Interrelationships between Cellular Density,Mosaic Patterning,and Dendritic Coverage of VGluT3 Amacrine Cells

Amacrine cells of the retina are conspicuously variable in their morphologies, their population demographics, and their ensuing functions. Vesicular glutamate transporter 3 (VGluT3) amacrine cells are a recently characterized type of amacrine cell exhibiting local dendritic autonomy. The present analysis has examined three features of this VGluT3 population, including their density, local distribution, and dendritic spread, to discern the extent to which these are interrelated, using male and female mice. We first demonstrate that Bax-mediated cell death transforms the mosaic of VGluT3 cells from a random distribution into a regular mosaic. We subsequently examine the relationship between cell density and mosaic regularity across recombinant inbred strains of mice, finding that, although both traits vary across the strains, they exhibit minimal covariation. Other genetic determinants must therefore contribute independently to final cell number and to mosaic order. Using a conditional KO approach, we further demonstrate that Bax acts via the bipolar cell population, rather than cell-intrinsically, to control VGluT3 cell number. Finally, we consider the relationship between the dendritic arbors of single VGluT3 cells and the distribution of their homotypic neighbors. Dendritic field area was found to be independent of Voronoi domain area, while dendritic coverage of single cells was not conserved, simply increasing with the size of the dendritic field. Bax-KO retinas exhibited a threefold increase in dendritic coverage. Each cell, however, contributed less dendrites at each depth within the plexus, intermingling their processes with those of neighboring cells to approximate a constant volumetric density, yielding a uniformity in process coverage across the population.SIGNIFICANCE STATEMENT Different types of retinal neuron spread their processes across the surface of the retina to achieve a degree of dendritic coverage that is characteristic of each type. Many of these types achieve a constant coverage by varying their dendritic field area inversely with the local density of like-type neighbors. Here we report a population of retinal amacrine cells that do not develop dendritic arbors in relation to the spatial positioning of such homotypic neighbors; rather, this cell type modulates the extent of its dendritic branching when faced with a variable number of overlapping dendritic fields to approximate a uniformity in dendritic density across the retina.     

A preliminary statistical model for identifying repeaters of parasuicide

This paper presents a statistical model constructed using logisticregression to identify those at high-risk of repeating parasuicide. Thesubjects in the study are Cork city residents who exhibited parasuicidalbehaviour between 1 January and 30 June 1995. Repetition of the behaviourwithin six months of the index episode distinguishes repeaters fromnon-repeaters. The model was designed so that it could be used bynon-clinicians and hence does not require information relating topsychiatric diagnosis or use of psychiatric services. The proportion ofsubjects correctly classified remained stable across a range of cut-pointprobabilities (mean = 86%, range: 83.9–87.5%). Using acut-point of 0.2, 96% of repeaters and 81% of non-repeaters were correctly classified. Using 0.45 led to the correct identification of81% of repeaters and 90% of non-repeaters. If these highlevels of sensitivity and specificity are maintained in validation tests onfuture cohorts in Cork city then the model could form the basis of anintervention programme designed to prevent the repetition of parasuicide.     

Neuroendocrine and juvenile hormone effects on fat body protein synthesis during the reproductive cycle in female Blaberus discoidalis cockroaches

Ovarian protein content and fat body protein synthesis were measured during the first gonotrophic cycle in virgin female Blaberus discoidalis cockroaches. Protein synthesis was measured for in vitro fat bodies from animals treated with combinations of a juvenile hormone analog (JHA = methoprene) and corpora cardiaca (CC) extracts. Ovarian protein content began to increase on Day 5 of adult life and reached its maximum at Days 20-22. Synthesis of proteins secreted by the in vitro fat body increased by 12-fold between emergence and its maximum on Day 18, then declined to nearly its original level by Day 33. Synthesis of nonsecreted, fat body proteins increased by 4-fold between emergence and a maximum on Day 21, then declined. CC extracts and JHA were administered to decapitated females to determine their regulative effects on fat body protein synthesis. The synthesis by the fat body of nonsecreted proteins was increased by both JHA and CC extracts. In contrast, synthesis of secreted proteins increased only in the presence of JHA. CC extracts, alone, had no effects on the synthesis of secreted proteins, but administration of CC extracts in combination with JHA increased the synthesis of the secreted proteins by 55% above that observed with JHA alone. SDS-PAGE of proteins secreted into the medium by the in vitro fat body demonstrated that JHA stimulated the synthesis of specific polypeptides, whereas CC extracts did not affect the synthesis of specific-secreted polypeptides. These results suggest that JH regulates specific protein synthesis by the fat body of B. discoidalis; neurohormones elevate the general capacity of the fat body for protein synthesis and amplify the specific effects of JH.     

Partial replication of a DRD4 association in ADHD individuals using a statistically derived quantitative trait for ADHD in a family-based association test.

