Home About us Contact
|
Home About us Contact | ||
|
|
||
Functional Integrity (functional + integrity)
Selected AbstractsEarly life modulators and predictors of adult synaptic plasticityEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2006Katherine G. Akers Abstract Early life experience can induce long-lasting changes in brain and behaviour that are opposite in direction, such as enhancement or impairment in regulation of stress response, structural and functional integrity of the hippocampus, and learning and memory. To explore how multiple early life events jointly determine developmental outcome, we investigated the combined effects of neonatal trauma (anoxia on postnatal day 1, P1) and neonatal novelty exposure (P2,21) on adult social recognition memory (3 months of age) and synaptic plasticity in the CA1 of the rat hippocampus (4.5,8 months of age). While neonatal anoxia selectively reduced post-tetanic potentiation (PTP), neonatal novel exposure selectively increased long-term potentiation (LTP). No interaction between anoxia and novelty exposure was found on either PTP or LTP. These findings suggest that the two contrasting neonatal events have selective and distinct effects on two different forms of synaptic plasticity. At the level of behaviour, the effect of novelty exposure on LTP was associated with increased social memory, and the effect of anoxia on PTP was not accompanied by changes in social memory. Such a finding suggests a bias toward the involvement of LTP over PTP in social memory. Finally, we report a surprising finding that an early behavioural measure of emotional response to a novel environment obtained at 25 days of age can predict adult LTP measured several months later. Therefore, individual differences in emotional responses present during the juvenile stage may contribute to adult individual differences in cellular mechanisms that underlie learning and memory. [source] Attack and defence in the gastric epithelium , a delicate balanceEXPERIMENTAL PHYSIOLOGY, Issue 4 2007Rod Dimaline The gastric epithelium is a complex structure formed into tubular branched gastric glands. The glands contain a wide variety of cell types concerned with the secretion of hydrochloric acid, proteases, mucus and a range of signalling molecules. All cell types originate from stem cells in the neck region of the gland, before migrating and differentiating to assume their characteristic positions and functions. Endocrine and local paracrine mediators are of crucial importance for maintaining structural and functional integrity of the epithelium, in the face of a hostile luminal environment. The first such mediator to be recognized, the hormone gastrin, was identified over a century ago and is now established as the major physiological stimulant of gastric acid secretion. Recent studies, including those using mice that overexpress or lack the gastrin gene, suggest a number of previously unrecognized roles for this hormone in the regulation of cellular proliferation, migration and differentiation. This review focuses on the identification of hitherto unsuspected gastrin-regulated genes and discusses the paracrine cascades that contribute to the maintenance of gastric epithelial architecture and secretory function. Helicobacter infection is also considered in cases where it shares targets and signalling mechanisms with gastrin. [source] Disruption of structural and functional integrity of ,2 -macroglobulin by cathepsin EFEBS JOURNAL, Issue 6 2003Mitsue Shibata ,2 -Macroglobulin (,2M) is an abundant glycoprotein with the intrinsic capacity for capturing diverse proteins for rapid delivery into cells. After internalization by the receptor- mediated endocytosis, ,2M-protein complexes were rapidly degraded in the endolysosome system. Although this is an important pathway for clearance of both ,2M and biological targets, little is known about the nature of ,2M degradation in the endolysosome system. To investigate the possible involvement of intracellular aspartic proteinases in the disruption of structural and functional integrity of ,2M in the endolysosome system, we examined the capacity of ,2M for interacting with cathepsin E and cathepsin D under acidic conditions and the nature of its degradation. ,2M was efficiently associated with cathepsin E under acidic conditions to form noncovalent complexes and rapidly degraded through the generation of three major proteins with apparent molecular masses of 90, 85 and 30 kDa. Parallel with this reaction, ,2M resulted in the rapid loss of its antiproteolytic activity. Analysis of the N-terminal amino-acid sequences of these proteins revealed that ,2M was selectively cleaved at the Phe811-Leu812 bond in about 100mer downstream of the bait region. In contrast, little change was observed for ,2M treated by cathepsin D under the same conditions. Together, the synthetic SPAFLA peptide corresponding to the Ser808,Ala813 sequence of human ,2M, which contains the cathepsin E-cleavage site, was selectively cleaved by