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Novel Observations (novel + observation)
Selected AbstractsHighly Regio-, Chemo- and Diastereoselective Synthesis of Oxa-Bridged Spirocycles: A Novel Observation of Reverse Selectivity.CHEMINFORM, Issue 50 2005Sengodagounder Muthusamy Abstract For Abstract see ChemInform Abstract in Full Text. [source] Behavior of o-Hydroxyacetophenones Towards Action of POCl3/DMF (Vilsmeier Reagent) in the Presence of BF3×Et2O: A Novel Observation in the Synthesis of Chromones.CHEMINFORM, Issue 36 2005Om Prakash Abstract For Abstract see ChemInform Abstract in Full Text. [source] PATTERNS OF PHENOTYPIC AND GENETIC VARIATION FOR THE PLASTICITY OF DIAPAUSE INCIDENCEEVOLUTION, Issue 7 2007Wade E. Winterhalter Phenotypic plasticity describes an organism's ability to produce multiple phenotypes in direct response to its environmental conditions. Over the past 15 years empiricists have found that this plasticity frequently exhibits geographic variation and often possesses a significant heritable genetic basis. However, few studies have examined both of these aspects of plasticity simultaneously. Here, we examined both the geographic and genetic variations of the plasticity for diapause incidence (the proportion of eggs that enter an arrested state of development capable of surviving over the winter) relative to temperatures and photoperiods associated with long and short season environments across six populations of the striped ground cricket, Allonemobius socius, using a half-sibling split brood quantitative genetic design. We found that plasticity, as measured by the slope of the reaction norm, was greater in the southern-low altitude region (where populations are bivoltine) relative to the southern-high and northern-low altitude regions (where populations are univoltine). However, the heritability of plasticity was only significantly different from zero in univoltine populations that experienced "intermediate" natal season lengths. These patterns suggest that selection may favor the plasticity of diapause incidence in bivoltine regions, but act against plasticity in regions in which populations are univoltine. Furthermore, our data suggest that under "intermediate" natal season length conditions, the interplay between local adaptation and gene flow may keep the plasticity of diapause incidence low (but still significant) while maintaining its genetic variation. As such, this study not only provides a novel observation into the geographic variation of phenotypic plasticity, but also provides much needed groundwork for tests of its adaptive significance. [source] Estrogen Receptor-, Inhibits Skeletal Growth and Has the Capacity to Mediate Growth Plate Fusion in Female Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2004AS Chagin Abstract To determine the long-term role of ER, in the regulation of longitudinal bone growth, appendicular and axial skeletal growth was followed and compared in female ER,,/,, ER,,/,, and ER,,/,,,/, mice. Our results show that ER, inhibits appendicular and axial skeletal growth and has the capacity to induce fusion of the growth plates. Introduction: Estrogen affects skeletal growth and promotes growth plate fusion in humans. In rodents, the growth plates do not fuse after sexual maturation, but prolonged treatment with supraphysiological levels of estradiol has the capacity to fuse the growth plates. It should be emphasized that the estrogen receptor (ER),,/, and the ER,,/,,,/,, but not the ER,,/,, mouse models have clearly increased serum levels of estradiol. Materials and Methods: The skeletal growth was monitored by X-ray and dynamic histomorphometry, and the growth plates were analyzed by quantitative histology, calcein double labeling, bromodeoxyuridine (BrdU) incorporation, and TUNEL assay in 4- and 18-month-old female ER,,/,, ER,,/,, and ER,,/,,,/, mice. Results: Young adult (4-month-old) ER,,/, mice demonstrated an increased axial- and appendicular-skeletal growth, supporting the notion that ER, inhibits skeletal growth in young adult female mice. Interestingly, the growth plates were consistently fused in the appendicular skeleton of 18-month-old female ER,,/, mice. This fusion of growth plates, caused by a prolonged exposure to supraphysiological levels of estradiol in female ER,,/, mice, must be mediated through ER, because old ER,,/,,,/, mice displayed unchanged, unfused growth plates. Conclusions: Our results confirm that ER, is a physiological inhibitor of appendicular- and axial-skeletal growth in young adult female mice. Furthermore, we made the novel observation that ER,, after prolonged