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Structural Alterations (structural + alteration)
Selected AbstractsShort-Term Antiandrogen Flutamide Treatment Causes Structural Alterations in Somatic Cells Associated with Premature Detachment of Spermatids in the Testis of Pubertal and Adult Guinea PigsREPRODUCTION IN DOMESTIC ANIMALS, Issue 3 2010LR Maschio Contents In spite of widespread application of flutamide in the endocrine therapies of young and adult patients, the side effects of this antiandrogen on spermatogenesis and germ-cell morphology remain unclear. This study evaluates the short-term androgen blockage effect induced by the administration of flutamide to the testes of pubertal (30-day old) and adult (65- and 135-day old) guinea pigs, with an emphasis on ultrastructural alterations of main cell types. The testes removed after 10 days of treatment with either a non-steroidal antiandrogen, flutamide (10 mg/kg of body weight) or a pharmacological vehicle alone were processed for histological, quantitative and ultrastructural analysis. In pubertal animals, flutamide androgenic blockage induces spermatogonial differentiation and accelerates testes maturation, causing degeneration and detachment of primary spermatocytes and round spermatids, which are subsequently found in great quantities in the epididymis caput. In post-pubertal and adult guinea pigs, in addition to causing germ-cell degeneration, especially in primary spermatocytes, and leading to the premature detachment of spherical spermatids, the antiandrogen treatment increased the relative volume of Leydig cells. In addition, ultrastructural evaluation indicated that irrespective of age antiandrogen treatment causes an increase in frequency of organelles involved with steroid hormone synthesis in the Leydig cells and a dramatic accumulation of myelin figures in their cytoplasm and, to a larger degree, in Sertoli cells. In conclusion, the transient exposition of the guinea pigs to flutamide, at all postnatal ages causes some degenerative lesions including severe premature detachment of spermatids and accumulation of myelin bodies in Leydig and Sertoli cells, compromising, at least temporarily, the spermatogenesis. [source] Temperature effects on the UV,Vis electronic spectrum of trans-stilbeneINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 4-5 2001S. P. Kwasniewski Abstract The ultraviolet (UV),Visible absorption spectrum of trans-stilbene (tS) is computed at different temperatures by coupling molecular dynamics (MD) simulations with the classical MM3 force field to ZINDO/S-CIS calculations of vertical excitation energies and transition dipole moments. The selection of a large number of structures along the MD trajectories enables a consistent treatment of temperature effects in the vacuum, whereas the ZINDO/S-CIS calculations permit a reliable treatment of electron correlation and relaxation, taking account of multistate interactions in the final state. Thermal motions are found to alter very differently the width and shape of bands. Structural alterations such as the stretching and the torsion of the vinyl single and double bonds very strongly influence the appearance of the first valence state, pertaining to the highest occupied and lowest unoccupied molecular orbital (HOMO,LUMO) transition. At temperatures less than 400 K, these are found to yield a merely Gaussian and very pronounced thermal broadening of the related band (A), up to nearly 30 nm, together with a minor blue shift of its maximum ,max. In contrast, a red shift by several nanometers occurs due to thermal motions for the remaining three valence bands. As can be expected, the broadening intensifies at higher temperatures, and for the A-band, becomes markedly asymmetric when T exceeds 400 K. The combination of MD(MM3) and ZINDO/S-CIS computations enables also consistent calculations of hot bands, which are forbidden by symmetry at 0 K. © 2001 John Wiley & Sons, Inc. Int J Quantum Chem, 2001 [source] Alzheimer-like changes in protein kinase B and glycogen synthase kinase-3 in rat frontal cortex and hippocampus after damage to the insulin signalling pathwayJOURNAL OF NEUROCHEMISTRY, Issue 4 2006Melita Salkovic-Petrisic Abstract The insulin-resistant brain state is related to late-onset sporadic Alzheimer's disease, and alterations in the insulin receptor (IR) and its downstream phosphatidylinositol-3 kinase signalling pathway have been found in human brain. These findings have not been confirmed in an experimental model related to sporadic Alzheimer's disease, for example rats showing a neuronal IR deficit subsequent to intracerebroventricular (i.c.v.) treatment with streptozotocin (STZ). In this study, western blot analysis performed 1 month after i.c.v. injection of STZ showed an increase of 63% in the level of phosphorylated glycogen synthase kinase-3,/, (pGSK-3,/,) protein in the rat hippocampus, whereas the levels of the unphosphorylated form (GSK-3,/,) and protein kinase B (Akt/PKB) remained unchanged. Three months after STZ treatment, pGSK-3,/, and Akt/PKB levels tended to decrease (by 8 and 9% respectively). The changes were region specific, as a different pattern was found in frontal cortex. Structural alterations were also found, characterized by ,-amyloid peptide-like aggregates in brain capillaries of rats treated with STZ. Similar neurochemical changes and cognitive deficits were recorded in rats treated with i.c.v. 5-thio- d -glucose, a blocker of glucose transporter (GLUT)2, a transporter that is probably involved in brain glucose sensing. The IR signalling cascade alteration and its consequences in rats treated with STZ are similar to those found in humans with sporadic Alzheimer's disease, and our results suggest a role for GLUT2 in Alzheimer's pathophysiology. [source] Functional immunohistochemistry of neuropeptides and nitric oxide synthase in the nerve fibers of the supratentorial dura mater in an experimental migraine modelMICROSCOPY RESEARCH AND TECHNIQUE, Issue 3 2001Elizabeth Knyihár-Csillik Abstract The supratentorial cerebral dura of the albino rat is equipped with a rich sensory innervation both in the connective tissue and around