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Biological Mechanisms (biological + mechanism)
Terms modified by Biological Mechanisms Selected AbstractsDetecting genotype combinations that increase risk for disease: Maternal-Fetal genotype incompatibility testGENETIC EPIDEMIOLOGY, Issue 1 2003Janet S. Sinsheimer Abstract Biological mechanisms that involve gene-by-environment interactions have been hypothesized to explain susceptibility to complex familial disorders. Current research provides compelling evidence that one environmental factor, which acts prenatally to increase susceptibility, arises from a maternal-fetal genotype incompatibility. Because it is genetic in origin, a maternal-fetal incompatibility is one possible source of an adverse environment that can be detected in genetic analyses and precisely studied, even years after the adverse environment was present. Existing statistical models and tests for gene detection are not optimal or even appropriate for identifying maternal-fetal genotype incompatibility loci that may increase the risk for complex disorders. We describe a new test, the maternal-fetal genotype incompatibility (MFG) test, that can be used with case-parent triad data (affected individuals and their parents) to identify loci for which a maternal-fetal genotype incompatibility increases the risk for disease. The MFG test adapts a log-linear approach for case-parent triads in order to detect maternal-fetal genotype incompatibility at a candidate locus, and allows the incompatibility effects to be estimated separately from direct effects of either the maternal or the child's genotype. Through simulations of two biologically plausible maternal-fetal genotype incompatibility scenarios, we show that the type-I error rate of the MFG test is appropriate, that the estimated parameters are accurate, and that the test is powerful enough to detect a maternal-fetal genotype incompatibility of moderate effect size. Genet Epidemiol 24:1,13, 2003. © 2003 Wiley-Liss, Inc. [source] Infection and preterm birth: Evidence of a common causal relationship with bronchopulmonary dysplasia and cerebral palsyJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 4 2000R Vigneswaran Abstract: Subclinical genital tract infection has been clearly established as a significant cause of spontaneous preterm birth, particularly in early gestations. Bacterial vaginosis organisms rank highly among the pathogens involved in preterm labour and there is considerable beneficial evidence from the use of prophylactic antibiotics for women at high risk of preterm birth. The pathogenesis involves activation of macrophages and the generation of pro-inflammatory cytokines. Bronchopulmonary dysplasia is seen in the most immature of survivors and appears to be secondary to interruption of normal development and maturation of the lungs. The link between chorioamnionitis and lung injury in utero and subsequent development of bronchopulmonary dysplasia has now been substantiated. Exposure to pro-inflammatory cytokines is implicated in the impairment of the fetal lung. A significant body of evidence supports the association between chorioamnionitis, periventricular leukomalacia and cerebral palsy. Biological mechanisms that explain the association between chorioamnionitis and fetal brain injury involve pro-inflammatory cytokines. Similarity in the pattern of expression of cytokines suggests a common pathway for the initiation of preterm labour and also injury to the lung and the central nervous system of the fetus. [source] Biological mechanisms of stroke prevention by physical activity in type 2 diabetesACTA NEUROLOGICA SCANDINAVICA, Issue 4 2009V. Agosti The principal modifiable risk factors for stroke are hypertension, diabetes mellitus, hypercholesterolaemia, hyperhomocysteinaemia, smoking and limited physical activity. However, it is not clear whether physical inactivity is a risk factor per se, or because it predisposes to pathological conditions that are risk factors for stroke. The limited availability of effective therapeutic approaches for stroke emphasizes the crucial role of prevention of risk factors. The global burden associated with type 2 diabetes is large and continues to grow. Convincing epidemiologic data support the role of physical activity in preventing type 2 diabetes. The increasing evidence of physical activity in preventing diabetic complications, including stroke, has generated interest in the molecular basis underlying these beneficial effects. The aim of the present review is to discuss the biological mechanisms underlying the effect of physical activity in preventing stroke in type 2 diabetes. [source] Oscillations in growth of multicellular tumour spheroids: a revisited quantitative analysisCELL PROLIFERATION, Issue 4 2010A. S. Gliozzi Objectives:, Multicellular tumour spheroids (MTS) provide an important tool for study of the microscopic properties of solid tumours and their responses to therapy. Thus, observation of large-scale volume oscillations in MTS, reported several years ago by two independent groups (1,2), in our opinion represent a remarkable discovery, particularly if this could promote careful investigation of the possible occurrence of volume oscillations of tumours ,in vivo'. Materials and methods:, Because of high background noise, quantitative analysis of properties of observed oscillations has not been possible in previous studies. Such an analysis can be now performed, thanks to a recently proposed approach, based on formalism of phenomenological universalities (PUN). Results:, Results have provided unambiguous confirmation of the existence of MTS volume oscillations, and quantitative evaluation of their properties, for two tumour cell lines. Proof is based not only on quality of fitting of the experimental datasets, but also on determination of well-defined values of frequency and amplitude of the oscillations for each line investigated, which would not be consistent with random fluctuation. Conclusions:, Biological mechanisms, which can be directly responsible for observed oscillations, are proposed, which relates also to recent work on related topics. Further investigations, both at experimental and at modelling levels, are also suggested. Finally, from a methodological point of