cathepsin E, but not cathepsin D. These results suggest the possible involvement of cathepsin E in disruption of the structural and functional integrity of ,2M in the endolysosome system. [source] Blue sucker stock characteristics in the upper Yazoo River basin, Mississippi, USAFISHERIES MANAGEMENT & ECOLOGY, Issue 3 2003G. R. Hand Abstract Blue sucker Cycleptus elongatus (L.) in the upper Yazoo River basin, Mississippi, USA was studied using overnight hoop net sets (n = 4093) during 1988 and 1990,1998 to determine the influence of channel dredging. There were 264 blue suckers captured, ranging from 3 to 11 years of age. Length ranged from 265 to 700 mm and weight from 120 to 4700 g. Concurrent studies with smaller mesh hoop nets failed to capture any juvenile blue suckers. Catch-per-unit-effort (CPUE: fish net,1) declined throughout the study in the Yalobusha River, a river subjected to channel dredging during 1988 and 1994. With the exception of limited hydraulic dredging in the Tallahatchie River, there was no dredging in the other Yazoo River tributaries, nor were there declines in blue sucker catch rates in these rivers. Throughout the upper Yazoo River basin, blue sucker stocks were dominated by adult fish, and there was little evidence of reproduction or recruitment. Conservation of the blue sucker in the upper Yazoo River basin should include actions that ensure the functional integrity of this floodplain river ecosystem and elimination of channel dredging throughout the basin. [source] Molecular mechanisms of calorie restriction's protection against age-related sclerosisIUBMB LIFE, Issue 12 2006Elena Chiarpotto Abstract The current knowledge on the molecular mechanisms of the protective effect of calorie restriction (CR) against age-related fibrosclerosis is tentatively reviewed with specific reference to the role of oxidative stress in aging. The effects of oxidative stress are often mediated by its own final products. Of these, 4-hydroxy-2,3-nonenal (HNE) induces the expression and synthesis of transforming growth factor ,1 (TGF,1) and activates nuclear binding of transcription factor activator protein 1 (AP-1) thus stimulating fibrogenesis. Several studies have shown that, as well as extending mean and maximum life span in a variety of species, CR delays the onset and slows the progression of a variety of age-associated diseases, including diabetes, cardiovascular diseases and neoplasia. However, the anti-aging mechanisms of CR are still not clearly understood. Of the numerous hypotheses put forward, one that still remains popular is protection against the age-associated increase of oxidative stress and consequent cell damage. CR protects the rat aorta from the age-related increase of both oxidative damage and fibrosis; as regards the possible mechanism/s of CR's protection against fibrosclerosis, it is conceivable that, by decreasing oxidative stress, CR reduces HNE levels and consequently TGF,1 expression and collagen deposition, likely by down-regulating the activation of Jun-N terminal kinase and of AP-1. Through the modulation of reactive oxygen species and oxidative stress CR may also attenuate the age-associated increase in the inflammatory milieu, thus preserving vascular functional integrity by suppressing the age-associated increase in inflammatory enzyme activities and prostanoids. iubmb Life, 58: 695-702, 2006 [source] Ecosystem functioning in stream assemblages from different regions: contrasting responses to variation in detritivore richness, evenness and densityJOURNAL OF ANIMAL ECOLOGY, Issue 3 2008B. G. McKie Summary 1The diversity of species traits in a biological assemblage varies not only with species richness, but also with species evenness and organism density, which together influence the concentration of traits within functional guilds. Potential trait diversity at local scales is also constrained by the regional species pool. Implications of such variation for spatio-temporal variability in biodiversity,ecosystem functioning relationships are likely to be complex, but are poorly understood. 2In microcosm experiments conducted at laboratories in Sweden, Ireland and Romania, we investigated effects of species richness, evenness and density of stream-living detritivores on two related processes: detritivore leaf-processing efficiency (LPE) and growth. Assemblage composition varied among laboratories: one taxonomic order (Plecoptera) was studied in Sweden, whereas two orders, encompassing wider trait variation, were studied in Romania (Trichoptera and Plecoptera) and Ireland (Trichoptera and Isopoda). 3Relationships between density and both LPE and growth ranged from negative to positive across the study species, highlighting the potential for density-dependent variation in process rates to alter ecosystem functioning, but indicating that such effects depend on species identity. 