blood vessels, which includes nociceptive axons and their terminals; these display intense calcitonin gene-related peptide (CGRP) immunoreactivity. Stereotactic electrical stimulation of the trigeminal (Gasserian) ganglion, regarded as an experimental migraine model, caused marked increase and disintegration of club-like perivascular CGRP-immunopositive nerve endings in the dura mater and induced an apparent increase in the lengths of CGRP-immunoreactive axons. Intravenous administration of sumatriptan or eletriptan, prior to electrical stimulation, prevented disintegration of perivascular terminals and induced accumulation of CGRP in terminal and preterminal portions of peripheral sensory axons. Consequently, immunopositive terminals and varicosities increased in size; accumulation of axoplasmic organelles resulted in the "hollow" appearence of numerous varicosities. Since triptans exert their anti-migraine effect by virtue of agonist action on 5-HT1D/B receptors, we suggest that these drugs prevent the release of CGRP from perivascular nerve terminals in the dura mater by an action at 5-HT1D/B receptors. Nitroglycerine (NitroPOHL), given subcutaneously to rats, induces increased beading of nitric oxide synthase (NOS)-immunoreactive nerve fibers in the supratentorial cerebral dura mater, and an apparent increase in the number of NOS-immunoreactive nerve fibers in the dural areas supplied by the anterior and middle meningeal arteries, and the sinus sagittalis superior. Structural alterations of nitroxidergic axons innervating blood vessels of the dura mater support the idea that nitric oxide (NO) is involved in the induction of headache, a well-known side effect of coronary dilator agents. Microsc. Res. Tech. 53:193,211, 2001. © 2001 Wiley-Liss, Inc. [source] Structural alterations in a type IV pilus subunit protein result in concurrent defects in multicellular behaviour and adherence to host tissueMOLECULAR MICROBIOLOGY, Issue 2 2001Hae-Sun Moon Park The ability of bacteria to establish complex communities on surfaces is believed to require both bacterial,substratum and bacterial,bacterial interactions, and type IV pili appear to play a critical but incompletely defined role in both these processes. Using the human pathogen Neisseria gonorrhoeae, spontaneous mutants defective in bacterial self-aggregative behaviour but quantitatively unaltered in pilus fibre expression were isolated by a unique selective scheme. The mutants, carrying single amino acid substitutions within the conserved amino-terminal domain of the pilus fibre subunit, were reduced in the ability to adhere to a human epithelial cell line. Co-expression of the altered alleles in the context of a wild-type pilE gene confirmed that they were dominant negative with respect to aggregation and human cell adherence. Strains expressing two copies of the altered alleles produced twice as much purifiable pili but retained the aggregative and adherence defects. Finally, the defects in aggregative behaviour and adherence of each of the mutants were suppressed by a loss-of-function mutation in the twitching motility gene pilT. The correlations between self-aggregation and the net capacity of the microbial population to adhere efficiently demonstrates the potential significance of bacterial cell,cell interactions to colonization. [source] Effects of Dry Grinding on the Structural Changes of Kaolinite PowdersJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 7 2000Pedro J. Sánchez-Soto The present study examined the effects of dry grinding, using ball-milling, on the structure of reference well-crystallized (KGa-1) and poorly crystallized (KGa-2) kaolinite powders from Georgia. Grinding produced a strong structural alteration, mainly along the c axis, resulting in disorder and total degradation of the crystal structure of the kaolinite and the formation of an amorphous product. The surface area increased with grinding time, mainly in KGa-2 (maximum value 50.27 m2/g), a result associated with particle-size reduction. These particles became more agglomerated with grinding, and the surface area decreased after 30 min, as confirmed by scanning electron microscopy and particle-size-distribution analysis. There was a limit to particle-size reduction with grinding time. When grinding time was increased, the original endothermic differential thermal analysis (DTA) effects of dehydroxylation in both samples shifted to lower temperatures, decreased in intensity, then disappeared completely after 120 min of grinding. The temperature of the characteristic first exothermic effect shifted slightly to lower temperatures with grinding, although the DTA effects did not increase with grinding time in either kaolinite sample, at least up to 325 min. The amorphous, mechanically activated kaolinite converted into low-crystalline mullite nuclei at a lower temperature than did the unground samples, as deduced by thermal and X-ray observations. This effect was especially important for the KGa-2 sample. Grinding did not seem to influence the formation of silicon-aluminum spinel from kaolinite. The present results may explain why ground kaolinite samples prepared via different routes,e.g., with differences in grinding,behave differently during high-temperature transformations, as reported in the related literature. [source] 1H-NMR Studies of Duplex DNA Decamer Containing a Uracil Cyclobutane Dimer: Implications Regarding the High UV Mutagenecity of CC Photolesions,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2002Hyun Mee Lee ABSTRACT To determine the origin of the UV-specific CC to TT tandem mutation at the CC site, we made a duplex DNA decamer containing a uracil cis,syn cyclobutane dimer (CBD) as the deaminated model of a cytosine dimer. Two-dimensional 1H-NMR spectroscopy studies were performed on this sequence where two adenines (Ade) were opposite to the uracil dimer. Two imino protons of the uracil dimer were found to retain Watson,Crick hydrogen bonding with the opposite Ade, although the 5,-U(NH) of the dimer site showed unusual upfield shift like that of the 5,-T(NH) of the TT dimer, which seemed to be associated with deshielding by the flanking base rather