view, results obtained represent further confirmation of applicability and usefulness of the PUN approach. [source] Physico-chemical requirements for cellular uptake of pAntp peptideFEBS JOURNAL, Issue 5 2001Role of lipid-binding affinity The pAntp peptide, corresponding to the third helix of the Antennapedia homeodomain, is internalized by a receptor-independent process into eucaryotic cells. The precise mechanism of entry remains unclear but the interaction between the phospholipids of plasma membrane and pAntp is probably involved in the translocation process. In order to define the role of peptide,lipid interaction in this mechanism and the physico-chemical properties that are necessary for an efficient cellular uptake, we have carried out an Ala-Scan mapping. The peptides were labeled with a fluorescent group (7-nitrobenz-2-oxo-1,3-diazol-4-yl-; NBD) and their cell association was measured by flow cytometry. Furthermore, we determined the fraction of internalized peptide by using a dithionite treatment. Comparison between cell association and cell uptake suggests that the affinity of pAntp for the plasma membrane is required for the import process. To further investigate which are the physico-chemical requirements for phospholipid-binding of pAntp, we have determined the surface partition coefficient of peptides by titrating them with phospholipid vesicles having different compositions. In addition, we estimated by circular dichroism the conformation adopted by these peptides in a membrane-mimetic environment. We show that the phospholipid binding of pAntp depends on its helical amphipathicity, especially when the negative surface charge density of phospholipid vesicles is low. The cell uptake of pAntp, related to lipid-binding affinity, requires a minimal hydrophobicity and net charge. As pAntp does not seem to translocate through an artificial phospholipid bilayer, this might indicate that it could interact with other cell surface components or enters into cells by a nonelucidated biological mechanism. [source] Isotretinoin and the controversy of psychiatric adverse effectsINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2006Jamison E. Strahan MD Isotretinoin is a synthetic oral retinoid that has great efficacy against severe, recalcitrant, nodulocystic acne. Since its introduction to the market, it has been associated with a variety of adverse psychiatric effects, including depression, psychosis, mood swings, violent behavior, suicide, and suicide attempts. A MEDLINE review was performed to compile all case reports, case series, adverse drug event reportings, and prospective and retrospective studies relating psychiatric adverse events to isotretinoin. In addition, literature linking a biological mechanism for psychiatric adverse events to retinoid signaling pathways was also reviewed. Although a variety of anecdotal and epidemiologic studies are available, the overall lack of concrete scientific data limits any conclusion that can be drawn about a causal relationship between istotretinoin and psychiatric adverse events. Several lines of evidence link retinoid signaling to theorized psychiatric pathogenesis, but are limited in their applicability to adult neurophysiology. [source] Black bear femoral geometry and cortical porosity are not adversely affected by ageing despite annual periods of disuse (hibernation)JOURNAL OF ANATOMY, Issue 2 2007Meghan E. McGee Abstract Disuse (i.e. inactivity) causes bone loss, and a recovery period that is 2,3 times longer than the inactive period is usually required to recover lost bone. However, black bears experience annual disuse (hibernation) and remobilization periods that are approximately equal in length, yet bears maintain or increase cortical bone material properties and whole bone mechanical properties with age. In this study, we investigated the architectural properties of bear femurs to determine whether cortical structure is preserved with age in bears. We showed that cross-sectional geometric properties increase with age, but porosity and resorption cavity density do not change with age in skeletally immature male and female bears. These findings suggest that structural properties substantially contribute to increasing whole bone strength with age in bears, particularly during skeletal maturation. Porosity was not different between skeletally immature and mature bears, and showed minimal regional variations between anatomical quadrants and radial positions that were similar in pattern and magnitude between skeletally immature and mature bears. We also found gender dimorphisms in bear cortical bone properties: females have smaller, less porous bones than males. Our results provide further support for the idea that black bears possess a biological mechanism to prevent disuse osteoporosis. [source] Increased Bone Resorption Is Associated With Increased Risk of Cardiovascular Events in Men: The MINOS Study,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2009Pawel Szulc Abstract Better assessment of the association between cardiovascular disease and osteoporosis in older men may help identify shared etiologies for bone and heart health in this population. We assessed the association of BMD and bone turnover markers (BTMs) with risk of cardiovascular events (myocardial infarction or stroke) in 744 men ,50 yr of age. During the 7.5-yr prospective follow-up, 43 strokes and 40 myocardial infarctions occurred in 79 men. After adjustment for confounders (age, weight, height, smoking, education, physical activity, self-reported history of diabetes, hypertension, and prevalent ischemic heart disease), men in the lowest quartile of BMD at the spine, whole body, and forearm had a 2-fold increased risk of cardiovascular events. Men in the highest quartile of bone resorption markers (deoxypyridinoline [DPD], C-telopeptide of type I collagen) had a 2-fold increased risk of cardiovascular events (e.g., multivariable-adjusted hazard ratio [including additional adjustment for BMD] was 2.11 [95% CI: 1.26,3.56], for the highest quartile of free DPD relative to the lowest three quartiles). The results were similar for men without prevalent ischemic heart disease and for myocardial infarction and stroke analyzed separately. Our data suggest that men with low BMD or high bone resorption