bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrastructural evidence of a vesicle‐mediated mode of cell degranulation in chicken chromaffin cells during the late phase of embryonic development
Authors: Crivellato Enrico , Nico Beatrice , Travan Luciana , Isola Miriam , Ribatti Domenico 
Published: February 2009

AbstractIn the present investigation, we attempted to determine whether ultrastructural features indicative of a vesicle‐mediated mode of cell secretion were detectable in chick chromaffin cells during embryo development. The adrenal anlagen of domestic fowls were examined at embryonic days (E) 12, 15, 19 and 21 by electron microscopy quantitative analysis. Morphometric evaluation revealed a series of granule and cytoplasmic changes highly specific for piecemeal degranulation (PMD), a secretory process based on vesicular transport of cargoes from within granules for extracellular release. At E19 and E21 we found a significant peak in the percentage of granules exhibiting changes indicative of progressive release of secretory materials, i.e. granules with lucent areas in their cores, reduced electron density, disassembled matrices, residual cores and membrane empty containers. A dramatic raise in the density of 30–80‐nm‐diameter, membrane‐bound, electron‐dense and electron‐lucent vesicles – which were located either next to granules or close to the plasma membrane – was recognizable at E19, that is, during the prehatching phase. The cytoplasmic burst of dense and clear vesicles was paralleled by the appearance of chromaffin granules showing outpouches or protrusions of their profiles (‘budding features’). These ultrastructural data are indicative of an augmented vesicle‐mediated transport of chromaffin granule products for extracellular release in chick embryo chromaffin cells during the prehatching stage. In conclusion, this study provides new data on the fine structure of chromaffin cell organelles during organ development and suggests that PMD may be part of an adrenomedullary secretory response that occurs towards the end of chicken embryogenesis. From an evolutionary point of view, this study lends support to the concept that PMD is a secretory mechanism highly conserved throughout vertebrate classes.
3D representation of the developing chick knee joint: a novel approach integrating multiple components
Authors: Roddy Karen A. , Nowlan Niamh C. , Prendergast Patrick J. , Murphy Paula 
Published: February 2009

AbstractThe knee joint has a highly complex 3‐dimensional (3D) morphology that is sculpted at the interface of the forming long bones as they are generated in the embryo. Although it is clear that regulatory genes guide joint formation, the mechanisms that are responsible for morphogenesis of the knee are poorly understood. Certainly the process involves integration across several tissues and physical/mechanical influences from neighbouring tissues are important. We describe the acquisition of shape in the chick knee joint in detail and show that by HH34 the joint already displays shape characteristics of the adult structure. Through imaging developing cartilage, tendons, ligaments and muscle across developmental stages from HH28–34 we have built 3D representations of the forming structure including the various components important in knee formation. We describe the timing of muscle and tendon development in parallel with the refinement of cartilage shape, showing when and where (tendon attachment points) muscle forces are applied to the cartilage elements. Shape begins to emerge as the tendons are forming (HH30–32) but is fully refined (HH34) in the presence of tendons. The resulting integrated 3D representations of the developing knee across time will serve as the foundation for computational analysis of the mechanical environment, and experimental approaches to investigating morphogenetic mechanisms.
Cranial dimensions and forces of biting in the domestic dog
Authors: Ellis Jennifer Lynn , Thomason Jeffrey , Kebreab Ermias , Zubair Kasim , France James 
Published: February 2009