than with reduced hydrogen bonding. (McAteer et al. 1998, J. Mol. Biol. 282:1013,1032). Hydrogen bondings at the dimer site were also supported by detecting typical strong nuclear Overhauser effects (NOE) between two imino protons and the opposite Ade H2 or NH2. But sequential NOE interactions of base protons with sugar protons were absent at the two flanking nucleotides of the 5, side of the uracil dimer and at the intradimer site, contrasting with its thymine analog where sequential NOE was absent only at the A4,T5 step. In addition, NOE cross peak for U5(NH) , A4(H2) was detected, although the NOE interactions of U6(NH) with A7(H2) and A17(H2) were not observed in contrast to the thymine dimer duplex. This different local structural alteration may be affected by the induced right-hand twisted puckering mode of cis,syn cyclobutane ring of the uracil dimer in the B-DNA duplex, even though the isolated uracil dimer had left-hand twisted puckering rigidly. In parallel, these observations may be correlated with observed differences in mutagenic properties between cis,syn UU dimer and cis,syn TT dimer. [source] Smaller amygdala is associated with anxiety in patients with panic disorderPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 3 2009Fumi Hayano phd Aims:, Anxiety a core feature of panic disorder, is linked to function of the amygdala. Volume alterations in the brain of patients with panic disorder have previously been reported, but there has been no report of amygdala volume association with anxiety. Methods:, Volumes of hippocampus and amygdala were manually measured using magnetic resonance imaging obtained from 27 patients with panic disorder and 30 healthy comparison subjects. In addition the amygdala was focused on, applying small volume correction to optimized voxel-based morphometry (VBM). State,Trait Anxiety Inventory and the NEO Personality Inventory Revised were also used to evaluate anxiety. Results:, Amygdala volumes in both hemispheres were significantly smaller in patients with panic disorder compared with control subjects (left: t = ,2.248, d.f. = 55, P = 0.029; right: t = ,2.892, d.f. = 55, P = 0.005). VBM showed that structural alteration in the panic disorder group occurred on the corticomedial nuclear group within the right amygdala (coordinates [x,y,z (mm)]: [26,,6,,16], Z score = 3.92, family-wise error-corrected P = 0.002). The state anxiety was negatively correlated with the left amygdala volume in patients with panic disorder (r = ,0.545, P = 0.016). Conclusions:, These findings suggested that the smaller volume of the amygdala may be associated with anxiety in panic disorder. Of note, the smaller subregion in the amygdala estimated on VBM could correspond to the corticomedial nuclear group including the central nucleus, which may play a crucial role in panic attack. [source] Crystal quality and differential crystal-growth behaviour of three proteins crystallized in gel at high hydrostatic pressureACTA CRYSTALLOGRAPHICA SECTION D, Issue 6 2005A. Kadri Pressure is a non-invasive physical parameter that can be used to control and influence protein crystallization. It is also found that protein crystals of superior quality can be produced in gel. Here, a novel crystallization strategy combining hydrostatic pressure and agarose gel is described. Comparative experiments were conducted on hen and turkey egg-white lysozymes and the plant protein thaumatin. Crystals could be produced under up to 75,100,MPa (lysozymes) and 250,MPa (thaumatin). Several pressure-dependent parameters were determined, which included solubility and supersaturation of the proteins, number, size and morphology of the crystals, and the crystallization volume. Exploration of three-dimensional phase diagrams in which pH and pressure varied identified growth conditions where crystals had largest size and best morphology. As a general trend, nucleation and crystal-growth kinetics are altered and nucleation is always enhanced under pressure. Further, solubility of the lysozymes increases with pressure while that of thaumatin decreases. Likewise, changes in crystallization volumes at high and atmospheric pressure are opposite, being positive for the lysozymes and negative for thaumatin. Crystal quality was estimated by analysis of Bragg reflection profiles and X-ray topographs. While the quality of lysozyme crystals deteriorates as pressure increases, that of thaumatin crystals improves, with more homogeneous crystal morphology suggesting that pressure selectively dissociates ill-formed nuclei. Analysis of the thaumatin structure reveals a less hydrated solvent shell around the protein when pressure increases, with ,20% less ordered water molecules in crystals grown at 150,MPa when compared with those grown at atmospheric pressure (0.1,MPa). Noticeably, the altered water distribution is seen in depressurized crystals, indicating that pressure triggers a stable structural alteration on the protein surface while its polypeptide backbone remains essentially unaltered. [source] No relationship between enzyme activity and structure of nucleotide binding site in sarcoplasmic reticulum Ca2+ -ATPase from short-term stimulated rat muscleACTA PHYSIOLOGICA, Issue 4 2009T. Mishima Abstract Aim:, We examined whether structural alterations to the adenine nucleotide binding site (ANBS) within sarcoplasmic (endo) reticulum Ca2+ -ATPase (SERCA) would account for contraction-induced changes in the catalytic activity of the enzyme as assessed in vitro. Methods:, Repetitive contractions were induced in rat gastrocnemius by electrical nerve stimulation. Measurements of sarcoplasmic reticulum properties were performed on control and stimulated muscles immediately after or at 30 min after the cessation of 5-min stimulation. In order to examine the properties at the ANBS, the binding capacity of SERCA to fluorescence isothiocyanate (FITC), a competitive inhibitor at the ANBS, was analysed in microsomes. Results:, Short-term electrical stimulation evoked a 23.9% and 32.6% decrease (P < 0.05) in SERCA activity and in the FITC binding capacity, respectively, in the superficial region of the muscle. Whereas SERCA activity reverted to