Quantification of the spatiotemporal microstructural organization of the human brain association, projection and commissural pathways across the lifespan using diffusion tensor tractography.

Using diffusion tensor tractography, we quantified the microstructural changes in the association, projection, and commissural compact white matter pathways of the human brain over the lifespan in a cohort of healthy right-handed children and adults aged 6-68 years. In both males and females, the diffusion tensor radial diffusivity of the bilateral arcuate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, corticospinal, somatosensory tracts, and the corpus callosum followed a U-curve with advancing age; fractional anisotropy in the same pathways followed an inverted U-curve. Our study provides useful baseline data for the interpretation of data collected from patients.

Organization of hue selectivity in macaque V2 thin stripes.

V2 has long been recognized to contain functionally distinguishable compartments that are correlated with the stripelike pattern of cytochrome oxidase activity. Early electrophysiological studies suggested that color, direction/disparity, and orientation selectivity were largely segregated in the thin, thick, and interstripes, respectively. Subsequent studies revealed a greater degree of homogeneity in the distribution of response properties across stripes, yet color-selective cells were still found to be most prevalent in the thin stripes. Optical recording studies have demonstrated that thin stripes contain both color-preferring and luminance-preferring modules. These thin stripe color-preferring modules contain spatially organized hue maps, whereas the luminance-preferring modules contain spatially organized luminance-change maps. In this study, the neuronal basis of these hue maps was determined by characterizing the selectivity of neurons for isoluminant hues in multiple penetrations within previously characterized V2 thin stripe hue maps. The results indicate that neurons within the superficial layers of V2 thin stripe hue maps are organized into columns whose aggregated hue selectivity is closely related to the hue selectivity of the optically defined hue maps. These data suggest that thin stripes contain hue maps not simply because of their moderate percentage of hue-selective neurons, but because of the columnar and tangential organization of hue selectivity.

Anatomical organization of the memory underlying sensitization in the siphon-withdrawal reflex circuit of {\it Aplysia californica}

Previous studies have shown that short-term sensitization of the Aplysia siphon-withdrawal reflex circuit results in multiple sites of change in synaptic efficacy. In this dissertation I have used a realistic modeling approach (using an integrate-and-fire scheme), in conjunction with electrophysiological experiments, to evaluate the contribution of each site of plasticity to the sensitized response.^ This dissertation contains a detailed description of methodology for the construction of the model circuit, consisting of the LFS motor neurons and ten interneurons known to convey excitatory input to them. The model replicates closely the natural motor neuron firing response to a brief tactile stimulus.^ The various circuit elements have different roles for producing circuit output. For example, the sensory connections onto the motor neuron are important for the production of the phasic response, while the polysynaptic interneuronal connections are important for producing the tonic response.^ The multiple sites of plasticity that produce changes in circuit output also have specialized roles. Presynaptic facilitation of the sensory neuron to LFS connection enhances only the phasic component of the motor neuron firing response. The sensory neuron to interneuron connections primarily enhance the tonic component of the motor neuron firing response. Also, the L29 posttetanic potentiation and the L30 presynaptic inhibition primarily enhance the tonic component of the motor neuron firing response. Finally, the information content at the various sites of plasticity can shift with changes in stimulus intensity. This suggests that while the sites of plasticity encoding memory are fixed, the information content at these sites can be dynamic, shifting in anatomical location with changes in the intensity of the test stimulus.^ These sites of plasticity also produce specific changes in the behavioral response. Sensory-LFS plasticity selectively increases the amplitude of the behavioral response, and has no effect on the duration of the behavioral response. Interneuronal plasticity (L29 and L30) affects both the amplitude and duration of the behavioral response. Other sensory plasticity also affect both the amplitude and duration of the behavioral response, presumably by increasing the recruitment of the interneurons, which provide all of the effect on duration of the behavioral response. ^

Modular organization of the cortical connections linking visual areas V1, V2 and V4 in Macaque monkeys