may be at increased risk of myocardial infarction and stroke in addition to fracture. Thus, men with osteoporosis may benefit from screening for cardiovascular disease. Further study to elucidate the biological mechanism shared by bone and vascular disease may help efforts to identify men at risk or develop treatment. [source] A new source of aging?JOURNAL OF COSMETIC DERMATOLOGY, Issue 2 2009Helen Knaggs MD Summary There has been a considerable increase in understanding how skin ages, along with significant progress toward the correction and prevention of the visible signs of aging. However, there are still many unknown factors regarding why we age , and why we all seem to age differently. An area of high interest is the biological or intrinsic processes that affect our appearance over time. This article describes a recent discovery of a membrane bound enzyme proven to be present in skin and increases its activity as biological age increases. The enzyme is located on the external surface of both fibroblast and keratinocytes, and generates free radicals. Therefore, as we age there appears to be a biological mechanism that further increases the production of free radicals. Additionally, there appears to be a relationship between activity of the enzyme and appearance. Data showed that subjects who look younger than their biological age had lower enzyme activity and conversely, subjects who looked older than their biological age had higher enzyme activity. Free radicals are believed to be a major contributing factor in the production of fine lines and wrinkles by destroying the collagen and elastin network keeping skin supple and firm. [source] Complete structure determination of the A chain of mistletoe lectin III from Viscum album L. ssp. albumJOURNAL OF PEPTIDE SCIENCE, Issue 3 2004Roland Wacker Abstract The complete primary structure of the A chain of mistletoe lectin III (ML3A), a type II ribosome-inactivating protein, was determined using proteolytic digests of ML3A, HPLC separation of the peptides, Edman degration and MALDI-MS. Based on our results, ML3A consists of 254 amino acid residues, showing a high homology to the A chain of isolectin ML1 with only 24 amino acid residue exchanges. A striking important structural difference compared with ML1A is the lack of the single N-glycosylation site in ML3A due to an amino acid exchange at position 112 (ML1A: N112GS,ML3A: T112GS). The alignment of ML3A with the A chains of ML1, isoabrins, ricin D, Ricinus communis agglutinin and three lectins, identified from the Korean mistletoe Viscum album ssp. coloratum, demonstrates the rigid conservation of all amino acid residues, responsible for the RNA-N-glycosidase activity as reported for ricin D. In addition, the fully determined primary structure of ML3A will give further information about the biological mechanism of mistletoe lectin therapy. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd. [source] Recent cancer drug development with xanthone structuresJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2009Younghwa Na Abstract Objectives Xanthones are simple three-membered ring compounds that are mainly found as secondary metabolites in higher plants and microorganisms. Xanthones have very diverse biological profiles, including antihypertensive, antioxidative, antithrombotic and anticancer activity, depending on their diverse structures, which are modified by substituents on the ring system. Although several reviews have already been published on xanthone compounds, few of them have focused on the anticancer activity of xanthone derivatives. In this review we briefly summarize natural and synthetic xanthone compounds which have potential as anticancer drugs. Key findings The interesting structural scaffold and pharmacological importance of xanthone derivatives have led many scientists to isolate or synthesize these compounds as novel drug candidates. In the past, extensive research has been conducted to obtain xanthone derivatives from natural resources as well as through synthetic chemistry. Xanthones interact with various pharmacological targets based on the different substituents on the core ring. The anticancer activities of xanthones are also dramatically altered by the ring substituents and their positions. Summary The biological activities of synthetic xanthone derivatives depend on the various substituents and their position. Study of the biological mechanism of action of xanthone analogues, however, has not been conducted extensively compared to the diversity of xanthone compounds. Elucidation of the exact biological target of xanthone compounds will provide better opportunities for these compounds to be developed as potent anticancer drugs. At the same time, modification of natural xanthone derivatives aimed at specific targets is capable of expanding the biological spectrum of xanthone compounds. [source] Melatonin modulates the expression of VEGF and HIF-1, induced by CoCl2 in cultured cancer cellsJOURNAL OF PINEAL RESEARCH, Issue 2 2008Min Dai Abstract:, Melatonin is an important natural oncostatic agent. At present there are no data available as to its possible influence on tumor angiogenesis, which is a major biological mechanism responsible for tumor growth and dissemination. It is well known that vascular endothelial growth factor (VEGF) is crucial to a solid tumor's higher vascularization and development. To investigate the possible influence of melatonin on angiogenesis, we studied the effect of melatonin on endogenous VEGF expression in three human cancer cell lines (PANC-1, HeLa and A549 cells). In this study, we report that physiologic concentrations of melatonin have no obvious impact on the VEGF expression, whereas pharmacologic concentrations of melatonin suppress the VEGF mRNA and protein levels induced by hypoxia mimetic cobalt chloride (CoCl2). Melatonin also decreases hypoxia-inducible factor (HIF)-1, protein levels, suggesting a role for transcription factor HIF-1 in the suppression of VEGF expression. The effect of pharmacologic concentrations of melatonin on VEGF and HIF-1, under normoxia is uncertain, which indicates that the regulatory mechanisms of VEGF in the absence or presence of CoCl2 are different and other or additional transcription factors may be involved. Taken