normal levels during 30-min recovery, a restoration of the FITC binding capacity did not occur. Conclusion:, The discordant changes between the enzyme activity and the FITC binding suggest that, at least during recovery after exercise, changes in SERCA activity may not correlate closely with structural alterations to the ANBS within the enzyme. [source] Corpus callosum and posterior fossa development in monozygotic females: a morphometric MRI study of Turner syndromeDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 5 2003Susannah L Fryer BA Previous neuroimaging research in Turner syndrome (TS) has indicated parietal lobe anomalies, while anomalies in other brain loci have been less well-substantiated. This study focused on potential cerebellar abnormalities and possible disruptions of interhemispheric (parietal) callosal connections in individuals with TS. Twenty-seven female children and adolescents with TS (mean age 13 years, SD 4 years 2 months) and 27 age-matched female control individuals (mean age 13 years 2 months, SD 4 years 1 month) underwent MRI. Age range of all participants was 7 to 20 years. Morphometric analyses of midline brain structures were conducted using standardized, reliable methods. When compared with control participants, females with TS showed reduced areas of the genu of the corpus callosum, the pons, and vermis lobules VI,VII, and an increased area of the fourth ventricle. No group difference in intracranial area measurements was observed. The reduced area of the genu in TS may reflect compromised connectivity between inferior parietal regions. Further, cerebellar vermis hypoplasia associated with TS agrees with literature that suggests the posterior fossa as a region prone to structural alterations in the face of early developmental insult. [source] Normal dendrite growth in Drosophila motor neurons requires the AP-1 transcription factorDEVELOPMENTAL NEUROBIOLOGY, Issue 10 2008Cortnie L. Hartwig Abstract During learning and memory formation, information flow through networks is regulated significantly through structural alterations in neurons. Dendrites, sites of signal integration, are key targets of activity-mediated modifications. Although local mechanisms of dendritic growth ensure synapse-specific changes, global mechanisms linking neural activity to nuclear gene expression may have profound influences on neural function. Fos, being an immediate-early gene, is ideally suited to be an initial transducer of neural activity, but a precise role for the AP-1 transcription factor in dendrite growth remains to be elucidated. Here we measure changes in the dendritic fields of identified Drosophila motor neurons in vivo and in primary culture to investigate the role of the immediate-early transcription factor AP-1 in regulating endogenous and activity-induced dendrite growth. Our data indicate that (a) increased neural excitability or depolarization stimulates dendrite growth, (b) AP-1 (a Fos, Jun hetero-dimer) is required for normal motor neuron dendritic growth during development and in response to activity induction, and (c) neuronal Fos protein levels are rapidly but transiently induced in motor neurons following neural activity. Taken together, these results show that AP-1 mediated transcription is important for dendrite growth, and that neural activity influences global dendritic growth through a gene-expression dependent mechanism gated by AP-1. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008 [source] Histopathological alterations in the liver of the sharptooth catfish Clarias gariepinus from polluted aquatic systems in South AfricaENVIRONMENTAL TOXICOLOGY, Issue 2 2009M. J. Marchand Abstract There is a need for sensitive bio-monitoring tools in toxicant impact assessment to indicate the effect of toxicants on fish health in polluted aquatic ecosystems. Histopathological assessment of fish tissue allows for early warning signs of disease and detection of long-term injury in cells, tissues, or organs. The aim of this study was to assess the degree of histopathological alterations in the liver of C. gariepinus from two dams in an urban nature reserve, (Gauteng, South Africa). Two dams (Dam 1 and Dam 2) were chosen for their suspected levels of toxicants. Water and sediments were sampled for metal and potential endocrine disrupting chemical analysis. A quantitative and qualitative histology-based health assessment protocol was employed to determine the adverse health effects in fish. The analysis of blood constituents, fish necropsy, calculation of condition factors, and hepatosomatic indices were employed to support the findings of the qualitative and quantitative histological assessment of liver tissue. Assessment of the liver tissue revealed marked histopathological alterations including: structural alterations (hepatic cord disarray) affecting 27% of field specimens; plasma alterations (granular degeneration 98% and fatty degeneration 25%) of hepatocytes; an increase in melanomacrophage centers (32%); hepatocyte nuclear alterations (90%); and necrosis of liver tissue (14%). The quantitative histological assessment indicated that livers of fish collected from Dam 1 were more affected than the fish livers collected from Dam 2. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009. [source] Molecular and diffusion tensor imaging of epileptic networksEPILEPSIA, Issue 2008Aimee F. Luat Summary Several studies have shown that seizure-induced cellular and molecular changes associated with chronic epilepsy can lead to functional and structural alterations in the brain. Chronic epilepsy, when medically refractory, may be associated with an expansion of the epileptic circuitry to involve complex interactions between cortical and subcortical neuroanatomical substrates. Progress in neuroimaging has led not only to successful identification of epileptic foci for surgical resection, but also to an improved understanding of the functional and microstructural changes in long-standing epilepsy. Positron emission tomography (PET), functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) are all promising tools that can assist in elucidating the underlying pathophysiology in