The macaque cortical visual system is hierarchically organized into two streams, the ventral stream for recognizing objects and the dorsal stream for analyzing spatial relationships. The ventral stream extends from striate cortex or area V1 to inferior temporal cortex (IT) through extra-striate areas V2 and V4. Between V1 and V2, the ventral stream consists of two roughly parallel sub-streams, one extending from the cytochrome oxidase (CO) rich blobs in V1 to the CO rich thin stripes in V2, the other extending from the interblobs in V1 to interstripes, in V2. The blob-dominated sub-stream is thought to analyze the surface features such as color, whereas the interblob-dominated one is thought to analyze the contour features such as shape. ^ In the current study, the organization of cortical pathways linking V2 thin stripe and interstripe compartments with area V4 was investigated using a combination of physiological and anatomical techniques. Different compartments of V2 were first characterized, in vivo, using optical recording of intrinsic cortical signals. These functionally derived maps of V2 stripe compartments were then used to guide iontophoretic injections of multiple, distinguishable, anterograde tracers into specific V2 compartments. The distribution of labeled axons was analyzed either in horizontal sections through the prelunate gyrus, or in tangentially sectioned portions of physically unfolded cortex containing the lunate sulcus, prelunate gyrus and superior temporal sulcus. When a V2 thin stripe and adjacent interstripe were injected with distinguishable tracers, a large primary and several secondary foci were observed in V4. The primary focus from the thin stripe injection was spatially segregated from the primary focus from the V2 interstripe injection, suggesting a retention of the pattern of compartmentation. ^ We examined the distribution of retrogradely labeled cells in V1 following the injections of tracers into V2 different compartments, in order to quantitate just how parallel the two sub-streams are from V1 to V2. Our results suggest that both blobs and interblobs project to thin stripes in V2, whereas only interblobs project to interstripes. This asymmetrical segregation argues against the original proposal of strict parallelism. (Abstract shortened by UMI.) ^

GENETIC ORGANIZATION OF THE STRUCTURAL GENES FOR NITRATE REDUCTASE (TN5)

Nitrate reductase in Escherichia coli is a membrane-bound anaerobic enzyme that is repressed by oxygen and induced by nitrate. The genetic organization of the structural genes for the two larger subunits of nitrate reductase ((alpha) and (beta)) was determined by immunoprecipitation analysis of the formation of these proteins in nitrate reductase-deficient mutants resulting from transposon Tn5 mutagenesis. The results suggested that the genes encoding the (alpha) and (beta) subunits (narG and H) were arranged in an operon with transcription in the direction promoter(--->)(alpha)(--->)(beta). Segments of the chromosome containing the Tn5 inserts from several of the mutants were cloned into plasmid pBR322 and the positions of the transposons determined by restriction mapping. The Tn5 insertion sites were localized on two contiguous EcoRI fragments spanning about 6.6 kilobases of DNA. The narI gene (proposed to encode the (gamma) subunit) was positioned immediately downstream from the (beta)-gene (narH) by Southern analysis of Tn10 insertions into the narI locus. A Tn10 insertion into the narK locus, proposed to encode a nitrate-sensitive repressor of other anaerobic enzymes, was located about 1.5 kilobases upstream from the narGHI operon promoter. The narL locus, proposed to encode a nitrate-sensitive positive regulator of the narGHI operon and known to be genetically linked to the other nar genes, was demonstrated to lie outside a 19.3-kilobase region of the chromosome which encompasses the other nar genes. The physical limit of the narGHI promoter was defined by studying the effect of Tn5 insertions into a hybrid plasmid containing the functional operon. The points of origin of the coding regions for the (alpha) and (beta) genes were deduced by alignment of the chromosomal map of Tn5 insertion sites with the sizes of (alpha) and (beta) subunit fragments produced by plasmids carrying these Tn5 inserts in the nar operon. The coding region for the (alpha) subunit (143,000 daltons) begins about 250 nucleotides downstream from the deduced limit of the promoter region and includes about 4.0 kilobases of DNA; the region encoding (beta) (60,000 daltons) lies immediately downstream from the (alpha)-gene and is approximately 1.6 kilobases in length. The adjacent region encoding the (gamma) subunit (19,000 daltons) is approximately 0.5 kilobase in length. ^