4LPE varied with species diversity in the two more heterogeneous assemblages, but whereas LPE in the Romanian study was generally enhanced as richness increased, LPE in the Irish study increased only in less-even polycultures dominated by particular species. Transgressive overyielding was detected in the Irish experiment, indicating complementary resource use and/or facilitation (complementarity). These mechanisms could not be distinguished from the selection effect in the Romanian study. 5Growth was elevated in Romanian species mixtures, reflecting positive complementarity, but lower than expected growth in some Swedish mixtures was associated with negative complementarity, indicating interspecific interference competition. 6Our results emphasize the potential importance of detritivore diversity for stream ecosystem functioning, but both the effects of diversity on the studied processes, and the mechanisms underlying those effects, were specific to each assemblage and process. Such variability highlights challenges in generalizing impacts of diversity change for functional integrity in streams and other ecosystems in which the occurrence of important species traits fluctuates over relatively small spatio-temporal scales. [source] Brain death and its implications for management of the potential organ donorACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2009J. F. BUGGE The systemic physiologic changes that occur during and after brain death affect all organs suitable for transplantation. Major changes occur in the cardiovascular, pulmonary, endocrine, and immunological systems, and, if untreated may soon result in cardiovascular collapse and somatic death. Understanding these complex physiologic changes is mandatory for developing effective strategies for donor resuscitation and management in such a way that the functional integrity of potentially transplantable organs is maintained. This review elucidates these physiological changes and their consequences, and based on these consequences the rationale behind current medical management of brain-dead organ donors is discussed. [source] Effects of anthropogenic disturbances on the diversity and composition of the butterfly fauna of sites in the Sango Bay and Iriiri areas, Uganda: implications for conservationAFRICAN JOURNAL OF ECOLOGY, Issue 2008Perpetra Akite Abstract In assessing environmental change, butterflies have been proven as replicable indicators of biodiversity and functional integrity that can be monitored at a range of scales. Butterflies have been identified as important bio-indicators for assessing biodiversity and monitoring ecosystem responses to environmental perturbations. The objectives of this study were to determine changes in the butterfly fauna of differing sites in the Sango Bay Area (SBA) and Iriiri (Karamoja) in comparison with data collected 10 years ago, and to investigate the impact of different degrees of habitat disturbance on butterflies. The general butterfly diversity was determined by trapping and sweep netting along transect lines and by random sweeping. The impact of human-induced disturbance was assessed by comparing species richness and composition between the sites and regressing the weighted disturbances against species diversity per site. There was a marked decrease in species diversity and varied species composition between the two studies and between the habitat types. Charcoal burning and grazing had significant negative correlations with diversity within forest sites (r2 = 0.825, P < 0.05), whereas cultivation and tree cutting/logging had significant negative correlations with diversity of open savannas (r2 = 0.718, P < 0.05 and r2 = 0.999, P < 0.05, respectively). [source] Reactive Oxygen Species Scavenging Enzymes and Down-Adjustment of Metabolism Level in Mitochondria Associated with Desiccation-Tolerance Acquisition of Maize EmbryoJOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 7 2009Jing-Hua Wu Abstract It is a well-known fact that a mature seed can survive losing most of its water, yet how seeds acquire desiccation-tolerance is not well understood. Through sampling maize embryos of different developmental stages and comparatively studying the integrity, oxygen consumption rate and activities of antioxidant enzymes in the mitochondria, the main origin site of reactive oxygen species (ROS) production in seed cells, we found that before an embryo achieves desiccation-tolerance, its mitochondria shows a more active metabolism, and might produce more ROS and therefore need a more effective ROS scavenging system. However, embryo dehydration in this developmental stage declined the activities of most main antioxidant enzymes and accumulated thiobarbituric acid-reactive products in mitochondria, and then destroyed the structure and functional integrity of mitochondria. In physiologically-matured embryos (dehydration-tolerant), mitochondria showed lower metabolism levels, and no decline in ROS scavenging enzyme activities and less accumulation of thiobarbituric acid-reactive products after embryo dehydration. These data indicate that seed desiccation-tolerance acquisition might be associated with