together, our data show that melatonin in high concentrations markedly reduces the expression of endogenous VEGF and HIF-1, induced by CoCl2 in cultured cancer cells. [source] Clinical presentation and management of antibody-induced failure of botulinum toxin therapyMOVEMENT DISORDERS, Issue S8 2004Dirk Dressler MD Abstract Therapy with botulinum toxin (BT) can fail due to numerous reasons, including failure due to formation of antibodies against BT (BT-AB, AB-TF). AB-TF is a secondary therapy failure, i.e. it occurs during the course of an ongoing BT therapy. It can be subjective or objective, temporary or permanent, and partial or complete. Complete AB-TF is usually preceded by injection series with partial AB-TF in which the therapeutic effect is reduced in its intensity and duration. AB-TF usually occurs within 2 or 3 years after initiation of BT therapy. After 4 years it is rare. BT-AB are neutralising or blocking by definition, i.e. they are directly interfering with BT's biological mechanism of action. Non-neutralizing or non-blocking antibodies occur. BT-AB can be detected by the mouse diaphragm assay, the mouse protection assay, and by patient-based tests such as the sternocleidomastoid test, the extensor digitorum brevis test, and the frowning test. Enzyme-linked immunosorbent assays (ELISA) have a low specificity and a low sensitivity for detection of BT-AB. BT-AB titres drop spontaneously after cessation of BT therapy but latencies are too long to be compatible with an effective BT therapy. BT dosage increase can be successful to overcome AB-TF when AB-TF is partial and when BT-AB titres are low. Usage of alternative BT type A preparations fail to overcome AB-TF. Alternative BT types, such as BT type B and BT type F, are initially successful in AB-TF, but stimulate formation of antibodies against the alternative BT types after few applications. BT-AB reduction with immunosuppressants and inactivation of BT-AB by intravenous immunoglobuline application has not yet been achieved. Extraction of BT-AB by plasmapheresis and immunoadsorption is possible but is associated with substantial logistic problems. Prevention of BT-AB formation, therefore, is of paramount importance. Identified risk factors for BT-AB formation must be taken into account when BT therapy is planned. The most interesting perspective seems to be the development of new BT preparations with reduced antigenicity. © 2004 Movement Disorder Society [source] Intrauterine exposure to polycyclic aromatic hydrocarbons, fine particulate matter and early wheeze.PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 4p2 2010Prospective birth cohort study in 4-year olds Jedrychowski WA, Perera FP, Maugeri U, Mrozek-Budzyn D, Mroz E, Klimaszewska-Rembiasz M, Flak E, Edwards S, Spengler J, Jacek R, Sowa A. Intrauterine exposure to polycyclic aromatic hydrocarbons, fine particulate matter and early wheeze. Prospective birth cohort study in 4-year olds. Pediatr Allergy Immunol 2010: 21: e723,e732. © 2010 John Wiley & Sons A/S The main goal of the study was to determine the relationship between prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) measured by PAH-DNA adducts in umbilical cord blood and early wheeze. The level of PAH-DNA adducts in the cord blood is assumed to reflect the cumulative dose of PAHs absorbed by the foetus over the prenatal period. The effect of prenatal PAH exposure on respiratory health measured by the incidence rate ratio (IRR) for the number of wheezing days in the subsequent 4 yr follow-up was adjusted for potential confounding factors such as personal prenatal exposure to fine particulate matter (PM2.5), environmental tobacco smoke (ETS), gender of child, maternal characteristics (age, education and atopy), parity and mould/dampness in the home. The study sample includes 339 newborns of non-smoking mothers 18,35 yr of age and free from chronic diseases, who were recruited from ambulatory prenatal clinics in the first or second trimester of pregnancy. The number of wheezing days during the first 2 yr of life was positively associated with prenatal level of PAH-DNA adducts (IRR = 1.69, 95%CI = 1.52,1.88), prenatal particulate matter (PM2.5) level dichotomized by the median (IRR = 1.38; 95%CI: 1.25,1.51), maternal atopy (IRR = 1.43; 95%CI: 1.29,1.58), mouldy/damp house (IRR = 1.43; 95%CI: 1.27,1.61). The level of maternal education and maternal age at delivery was inversely associated with the IRRs for wheeze. The significant association between frequency of wheeze and the level of prenatal environmental hazards (PAHs and PM2.5) was not observed at ages 3 or 4 yrs. Although the frequency of wheezing at ages 3 or 4 was no longer associated with prenatal exposure to PAHs and PM2.5, its occurrence depended on the presence of wheezing in the first 2 yr of life, which nearly tripled the risk of wheezing in later life. In conclusion, the findings may suggest that driving force for early wheezing (<24 months of age) is different to those leading to later onset of wheeze. As we reported no synergistic effects between prenatal PAH (measured by PAH-DNA adducts) and PM2.5 exposures on early wheeze, this suggests the two exposures may exert independent effects via different biological mechanism on wheeze. [source] Severe iron overload in Blackfan-Diamond anemia: A case-control study,AMERICAN JOURNAL OF HEMATOLOGY, Issue 11 2009Simona Roggero Chronic iron overload is a serious complication in transfusion-dependent patients. Few studies have addressed this issue in Diamond-Blackfan anemia (DBA). We describe a retrospective analysis of iron overload, and its related complications in 31 transfusion-dependent Italian DBA patients whose records included one or more evaluation of liver iron concentration (LIC) by means of noninvasive magnetic liver susceptometry with a superconductive quantum interference device (SQUID). This cohort is also matched with a group of transfusion-dependent ,-thalassemia major patients to look for differences. A severe iron overload was observed in 54% patients, especially among those inadequately chelated. The DBA patients displayed a significantly higher LIC than the regularly chelated ,-thalassemics. This difference may have been attributable to nonoptimal chelation (late onset, type, dose, prescription, and compliance), or an unknown biological mechanism that lead to an early severe iron overload. We therefore suggest that all transfusion patients should have an accurate record of their iron intake, a regular monitoring of iron overload, in order to start chelation when a critical transfusion load is reached, and to test the efficacy/compliance of chelation treatment. Physicians taking care of transfusion-dependent DBA patients must be concerned about the frequent and early complications such as cardiac toxicity. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Are We all Natural Dualists?THE JOURNAL OF THE ROYAL ANTHROPOLOGICAL INSTITUTE, Issue 3 2001A Cognitive Developmental Approach The article takes to task the well-established anthropological claim that non-Western peoples are free from the traps of dualistic thinking. Although Vezo informants in Madagascar produce statements that could be used to support such a claim, experimental procedures that target their inferential reasoning reveal that they systematically differentiate between mind and body, between the biological processes that determine the organism and the social processes that shape personhood. This suggests that there is a significant discrepancy between people's explicit linguistic statements and their implicit theoretical knowledge. Moreover, developmental data show that such implicit theoretical presuppositions are essential to the production and transmission of cultural knowledge. Thus, Vezo children, who do not as yet differentiate between the biological mechanism of birth and the social mechanism of nurture, are still unable to grasp a salient aspect of Vezo culture, namely the causally integrated set of ideas that guide the way adults classify the social world. These findings have significant theoretical and methodological implications for the constitution of anthropological knowledge. [source] Parental lead exposure and total anomalous pulmonary venous returnBIRTH DEFECTS RESEARCH, Issue 4 2004Leila W. Jackson Abstract BACKGROUND Investigators from the Baltimore-Washington Infant Study (BWIS) reported an association between self-reported maternal lead exposure and total anomalous pulmonary venous return (TAPVR) in their offspring. This association was further evaluated in the BWIS population using a more sensitive exposure estimate. METHODS Cases included 54 live-born infants with TAPVR; controls were a stratified random sample of 522 live-born infants from the BWIS control group. Parental lead exposure was based on three assessment methods, including: an industrial hygiene assessment, an a priori job exposure matrix, and self-reported exposures. A parent was classified as exposed to lead if he/she was classified as exposed by any one of the assessment methods. RESULTS Approximately 17% of case mothers and 11% of control mothers were classified as exposed to lead during the three months prior to conception through the first trimester (odds ratio [OR], 1.57; 95% confidence interval [CI], 0.64,3.47). Among fathers, 61% of case fathers and 46% of control fathers were classified as exposed to lead during the six months prior to conception (paternal critical period) (OR, 1.83; 95% CI, 1.00,3.42). During the paternal critical period, when only the father was exposed compared to neither parent exposed, the OR for any lead exposure and TAPVR was 1.65 (95% CI, 0.84,3.25). CONCLUSIONS This study supports a possible association between paternal lead exposure and TAPVR. Further studies are warranted using validated assessment methods for occupational and nonoccupational lead exposures to corroborate this association and to elucidate the possible biological mechanism. Birth Defects Research (Part A), 2004. © 2004 Wiley-Liss, Inc. [source] The Total Synthesis and Biological Properties of the Cytotoxic Macrolide FD-891 and Its Non-Natural (Z)-C12 IsomerCHEMISTRY - A EUROPEAN JOURNAL, Issue 18 2007Jorge García-Fortanet Dr. Abstract A total, stereoselective synthesis of the naturally occurring, cytotoxic macrolide FD-891 and of its non-natural (Z)-C12 isomer is described. Three fragments of the main carbon chain were stereoselectively prepared by using asymmetric aldol and allylation reactions as the key steps. The molecule was then assembled by using two Julia,Kocienski olefinations to connect the three fragments and a Yamaguchi reaction to close the macrolactone ring. Some specific biological properties (cytotoxicity, binding to tubulin) have been determined for both macrolides. The E configuration of the C12,C13 olefinic bond seems to be an important feature in determining the cytotoxicity but the precise biological mechanism of the latter still remains to be cleared. [source] An investigation into dentists' management methods of dental trauma to maxillary permanent incisors in Victoria, AustraliaDENTAL TRAUMATOLOGY, Issue 4 2008Thai Yeng To a large extent, the management actions of the dentists involved will determine the clinical outcome and, in turn, these actions will be related to their levels of knowledge. The aim of this study was to investigate dentists' knowledge of managing traumatic injuries to maxillary permanent incisors in children. A self-completion questionnaire containing 19 questions on management methods of treating dental trauma was mailed to 693 dentists in Victoria, Australia. The response rate achieved was 61%. This survey found that some of the respondents had adequate management knowledge for the different types of traumatic injuries, while others did not have the correct information. Approximately half the dentists considered milk as the preferred extraoral storage medium of choice for avulsed teeth and a period of 7,10 days splinting after replantation. A large proportion of dentists showed inadequate knowledge with regard to understanding the biological mechanisms causing replacement root resorption (61%) and external inflammatory root resorption (74%). Overall, the respondents to this survey demonstrated only a moderate level of knowledge in management of traumatic injuries to maxillary permanent incisors in children. Continuing professional development programmes may be a means of improving this deficient knowledge base. [source] An evidence-based appraisal of splinting luxated, avulsed and root-fractured teethDENTAL TRAUMATOLOGY, Issue 1 