AbstractThe purpose of this paper is to analyse the effects of cranial size and shape in domestic dogs (Canis familiaris) on predicted forces of biting. In addition to continuous size‐shape analysis, nine size‐shape groups were developed based on three skull shape categories and three skull size categories. Bite forces were predicted from measurements made on dried skulls using two lever models of the skull, as well as simple models derived by regression analysis. Observed bite force values were not available for the database used in this study, so only comparisons between categories and models were undertaken. The effects of shape and size on scaled predicted bite forces were evaluated. Results show that bite force increases as size increases, and this effect was highly significant (P < 0.0001). The effect of skull shape on bite force was significant in medium and large dogs (P < 0.05). Significant differences were not evident in small dogs. Size × shape interactions were also significant (P < 0.05). Bite force predictions by the two lever models were relatively close to each other, whereas the regression models diverged slightly with some negative numbers for very small dogs. The lever models may thus be more robust across a wider range of skull size‐shapes. Results obtained here would be useful to the pet food industry for food product development, as well as to paleontologists interested in methods of estimating bite force from dry skulls.
C cells evolve at the same rhythm as follicular cells when thyroidal status changes in rats
Authors: Martín‐Lacave Inés , Borrero María J. , Utrilla José C. , Fernández‐Santos José M. , De Miguel Manuel , Morillo Jesús , Guerrero Juan M. , García‐Marín Rocío , Conde Esperanza 
Published: February 2009

AbstractC cells are primarily known for producing calcitonin, a hypocalcemic and hypophosphatemic hormone. Nevertheless, besides their role in calcium homeostasis, C cells may be involved in the intrathyroidal regulation of follicular cells, suggesting a possible interrelationship between the two endocrine populations. If this premise is true, massive changes induced by different agents in the activity of follicular cells may also affect calcitonin‐producing cells. To investigate the behaviour of C cells in those circumstances, we have experimentally induced two opposite functional thyroid states. We hyperstimulated the follicular cells using a goitrogen (propylthiouracil), and we suppressed thyroid hormone synthesis by oral administration of thyroxine. In both scenarios, we measured T4, TSH, calcitonin, and calcium serum levels. We also completely sectioned the thyroid gland, specifically immunostained the C cells, and rigorously quantified this endocrine population. In hypothyroid rats, not only follicular cells but also C cells displayed hyperplastic and hypertrophic changes as well as increased calcitonin levels. When exogenous thyroxine was administered to the rats, the opposite effect was noted as a decrease in the number and size of C cells, as well as decreased calcitonin levels. Additionally, we noted that the two cell types maintain the same numerical relation (10 ± 2.5 follicular cells per C cell), independent of the functional activity of the thyroid gland. Considering that TSH serum levels are increased in hypothyroid rats and decreased in thyroxine‐treated rats, we discuss the potential involvement of thyrotropin in the observed results.
The connective tissue of the adductor canal – a morphological study in fetal and adult specimens
Authors: De Oliveira Flavia , De Vasconcellos Fontes Ricardo Bragança , Da Silva Baptista Josemberg , Mayer William Paganini , De Campos Boldrini Silvia , Liberti Edson Aparecido 
Published: February 2009

AbstractThe adductor canal is a conical or pyramid‐shaped pathway that contains the femoral vessels, saphenous nerve and a varying amount of fibrous tissue. It is involved in adductor canal syndrome, a claudication syndrome involving young individuals. Our objective was to study modifications induced by aging on the connective tissue and to correlate them to the proposed pathophysiological mechanism. The bilateral adductor canals and femoral vessels of four adult and five fetal specimens were removed en bloc and analyzed. Sections 12 µm thick were obtained and the connective tissue studied with Sirius Red, Verhoeff, Weigert and Azo stains. Scanning electron microscopy (SEM) photomicrographs of the surfaces of each adductor canal were also analyzed. Findings were homogeneous inside each group. The connective tissue of the canal was continuous with the outer layer of the vessels in both groups. The pattern of concentric, thick collagen type I bundles in fetal specimens was replaced by a diffuse network of compact collagen bundles with several transversal fibers and an impressive content of collagen III fibers. Elastic fibers in adults were not concentrated in the thick bundles but dispersed in line with the transversal fiber system. A dynamic compression mechanism with or without an evident constricting fibrous band has been proposed previously for adductor canal syndrome, possibly involving the connective tissue inside the canal. The vessels may not slide freely during movement. These age‐related modifications in normal individuals may represent necessary conditions for this syndrome to develop.
Graft outcomes influenced by co‐expression of Pax7 in graft and host tissue
Authors: Thomas Meghan , Tyers Pam , Lazic Stanley E. , Barker Roger A. , Beazley Lyn , Ziman Mel 
Published: February 2009