down-adjustment of the metabolism level in the late development stage, resulting in less ROS production, and ROS scavenging enzymes becoming desiccation-tolerant and then ensuring the structure and functional integrity of mitochondria. [source] Spinal somatosensory evoked potential evaluation of acute nerve-root injury associated with pedicle-screw placement procedures: An experimental studyJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2003I-Ming Jou Pedicle screws for spinal fixation risk neural damage because of the proximity between screw and nerve root. We assessed whether spinal somatosensory evoked potential (SSEP) could selectively detect pedicle-screw-related acute isolated nerve injury. Because pedicle screws are too large for a rat's spine, we inserted a K-wire close to the pedicle in 32 rats, intending not to injure the nerve root in eight (controls), and to injure the L4 or L5 root in 24. We used sciatic-nerve-elicited SSEP pre- and postinsertion. Radiologic, histologic, and postmortem observations confirmed the level and degree of root injury. Sciatic (SFI), tibial (TFI), and peroneal function indices (PFI) were calculated and correlated with changes in potential. Although not specific for injuries to different roots, amplitude reduction immediately postinsertion was significant in the experimental groups. Animals with the offending wire left in place for one hour showed a further non-significant deterioration of amplitude. Electrophysiologic changes correlated with SFI and histologic findings in all groups. SSEP monitoring provided reliable, useful diagnostic and intraoperative information about the functional integrity of single nerve-root injury. These findings are clinically relevant to acute nerve-root injury and pedicle-screw insertion. If a nerve-root irritant remains in place, a considerable neurologic deficit will occur. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Proton release by N2 -fixing plant roots: A possible contribution to phytoremediation of calcareous sodic soilsJOURNAL OF PLANT NUTRITION AND SOIL SCIENCE, Issue 1 2003Manzoor Qadir Prof. Dr. Abstract With a world-wide occurrence on about 560 million hectares, sodic soils are characterized by the occurrence of excess sodium (Na+) to levels that can adversely affect crop growth and yield. Amelioration of such soils needs a source of calcium (Ca2+) to replace excess Na+ from the cation exchange sites. In addition, adequate levels of Ca2+ in ameliorated soils play a vital role in improving the structural and functional integrity of plant cell walls and membranes. As a low-cost and environmentally feasible strategy, phytoremediation of sodic soils , a plant-based amelioration , has gained increasing interest among scientists and farmers in recent years. Enhanced CO2 partial pressure (PCO2) in the root zone is considered as the principal mechanism contributing to phytoremediation of sodic soils. Aqueous CO2 produces protons (H+) and bicarbonate (HCO3 - ). In a subsequent reaction, H+ reacts with native soil calcite (CaCO3) to provide Ca2+ for Na+ Ca2+ exchange at the cation exchange sites. Another source of H+ may occur in such soils if cropped with N2 -fixing plant species because plants capable of fixing N2 release H+ in the root zone. In a lysimeter experiment on a calcareous sodic soil (pHs = 7.4, electrical conductivity of soil saturated paste extract (ECe) = 3.1 dS m -1, sodium adsorption ratio (SAR) = 28.4, exchangeable sodium percentage (ESP) = 27.6, CaCO3 = 50 g kg -1), we investigated the phytoremediation ability of alfalfa (Medicago sativa L.). There were two cropped treatments: Alfalfa relying on N2 fixation and alfalfa receiving NH4NO3 as mineral N source, respectively. Other treatments were non-cropped, including a control (without an amendment or crop), and soil application of gypsum or sulfuric acid. After two months of cropping, all lysimeters were leached by maintaining a water content at 130% waterholding capacity of the soil after every 24±1 h. The treatment efficiency for Na+ removal in drainage water was in the order: sulfuric acid > gypsum = N2 -fixing alfalfa > NH4NO3-fed alfalfa > control. Both the alfalfa treatments produced statistically similar root and shoot biomass. We attribute better Na+ removal by the N2 -fixing alfalfa treatment to an additional source of H+ in the rhizosphere, which helped to dissolve additional CaCO3 and soil sodicity amelioration. Protonenabgabe durch N2 -fixierende Pflanzenwurzeln: ein möglicher Beitrag zur Phytomelioration von kalkreichen Natriumböden Bei einem weltweiten Vorkommen auf etwa 560 Millionen Hektar sind Natriumböden durch einen Überschuss an Natrium (Na+) gekennzeichnet, der das Wachstum und den Ertrag von Kulturpflanzenbeständen nachteilig beeinflussen kann. Die Melioration solcher Böden erfordert Calcium (Ca2+), um überschüssiges Na+ von Kationen-Austauscherplätzen zu verdrängen. Außerdem spielt Ca2+ eine wichtige Rolle bei der Verbesserung der strukturellen und funktionellen Integrität