2008Bill Kahler For this systematic review of splinting of teeth that have been luxated, avulsed or root-fractured, the clinical PICO question is (P) what are splinting intervention decisions for luxated, avulsed and root-fractured teeth (I) considering that the splinting intervention choice may include (i) no splinting, (ii) rigid or functional splinting for the different types of trauma and (iii) different durations of the splinting period (C) when comparing these splinting choices for the different types of trauma and their effect on (O) healing outcomes for the teeth. A keyword search of PubMed was used. Reference lists from identified articles and dental traumatology texts were also appraised. The inclusion criterion for this review was either a multivariate analysis or controlled stratified analyses as many variables have the potential to confound the assessment and evaluation of healing outcomes for teeth that have been luxated, avulsed or root-fractured. A positive statistical test is not proof of a causal conclusion, as a positive statistical relationship can arise by chance, and so this review also appraises animal studies that reportedly explain biological mechanisms that relate to healing outcomes of splinted teeth. The clinical studies were ranked using the ,Centre of Evidence-based Medicine' categorization (levels 1,5). All 12 clinical studies selected were ranked as level 4. The studies generally indicate that the prognosis is determined by the type of injury rather than factors associated with splinting. The results indicate that the types of splint and the fixation period are generally not significant variables when related to healing outcomes. This appraisal identified difficulties in the design of animal experimentation to correctly simulate some dental injuries. Some of the studies employed rigid splinting techniques, which are not representative of current recommendations. Recommended splinting treatment protocols for teeth that have been luxated, avulsed or root-fractured teeth are formulated on the strength of research evidence. Despite the ranking of these studies in this appraisal as low levels of evidence, these recommendations should be considered ,best practice', a core philosophy of evidence-based dentistry. [source] Childhood trauma, psychosis and schizophrenia: a literature review with theoretical and clinical implicationsACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2005J. Read Objective:, To review the research addressing the relationship of childhood trauma to psychosis and schizophrenia, and to discuss the theoretical and clinical implications. Method:, Relevant studies and previous review papers were identified via computer literature searches. Results:, Symptoms considered indicative of psychosis and schizophrenia, particularly hallucinations, are at least as strongly related to childhood abuse and neglect as many other mental health problems. Recent large-scale general population studies indicate the relationship is a causal one, with a dose-effect. Conclusion:, Several psychological and biological mechanisms by which childhood trauma increases risk for psychosis merit attention. Integration of these different levels of analysis may stimulate a more genuinely integrated bio-psycho-social model of psychosis than currently prevails. Clinical implications include the need for staff training in asking about abuse and the need to offer appropriate psychosocial treatments to patients who have been abused or neglected as children. Prevention issues are also identified. [source] Abrupt community change on a rocky shore , biological mechanisms contributing to the potential formation of an alternative stateECOLOGY LETTERS, Issue 6 2004Robert T. Paine Abstract The 1997/1998 El Niño initiated a major shift in the intertidal assemblage on the Washington State outer coast. A 25 year time series (1978,2003) shows stands of dominant canopy algae replaced by mussel beds. A prior experiment had indicated that mussels can become too large to be eaten by starfish; newly initiated starfish removals predict mussel attainment of a size refuge. Such escapes inhibit recovery towards prior community composition and enhance development of alternative community states which may persist long after the originating forcing has lessened or disappeared. [source] Remediation of sites contaminated by oil refinery operationsENVIRONMENTAL PROGRESS & SUSTAINABLE ENERGY, Issue 1 2006S. Khaitan The oil industry contributes to contamination of groundwater and aquifers beneath refineries and oil terminals. The successful remediation of a contaminated site requires understanding both the hydrogeology and the nature and extent of contamination. The physical,chemical and biological mechanisms that govern contaminant release, transport and fate in soils, sediments, and associated fluid phases must be understood and quantified. In addition, understanding the flow and entrapment of nonaqueous phase liquids (NAPLs) including lighter-than-water nonaqueous phase liquids (LNAPLs) in contaminated aquifers is important for the effective design of the recovery and remediation schemes. Current remedial technologies and risk assessment techniques to remediate former oil refinery sites contaminated by NAPLs are described in this paper. Emphasis is given to the most promising remediation techniques such as pump-and-treat, on-site bioremediation, phytoremediation, in situ soil washing, and thermal-based technologies, such as steam-enhanced extraction. Some enhancements to pump-and-treat techniques such as solvent flushing, polymer enhanced flushing, and air stripping are also discussed. Finally, important risk-based cleanup criteria associated with contaminated soil at refineries are presented. © 2005 American Institute of Chemical Engineers Environ Prog, 2005 [source] Nutrient dependent effects of consumer identity and diversity on freshwater ecosystem functionFRESHWATER BIOLOGY, Issue 1 2008ANDREW R. DZIALOWSKI Summary 1. Over the past decade, ecologists have tried to determine how changes in species composition and diversity affect ecosystem structure and function. Until recently, the majority of these studies have been conducted in terrestrial ecosystems and have not taken into account environmental variability. The purpose of this research was to determine how species identity and diversity in the freshwater zooplankton affected biomass of algae and zooplankton at two levels of nutrient enrichment. 