AbstractCell replacement therapies offer promise in the treatment of neurotrauma and neurodegenerative disorders and have concentrated on the use of primary fetal brain tissue. However, there is a growing promise of using neural stem cells, in which case other factors may be important in their successful engraftment. We therefore investigated whether the co‐expression of the major developmental transcription factor (Pax7 in this study) of donor tissue to graft site influences transplant survival and differentiation in the rat midbrain. Neural progenitor cells were prepared from either the Pax7‐expressing dorsal (DM) or non‐Pax7‐expressing ventral mesencephalon (VM) of embryonic EGFP+/+ rats. Cells were dissociated and grafted into the adult rat superior colliculus (SC) lesioned with quinolinic acid 3 days previously, a time shown to be associated with the up‐regulation of Pax7. Grafts were then examined 4 weeks later. Our results suggest the origin of the graft tissue did not alter graft survival in the SC; however, dorsal grafts appear to have a higher incidence of neuronal survival, whereas ventral grafts have a higher incidence of astrocytic survivors.
Amyloid‐β(1‐42) alters structure and function of retinal pigmented epithelial cells
Authors: Bruban Julien , Glotin Anne‐Lise , Dinet Virginie , Chalour Naïma , Sennlaub Florian , Jonet Laurent , An Na , Faussat Anne Marie , Mascarelli Frédéric 
Published: February 2009

SummaryAge‐related macular degeneration (AMD) is characterized by the formation of drusen, extracellular deposits associated with atrophy of the retinal pigmented epithelium (RPE), disturbance of the transepithelial barrier and photoreceptor death. Amyloid‐β (Aβ) is present in drusen but its role during AMD remains unknown. This study investigated the in vitro and in vivo effects of the oligomeric form of Aβ(1‐42) – OAβ(1‐42) – on RPE and found that it reduced mitochondrial redox potential and increased the production of reactive oxygen species, but did not induce apoptosis in RPE cell cultures. It also disorganized the actin cytoskeleton and halved occludin expression, markedly decreasing attachment capacity and abolishing the selectivity of RPE cell transepithelial permeability. Antioxidant pretreatment partially reversed the effects of OAβ(1‐42) on mitochondrial redox potential and transepithelial permeability. Subretinally injected OAβ(1‐42) induced pigmentation loss and RPE hypertrophy but not RPE cell apoptosis in C57BL/6 J mice. Rapid OAβ(1‐42)‐induced disorganization of cytoskeletal actin filaments was accompanied by decreased RPE expression of the tight junction proteins occludin and zonula occludens‐1 and of the visual cycle proteins cellular retinaldehyde‐binding protein and RPE65. The number of photoreceptors decreased by half within a few days. Our study pinpoints the role of Aβ in RPE alterations and dysfunctions leading to retinal degeneration and suggests that targeting Aβ may help develop selective methods for treating diseases involving retinal degeneration, such as AMD.
A free radical‐generating system induces the cholesterol biosynthesis pathway: a role in Alzheimer's disease
Authors: Recuero María , Vicente Ma Carmen , Martínez‐García Ana , Ramos María C. , Carmona‐Saez Pedro , Sastre Isabel , Aldudo Jesús , Vilella Elisabet , Frank Ana , Bullido María J. , Valdivieso Fernando 
Published: February 2009

