modulation
of cGMP production by GABAA and GABAC receptors
(GABAARs and GABACRs). This study used cGMP
immunocytochemistry and NO imaging to investigate how the inhibitory
GABAergic and glycinergic systems modulate the production of NO and cGMP.
Our data show that blocking glycine receptors (GLYR) with strychnine
(STRY) produced moderate increases in cGMP-like immunoreactivity (cGMP-LI)
in select types of amacrine and bipolar cells, and strong increases in
NO-induced fluorescence (NO-IF). TPMPA, a selective GABACR
antagonist, greatly reduced the increases in cGMP-LI stimulated by STRY,
but did not influence the increase in NO-IF stimulated by STRY.
Bicuculline (BIC), a GABAAR antagonist, however, enhanced the
increases in both the cGMP-LI and NO-IF stimulated by STRY. CNQX, a
selective antagonist for
α-Amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid
hydrobromide/kainic acid (AMPA/KA) receptors, eliminated both the
increases in cGMP-LI and NO-IF stimulated by STRY, while MK801, a
selective antagonist for NMDA receptors, slightly increased the cGMP-LI
and slightly decreased the NO-IF stimulated by STRY. Finally, double
labeling of NO-stimulated cGMP and either GLY or GABA indicated that cGMP
predominantly colocalized with GLY. Taken together, these findings support
the hypothesis that GLY and GABA interact in the regulation of the
NO/cGMP signaling pathway, where GLY primarily inhibits NO production
and GABA has a greater effect on cGMP production. Such interacting
inhibitory pathways could shape the course of signal transduction of the
NO/cGMP pathway under different physiological situations.
Muscimol and baclofen differentially suppress retinotopic and
nonretinotopic responses in visual cortex
Authors: KASAMATSU TAKUJI , MIZOBE KEIKO , SUTTER ERICH E.
Published: April 2008

This study relates to local field potentials and single-unit responses
in cat visual cortex elicited by contrast reversal of bar gratings that
were presented in single, double, or multiple discrete patch (es) of the
visual field. Concurrent stimulation of many patches by means of the
pseudorandom, binary m-sequence technique revealed interactions between
their respective responses. An analysis identified two distinct components
of local field potentials: a fast local component (FLC) and a slow
distributed component (SDC). The FLC is thought to be a primarily
postsynaptic response, as judged by its relatively short latency. It is
directly generated by thalamocortical volleys following retinotopic
stimulation of receptive fields of a small cluster of single cells,
combined with responses to recurrent excitation and inhibition derived
from the cells under study and immediately neighboring cells. In contrast,
the SDC is thought to be an aggregate of dendritic potentials related to
the long-range lateral connections (i.e. long-range coupling). We compared
the suppressive effects of a GABAA-receptor agonist, muscimol,
on the FLC and SDC with those of a GABAB-receptor agonist,
baclofen, and found that muscimol more strongly suppressed the FLC than
the SDC, and that the reverse was the case for baclofen. The differential
suppression of the FLC and SDC found in the present study is consistent
with the notion that intracortical electrical signals related to the FLC
terminate on the somata and proximal/basal dendrites, while those
related to the SDC terminate on distal dendrites.
Association amacrine cells of Ramón y Cajal: Rediscovery and reinterpretation
Authors: UCHIYAMA H. , STELL W.K.
Published: April 2008

In 1895, by means of the Golgi method, Santiago Ramón y Cajal discovered a cell having a unique morphology in the avian retina. This cell had its cell body in the amacrine cell level of the inner nuclear layer, only a few rudimentary dendrites at the outermost level of the inner plexiform layer (IPL), and a long axon coursing horizontally and terminating in the IPL. Despite having defined amacrine cells as cells without axons, Cajal named this cell type “association amacrine cell” (AAC). This discovery was not confirmed by other investigators for nearly a century. Very recently, however, isthmo-optic target cells (IOTCs), which receive the terminals of centrifugal fibers emanating from the isthmo-optic nucleus, have been identified as one type of AAC. As summarized and discussed in this review, the morphology of the AACs as described by Cajal has been completely confirmed. However, since these cells appear to be classical polarized, monoaxonal neurons and lack the dendritic interactions that are typical of amacrine cells, they should be regarded as a distinct type of retinal interneuron and not as amacrine cells.
Effortful control as a moderator of the relation between contextual risk factors and growth in adjustment problems
Authors: Lengua Liliana J. , Bush Nicole R. , Long Anna C. , Kovacs Erica A. , Trancik Anika M.
Published: April 2008

