bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional vulnerability of developing central nervous system to maternal thiamine deficiencies in the rat
Authors: Bâ Abdoulaye 
Published: November 2005

AbstractThiamine deficiency (B1 vitamin) was induced during three periods of rat central nervous system (CNS) ontogenesis. Females were fed a thiamine deficient diet such that developing offspring were exposed either to pre‐, peri‐, or postnatal thiamine deficiency. To control the effects of undernourishment generated by different thiamine deficiencies, every treatment group had its own pair‐fed control pup from a non drug‐treated but undernourished dam. Seven different developmental abilities (exploratory activity, emotional reaction, hind paws lifting reflex, wire grasping times, crawling and leap execution latencies, and nociception) were recorded in the offspring from the 10th to the 45th postnatal day. The vulnerability of developing brain to the specific lack of B1 vitamin increases from prenatal (28%) to perinatal (43%) and postnatal periods (57%). © 2005 Wiley Periodicals, Inc. Dev Psychobiol 47: 408–414, 2005.
Soluble adhesion molecules in young children with signs of β‐cell autoimmunity—prospective follow‐up from birth
Authors: Toivonen Anna M. , Kimpimäki Teija , Kupila Antti , Korhonen Sari , Hyöty Heikki , Virtanen Suvi M. , Ilonen Jorma , Simell Olli , Knip Mikael 
Published: November 2005

AbstractBackgroundThis study aimed at evaluating the relationship between the circulating concentrations of soluble intercellular adhesion molecule‐1 (sICAM‐1) and sL‐selectin and the appearance of β‐cell autoimmunity, and at assessing whether these molecules could assist in the identification of environmental factors implicated in the immune process damaging the pancreatic β‐cells.MethodsSerum levels of soluble adhesion molecules were measured with enzyme‐linked immunosorbent assays over the first 2 years of life in 65 children seroconverting to positivity for autoantibodies and 65 control children, all with HLA‐conferred susceptibility to type 1 diabetes (T1D).ResultsThe total integrated concentrations of soluble adhesion molecules were comparable between the two groups. The autoantibody‐positive children tended to have higher sL‐selectin concentrations during the 3‐month seroconversion (SC) period than did the control children during the corresponding period (P = 0.07), the difference being significant (P = 0.03) after excluding subjects with signs of a concurrent enterovirus infection. Autoantibody‐positive children had higher concentrations of sL‐selectin in the 3‐month period when an enterovirus infection was detectable than did the control children (P = 0.018). No significant difference could, however, be seen after excluding the children with concomitant seroconversion to autoantibody positivity.ConclusionsElevated concentrations of sL‐selectin are temporally associated with seroconversion to autoantibody positivity suggesting that leukocyte activation might coincide with the appearance of β‐cell autoimmunity. Early‐onset progressive β‐cell autoimmunity, on the other hand, is not reflected in overall increased concentrations of soluble adhesion molecules in the peripheral circulation during the first 2 years of life in children carrying increased HLA‐conferred disease susceptibility. Enterovirus infections (EVIs) are not independently associated with increased circulating sL‐selectin concentrations in young children with enhanced HLA‐conferred susceptibility to T1D. Copyright © 2005 John Wiley & Sons, Ltd.
Pulse pressure and mortality in hypertensive type 2 diabetic patients. A cohort study
Authors: Mannucci Edoardo , Lambertucci Lorella , Monami Matteo , Fedeli Angela , Chiasserini Veronica , Marchionni Niccolò , Masotti Giulio , Ungar Andrea 
Published: November 2005

AbstractHypothesisHypertension is a well‐known cardiovascular risk factor in type 2 diabetic patients. It has been suggested that pulse pressure (PP) could be an independent cardiovascular risk factor in the general population, particularly in the elderly. An association between office PP and cardiovascular mortality has been previously reported in diabetic patients, while the relationship between ambulatory measurements of PP and all‐cause mortality has not been assessed so far.AimTo assess the relationship between ambulatory PP and all‐cause mortality in diabetic patients with hypertension.MethodsA cohort study was performed on a consecutive series of 435 diabetic outpatients. All patients underwent office blood pressure measurement (OBP) and 24‐h ambulatory blood pressure monitoring (ABPM). Mortality was assessed through queries at the Registry Offices of the city of residence for each patient. Mean follow‐up was 3.8 ± 1.2 years.ResultsFifty‐eight patients (13.3%) died during the follow‐up. Mortality was significantly (p < 0.05) higher in patients in the highest quartile and lower in patients in the lowest quartile, when compared to the intermediate quartiles, both for office and ABPM‐PP. In a multivariate analysis, after adjustment for numerous variables (including current hypoglycaemic, antihypertensive statin and aspirin treatment), mortality was increased by 3.1 and 5.3% for each incremental mmHg of office PP (p < 0.05) and ABPM‐PP (p < 0.001) respectively.ConclusionsHigh PP, assessed through office measurement or ABPM, was associated with increased mortality in hypertensive type 2 diabetic patients. In our sample, PP assessed with ABPM is a better predictor of mortality than office PP. Copyright © 2005 John Wiley & Sons, Ltd.
Migratory routes and fates of cells transcribing the Wnt‐1 gene in the murine hindbrain
Authors: Nichols David H. , Bruce Laura L. 
Published: November 2005