2. Several species of cladocerans were grown alone and together in microcosms at both ambient and raised phosphorus concentrations to determine if the effects of consumer identity and diversity were nutrient dependent. 3. Total zooplankton biomass was greater, while algal biomass was lower, in mixed culture than in monoculture. The effects of zooplankton diversity on algal biomass, however, were only observed at raised phosphorus concentrations, suggesting that diversity effects were nutrient dependent. Specifically, diversity effects appeared to be related with biological mechanisms such as complementarity in resource use and/or facilitation. 4. More diverse communities of zooplankton appear to be better able to control algae than single species of zooplankton at high nutrient concentrations; therefore, zooplankton diversity may provide a buffer against eutrophication in freshwater ecosystems. [source] Effect of forklift operation on lower back pain: An evidence-based approachHUMAN FACTORS AND ERGONOMICS IN MANUFACTURING & SERVICE INDUSTRIES, Issue 2 2008Heriberto Barriera Viruet Most studies on the occupational hazards associated with forklift operation have examined risks of fatalities and traumatic injuries. Few studies have examined the magnitude of risk of lower back pain. This research deals with an evidence-based approach designed to examine if there is a relationship between whole-body vibration and driver postures with lower back pain among forklift operators and to offer some recommendations to minimize the risk of lower back pain. To accomplish the study goal, an evidence-based approach was adopted from evidence-based medicine. The basic steps of this evidence-based approach were: (1) formulation of a clear research question from a worker-occupational problem; (2) search of the literature for the best evidence with which to answer the question; (3) critically appraise the evidence; and (4) implement useful findings in occupational health and safety practices. In addition, the metarelative risk was calculated and the biological plausibility between whole body vibration (WBV) and operator posture with lower back pain was investigated. Six observational articles satisfied the inclusion criteria adopted in this research. The methodological qualities of the published studies ranged from marginal to average. The metarelative risk was 2.1, indicating that operators exposed to driving forklifts are greater than twice the risk of those not exposed to driving forklifts to experience lower back pain. There are biological mechanisms by which WBV and operator postures could develop lower back pain. Some aspects of the work environment that influenced vibration are seat, speed, track, and tires. Awkward postures and static postures are affected by cab design, seat, time spent seated, and the task performed. It appears that there is a causal relationship between forklift operation and lower back pain. The evidence examined shows a strong association and consistency between all studies and this relationship is biologically plausible. It is recommended that intervention studies be conducted to determine the effectiveness of ergonomic controls. © 2008 Wiley Periodicals, Inc. [source] Melatonin and ulcerative colitis: Evidence, biological mechanisms, and future researchINFLAMMATORY BOWEL DISEASES, Issue 1 2009Paul D. Terry PhD Abstract Ulcerative colitis (UC) is an inflammatory bowel disease that afflicts up to 1 million people in the US. Current treatments for UC are mostly nonspecific, not always effective, and often accompanied by serious side effects. Therefore, there is considerable interest in finding alternative and more tolerable treatments for this disease. Physiologic data suggest that melatonin is an important regulator of both inflammation and motility in the gastrointestinal tract, and data from in vitro studies, animal experiments, and limited studies in humans suggest that supplemental melatonin may have an ameliorative effect on colitis. In this review we summarize the evidence regarding melatonin as a possible therapeutic agent in UC and discuss possible biological mechanisms and directions for future research. (Inflamm Bowel Dis 2008) [source] Biotic homogenization: a new research agenda for conservation biogeographyJOURNAL OF BIOGEOGRAPHY, Issue 12 2006Julian D. Olden Abstract Aim, Biotic homogenization describes the process by which species invasions and extinctions increase the genetic, taxonomic or functional similarity of two or more biotas over a specified time interval. The study of biotic homogenization is a young and rapidly emerging research area in the budding field of conservation biogeography, and this paper aims to synthesize our current knowledge of this process and advocate a more systematic approach to its investigation. Methods, Based on a comprehensive examination of the primary literature this paper reviews the process of biotic homogenization, including its definition, quantification, underlying ecological mechanisms, environmental drivers, the empirical evidence for different taxonomic groups, and the potential ecological and evolutionary implications. Important gaps in our knowledge are then identified, and areas of new research that show the greatest promise for advancing our current thinking on biotic homogenization are highlighted. Results, Current knowledge of the patterns, mechanisms and implications of biotic homogenization is highly variable across taxonomic groups, but in general is incomplete. Quantitative estimates are almost exclusively limited to freshwater fishes and plants in the United States, and the principal mechanisms and drivers of homogenization remain elusive. To date research has focused on taxonomic homogenization, and genetic and functional homogenization has received inadequate attention. Trends over the past decade, however, suggest that biotic homogenization is emerging as a topic of greater research interest. Main conclusions, My investigation revealed a number of important knowledge gaps and priority research needs in the science of biotic homogenization. Future studies should examine