Effortful control was examined as a moderator of the relations of three domains of contextual risk factors to growth in internalizing and externalizing problems in a community sample (N= 189) of children (8–12 years at Time 1). Socioeconomic, maternal, and environmental risk factors were examined as predictors of initial levels and growth in children's adjustment problems across 3 years. The effects of the risk factors depended on children's level of effortful control. For children lower in effortful control, socioeconomic risk was related to significantly higher initial levels of internalizing and externalizing problems and decreases over time. However, children lower in effortful control had higher levels of problems at all three time points than children higher in effortful control. Maternal risk was associated with increases in internalizing for children lower in effortful control, and environmental risk was related to increases in internalizing and externalizing problems for children lower in effortful control, but not those higher in effortful control. Children who were lower in effortful control appeared to experience more adverse effects of contextual risk than those higher in effortful control, suggesting that interventions aimed at improving children's effortful control might serve to protect children from increased risk of adjustment problems associated with contextual risk factors.
Face emotion labeling deficits in children with bipolar disorder and severe mood dysregulation
Authors: Rich Brendan A. , Grimley Mary E. , Schmajuk Mariana , Blair Karina S. , Blair R. J. R. , Leibenluft Ellen
Published: April 2008

Children with narrow phenotype bipolar disorder (NP-BD; i.e., history of at least one hypomanic or manic episode with euphoric mood) are deficient when labeling face emotions. It is unknown if this deficit is specific to particular emotions, or if it extends to children with severe mood dysregulation (SMD; i.e., chronic irritability and hyperarousal without episodes of mania). Thirty-nine NP-BD, 31 SMD, and 36 control subjects completed the emotional expression multimorph task, which presents gradations of facial emotions from 100% neutrality to 100% emotional expression (happiness, surprise, fear, sadness, anger, and disgust). Groups were compared in terms of intensity of emotion required before identification occurred and accuracy. Both NP-BD and SMD youth required significantly more morphs than controls to label correctly disgusted, surprised, fearful, and happy faces. Impaired face labeling correlated with deficient social reciprocity skills in NP-BD youth and dysfunctional family relationships in SMD youth. Compared to controls, patients with NP-BD or SMD require significantly more intense facial emotion before they are able to label the emotion correctly. These deficits are associated with psychosocial impairments. Understanding the neural circuitry associated with face-labeling deficits has the potential to clarify the pathophysiology of these disorders.
Callous-unemotional traits and the emotional processing of distress cues in detained boys: Testing the moderating role of aggression, exposure to community violence, and histories of abuse
Authors: Kimonis Eva R. , Frick Paul J. , Munoz Luna C. , Aucoin Katherine J.
Published: April 2008

Callous-unemotional (CU) traits in antisocial youth have been associated with deficits in the processing of emotionally distressing stimuli in a number of past studies. In the current study, we investigated moderators of this association in a sample of 88 ethnically diverse detained boys (mean age = 15.57, SD = 1.28). Overall, emotional processing of distressing stimuli using a dot-probe task was not related to CU traits and there was no moderating effect of ethnicity. However, CU traits were related to deficits in emotional processing in youth high on aggression and youth high on exposure to community violence. Further, youth high on CU traits but with enhanced orienting to distressing stimuli had stronger histories of abuse, supporting the possibility that there may be environmentally influenced pathways in the development of these traits.
Socioeconomic background and the developmental course of schizotypal and borderline personality disorder symptoms
Authors: Cohen Patricia , Chen Henian , Gordon Kathy , Johnson Jeffrey , Brook Judith , Kasen Stephanie
Published: April 2008