pflanzlicher Zellwände und Membranen. Als kostengünstige und umweltfreundliche Strategie hat die Phytomelioration von Natriumböden , eine auf Pflanzen beruhende Melioration , in den letzten Jahren zunehmendes Interesse bei Wissenschaftlern und Landwirten gefunden. Ein erhöhter CO2 -Partialdruck (PCO2) in der Rhizosphäre wird als hauptsächlicher Mechanismus angesehen, der zur Phytomelioration von Natriumböden beiträgt. In Wasser gelöst, erzeugt CO2 Protonen (H+) und Bikarbonate (HCO3 - ). Anschließend reagiert H+ mit nativem Calcit (CaCO3), wobei sich Ca2+ löst und Na+ von Austauscherplätzen verdrängt. Eine weitere H+ -Quelle könnte die H+ -Abgabe von Wurzeln N2 -fixierender Pflanzen sein, da diese in der Lage sind, H+ in die Rhizosphäre abzugeben. In einem Lysimeterversuch mit einem kalkreichen Natriumboden (pHs = 7, 4; ECe = 3, 1 dS m -1; SAR = 28, 4; ESP = 27, 6; CaCO3 = 50 g kg -1) wurde die Möglichkeit einer Phytomelioration mit N2 -fixierender Luzerne (Medicago sativa L.) im Vergleich zu einer mit mineralischem N ernährten Luzerne (NH4NO3) untersucht. In weiteren Varianten (Applikation von Gips bzw. Schwefelsäure) wurde die chemische Melioration einer nicht behandelten Kontrolle gegenübergestellt. Beide Ernährungsformen führten zu statistisch ähnlicher Wurzelund Sprossmasse der Luzerne. Nach zweimonatigem Pflanzenwachstum erfolgte alle 24±1 h eine Dränung der Lysimeter durch Zugabe einer Wassermenge von 130% der maximalen Wasserkapazität zum Boden. Hinsichtlich der Effizienz, Na+ über Auswaschung aus dem Boden zu entfernen, zeigte sich folgende Reihenfolge: Schwefelsäure > Gips = N2 -fixierende Luzerne > NH4NO3 -ernährte Luzerne > Kontrolle. Wir führen das bessere Meliorationsergebnis in der Variante der N2 -fixierenden Luzerne auf eine zusätzliche H+ -Quelle in der Rhizosphäre zurück, die zur Lösung von zusätzlichem CaCO3 beitrug. [source] Characterization of a human fetal spinal cord stem cell line, NSI-566RSC, and its induction to functional motoneuronsJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 3 2010Xiufang Guo Abstract Specific neuronal subtypes, especially motoneurons (MNs), derived from human stem cells provide a significant therapeutic potential for spinal cord diseases, such as amyotrophic lateral sclerosis (ALS) and spinal cord injury. So far, in vitro, MNs have only been successfully induced from embryonic stem cells (hESC) and human fetal cortical progenitors. Although neural progenitors from spinal cord would be a likely source for generating MNs, there has been no study reporting successful in vitro differentiation of MNs from spinal cord progenitors. This study first characterized a polyclonal spinal cord stem cell line isolated from an 8 week-old fetus. Then a paradigm was introduced to successfully induce MNs from this cell line, which was demonstrated by immunostaining using the MN markers HB9, Islet1 and choline acetyl transferase (ChAT). The combination of HB9 and ChAT immunostainings indicated that ,20% of the cells were MNs after this induction protocol. The presence of other cell types in the differentiated culture was also analysed. Finally, the electrophysiological properties of these differentiated MNs were characterized to confirm their functional integrity. The majority of these MNs fired repetitive action potentials (APs), which is an indicator of functional maturation. The recordings of spontaneous excitatory postsynaptic currents (EPSCs) confirmed the formation of synapses onto these MNs. This study reports the first successful differentiation of MNs from human spinal cord stem cells in vitro, providing a novel approach for obtaining functional MNs when designing the therapeutic strategy for spinal cord diseases or injuries. Copyright © 2009 John Wiley & Sons, Ltd. [source] Recent trends in diagnosis and treatment of faecal incontinenceALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2004A. K. Tuteja Summary The inability to control bowel discharge is not only common but extremely distressing. It has a negative impact on a patient's lifestyle, leads to a loss of self-esteem, social isolation and a diminished quality of life. Faecal incontinence is often due to multiple pathogenic mechanisms and rarely due to a single factor. Normal continence to stool is maintained by the structural and functional integrity of the anorectal unit. Consequently, disruption of the normal anatomy or physiology of the anorectal unit leads to faecal incontinence. Currently, several diagnostic tests are available that can provide an insight regarding the pathophysiology of faecal incontinence and thereby guide management. The treatment of faecal incontinence includes medical, surgical or behavioural approaches. Today, by using logical approach to management, it is possible to improve symptoms and bowel function in many of these patients. [source] External anal sphincter responses after S3 spinal root surface electrical stimulationNEUROUROLOGY AND URODYNAMICS, Issue 7 2006Giuseppe Pelliccioni Abstract Aims The aim of this study is