THE ULTRASTRUCTURAL ORGANIZATION OF THE HYPOGLOSSAL NUCLEUS IN THE RAT (SYNAPTOLOGY, CRANIAL NERVES)

An ultrastructural study of the hypoglossal nucleus (XII) in the rat has revealed two distinct neuronal populations. Hypoglossal motoneurons comprised the largest population of neurons in XII and were identified following injection of horseradish peroxidase (HRP) into the tongue. Motoneurons were large (25-50(mu)m), multipolar in shape and distributed throughout XII. The nucleus was large, round and centrally located, and the cytoplasm was characterized by dense lamellar arrays of rough endoplasmic reticulum. In contrast, a second population of small (10-18(mu)m), round to oval shaped neurons was found restricted to the ventral and dorsolateral regions of XII. The nucleus was markedly invaginated and eccentric, the cytoplasm scant and filled with free ribosomes, and the absence of lamellar arrays of rough endoplasmic reticulum was conspicuous. Neurons of this type were never found to contain HRP reaction product. These results demonstrate that the hypoglossal nucleus does not consist solely of motoneurons, but includes a distinctly separate, presumably non-motoneuronal pool. Arguments are presented in favor of this second neuron population being interneurons. The functional significance of these findings in relation to tongue control is discussed. ^

An analysis of Texas's school based HPV vaccine mandate: A public health risk communication failure: HPVETO!

Genital human papillomavirus (HPV) is of public health concern because persistent infection with certain HPV types can cause cervical cancer. In response to a nationwide push for cervical cancer legislation, Texas Governor Rick Perry bypassed the traditional legislative process and issued an executive order mandating compulsory HPV vaccinations for all female public school students prior to their entrance in the sixth grade. By bypassing the legislative process Governor Perry did not effectively mitigate the risk perception issues that arose around the need for and usefulness of the vaccine mandate. This policy paper uses a social policy paradigm to identify perception as the key intervening factor on how the public responds to risk information. To demonstrate how the HPV mandate failed, it analyzes four factors, economics, politics, knowledge and culture, that shape perception and influence the public's response. By understanding the factors that influence the public's perception, public health practitioners and policy makers can more effectively create preventive health policy at the state level. ^

Organization of the inferotemporal cortex in the macaque monkey: Connections of areas PITv and CITvp

Visual cortex of macaque monkeys consists of a large number of cortical areas that span the occipital, parietal, temporal, and frontal lobes and occupy more than half of cortical surface. Although considerable progress has been made in understanding the contributions of many occipital areas to visual perceptual processing, much less is known concerning the specific functional contributions of higher areas in the temporal and frontal lobes. Previous behavioral and electrophysiological investigations have demonstrated that the inferotemporal cortex (IT) is essential to the animal's ability to recognize and remember visual objects. While it is generally recognized that IT consists of a number of anatomically and functionally distinct visual-processing areas, there remains considerable controversy concerning the precise number, size, and location of these areas. Therefore, the precise delineation of the cortical subdivisions of inferotemporal cortex is critical for any significant progress in the understanding of the specific contributions of inferotemporal areas to visual processing. In this study, anterograde and/or retrograde neuroanatomical tracers were injected into two visual areas in the ventral posterior and central portions of IT (areas PITv and CITvp) to elucidate the corticocortical connections of these areas with well known areas of occipital cortex and with less well understood regions of inferotemporal cortex. The locations of injection sites and the delineation of the borders of many occipital areas were aided by the pattern of interhemispheric connections, revealed following callosal transection and subsequent labeling with HRP. The resultant patterns of connections were represented on two-dimensional computational (CARET) and manual cortical maps and the laminar characteristics and density of the projection fields were quantified. The laminar and density features of these corticocortical connections demonstrate thirteen anatomically distinct subdivisions or areas distributed within the superior temporal sulcus and across the inferotemporal gyrus. These results serve to refine previous descriptions of inferotemporal areas, validate recently identified areas, and provide a new description of the hierarchical relationships among occipitotemporal cortical areas in macaques. ^