chronic epilepsy. Studies using PET scanning have demonstrated dynamic changes associated with the evolution from acute to chronic intractable epilepsy. Among these changes are data to support the existence of secondary epileptogenesis in humans. MRI with DTI is a powerful tool which has the ability to characterize microstructural abnormalities in epileptic foci, and to demonstrate the white matter fibers and tracts participating in the epileptic network. In this review, we illustrate how PET and DTI can be applied to depict the functional and microstructural alterations associated with chronic epilepsy. [source] Disruption of transport activity in a D93H mutant thiamine transporter 1, from a Rogers Syndrome familyFEBS JOURNAL, Issue 22 2003Dana Baron Rogers syndrome is an autosomal recessive disorder resulting in megaloblastic anemia, diabetes mellitus, and sensorineural deafness. The gene associated with this disease encodes for thiamine transporter 1 (THTR1), a member of the SLC19 solute carrier family including THTR2 and the reduced folate carrier (RFC). Using transient transfections into NIH3T3 cells of a D93H mutant THTR1derived from a Rogers syndrome family, we determined the expression, post-translational modification, plasma membrane targeting and thiamine transport activity. We also explored the impact on methotrexate (MTX) transport activity of a homologous missense D88H mutation in the human RFC, a close homologue of THTR1. Western blot analysis revealed that the D93H mutant THTR1 was normally expressed and underwent a complete N -glycosylation. However, while this mutant THTR1 was targeted to the plasma membrane, it was completely devoid of thiamine transport activity. Consistently, introduction into MTX transport null cells of a homologous D88H mutation in the hRFC did not result in restoration of MTX transport activity, thereby suggesting that D88 is an essential residue for MTX transport activity. These results suggest that the D93H mutation does not interfere with transporter expression, glycosylation and plasma membrane targeting. However, the substitution of this negatively charged amino acid (Asp93) by a positively charged residue (His) in an extremely conserved region (the border of transmembrane domain 2/intracellular loop 2) in the SLC19 family, presumably inflicts deleterious structural alterations that abolish thiamine binding and/or translocation. Hence, this functional characterization of the D93H mutation provides a molecular basis for Rogers syndrome. [source] Novel mechanisms of gene disruption at the medulloblastoma isodicentric 17p11 breakpointGENES, CHROMOSOMES AND CANCER, Issue 2 2009Martin G. McCabe Isodicentric 17q is the most commonly reported chromosomal abnormality in medulloblastomas. Its frequency suggests that genes disrupted in medulloblastoma formation may play a role in tumorigenesis. We have previously identified two chromosome 17 breakpoint at a 1 Mb resolution. Our aims were to accurately map the position of these breakpoints and to identify mechanisms of gene disruption at this site. CGH with a custom tiling path genomic BAC array of chromosome 17 enriched with fosmids at the breakpoint regions was used to analyze a series of 45 medulloblastomas and three medulloblastoma-derived cell lines. In total, 17 of 45 medulloblastomas had an isodicentric 17q. Two breakpoint regions were identified and their positions were mapped. The array identified a more complex arrangement at the breakpoint than has been reported previously using lower resolution BAC arrays. The patterns observed indicated that dicentric chromosome formation occurs both via nonallelic homologous recombination between palindromically arranged low copy repeats (the previously accepted mechanism) and by recombination between nonidentical sequences. In addition, novel alternative structural alterations, a homozygous deletion and a duplication, were identified within the chromosome breakpoint region in two cases. At the resolution of the array, these structural alterations spanned the same genes as cases with dicentric 17q formation, implying that the disruption of genes at the chromosome breakpoint itself may be of greater biological significance than has previously been suspected. © 2008 Wiley-Liss, Inc. [source] Running induces widespread structural alterations in the hippocampus and entorhinal cortexHIPPOCAMPUS, Issue 11 2007Alexis M. Stranahan Abstract Physical activity enhances hippocampal function but its effects on neuronal structure remain relatively unexplored outside of the dentate gyrus. Using Golgi impregnation and the lipophilic tracer DiI, we show that long-term voluntary running increases the density of dendritic spines in the entorhinal cortex and hippocampus of adult rats. Exercise was associated with increased dendritic spine density not only in granule neurons of the dentate gyrus, but also in CA1 pyramidal neurons, and in layer III pyramidal neurons of the entorhinal cortex. In the CA1 region, changes in dendritic spine density are accompanied by changes in dendritic arborization and alterations in the morphology of individual spines. These findings suggest that physical activity exerts pervasive effects on neuronal morphology in the hippocampus and one of its afferent populations. These structural changes may contribute to running-induced changes in cognitive function. © 2007 Wiley-Liss, Inc. [source] Improvements in early care in Russian orphanages and their relationship to observed behaviorsINFANT MENTAL HEALTH JOURNAL, Issue 2 2005Christina J. Groark This article describes a unique study that attempts to promote positive social-emotional relationships and attachment between caregivers and children in orphanages in St. Petersburg, Russia. The children who reside in these orphanages are typically between birth and 48 months of age; approximately 50% are diagnosed with disabilities, and approximately 60% leave through foreign adoption. Initially, their orphanage caregivers showed a high level of current anxiety and depression and were detached from and communicated little with the children. Likewise, during baseline observations, the children demonstrated poor attachment