SummaryOxidative stress, which plays a critical role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD), is intimately linked to aging – the best established risk factor for AD. Studies in neuronal cells subjected to oxidative stress, mimicking the situation in AD brains, are therefore of great interest. This paper reports that, in human neuronal cells, oxidative stress induced by the free radical‐generating xanthine/xanthine oxidase (X‐XOD) system leads to apoptotic cell death. Microarray analyses showed a potent activation of the cholesterol biosynthesis pathway following reductions in the cell cholesterol synthesis caused by the X‐XOD treatment; furthermore, the apoptosis was reduced by inhibiting 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase (HMGCR) expression with an interfering RNA. The potential importance of this mechanism in AD was investigated by genetic association, and it was found that HMGCR, a key gene in cholesterol metabolism and among those most strongly upregulated, was associated with AD risk. In summary, this work presents a human cell model prepared to mimic the effect of oxidative stress in neurons that might be useful in clarifying the mechanism involved in free radical‐induced neurodegeneration. Gene expression analysis followed by genetic association studies indicates a possible link among oxidative stress, cholesterol metabolism and AD.
Anti‐aging activity of the Ink4/Arf locus
Authors: Matheu Ander , Maraver Antonio , Collado Manuel , Garcia‐Cao Isabel , Cañamero Marta , Borras Consuelo , Flores Juana M. , Klatt Peter , Viña Jose , Serrano Manuel 
Published: February 2009

SummaryThe proteins encoded by the Ink4/Arf locus, p16Ink4a, p19Arf and p15Ink4b are major tumour suppressors that oppose aberrant mitogenic signals. The expression levels of the locus are progressively increased during aging and genome‐wide association studies have linked the locus to a number of aging‐associated diseases and frailty in humans. However, direct measurement of the global impact of the Ink4/Arf locus on organismal aging and longevity was lacking. In this work, we have examined the fertility, cancer susceptibility, aging and longevity of mice genetically modified to carry one (Ink4/Arf‐tg) or two (Ink4/Arf‐tg/tg) intact additional copies of the locus. First, increased gene dosage of Ink4/Arf impairs the production of male germ cells, and in the case of Ink4/Arf‐tg/tg mice results in a Sertoli cell‐only‐like syndrome and a complete absence of sperm. Regarding cancer, there is a lower incidence of aging‐associated cancer proportional to the Ink4/Arf gene dosage. Interestingly, increased Ink4/Arf gene dosage resulted in lower scores in aging markers and in extended median longevity. The increased survival was also observed in cancer‐free mice indicating that cancer protection and delayed aging are separable activities of the Ink4/Arf locus. In contrast to these results, mice carrying one or two additional copies of the p53 gene (p53‐tg and p53‐tg/tg) had a normal longevity despite their increased cancer protection. We conclude that the Ink4/Arf locus has a global anti‐aging effect, probably by favouring quiescence and preventing unnecessary proliferation.
Molecular architecture of myelinated peripheral nerves is supported by calorie restriction with aging
Authors: Rangaraju Sunitha , Hankins David , Madorsky Irina , Madorsky Evgenia , Lee Wei‐Hua , Carter Christy S. , Leeuwenburgh Christiaan , Notterpek Lucia 
Published: February 2009

SummaryPeripheral nerves from aged animals exhibit features of degeneration, including marked fiber loss, morphological irregularities in myelinated axons and notable reduction in the expression of myelin proteins. To investigate how protein homeostatic mechanisms change with age within the peripheral nervous system, we isolated Schwann cells from the sciatic nerves of young and old rats. The responsiveness of cells from aged nerves to stress stimuli is weakened, which in part may account for the observed age‐associated alterations in glial and axonal proteins in vivo. Although calorie restriction is known to slow the aging process in the central nervous system, its influence on peripheral nerves has not been investigated in detail. To determine if dietary restriction is beneficial for peripheral nerve health and glial function, we studied sciatic nerves from rats of four distinct ages (8, 18, 29 and 38 months) kept on an ad libitum (AL) or a 40% calorie restricted diet. Age‐associated reduction in the expression of the major myelin proteins and widening of the nodes of Ranvier are attenuated by the dietary intervention, which is paralleled with the maintenance of a differentiated Schwann cell phenotype. The improvements in nerve architecture with diet restriction, in part, are underlined by sustained expression of protein chaperones and markers of the autophagy–lysosomal pathway. Together, the in vitro and in vivo results suggest that there might be an age‐limit by which dietary intervention needs to be initiated to elicit a beneficial response on peripheral nerve health.
Unmet Mental Health Care Needs for Children with Special Health Care Needs Stratified by Socioeconomic Status
Authors: Fulda Kimberly G. , Lykens Kristine K. , Bae Sejong , Singh Karan P. 
Published: February 2009