Low socioeconomic status (SES) background has been identified as a risk for several mental disorders. However evidence regarding SES and the developmental course of personality disorder (PD) has not been addressed. Nor is it clear whether an SES relationship to PD symptom course may be attributable to known associated risks. Further, specificity of such relationships to a particular PD diagnostic pattern independent of comorbidity with other PD or with depression has not been investigated. Data are from a general population studied longitudinally between ages 10 and 36 in four assessment waves. Effects of SES-associated risks on the level of symptoms of schizotypal and borderline disorders are estimated and compared to effects on depressive symptoms. Low family SES had robust modest independent effects on both PDs over the entire age span despite substantial cumulative effects of trauma history, stressful recent life events, IQ, poor parenting, and comorbid symptoms. SES effects on depressive symptoms were generally absent, but a small “protective” effect of low SES appeared when comorbidity with PD symptoms was taken into account. Cumulatively, these risks account for developmental failures of substantial magnitude and consequence, marking the importance of understanding the remaining mechanisms of SES effects and programmatic implications for minimizing associated risk.
Unresolved loss in the Adult Attachment Interview: Implications for marital and parenting relationships
Authors: Busch Amy L. , Cowan Philip A. , Cowan Carolyn P.
Published: April 2008

This study examined links between the unresolved loss of a significant person and current functioning in marital and parenting relationships. Participants were 80 women who had experienced loss, their husbands, and their preschool children. Unresolved loss was assessed using the Adult Attachment Interview, and individual, marital, and parenting adaptation was assessed through videotaped observations and women's self-reports. As predicted, women with unresolved loss displayed less positive emotion and more anxiety and anger with both their husbands and children, compared to women who were not unresolved. They also displayed less authoritative and more authoritarian parenting styles with their children. Yet unresolved women did not report more individual or relationship difficulties, suggesting that direct observations are needed to assess the implications of unresolved loss for family functioning.
Biotechnology and Conceptualizations of the Soul
Authors: SILVER LEE M.
Published: April 2008

In 1970, Jacque Monod, a Nobel Laureate and a founding father of
molecular biology, wrote a short celebrated book entitled Chance
and Necessity.
The Ethical Case against Stem Cell Research
Authors: HOLM SØREN
Published: April 2008

The possibility of creating human embryonic stem cell lines from the
inner cell mass of blastocysts has led to considerable debate about how
these scientific developments should be regulated. Part of this debate
has focused on the ethical analysis and part on how this analysis
should influence policymaking.
Cloning and Genetic Parenthood
Authors: KOLERS AVERY
Published: April 2008

This paper explores the implications of human reproductive cloning
for our notions of parenthood. Cloning comes in numerous varieties,
depending on (among other things) the kind of cell to be cloned, the
age of the source at the time the clone is created, the intended social
relationship, if any, between source and clone, and whether the clone
is to be one of one, or one of many, genetically identical individuals
alive at a time. The moral and legal character of an act of cloning
may, moreover, differ in light of these distinctions.
Surprisingly, however, reproductive cloning in all its variety seems to
undermine the view of parenthood that is most popular among proponents
of reproductive technology in the bioethics literature. This view,
geneticism, has much to recommend it. I will show, however,
that as commonly understood, geneticism is incompatible with the
reproductive view of cloning. I then canvass alternative accounts of
parenthood—namely, conventionalism, gestationalism, and
intentionalism—but none succeeds in explaining reproductive
cloning. I thus return to a reconstructed version of geneticism. I
argue that the problem for geneticism rests not with the notion of
genetic parenthood as such but with a particular, flawed, understanding
of it, which I call informational geneticism. Informational
geneticism should be rejected in favor of a “physicalistic”
version of geneticism, which treats genes as particular objects, not
abstract types, and takes seriously the essentially embodied character
of reproduction. For these reasons, physicalistic geneticism survives
the challenge represented by reproductive cloning. Additionally,
physicalistic geneticism accommodates attractive aspects of competing
views of parenthood, meeting some powerful objections in the
process.
Public-Private Partnerships in Drug Development for Underdeveloped
Countries: An Interview with Craig Wheeler, President of Chiron's
Biopharmaceutical Division
Authors: KUSHNER THOMASINE
Published: April 2008