to present the normative data of direct and reflex motor anal sphincter responses, simultaneously evoked by S3 surface electrical stimulation. By this method, it is possible to test the functional integrity of the nervous pathways activated during sacral neuromodulation (SNM). Methods Twenty healthy subjects were studied. Motor-evoked potentials (MEPs) were recorded by concentric needle electrode from external anal sphincter (EAS). Electrical stimulation was applied by means of a bipolar surface electrode over the S3 right or left sacral foramina. Results Direct (R1) and reflex responses (R2 and R3) were found at latencies of 6.98, 25.12, and 50.31 msec, respectively. The two first responses were recorded in all the cases; the last response is steadily recorded in 17 out of 20 subjects. Conclusions Our data can serve as reference values for future study in patients with pelvic floor dysfunction. EAS responses following S3 percutaneous electrical stimulation can represent a useful aid in the selection of candidates to SNM. Neurourol. Urodynam. 25:788,791, 2006. © 2006 Wiley-Liss, Inc. [source] Diagnosis and Management of the Painful Ankle/Foot.PAIN PRACTICE, Issue 4 2003Interpretation, Management, Part 2: Examination ,,Abstract: Diagnosis, interpretation, and subsequent management of ankle/foot pathology can be challenging to clinicians. A sensitive and specific physical examination is the strategy of choice for diagnosing selected ankle/foot injuries and additional diagnostic procedures, at considerable cost, may not provide additional information for clinical diagnosis and management. Because of a distal location in the sclerotome and the reduced convergence of afferent signals from this region to the dorsal horn of the spinal cord, pain reference patterns are low and the localization of symptoms is trustworthy. Effective management of the painful ankle/foot is closely linked to a tissue-specific clinical examination. The examination of the ankle/foot should include passive and resistive tests that provide information regarding movement limitations and pain provocation. Special tests can augment the findings from the examination, suggesting compromises in the structural and functional integrity of the ankle/foot complex. The weight bearing function of the ankle/foot compounds the clinician's diagnostic picture, as limits and pain provocation are frequently produced only when the patient attempts to function in weight bearing. As a consequence, clinicians should consider this feature by implementing numerous weightbearing components in the diagnosis and management of ankle/foot afflictions. Limits in passive motion can be classified as either capsular or non-capsular patterns. Conversely, patients can present with ankle/foot pain that demonstrates no limitation of motion. Bursitis, tendopathy, compression neuropathy, and instability can produce ankle/foot pain that is challenging to diagnose, especially when they are the consequence of functional weight bearing. Numerous non-surgical measures can be implemented in treating the painful ankle/foot, reserving surgical interventions for those patients who are resistant to conservative care.,, [source] Toward a cure for type 1 diabetes mellitus: diabetes-suppressive dendritic cells and beyondPEDIATRIC DIABETES, Issue 3pt2 2008Nick Giannoukakis Abstract:, Insulin has been the gold standard therapy for diabetes since its discovery and commercial availability. It remains the only pharmacologic therapy for type 1 diabetes (T1D), an autoimmune disease in which autoreactive T cells specifically kill the insulin-producing beta cells. Nevertheless, not even molecularly produced insulin administered four or five times per day can provide a physiologic regulation able to prevent the complications that account for the morbidity and mortality of diabetic patients. Also, insulin does not eliminate the T1D hallmark: beta-cell-specific autoimmunity. In other words, insulin is not a ,cure'. A successful cure must meet the following criteria: (i) it must either replace or maintain the functional integrity of the natural, insulin-producing tissue, the endocrine islets of Langerhans' and, more specifically, the insulin-producing beta cells; (ii) it must, at least, control the autoimmunity or eliminate it altogether; and (iii) it must be easy to apply to a large number of patients. Criterion 1 has been partially realized by allogeneic islet transplantation. Criterion 2 has been partially realized using monoclonal antibodies specific for T-cell surface proteins. Criterion 3 has yet to be realized, given that most of the novel therapies are currently quasi-patient-specific. Herein, we outline the current status of non-insulin-based therapies for T1D, with a focus on cell-based immunomodulation which we propose can achieve all three criteria illustrated above. [source] The impact of major surgery on blood coagulation factors and thrombin generation,AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2007McDonald K. Horne III We