AbstractTo investigate the origins, migrations, and fates of Wnt‐1–expressing cells in the murine hindbrain, mice carrying a Wnt‐1 enhancer/lacZ transgene were observed from embryonic day (E) 8 through postnatal day 18. The transgene‐stained ventricular layer waxed and waned prior to and following migrations from it. Stained cells migrated first external to the hindbrain as neural crest and then within it to form typical populations of the rhombic lip, as well as others not recognized as lip derivatives. Migrations originated in a temporally defined sequence, many from discrete rhombomeres. All moved first radially, then rostrally and/or ventrally, ipsi‐, or contralaterally, in the mantle or marginal layers. These movements ultimately formed elements of several nuclei, aligned in four longitudinal bands: dorsal (including the gracile, cuneate, cochlear, and vestibular nuclei, plus cerebellar granular cells), dorsal intermediate (including trigeminal sensory, parvicellular reticular, and deep cerebellar nuclei), ventral intermediate (including lateral and intermediate reticular nuclei), and ventral (including the raphe obscurus and pontine nuclei). Transgene staining often persisted long enough to identify stained cells in their definitive, adult nuclei. However, staining was transient. The strength of the staining, however, was in its ability to reveal origins and migrations in both whole‐mounts and sections, in single cell detail. The present results will permit analyses of the effects of genetic manipulations on Wnt‐1 lineage cells. Developmental Dynamics 235:285–300, 2006. © 2005 Wiley‐Liss, Inc.
Imbalance in liver homeostasis leading to hyperplasia by overexpressing either one of the Bcl‐2‐related genes, zfBLP1 and zfMcl‐1a
Authors: Her Guor Mour , Cheng Chih‐Hung , Hong Jiann‐Ruey , Sundaram Gnanapackiam Sheela , Wu Jen‐Leih 
Published: November 2005

AbstractApoptosis is an essential part of normal embryonic development in vertebrates, and it is involved in sculpturing organs and controlling cell populations. In previous studies, we identified two novel proteins, zfBLP1 and zfMcl‐1a, which are similar to those of the Bcl‐2 family as a group of evolutionarily conserved proteins that regulate cellular anti‐apoptosis. To evaluate the effect of dysregulated hepatocyte apoptosis during zebrafish hepatogenesis, we demonstrate the transgenic overexpression of either zfBLP1 or zfMcl‐1a in zebrafish larval liver. Results showed that 18%–43% of larvae overexpressed zfBLP1 and that 16%–37% of larvae overexpressed zfMc1‐1a in the liver leading to liver hyperplasia in 5‐day postfertilization (dpf) zebrafish larvae. Histologically, zebrafish larvae exhibiting liver hyperplasia displayed a normal type of hepatocyte and the same cell numbers in their two liver buds compared with only one liver bud of wild‐type larvae. Of interest, the expression of cyclin genes (A2, B, D1, and E), hepatocyte nuclear factor genes (HNF‐1α, β, ‐3β, and 4α), and oncogenic markers (P53, c‐myc, β‐catenin, N‐ras, and gankyrin) were up‐regulated, while the expression of C/EBP‐α was down‐regulated in a zfMcl‐1a–mediated anti‐apoptotic process of the liver. Increased cell death and proliferation was found in both hepatic cells of zebrafish larvae overexpressing either zfBLP1 or zfMcl‐1a. However, those zebrafish larvae with liver hyperplasia only lived approximately 10 days. (This finding may have been due to liver abnormalities that led to failure of liver function.) In conclusion, transgenic overexpression of zfBLP1 or zfMcl‐1a in zebrafish larvae interrupts regulation of the homeostatic balance between cell proliferation and programmed cell death during hepatogenesis and leads to liver hyperplasia. Developmental Dynamics 235:515–523, 2006. © 2005 Wiley‐Liss, Inc.
Genomic profiling of Mixer and Sox17β targets during Xenopus endoderm development
Authors: Dickinson Kari , Leonard Jeff , Baker Julie C. 
Published: November 2005