behaviors such as indiscriminant friendliness, lack of eye contact with adults, aggression, and impulsive behavior. Two interventions were used in a quasiexperimental design: (a) training of caregivers to promote warm, responsive caregiving and (b) staffing and structural alterations to support relationship building, especially increasing the consistency of caregivers. The methodology required that both the training and staffing interventions be provided to one orphanage, only the training to a second, and neither to a third. (At any one time, ns = 80,120 in each condition.) Initial informal observations reveal positive behaviors for both the caregivers and the children, such as increased two-way conversations, animated and enthusiastic emotional responses, and positive social and language interactions. Early data analyses show an increase in the consistency and stability of caregivers and increased scores for caregivers on every subscale of the HOME Scales. Children showed improvements in physical growth, cognition, language, motor, personal-social, and affect, with children having severe disabilities improving the most. The implications of these findings suggest that training staff with modest educational backgrounds and structural changes are effective, can increase socially responsive caregiving behaviors, and improves social interactions of children, at least temporarily. ©2005 Michigan Association for Infant Mental Health. [source] Physical indicators of cartilage health: the relevance of compliance, thickness, swelling and fibrillar textureJOURNAL OF ANATOMY, Issue 6 2003Neil D. Broom Abstract This study uses a bovine patella model to compare the relative merits of on-bone compliance and thickness measurements, free-swelling behaviour, and structural imaging with differential interference contrast (DIC) light microscopy to assess the biomechanical normality of the cartilage matrix. The results demonstrate that across a spectrum of cartilage tissues from immature, mature, through to mildly degenerate, and all with intact articular surfaces, there is a consistent pattern of increased free swelling of the isolated general matrix with age and degeneration. High swelling was always associated with major structural alterations of the general matrix that were readily imaged using DIC light microscopy. Conversely, for all tissue groups, no relationship was observed between thickness vs. compliance and compliance vs. general matrix swelling. Only in the proximal aspects of the normal mature and degenerate tissues was there a correlation between thickness and general matrix swelling. Free-swelling measurements combined with fibrillar texture imaging using DIC light microscopy are therefore recommended as providing a reliable and quick method of assessing the biomechanical condition of the cartilage general matrix. [source] Nonmalignant Complications of Paget's DiseaseJOURNAL OF BONE AND MINERAL RESEARCH, Issue S2 2006Henry G Bone Abstract Paget's disease of bone is a focal or multifocal disorder characterized by intense disorderly remodeling activity at sites of involvement, producing dramatic alterations of local bone architecture. These functional and structural alterations, interacting with the specific characteristics of the site of involvement, account for most of the complications of the disease. This presentation will focus on selected nonneoplastic complications of particular current interest. [source] Effects of the wood extractive betulinol and 17, -oestradiol on reproduction in zebrafish, Danio rerio (Hamilton) , complications due to a bacterial infectionJOURNAL OF FISH DISEASES, Issue 5 2004I Christianson-Heiska Abstract Zebrafish were exposed to the wood extractive betulinol (5 ,g L,1) and to 17, -oestradiol (E2, 0.27 ,g L,1) for 8 weeks in an attempt to study the possible endocrine-disrupting activity of betulinol. Females exposed to betulinol showed increased spawning intensity, while males exposed to betulinol and E2 had increased incidences of structural alterations in the testes. However, histological examination of the fish revealed that they were infected by acid-fast bacteria suspected to be Mycobacterium sp. despite a careful examination of their health state prior to the onset of the experiment. Fish exposed to betulinol and E2 showed more serious consequences of the bacterial infection than control fish indicating that the test chemicals had weakened the immune defence of the fish. When the exposure was repeated with healthy fish, an increase in the proportion of spermatogonia was seen in the testes of betulinol-treated males. A similar alteration, although not statistically significant, was also seen in the first experiment. However, no increase in the incidences of structural alterations in the testes was seen in betulinol- and E2-treated fish in the second experiment. Our study indicates that betulinol might have an endocrine-disrupting effect in zebrafish, but the increase in incidences of structural alterations in the testes might have been caused by a synergistic action between the test compounds and the bacterial infection. Our study stresses the importance of carefully checking the health of experimental fish, not only prior to the onset of an experiment but also upon termination of the experiment, in order to avoid misinterpretation of the results. [source] Impact of Thermal Treatment on Color and Pigment Pattern of Red Beet (Beta vulgaris L.) PreparationsJOURNAL OF FOOD SCIENCE, Issue 6 2004K.M. Herbach ABSTRACT: The impact of heating at 85°C during 8 h on overall color and betalain pattern of red beet (Beta vulgaris L. ssp. vulgaris) juice was investigated. Although the hue angle of 358° in fresh juice was indicative of the typical red-purple appearance, heating for 8 h induced an unexpected shift to 62° resulting in a yellow-orange solution. To monitor the underlying structural alterations of betalains, a new high-performance liquid chromatography separation compatible with mass spectrometry was developed. Applying this method, 2 novel yellow neobetanin structures and 2 orange-red betanin degradation products were preliminarily identified, and neobetanin formation resulting