studied the blood coagulation system of 14 patients with metastatic malignancies before and after they had undergone major surgery. In addition to measuring a battery of coagulation factors, we assessed the function of the system with assays of whole blood thrombin generation. With the exceptions of factor VIII (fVIII), which increased, and fibrinogen and fIX, which did not change, the activities of all the pro- and anticoagulant proteins were significantly lower postoperatively. However, the thrombin generating capacity of the system was relatively preserved. Although the integral of thrombin activity over time was lower after surgery, the mean peak thrombin concentration was unchanged and the time to clot formation was shortened. Similar changes could be reproduced by lowering the concentrations of pro- and anticoagulant factors together in control blood samples. Therefore, simultaneous reductions in pro- and anticoagulant proteins postoperatively worked to maintain the functional integrity of the blood coagulation system. Am. J. Hematol., 2007. Published 2007 Wiley-Liss, Inc. [source] Impaired conflict resolution and alerting in children with ADHD: evidence from the Attention Network Task (ANT)THE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 12 2008Katherine A. Johnson Background:, An important theory of attention suggests that there are three separate networks that execute discrete cognitive functions. The ,alerting' network acquires and maintains an alert state, the ,orienting' network selects information from sensory input and the ,conflict' network resolves conflict that arises between potential responses. This theory holds promise for dissociating discrete patterns of cognitive impairment in disorders where attentional deficits may often be subtle, such as in attention deficit hyperactivity disorder (ADHD). Methods:, The Attentional Network Test (ANT), a behavioural assay of the functional integrity of attention networks, was used to examine the performance of 73 children with ADHD and 73 controls. Results:, Performance on the ANT clearly differentiated the children with and without ADHD in terms of mean and standard deviation (SD) of reaction time (RT), the number of incorrect responses made and the number of omission errors made. The ADHD group demonstrated deficits in the conflict network in terms of slower RT and a higher number of incorrect responses. The ADHD group showed deficits in the alerting network in terms of the number of omission errors made. There was no demonstration of a deficit in the orienting network in ADHD on this task. Conclusions:, The children with ADHD demonstrated deficits in the alerting and conflict attention networks but normal functioning of the orienting network. [source] Function of a mitogen-activated protein kinase pathway in N gene-mediated resistance in tobaccoTHE PLANT JOURNAL, Issue 4 2003Hailing Jin Summary The active defense of plants against pathogens often includes rapid and localized cell death known as hypersensitive response (HR). Protein phosphorylation and dephosphorylation are implicated in this event based on studies using protein kinase and phosphatase inhibitors. Recent transient gain-of-function studies demonstrated that the activation of salicylic acid-induced protein kinase (SIPK) and wounding-induced protein kinase (WIPK), two tobacco mitogen-activated protein kinases (MAPKs) by their upstream MAPK kinase (MAPKK), NtMEK2 leads to HR-like cell death. Here, we report that the conserved kinase interaction motif (KIM) in MAPKKs is required for NtMEK2 function. Mutation of the conserved basic amino acids in this motif, or the deletion of N-terminal 64 amino acids containing this motif significantly compromised or abolished the ability of NtMEK2DD to activate SIPK/WIPK in vivo. These mutants were also defective in interacting with SIPK and WIPK, suggesting protein,protein interaction is required for the functional integrity of this MAPK cascade. To eliminate Agrobacterium that is known to activate a number of defense responses in transient transformation experiments, we generated permanent transgenic plants. Induction of NtMEK2DD expression by dexamethasone induced HR-like cell death in both T1 and T2 plants. In addition, by using PVX-induced gene silencing, we demonstrated that the suppression of all three known components in the NtMEK2,SIPK/WIPK pathway attenuated N gene-mediated TMV resistance. Together with previous report that SIPK and WIPK are activated by TMV in a gene-for-gene-dependent manner, we conclude that NtMEK2,SIPK/WIPK pathway plays a positive role in N gene-mediated resistance, possibly through regulating HR cell death. [source] Metabolic evaluation of cooled equine spermatozoaANDROLOGIA, Issue 2 2010A. B. Vasconcelos Summary Microscopy has been used in the routine evaluation of sperm metabolism. Nevertheless, it has limited capacity to preview male fertility. As calorimetry may be used to evaluate directly the metabolic activity of a biological system, the aim of this study