Background:  The purpose of this research study was to identify factors that affect mental health care for children with special health care needs (CSHCN) and to identify how these factors vary among different socioeconomic levels.Methods:  Data were obtained from the National Survey of Children with Special Health Care Needs, 2000–2002. The analysis examined the relationships of demographic characteristics, geographical location of household, severity of condition, and social factors on unmet need for mental health care. Multiple logistic regression models were constructed for four socioeconomic status (SES) levels defined by the federal poverty level (FPL): <133%; 133–199%; 200–299%; ≥300%. Standardised regression coefficients were calculated to compare among SES strata.Results:  There were 38,866 CSHCNs represented in the survey with 9,639 needing mental health care in the past 12 months. The household income distribution was 22% below the 133% FPL, 15% between 133–199% FPL, 18% between 200–299% FPL, and 45% at or above 300% FPL. Black race, ethnicity, insurance type/status, geographical location of household, and number of kids in the household were significant in the <133% of FPL stratum for predicting having received all needed mental health care in the last 12 months. Age and geographical location of household were significant in the 133–199% of FPL stratum. Maternal education was significant in the 200–299% of FPL stratum. Severity of condition, other race, and insurance type/status were significant in the ≥300% of FPL stratum.Conclusions:  Factors affecting unmet needs for mental health care differed by socioeconomic status. Future research should explore a more in‐depth picture of the CSHCN population that includes stratification by income groups to better understand and serve this population.
An annotated bibliography of GRASP–Part II: Applications
Authors: Festa Paola , Resende Mauricio G. C. 
Published: February 2009

AbstractA greedy randomized adaptive search procedure (GRASP) is a metaheuristic for combinatorial optimization. It is a multi‐start or iterative process, in which each GRASP iteration consists of two phases, a construction phase, in which a feasible solution is produced, and a local search phase, in which a local optimum in the neighborhood of the constructed solution is sought. Since 1989, numerous papers on the basic aspects of GRASP, as well as enhancements to the basic metaheuristic, have appeared in the literature. GRASP has been applied to a wide range of combinatorial optimization problems, ranging from scheduling and routing to drawing and turbine balancing. This is the second of two papers with an annotated bibliography of the GRASP literature from 1989 to 2008. In the companion paper, algorithmic aspects of GRASP are surveyed. In this paper, we cover the literature where GRASP is applied to scheduling, routing, logic, partitioning, location, graph theory, assignment, manufacturing, transportation, telecommunications, biology and related fields, automatic drawing, power systems, and VLSI design.
Capturing the environment, a metafrontier approach to the drinking water sector
Authors: De Witte Kristof , Marques Rui C. 
Published: February 2009

AbstractEnvironmental factors add complexity to the comparison between specific activities or entire entities. Decision making units with an inferior performance are tempted to invoke that their organization is “different” from the others in the data set. By reinterpreting and extending the metafrontier literature, we propose an all‐embracing concept to fully capture the operational environment. We suggest the “Group Specific Technical Efficiency” as a new measure to assess the overall efficiency of a utility while allowing for environmental differences. A real‐world example of drinking water utilities from five different countries illustrates the concept.
A genetic algorithm for a bicriteria supplier selection problem
Authors: Basnet Chuda , Weintraub Andres 
Published: February 2009

AbstractIn this paper, we discuss the problem of selecting suppliers for an organisation, where a number of suppliers have made price offers for supply of items, but have limited capacity. Selecting the cheapest combination of suppliers is a straightforward matter, but purchasers often have a dual goal of lowering the number of suppliers they deal with. This second goal makes this issue a bicriteria problem – minimisation of cost and minimisation of the number of suppliers. We present a mixed integer programming (MIP) model for this scenario. Quality and delivery performance are modelled as constraints. Smaller instances of this model may be solved using an MIP solver, but large instances will require a heuristic. We present a multi‐population genetic algorithm for generating Pareto‐optimal solutions of the problem. The performance of this algorithm is compared against MIP solutions and Monte Carlo solutions.