from heat exposure was proven for the 1st time. These 5 compounds were held responsible for the orange shift of red beet juice during thermal treatment. The relevance of these findings for industrial beet processing was demonstrated by comparison of pigment patterns of heated red beet juice samples and a commercial concentrate. On the basis of these results, a scheme for the thermal degradation of betanin is proposed. [source] Structural and functional changes in spastic skeletal muscle,MUSCLE AND NERVE, Issue 5 2004Richard L. Lieber PhD Abstract This review summarizes current information regarding the changes in structure or function that occur in skeletal muscle secondary to spasticity. Most published studies have reported an increase in fiber size variability in spastic muscle. There is no general agreement regarding any shift in fiber type distribution secondary to spasticity. Mechanical studies in whole limbs as well as in isolated single cells support the notion of an intrinsic change in the passive mechanical properties of muscle after spasticity in addition to the more widely reported neural changes that occur. Evidence is presented for changes within both the muscle cell and extracellular matrix that contribute to the overall changes in the tissue. Taken together, the literature supports the notion that, although spasticity is multifactorial and neural in origin, significant structural alterations in muscle also occur. An understanding of the specific changes that occur in the muscle and extracellular matrix may facilitate the development of new conservative or surgical therapies for this problem. Muscle Nerve 29: 615,627, 2004 [source] Hypoplasia of the arcuate nucleus and maternal smoking during pregnancy in sudden unexplained perinatal and infant deathNEUROPATHOLOGY, Issue 4 2004Anna Maria Lavezzi Maternal smoking during pregnancy is the most important risk factor for sudden perinatal and infant death in more industrialized countries. The frequent observation of hypoplasia of the arcuate nucleus in the brainstem of these victims prompted the verification of whether maternal cigarette smoking could be related to defective development of this nucleus during intrauterine life, by affecting the expression of specific genes involved in its developmental process. In serial sections of the brainstem of 54 cases of sudden and unexplained fetal and infant deaths (13 stillbirths, 7 neonatal deaths and 34 sudden infant death syndrome (SIDS) victims), morphological and morphometrical analysis was used to observe the different structural alterations of the arcuate nucleus (bilateral hypoplasia, monolateral hypoplasia, partial hypoplasia, delayed neuronal maturation and decreased neuronal density) detected in 24 cases (44%). Correlating this finding with smoking in pregnancy, a significantly increased incidence of cytoarchitectural alterations of the arcuate nucleus was found in stillborns and SIDS victims with smoker mothers compared to victims with non-smoker mothers. Moreover, the observation of a wide range of developing morphological defects of the arcuate nucleus related to maternal smoking led to the hypothesis that the constituents of the gas phase in cigarette smoke could directly affect the expression of genes involved in the development of this nucleus, such as the homeobox En-2 gene. [source] Correlation of tracheal smooth muscle function with structure and protein expression during early development,PEDIATRIC PULMONOLOGY, Issue 5 2007Aaron B. Cullen MD Abstract With increased survival of premature infants, understanding the impact of development on airway function and structure is imperative. Airway smooth muscle plays a primary role in the modulation of airway function. The purpose of this study is to correlate the functional maturation of airway smooth muscle during the perinatal period with structural alterations at the cellular, ultrastructural, and molecular levels. Length-tension and dose-response analyses were performed on tracheal rings acquired from preterm and term newborn lambs. Subsequent structural analyses included isolated airway smooth muscle cell length, electron microscopy, and myosin heavy chain isoform expression measurements. Functionally the compliance, contractility, and agonist sensitivity of the tracheal rings matured during preterm to term development. Structurally, isolated cell lengths and electron microscopic ultrastructure were not significantly altered during perinatal development. However, expression of myosin heavy chain isoforms increased significantly across the age range analyzed, correlating with the maturational increase in smooth muscle contractility. In conclusion, the developmental alterations in tracheal function appear due, in part, to enhanced smooth muscle myosin heavy chain expression. Pediatr Pulmonol. 2007; 42:421,432. © 2007 Wiley-Liss, Inc. [source] Effects of fetal growth restriction on lung development before and after birth: A morphometric analysisPEDIATRIC PULMONOLOGY, Issue 3 2001G.S. Maritz PhD Abstract Our aim was to determine the effects of fetal growth restriction (FGR) during late gestation on the structure of the lungs in the fetus near term and at 8 weeks after birth. The studies were performed using two groups of pregnant sheep and their offspring. In both groups, FGR was induced by umbilico-placental embolisation (UPE); for fetal studies, UPE was performed from 120 days of gestation until 140 days (term, ,146 days), when fetuses were killed for tissue analysis. For postnatal studies, UPE continued from 120 days until delivery at term; postnatal lambs were killed at 8 weeks after birth for tissue analysis. UPE led to a thicker pulmonary blood-air barrier at 140 days of gestation and this difference, which was due to a thickened basement membrane, was still present at 8 weeks after birth. At 8 weeks, we also observed a smaller number of alveoli per respiratory unit, thicker interalveolar septa, and a greater volume density of lung tissue in FGR lambs compared to controls. These changes would be expected to impair gas exchange and alter the mechanical properties of the lungs. Our data show that structural alterations in the lungs induced by placental insufficiency were more evident at 8 weeks of postnatal age than near term, indicating that the effects of FGR on the lung may become more serious with age and may affect respiratory health later in life. Pediatr Pulmonol. 