AbstractThe transcription factors Mixer and Sox17β have well‐characterized roles in endoderm specification during Xenopus embryogenesis. In order to more thoroughly understand the mechanisms by which these endodermal regulators act, we expressed Mixer and Sox17β in naïve ectodermal tissue and, using oligonucleotide‐based microarrays, compared their genomic transcriptional profile to that of unaffected tissue. Using this approach, we identified 71 transcripts that are upregulated by Mixer or Sox17β, 63 of which have previously uncharacterized roles in endoderm development. Furthermore, an in situ hybridization screen using antisense probes for several of these clones identified six targets of Mixer and/or Sox17β that are expressed in the endoderm during gastrula stages, providing new and regional markers of the endoderm. Our results contribute further insight into the functions of Mixer and Sox17β and bring us closer to understanding at the molecular level the pathways that regulate endoderm development. Developmental Dynamics 235:368–381, 2006. © 2005 Wiley‐Liss, Inc.
The pattern of MyoD and contractile protein localization in primary epaxial myotome reflects the dynamic progression of nascent myoblast differentiation
Authors: Yang Yagai , Ordahl Charles P. 
Published: November 2005

AbstractThe localization of contractile and regulatory proteins in early stages of epaxial primary myotome development was analyzed by immunofluorescence microscopy. Contractile proteins that appear in an ordered sequence in the rostro‐caudal axis of somite development were found to reiterate that sequence in the dorso‐medial‐to‐ventro‐lateral axis of primary epaxial myotome development. Pair‐wise localization of MyoD–titin, desmin–titin, and desmin–myosin defined three zones extending from the dermomyotome dorso‐medial lip (DML) into the primary myotome layer. Zones M1 and M2, which were positive for MyoD + titin and MyoD + titin + desmin, respectively, were restricted to the dorso‐medial‐most extremity of the myotome layer and did not expand during the course of myotome development. Zone M3 was positive for MyoD, desmin, titin, myosin, and cardiac troponin T and was the only zone that expanded during primary myotome development. Myotome fibers in zone M3 were unit‐length, spanning the full rostro‐caudal axis of the myotome while fibers in zones M1 and M2 were shorter than unit length. Anti‐myoD immunofluorescence, when detected in cells lacking contractile‐protein‐positive cytoplasm, was restricted to the DML and nascent myotome cells immediately subjacent to the DML. These results demonstrate a dynamic spatio‐temporal sequence in the differentiation program of nascent myotome cells as they emerge from the DML; zones M1 and M2 reflect standing waves of sequential contractile protein activation during the maturation of nascent myotomal myoblasts, while the expanding zone M3 reflects the accumulation of mature myotome fibers expressing a full cohort contractile proteins. Developmental Dynamics 235:382–394, 2006. © 2005 Wiley‐Liss, Inc.
Analysis of Meox‐2 mutant mice reveals a novel postfusion‐based cleft palate
Authors: Jin Jiu‐Zhen , Ding Jixiang 
Published: November 2005

AbstractCleft palate represents a common human congential disease involving defects in the development of the secondary palate. Major steps in mammalian palatogenesis include vertical growth, elevation, and fusion of the palate shelves. Our current study with the homeobox gene Meox‐2 during mouse secondary palate development reveals a novel postfusion‐based mechanism for cleft palate. Meox‐1 and Meox‐2 are two functionally related homeobox genes playing important roles in somitogenesis and limb muscle differentiation. We found that the expression of Meox‐2, not Meox‐1, marks the specification of early mouse palatal mesenchymal cells in the maxillary processes at embryonic day 11.5 (E11.5). From E12.5 to E15.5, the expression of Meox‐2 occupies only the posterior part of the palate, providing an early molecular marker for the anterior–posterior polarity in mouse secondary palate formation. A total of 35.3% of Meox‐2−/− (n = 17) and 25.5% of Meox‐2+/− (n = 55) mouse embryos display a cleft palate phenotype at E15.5, indicating that the reduction of Meox‐2 function is associated with susceptibility to cleft palate. Unlike previously reported clefts, none of the clefts found in Meox‐2 mutants contain any epithelial sheets in the medial edge areas, and detailed examination revealed that the clefts resulted from the breakdown of newly fused palates. This article is the first report of a gene required to maintain adherence of the palatal shelves after fusion. Developmental Dynamics 235:539–546, 2006. © 2005 Wiley‐Liss, Inc.
Development of the upper lip: Morphogenetic and molecular mechanisms
Authors: Jiang Rulang , Bush Jeffrey O. , Lidral Andrew C. 
Published: November 2005