A path analysis of an after-school health and exercise program for elementary school children in El Paso, Texas

As schools are pressured to perform on academics and standardized examinations, schools are reluctant to dedicate increased time to physical activity. After-school exercise and health programs may provide an opportunity to engage in more physical activity without taking time away from coursework during the day. The current study is a secondary data analysis of data from a randomized trial of a 10-week after-school program (six schools, n = 903) that implemented an exercise component based on the CATCH physical activity component and health modules based on the culturally-tailored Bienestar health education program. Outcome variables included BMI and aerobic capacity, health knowledge and healthy food intentions as assessed through path analysis techniques. Both the baseline model (χ2 (df = 8) = 16.90, p = .031; RMSEA = .035 (90% CI of .010–.058), NNFI = 0.983 and the CFI = 0.995) and the model incorporating intervention participation proved to be a good fit to the data (χ2 (df = 10) = 11.59, p = .314. RMSEA = .013 (90% CI of .010–.039); NNFI = 0.996 and CFI = 0.999). Experimental group participation was not predictive of changes in health knowledge, intentions to eat healthy foods or changes in Body Mass Index, but it was associated with increased aerobic capacity, β = .067, p < .05. School characteristics including SES and Language proficiency proved to be significantly associated with changes in knowledge and physical indicators. Further effects of school level variables on intervention outcomes are recommended so that tailored interventions can be developed aimed at the specific characteristics of each participating school. ^

THE EFFECT OF IRON SUPPLEMENT ON THE GROWTH OF RURAL INDONESIAN SCHOOL CHILDREN

The effect of oral iron supplementation on blood iron levels and physical growth in 119 Indonesian rural school children was assessed in the double-blind study. The children were classified into anemic and normal groups according to their initial hemoglobin and transferrin saturation levels and were randomly assigned to either iron or placebo treatment for twelve weeks. Biochemical, anthropometric and morbidity data were collected prior to and after the treatment period. Before treatment, anemic subjects were smaller and had higher morbidity than normal subjects. Treatment with 10 mg ferrous sulfate/kg/day for twelve weeks resulted in a significant improvement in blood iron biochemical status of the anemic subjects and in their growth velocity and morbidity. ^

THE FUNCTIONAL ORGANIZATION OF SYNAPTIC VESICLE POOLS IN A RETINAL BIPOLAR NEURON

Ribbon synapses are found in sensory systems and are characterized by ‘ribbon-like’ organelles that tether synaptic vesicles. The synaptic ribbons co-localize with sites of calcium entry and vesicle fusion, forming ribbon-style active zones. The ability of ribbon synapses to maintain rapid and sustained neurotransmission is critical for vision, hearing and balance. At retinal ribbon synapses, three vesicle pools have been proposed. A rapid pool of vesicles that are docked at the plasma membrane, and whose fusion is limited only by calcium entry, a releasable pool of ATP-primed vesicles whose size also correlates with the number of ribbon-tethered vesicles, and a reserve pool of non-ribbon-tethered cytoplasmic vesicles. However evidence of vesicle fusion at sites away from ribbon-style active zones questions this organization. Another fundamental question underlying the mechanism of vesicle fusion at these synapses is the role of SNARE (Soluble N-ethylmaleimide sensitive factor Attachment Protein Receptor) proteins. Vesicles at conventional neurons undergo SNARE complex-mediated fusion. However a recent study has suggested that ribbon synapses involved in hearing can operate independently of neuronal SNAREs. We used the well-characterized goldfish bipolar neuron to investigate the organization of vesicle pools and the role of SNARE proteins at a retinal ribbon synapse. We blocked functional refilling of the releasable pool and then stimulated bipolar terminals with brief depolarizations that triggered the fusion of the rapid pool of vesicles. We found that the rapid pool draws vesicles from the releasable pool and that both pools undergo release at ribbon-style active zones. To assess the functional role of SNARE proteins at retinal ribbon synapses, we used peptides derived from SNARE proteins that compete with endogenous proteins for SNARE complex formation. The SNARE peptides blocked fusion of reserve vesicles but not vesicles in the rapid and releasable pools, possibly because both rapid and releasable vesicles were associated with preformed SNARE complexes. However, an activity-dependent block in refilling of the releasable pool was seen, suggesting that new SNARE complexes must be formed before vesicles can join a fusion-competent pool. Taken together, our results suggest that SNARE complex-mediated exocytosis of serially-organized vesicle pools at ribbon-style active zones is important in the neurotransmission of vision.