In an effort to create a mechanism for addressing a critical need of
providing medicines for economically developing countries, the Chiron
Corporation and the Global Alliance for TB Drug Development have
entered into an innovative public-private partnership. In the following
interview, Craig Wheeler discusses the origins and nature of this agreement
that could set a pattern for how corporations and nonprofit organizations
can work together in drug development.
Utilitarianism Shot Down by Its Own Men?
Authors: TAKALA TUIJA
Published: April 2008

I think that utilitarianism is a good moral theory, and definitely
better than its rivals, deontology and teleology. For practical
purposes in multicultural contexts, at least, I think that no one
should overlook a theory that is able to take into account a variety of
ethical views and accommodate the ever-changing facts of the material
world. But utilitarianism has a bad reputation in bioethics. It is
often seen as the inhumane theory that allows the sacrifice of
minorities, the killing of the innocent, and simplistic calculations on
the value of life. Hardly anyone cares to remember that most
formulations of the theory do not allow these actions. The economic
doctrine sometimes labeled as utilitarianism could be guilty as
charged, but ethics and economy are not interchangeable words. Also as
a theory that can actually propose answers to no-win situations,
utilitarianism has been an easy target for criticism.
2005 APSA Teaching and Learning Conference Track
Summaries: Track Two: Diversity
Authors: Stewart Kendra , Light Steven Andrew , Pappas Christine , Rand Kathryn R.L.
Published: April 2008

In the 2005 APSA Teaching and Learning Conference's Diversity Track,
some 30 participants representing a wide range of colleges and
universities came together to discuss issues related to teaching and
learning about diversity. Diversity-focused pedagogy recognizes
commonalities of individual and group experience defined by race,
gender, ethnicity, class, sexual orientation, age, and ability, but
it touches much broader circles. One of the most important aspects
of the track was the diversity of its participants—not usually one
of the discipline's strong points. The wide range of backgrounds and
experiences reflected by the track's participants highlighted the
value of diversity to the profession, as well as the fact that
political scientists carry different burdens at a wide range of
institutions. Participants in this track found that our senses of
what defines diversity, the importance of teaching about diversity,
and what teaching techniques effectively illustrate diversity were,
well, diverse.
2005 APSA Teaching and Learning Conference Track
Summaries: Track Three: Experiential Learning
Authors: Barrow Lynda , Hofrenning Daniel , Parkhurst Jocelyn
Published: April 2008

Teachers usually turn to experiential education when they are
dissatisfied with the so-called traditional classroom. At its worst,
conventional teaching dissects the political world into an array of
component parts. Sometimes students read the latest scholarship, but
the treatment of politics is often either blandly descriptive or too
abstract. This type of teaching can rob politics of its pulsing
energy, which, ironically, attracted many political scientists into
the field. While most political scientists find politics exciting,
the norms of the discipline can enervate the importance and drama of
politics. Student calls for more “current events” are a frequent
response to these academic experiences.
2005 APSA Teaching and Learning Conference Track
Summaries: Track Five: Research Methods and
Techniques
Authors: Botteron, Cynthia A. , Harkness, S. Suzan J.
Published: April 2008

From February 19–21, 2005, several hundred political scientists met
at the second annual APSA Conference on Teaching and Learning in
Bethesda, Maryland. To facilitate an atmosphere of intensive
interaction and mutual learning, the conference was conducted in the
“European format” where topic-specific Tracks worked as a
deliberative community over three days rather than the format of
American conferences—paper, paper, paper, comment, question, then on
to a different session. Track Five's task was to exchange ideas
about teaching methodology with the goal of formulating proposals
that could be disseminated to the discipline. Interestingly, the
topic was taken up by contributors in Track Five from two angles:
first, “teaching methods” as a pedagogical issue and second,
teaching research methodology.
“YES to the Europe I want; NO to this one.” Some
Reflections on France's Rejection of the EU
Constitution
Authors: Milner Henry
Published: April 2008