AbstractThe vertebrate upper lip forms from initially freely projecting maxillary, medial nasal, and lateral nasal prominences at the rostral and lateral boundaries of the primitive oral cavity. These facial prominences arise during early embryogenesis from ventrally migrating neural crest cells in combination with the head ectoderm and mesoderm and undergo directed growth and expansion around the nasal pits to actively fuse with each other. Initial fusion is between lateral and medial nasal processes and is followed by fusion between maxillary and medial nasal processes. Fusion between these prominences involves active epithelial filopodial and adhering interactions as well as programmed cell death. Slight defects in growth and patterning of the facial mesenchyme or epithelial fusion result in cleft lip with or without cleft palate, the most common and disfiguring craniofacial birth defect. Recent studies of craniofacial development in animal models have identified components of several major signaling pathways, including Bmp, Fgf, Shh, and Wnt signaling, that are critical for proper midfacial morphogenesis and/or lip fusion. There is also accumulating evidence that these signaling pathways cross‐regulate genetically as well as crosstalk intracellularly to control cell proliferation and tissue patterning. This review will summarize the current understanding of the basic morphogenetic processes and molecular mechanisms underlying upper lip development and discuss the complex interactions of the various signaling pathways and challenges for understanding cleft lip pathogenesis. Developmental Dynamics 235:1152–1166, 2006. © 2005 Wiley‐Liss, Inc.
Transient T cell accumulation in lymph nodes and sustained lymphopenia in mice treated with FTY720
Authors: Morris Margaret A. , Gibb David R. , Picard Franck , Brinkmann Volker , Straume Marty , Ley Klaus 
Published: November 2005

AbstractFTY720 (2‐amino‐2‐[2‐(4‐octylphenyl)ethyl]propane‐1,3‐diol hydrochloride) is an orally available immunomodulatory agent that induces severe peripheral blood lymphopenia. Most studies of these lymphopenic effects have been limited to short‐term exposure to FTY720. FTY720 alters the ability of lymphocytes to respond to sphingosine‐1‐phosphate (S1P) through S1P receptors, particularly S1P1. FTY720 affects different leukocyte populations and their trafficking through major lymphoid organs. We show the dynamics of CD4 T, CD8 T, and B lymphocyte recirculation in all major lymphoid compartments during 21‐day FTY720 treatment of normal C57BL/6 mice. Following a transient increase in peripheral lymph nodes and Peyer's patches, lymphocyte recirculation reaches a new steady state. Other lymphoid organs show transient changes in lymphocyte composition with various patterns. At 21 days of FTY720 treatment, total body lymphocyte content is reduced by 20% and blood lymphocytes by 80%. Modeling suggests that the new steady state is due to a combination of reduced naive lymphocyte release from the thymus and a transient reduction of lymphocyte egress from lymph nodes. Our data indicate that the commonly held belief that FTY720 blocks lymphocyte egress from lymph nodes cannot fully explain the lymphocyte dynamics observed with prolonged treatment.
The Escherichia coli heat‐labile enterotoxin induces apoptosis of immature lymphocytes in vivo via a glucocorticoid‐dependent pathway
Authors: Tamayo Esther , Merino Ramón , González‐Rojas Jovanna , Marquina Regina , Santiuste Inés , Amado José Antonio , Rappuoli Rino , Del Giudice Giuseppe , Merino Jesús 
Published: November 2005

AbstractEscherichia coli heat‐labile enterotoxin (LT) exhibits a broad range of immunomodulatory activities, including the induction of lymphocyte‐programmed cell death. However, the nature of the lymphoid populations sensitive to LT‐induced apoptosis and the mechanisms used by this toxin to promote such activity are still unclear. In this study, we demonstrate that LT induces in mice a rapid increase in the levels of circulating corticosterone, resulting in a dramatic induction of cell death of immature CD4+CD8+, B220+IgM– and IgM+IgD– T and B cell progenitors, respectively. Apoptosis of these cell populations is similar to that reported after experimental treatment with corticosteroids, it is inhibited by mifepristone, a glucocorticoid receptor antagonist, and does not occur in adrenalectomized animals. These results clearly indicate that endogenous glucocorticoids are the mediators of the LT‐induced cell death, which involves Bcl‐2‐dependent apoptotic pathways. The LT‐mediated programmed cell death requires systemic exposure and the enzymatic activity of LT, since a mutant devoid of any enzymatic activity have no pro‐apoptotic effect at any dose tested.
Dynamic regulation of FoxP3 expression controls the balance between CD4+ T cell activation and cell death
Authors: Kasprowicz Deborah J. , Droin Nathalie , Soper David M. , Ramsdell Fred , Green Douglas R. , Ziegler Steven F. 
Published: November 2005