The Hospital Study of the City of Houston and Harris County

In 1941 the Texas Legislature appropriated $500,000 to the Board of Regents of the University of Texas to establish a cancer research hospital. The M. D. Anderson Foundation offered to match the appropriation with a grant of an equal sum and to provide a permanent site in Houston. In August, 1942 the Board of Regent of the University and the Trustees of the Foundation signed an agreement to embark on this project. This institution was to be the first one in the medical center, which was incorporated in October, 1945. The Board of Trustees of the Texas Medical Center commissioned a hospital survey to: - Define the needed hospital facilities in the area - Outline an integrated program to meet these needs - Define the facilities to be constructed - Prepare general recommendations for efficient progress The Hospital Study included information about population, hospitals, and other health care and education facilities in Houston and Harris County at that time. It included projected health care needs for future populations, education needs, and facility needs. It also included detailed information on needs for chronic illnesses, a school of public health, and nursing education. This study provides valuable information about the general population and the state of medicine in Houston and Harris County in the 1940s. It gives a unique perspective on the anticipated future as civic leaders looked forward in building the city and region. This document is critical to an understanding of the Texas Medical Center, Houston and medicine as they are today. SECTIONS INCLUDE: Abstract The Abstract was a summary of the 400 page document including general information about the survey area, community medical assets, and current and projected medical needs which the Texas Medical Center should meet. The 123 recommendations were both general (e.g., 12. “That in future planning, the present auxiliary department of the larger hospitals be considered inadequate to carry an added teaching research program of any sizable scope.”) and specific (e.g., 22. That 14.3% of the total acute bed requirement be allotted for obstetric care, reflecting a bed requirement of 522 by 1950, increasing to 1,173 by 1970.”) Section I: Survey Area This section basically addressed the first objective of the survey: “define the needed hospital facilities in the area.” Based on the admission statistics of hospitals, Harris County was included in the survey, with the recognition that growth from out-lying regional areas could occur. Population characteristics and vital statistics were included, with future trends discussed. Each of the hospitals in the area and government and private health organizations, such as the City-County Welfare Board, were documented. Statistics on the facilities use and capacity were given. Eighteen recommendations and observations on the survey area were given. Section II: Community Program This section basically addressed the second objective of the survey: “outline an integrated program to meet these needs.” The information from the Survey Area section formed the basis of the plans for development of the Texas Medical Center. In this section, specific needs, such as what medical specialties were needed, the location and general organization of a medical center, and the academic aspects were outlined. Seventy-four recommendations for these plans were provided. Section III: The Texas Medical Center The third and fourth objectives are addressed. The specific facilities were listed and recommendations were made. Section IV: Special Studies: Chronic Illness The five leading causes of death (heart disease, cancer, “apoplexy”, nephritis, and tuberculosis) were identified and statistics for morbidity and mortality provided. Diagnostic, prevention and care needs were discussed. Recommendations on facilities and other solutions were made. Section IV: Special Studies: School of Public Health An overview of the state of schools of public health in the US was provided. Information on the direction and need of this special school was also provided. Recommendations on development and organization of the proposed school were made. Section IV: Special Studies: Needs and Education Facilities for Nurses Nursing education was connected with hospitals, but the changes to academic nursing programs were discussed. The needs for well-trained nurses in an expanded medical environment were anticipated to result in significant increased demands of these professionals. An overview of the current situation in the survey area and recommendations were provided. Appendix A Maps, tables and charts provide background and statistical information for the previous sections. Appendix B Detailed census data for specific areas of the survey area in the report were included. Sketches of each of the fifteen hospitals and five other health institutions showed historical information, accreditations, staff, available facilities (beds, x-ray, etc.), academic capabilities and financial information.