was to use microcalorimetry as an additive method for sperm metabolism evaluation of cooled equine semen. Two ejaculates of four stallions were collected and motility, viability (eosin 3%) and membrane functional integrity (hyposmotic swelling test) of spermatozoa were evaluated. Sperm samples were processed following different protocols and the metabolism of these samples was accessed by calorimetry. Centrifugation is part of some of these processing protocols and although this procedure has been deleterious for sperm viability and plasma membrane integrity, no decrease in sperm motility was observed. Microcalorimetry was capable of detecting the positive effect of re-suspending the sperm pellet with Kenney extender. Thus, the use of microcalorimetry offered additional information for equine sperm metabolism evaluation and was efficient in detecting important information from sperm cell metabolism. [source] Better sperm selection for intracytoplasmic sperm injection with the side migration techniqueANDROLOGIA, Issue 6 2001A. Hinting Summary. The side migration technique (SMT) is a recent method for preparing very poor-quality semen samples to be used in intracytoplasmic sperm injection (ICSI). In most centres, the washing swim-up and Percoll gradient columns techniques have been routinely used. The present study is aimed at comparing the quality of oligozoospermic semen samples selected after these three methods. All three methods were found to select better percentage motility, normal morphology, viability, functional integrity of plasma membrane and nuclear chromatin integrity compared with the original semen samples. Among the three methods, however, SMT yielded better sperm quality, including morphology, viability, membrane integrity and nuclear chromatin integrity. The results of this study and our experience have confirmed that SMT is an effective and physiological method to prepare sperm for ICSI. [source] Life-span phenotypes of elav and Rbp9 in Drosophila suggest functional cooperation of the two elav-family protein genesARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 4 2010Gakuta Toba Abstract The ELAV family of RNA-binding proteins is involved in various aspects of the post-transcriptional regulation of gene expression, from alternative splicing to translation. The members of this family have been shown to interact with each other and have been suggested to function as homo- and/or hetero-multimers. However, the functional interactions among them have not been demonstrated in vivo. In this study, we examined the genetic interaction between elav and Rbp9, two of the three genes encoding ELAV-family proteins in Drosophila. Mutants of both elav and Rbp9 showed shorter life spans than the control, with elav showing a shorter life span than Rbp9. The survival curve of elav-Rbp9 double-mutant flies was indistinguishable from that of elav single-mutant flies, suggesting that both mutations affect longevity through the same pathway. Considering the fact that both genes are co-expressed in adult neurons, we hypothesize that ELAV and Rbp9 cooperate to maintain the functional integrity of the adult nervous system. © 2010 Wiley Periodicals, Inc. [source] Eyeblink conditioning anomalies in bipolar disorder suggest cerebellar dysfunctionBIPOLAR DISORDERS, Issue 1 2009Amanda R Bolbecker Objectives:, Accumulating research implicates the cerebellum in non-motor psychological processes and psychiatric diseases, including bipolar disorder (BD). Despite recent evidence that cerebellar lesions have been documented to trigger bipolar-like symptoms, few studies have directly examined the functional integrity of the cerebellum in those afflicted with BD. Methods:, Using a single-cue delay eyeblink conditioning procedure, the functional integrity of the cerebellum was examined in 28 individuals with BD (9 manic, 8 mixed, and 11 euthymic) and 28 age-matched healthy controls. Results:, Analysis of the bipolar group as a whole indicated a conditioned response acquisition and timing deficit compared to controls. However, when the bipolar group was categorized according to mood state (mixed, manic, euthymic), individuals tested during mixed episodes were strikingly impaired, performing significantly worse than all other groups on both the acquisition and timing of conditioned responses. Conclusions:, These findings extend prior research implicating cerebellar functional abnormalities in BD and suggest that cerebellar dysfunction may be associated with mood state and course of illness. [source] Preparation of a Functional GABARAP,Lipid Conjugate in Nanodiscs and its Investigation by Solution NMR SpectroscopyCHEMBIOCHEM, Issue 14 2010Peixiang Ma The state you're in: GABARAP, a protein relevant for autophagic processes, has been enzymatically coupled to phosphatidylethanolamine in a ubiquitin-like modification cascade. The lipidation state of GABARAP defines its subcellular localization pattern and is crucial to its functional integrity. [source] | |||||||||||||||||||