AbstractThe forkhead‐family transcription factor FoxP3 is important for the development and function of CD4+CD25+ regulatory T cells. While the overall phenotypic effects of FoxP3 expression are evident, the mechanism by which FoxP3 regulates T cell activation is not well understood. CD4+ T cells from mice that express a FoxP3 Tg are refractory to TCR‐mediated stimulation, failing to proliferate or produce cytokines, but possess suppressive activity towards normal T cells. In this report we show that these T cells express elevated levels of mRNA for pro‐apoptotic genes and undergo rapid apoptosis following stimulation. These T cells also display slower cell cycle transit following activation, suggesting that FoxP3 is capable of regulating the ability of T cells to respond to TCR‐mediated activation. Lastly, we show that contrary to expected results, under Th1 or Th2 driving conditions, CD4+ T cells from FoxP3 Tg mice differentiate into effector cells. Concomitant with differentiation is a loss of FoxP3 mRNA and protein. These data demonstrate that FoxP3 levels regulate T cell function, and that FoxP3 itself is dynamically regulated during effector T cell differentiation.
PD‐L2:PD‐1 involvement in T cell proliferation, cytokine production, and integrin‐mediated adhesion
Authors: Saunders Paul A. , Hendrycks Vana R. , Lidinsky William A. , Woods Melody L. 
Published: November 2005

AbstractThe B7 family member programmed death ligand 2 (PD‐L2) has been implicated in both positive and negative regulation of T cell activity. In this study, we demonstrate that on human T cells, PD‐L2 acts only as a negative regulator of T cell activity, inhibiting proliferation, IL‐2 production, and IFN‐γ production via its interaction with programmed death‐1 (PD‐1). This study also shows a novel role for PD‐1 in inhibiting β1 and β2 integrin‐mediated adhesion. PD‐L2 inhibition of T cell function involves modulation of the phosphoinositide 3‐OH kinase (PI 3‐K)/AKT and extracellular signal‐related kinase (ERK)/mitogen‐activated protein kinase (MAPK) pathways, with PD‐L2 inhibiting anti‐CD3‐induced AKT phosphorylation within minutes and ERK phosphorylation after hours. Analysis of phosphatase activity of Src homology 2 domain‐containing tyrosine phosphatase (SHP)‐1 and SHP‐2 in response to anti‐CD3 mAb or anti‐CD3 mAb + PD‐L2 stimulation revealed that while SHP‐1 phosphatase activity is not affected by stimulation, SHP‐2 phosphatase activity is significantly increased by anti‐CD3 mAb + PD‐L2 stimulation. Anti‐CD3 mAb + PD‐L2 stimulation also increased the level of SHP‐2 associated with the PD‐1 receptor. These results suggest that catalytically active SHP‐2 associated with the PD‐1 receptor is involved in modulating T cell function.
The effects of thymic selection on the range of T cell cross‐reactivity
Authors: Chao Dennis L. , Davenport Miles P. , Forrest Stephanie , Perelson Alan S. 
Published: November 2005

AbstractBased on the results of a computational model of thymic selection, we propose a mechanism that produces the observed wide range of T cell cross‐reactivity. The model suggests that the cross‐reactivity of a T cell that survives thymic selection is correlated with its affinity for self peptides. In order to survive thymic selection, a T cell with low affinity for all self peptides expressed in the thymus must have high affinity for major histocompatibility complex (MHC), which makes it highly cross‐reactive. A T cell with high affinity for any self peptide must have low MHC affinity to survive selection, which makes it highly specific for its cognate peptide. Our model predicts that (1) positive selection reduces by only 17% the number of T cells that can detect any given foreign peptide, even though it eliminates over 95% of pre‐selection cells; (2) negative selection decreases the average cross‐reactivity of the pre‐selection repertoire by fivefold; and (3) T cells responding to foreign peptides similar to self peptides will have a lower average cross‐reactivity than cells responding to epitopes dissimilar to self.