the homogenization process for different community properties (species occurrence and abundance) at multiple spatial and temporal scales, with careful attention paid to the various biological mechanisms (invasions vs. extinctions) and environmental drivers (environmental alteration vs. biotic interactions) involved. Perhaps most importantly, this research should recognize that there are multiple possible outcomes resulting from the accumulation of species invasions and extinctions, including biotic differentiation whereby genetic, taxonomic or functional similarity of biotas decreases over time. [source] In Silico Modeling and Simulation of Bone Biology: A ProposalJOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2005Nadine A Defranoux Abstract Contemporary, computer-based mathematical modeling techniques make it possible to represent complex biological mechanisms in a manner that permits hypothesis testing in silico. This perspective shows how such approaches might be applied to bone remodeling and therapeutic research. Currently, the dominant conceptual model applied in bone research involves the dynamic balance between the continual build-up and breakdown of bone matrix by two cell types, the osteoblasts and osteoclasts, acting together as a coordinated, remodeling unit. This conceptualization has served extraordinarily well as a focal point for understanding how mutations, chemical mediators, and mechanical force, as well as external influences (e.g., drugs, diet) affect bone structure and function. However, the need remains to better understand and predict the consequences of manipulating any single factor, or combination of factors, within the context of this complex system's multiple interacting pathways. Mathematical models are a natural extension of conceptual models, providing dynamic, quantitative descriptions of the relationships among interacting components. This formalization creates the ability to simulate the natural behavior of a system, as well as its modulation by therapeutic or dietetic interventions. A number of mathematical models have been developed to study complex bone functions, but most include only a limited set of biological components needed to address a few specific questions. However, it is possible to develop larger, multiscale models that capture the dynamic interactions of many biological components and relate them to important physiological or pathological outcomes that allow broader study. Examples of such models include Entelos' PhysioLab platforms. These models simulate the dynamic, quantitative interactions among a biological system's biochemicals, cells, tissues, and organs and how they give rise to key physiologic and pathophysiologic outcomes. We propose that a similar predictive, dynamical, multiscale mathematical model of bone remodeling and metabolism would provide a better understanding of the mechanisms governing these phenomena as well as serve as an in silico platform for testing pharmaceutical and clinical interventions on metabolic bone disease. [source] New concepts in radiation-induced apoptosis: ,premitotic apoptosis' and ,postmitotic apoptosis'JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2001N. ShinomiyaArticle first published online: 1 MAY 200 Abstract Formerly, the mechanisms responsible for the killing of cells by ionizing radiation were regarded as being divided into two distinct forms, interphase death and reproductive death. Since they were defined based on the classical radiobiological concepts using a clonogenic cell survival assay, biochemical and molecular biological mechanisms involved in the induction of radiation-induced cell death were not fully understood in relation to the modes of cell death. Recent multidisciplinary approaches to cell death mechanism have revealed that radiation-induced cell death is divided into several distinct pathways by the time course and cell-cycle position, and that apoptotic cell death plays a key role in almost every mode of cell death. This review discusses the mechanisms of radiation-induced apoptosis in relation to cellcycle progression and highlights a new concept of the mode of cell death: ,premitotic apoptosis' and ,postmitotic apoptosis'. The former is a rapid apoptotic cell death associated with a prompt activation of caspase-3, a key enzyme of intracellular signaling of apoptosis. Arapid execution of cell killing in premitotic apoptosis is presumably due to the prompt activation of a set of pre-existed molecules following DNA damages. In contrast, the latter is a delayed apoptotic cell death after cell division, and unlike premitotic apoptosis, it neither requires a rapid activation of caspase-3 nor is inhibited by a specific inhibitor, Ac-DEVD-CHO. A downregulation of anti-apoptotic genes such as MAPK and Bcl-2 may play a key role in this mode of cell death. Characterization of these two types of apoptotic cell death regarding the cell cycle regulation and intrcellular signaling will greatly help to understand the mechanisms of radiation-induced apoptosis. [source] Obligate asex in a rotifer and the role of sexual signalsJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 1 2008C.-P. STELZER Abstract Transitions to asexuality have occurred in many animals and plants, yet the biological mechanisms causing such transitions have often remained unclear. Cyclical parthenogens, such as cladocerans, rotifers or aphids often give rise to obligate asexual lineages. In many rotifers, chemical signals that accumulate during population crowding trigger the induction of sexual stages. In this study, I tested two hypotheses on the origin of obligate parthenogenesis in the rotifer Brachionus calyciflorus: (i) that obligate parthenogens have lost the responsiveness to the sexual signal; and (ii) that obligate parthenogens have lost the ability to produce the sexual signal. Pairwise cross-induction assays among three obligate parthenogenetic strains and two cyclically parthenogenetic (sexual) strains were used to test these hypotheses. I found that obligate parthenogens can induce sexual reproduction in sexual strains, but not vice versa. This demonstrates that obligate parthenogens do still produce the sexual signal, but have lost responsiveness to that signal. [source] | |||||||||||||||||||||||||||||||||||||