2001; 32:201,210. © 2001 Wiley-Liss, Inc. [source] Lack of universal conductance features in disordered graphene nanoribbonsPHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 3-4 2010Antonino La Magna Abstract Recent experimental characterisation of graphene flakes has demonstrated the existence of local structural alterations of the ideal honeycomb lattice whose influence on the conductance mechanism of this material has not yet been fully evaluated. In this study a numerical statistical analysis of the conductance distribution function in disordered graphene nanoribbons is presented. Calculations are performed in statistically equivalent replica large systems within the Non Equilibrium Green's Function formalism. Different kinds of local scattering centers have been considered. A characteristic general behavior of the conductance variance in these quasi one-dimensional systems is the linear scaling with the average of logarithm of the conductance, in the localization regime. However, in a broad class of realization of the local disorder, the slope is not a constant as the disorder degree varies in any region of the energy spectrum, i.e. the single parameters scaling hypothesis is not verified (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Lessons in stability from thermophilic proteinsPROTEIN SCIENCE, Issue 7 2006Abbas Razvi Abstract Studies that compare proteins from thermophilic and mesophilic organisms can provide insights into ability of thermophiles to function at their high habitat temperatures and may provide clues that enable us to better define the forces that stabilize all proteins. Most of the comparative studies have focused on thermal stability and show, as expected, that thermophilic proteins have higher Tm values than their mesophilic counterparts. Although these comparisons are useful, more detailed thermodynamic analyses are required to reach a more complete understanding of the mechanisms thermophilic protein employ to remain folded over a wider range of temperatures. This complete thermodynamic description allows one to generate a stability curve for a protein that defines how the conformational stability (,G) varies with temperature. Here we compare stability curves for many pairs of homologous proteins from thermophilic and mesophilc organisms. Of the basic methods that can be employed to achieve enhanced thermostability, we find that most thermophilic proteins use the simple method that raises the ,G at all temperatures as the principal way to increase their Tm. We discuss and compare this thermodynamic method with the possible alternatives. In addition we propose ways that structural alterations and changes to the amino acid sequences might give rise to varied methods used to obtain thermostability. [source] Redox signalling in cardiovascular diseasePROTEOMICS - CLINICAL APPLICATIONS, Issue 6 2008Rebecca L. Charles Abstract Oxidative stress has almost universally and unequivocally been implicated in the pathogenesis of all major diseases, including those of the cardiovascular system. Oxidative stress in cells and cardiovascular biology was once considered only in terms of injury, disease and dysfunction. However, it is now appreciated that oxidants are also produced in healthy tissues, and they function as signalling molecules transmitting information throughout the cell. Conversely, when cells move to a more reduced state, as can occur when oxygen is limiting, this can also result in alterations in the function of biomolecules and subsequently cells. At the centre of this ,redox signalling' are oxidoreductive chemical reactions involving oxidants or reductants post translationally modifying proteins. These structural alterations allow changes in cellular redox state to be coupled to alterations in cell function. In this review, we consider aspects of redox signalling in the cardiovascular system, focusing on the molecular basis of redox sensing by proteins and the array of post-translational oxidative modifications that can occur. In addition, we discuss studies utilising proteomic methods to identify redox-sensitive cardiac proteins, as well as those using this technology more broadly to assess redox signalling in cardiovascular disease. [source] A proteome analysis of the dorsolateral prefrontal cortex in human alcoholic patientsPROTEOMICS - CLINICAL APPLICATIONS, Issue 1 2007Kimberley Alexander-Kaufman Abstract Alcoholic patients commonly experience cognitive decline. It is postulated that cognitive dysfunction is caused by an alcohol-induced region-selective brain damage, particularly to the prefrontal region, and grey and white matter may be affected differently. We used a proteomics-based approach to compare protein expression profiles of the dorsolateral prefrontal cortex (Brodmann area 9 (BA9)) from human alcoholic and healthy control brains. Changes in the relative expression of 110 protein 'spots' were identified in the BA9 grey matter, of which 54 were identified as 44 different proteins. In our recent article, 60 protein spots were differentially expressed in the BA9 white matter and 18 of these were identified (Alexander-Kaufman, K., James, G., Sheedy, D., Harper, C., Matsumoto, I., Mol. Psychiatry 2006, 11, 56-65). Additional BA9 white matter proteins are identified here and discussed in conjunction to our grey matter results. Thiamine-dependent enzymes transketolase and pyruvate dehydrogenase (E1, ubunit) were among the proteins identified. To our knowledge, this is the first time a disruption in thiamine-dependent enzymes has been demonstrated in the brains of ,neurologically uncomplicated' alcoholics. By identifying protein expression changes in prefrontal grey and white matter separately, hypotheses may draw upon more mechanistic explanations as to how alcoholism causes the structural alterations associated with alcohol-related brain damage and cognitive dysfunction. [source] | ||||||||||||||||||||||||||||||||||