BACKGROUND: Previous research found an association between single nucleotide polymorphisms (SNPs) in the promoter region of DRD4 and statistically derived phenotypes generated from attention-deficit/hyperactivity disorder (ADHD) symptoms. We sought to replicate this finding by using the same methodology in an independent sample of ADHD individuals. METHODS: Four SNPs were genotyped in and around DRD4 in 2631 individuals in 642 families. We developed a quantitative phenotype at each SNP by weighting nine inattentive and nine hyperactive-impulsive symptoms. The weights were selected to maximize the heritability at each SNP. Once a quantitative phenotype was generated at each SNP, the screening procedure implemented in PBAT was used to select and test the five SNPs/genetic model combinations with the greatest power to detect an association for DRD4. RESULTS: One of the four SNPs was associated with the quantitative phenotypes generated from the ADHD symptoms (corrected p-values = .02). A rank ordering of the correlation between each of the ADHD symptoms and the quantitative phenotype suggested that hyperactive-impulsive symptoms were more strongly correlated with the phenotype; however, including inattentive symptoms was necessary to achieve a significant result. CONCLUSIONS: This study partially replicated a previous finding by identifying an association between rs7124601 and a quantitative trait generated from ADHD symptoms. The rs7124601 is in linkage disequilibrium (LD) with the SNPs identified previously. In contrast to the previous study, this finding suggests that both hyperactive-impulsive and inattentive symptoms are important in the association.     

Type IV Ehlers-Danlos syndrome presenting as sudden infant death

A previously healthy 5-month-old female infant presented with sudden death due to spontaneous subarachnoid hemorrhage associated with minor multifocal visceral hemorrhages. The clinical diagnosis had been sudden infant death syndrome. Although the family history was noncontributory and other features of type IV Ehlers-Danlos syndrome (EDS) were absent, the pattern of hemorrhage was consistent with this type of connective tissue disorder. The diagnosis was confirmed after postmortem analysis of skin and aorta showed less than 5% type III collagen (normal greater than 15%). Extensive literature review failed to find any other reported cases of sudden death in infancy due to intracranial hemorrhage in patients with previously unsuspected type IV EDS. The authors suggest that collagen analysis should be performed in cases of unexplained multifocal spontaneous hemorrhage in infancy so that this rare diagnosis will not be missed.     

Adeno-associated viral vectors for retinal gene transfer and treatment of retinal diseases

Retinal gene transfer holds big promises for the treatment of inherited and non-inherited blinding diseases, such as retinitis pigmentosa or age-related macular degeneration. Key to the development of successful gene-based therapies for the eye are efficient tools for retinal gene transfer. Vectors based on adeno-associated viruses (AAV) are able to transduce robustly and persistently different retinal cell types of animal models after a single intraocular administration. Recombinant AAV (rAAV) vectors are versatile gene transfer tools in that capsid proteins from dozens of AAV serotypes can be easily interchanged, resulting in the creation of recombinant vectors with unique transduction properties. This has allowed successful proof-of-principle studies using rAAV-mediated gene transfer to restore retinal morphology and function in small and large animal models of retinal diseases. In addition, gene delivery using rAAV vectors in the eye seems to have appropriate biosafety characteristics to rapidly move it from bench to bedside. All the above aspects will be reviewed and discussed in detail below.     

Synthetic nerve graft containing collagen and synthetic Schwann cells inproves functional, electrophysiological, and histological parameters of peripheral nerve regeneration

Current methods of peripheral nerve repair are to directly suture cut nerve stumps, or to bridge large gaps with an autograft repair. Autograft-associated problems include donor site morbidity and limited supply. Many of the present limitations of nerve repair might be overcome by expanding the patients own Schwann cells in vitro, then combining the cells with other neuro-tropic and -trophic materials into an Artificial Nerve Graft (ANG) for bridging a nerve gap. In this 4.5 month experiment, a rat peroneal nerve model with a 10 mm gap was used to evaluate the effect of live Schwann cells on peripheral nerve regeneration. Nerve gaps were repaired with cellular ANGs containing live Schwann cell, dead Schwann cell, or mixed fibroblast/Schwann cell populations suspended in a collagen I matrix, and with sutured autografts or ANGs containing just collagen or medium. Regenerated nerves were evaluated by walking track analysis, qualitative and quantitative histology, and electrophysiology. Overall, the autograft was the best repair method, while the ANG containing live Schwann cells was statistically superior to other ANG repair methods. This study demonstrates that an ANG containing cultured syngeneic Schwann cells improves functional, histological, and electrophysiological parameters of peripheral nerve regeneration.     

PEDIATRIC OBSESSIVE-COMPULSIVE DISORDER: A GUIDE TO ASSESSMENT AND TREATMENT

Obsessive-compulsive disorder (OCD) is an anxiety disorder characterized by recurrent or persistent thoughts, impulses, or images that are experienced as intrusive or distressing (obsessions), and repetitive behaviors or mental acts (compulsions) often performed in response to an obsession. Recent epidemiological studies have found lifetime prevalence of pediatric OCD to be approximately 1-4% in the USA. OCD begins before the age of 18 years for as many as 80% of cases and follows a chronic, unremitting course. Due to the distressing, time-consuming, and debilitating nature of OCD, impairments in academic, social, and family functioning are often substantial. Despite the relatively high prevalence rate of OCD, dissemination about effective assessment and treatment has lagged. Increasing the awareness of OCD symptoms and its treatment among nurses and other health professionals will enhance identification of children presenting with unrecognized or untreated symptoms of OCD and will stimulate appropriate referrals for treatment to improve children's psychological functioning and overall quality of life. This paper reviews the nature, etiology, assessment, and treatment of OCD, highlighting clinical implications for nurses involved in mental health care.