I spent the 2004–2005 academic year in France, culminating with the
May 29th referendum on the European Union constitutional
treaty. Fifty-five percent of voters rejected it. Three days later,
62% of Dutch voters followed suit. These were unexpected results,
especially in France, a country where 80% declare themselves in
favor of European integration. In other member states, a simple rule
generally applies: those whose priority is to strengthen the EU are
on the “yes” side, while the “no” is identified with those who
emphasize national interests. In the Netherlands, though the murder
of filmmaker Theo van Gogh by an Islamic radical was a factor, the
“no” forces won essentially because they persuaded enough people
that the direction the Constitution would take the Netherlands went
against Dutch interests. To do so, they played on the resentment
that Brussels took their money but ignored Dutch concerns—“the same
people who fooled you with the euro are fooling you now with this
constitution.”
The French Referendum: The Not So Simple Act of Saying
Nay
Authors: Brouard Sylvain , Tiberj Vincent
Published: April 2008

For the second time in the history of the French Vth Republic, the
first having led to the resignation of Charles De Gaulle in 1969, a
president lost a national referendum. On May 29, 2005, 54.7% of
French voters rejected the European Constitutional Treaty, even
though France was one of the major proponents of the European
Convention which led to the Constitution's drafting. The victory of
the “no” vote had been foreseen, but neither the margin of victory,
nor the high turnout (almost 70.5%) were expected. The rejection of
the Constitution raised two concerns: the first related to the
position of France in Europe, the second to its domestic impact. Why
did the French electorate vote as it did? Did voters make up their
minds based on national cues, the European issue being generally of
little importance even in European elections (Franklin, Marsh, and McLaren 1994; Van der Eijk and Franklin 1996)? Is the referendum
result the consequence of a growing anti-European attitude, which
could cause considerable damage to the process of EU integration?
Will a new cleavage grounded on attitudes to Europe and capable of
altering the traditional left-right organization emerge in the
French political system? Our warmest
thanks to our colleagues, Chantal Barry, Arianne Chebel
d'Appolonia, and Manlio Cinnalli for their remarks on and their
help with this piece.
Understanding the Dutch “No”: The Euro, the East, and the
Elite
Authors: Aarts Kees , van der Kolk Henk
Published: April 2008

The Dutch have been counted among the staunchest supporters of
European integration ever since the parliamentary ratification of
the European Community for Coal and Steel in late 1951. The major
political parties—the Christian Democrats (CDA) and its forerunners,
the Labor Party (PvdA), and the liberal parties VVD and
D66—supported all important European treaties of the past decades.
Only the smaller orthodox-Calvinist parties, some smaller left-wing
parties, and, more recently, the List Pim Fortuyn (LPF) have opposed
these treaties in parliament. This overwhelmingly large support in
the Second Chamber of the Dutch parliament included the Treaty of
Rome of 2004—the treaty establishing a constitution for Europe. One
hundred twenty-eight out of 150 members of parliament favored the
ratification of the European Constitution. This article draws on several chapters in Aarts and van der Kolk 2005.
Appropriating the “No”: The French National Front, the
Vote on the Constitution, and the “New” April 21
Authors: Berezin Mabel
Published: April 2008

On the evening of May 26, 2005, with the polls suggesting that the
European Constitution was veering toward defeat, Jacques Chirac made
a final exhortation to the French public. He argued that the French
were voting not on a sectarian political issue but on an issue that
would determine the future of themselves, their children, France,
and Europe. Chirac characterized the choice before French citizens
as “neither right nor left.” His use of a phrase more commonly
associated with Vichy displayed an uncharacteristic historical
amnesia and suggests that Chirac and his party were grabbing at
straws in those final days.