supraphysiological estradiol exposure, has the capacity to mediate growth plate fusion in old female mice. [source] Gnathodiaphyseal Dysplasia: A Syndrome of Fibro-Osseous Lesions of Jawbones, Bone Fragility, and Long Bone BowingJOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2001Mara Riminucci Abstract We report an unusual generalized skeletal syndrome characterized by fibro-osseous lesions of the jawbones with a prominent psammomatoid body component, bone fragility, and bowing/sclerosis of tubular bones. The case fits with the emerging profile of a distinct syndrome with similarities to previously reported cases, some with an autosomal dominant inheritance and others sporadic. We suggest that the syndrome be named gnathodiaphyseal dysplasia. The patient had been diagnosed previously with polyostotic fibrous dysplasia (PFD) elsewhere, but further clinical evaluation, histopathological study, and mutation analysis excluded this diagnosis. In addition to providing a novel observation of an as yet poorly characterized syndrome, the case illustrates the need for stringent diagnostic criteria for FD. The jaw lesions showed fibro-osseous features with the histopathological characteristics of cemento-ossifying fibroma, psammomatoid variant. This case emphasizes that the boundaries between genuine GNAS1 mutation-positive FD and other fibro-osseous lesions occurring in the jawbones should be kept sharply defined, contrary to a prevailing tendency in the literature. A detailed pathological study revealed previously unreported features of cemento-ossifying fibroma, including the participation of myofibroblasts and the occurrence of psammomatoid bodies and aberrant mineralization, within the walls of blood vessels. Transplantation of stromal cells grown from the lesion into immunocompromised mice resulted in a close mimicry of the native lesion, including the sporadic formation of psammomatoid bodies, suggesting an intrinsic abnormality of bone-forming cells. [source] Soft reliability: an interdisciplinary approach with a user,system focusQUALITY AND RELIABILITY ENGINEERING INTERNATIONAL, Issue 1 2009A. Koca Abstract A recent trend in technological innovation is towards the development of increasingly multifunctional and complex products to be used within rich socio-cultural contexts such as the high-end office, the digital home, and professional or personal healthcare. One important consequence of the development of strongly innovative products is a growing market uncertainty regarding ,if', ,how', and ,when' users can and will adopt such products. Often, it is not even clear to what extent these products are understood and interacted with in the intended manner. The mentioned problems have already become an evident concern in the field, where there is a significant rise in the numbers of seemingly sound products being complained about, signaling a lack of soft reliability. In this paper, we position soft reliability as a growing and critical industrial problem, whose solution requires new academic expertise from various disciplines. We illustrate potential root causes for soft reliability problems, such as discrepancy between the perceptions of users and designers. We discuss the necessary approach to effectively capture subjective feedback data from actual users, e.g. when they contact call centers. Furthermore, we present a novel observation and analysis approach that enables insight into actual product usage, and outline opportunities for combining such objective data with the subjective feedback provided by users. Copyright © 2008 John Wiley & Sons, Ltd. [source] Gas-phase formation of protonated benzene during collision-induced dissociation of certain protonated mono-substituted aromatic molecules produced in electrospray ionizationRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 11 2010Min Li Protonated benzene, C6H, has been studied extensively to understand the structure and energy of a protonated organic molecule in the gas phase. The formation of C6H is either through direct protonation of benzene, i.e., chemical ionization, or through fragmentation of certain radical cations produced from electron ionization or photon ionization. We report a novel observation of C6H as a product ion formed in the collision-induced dissociation (CID) of protonated benzamide and related molecules produced via electrospray ionization (ESI). The formation of C6H from these even-electron precursor ions during the CID process, which has not been previously reported, is proposed to occur from the protonated molecules via a proton migration in a five-membered ring intermediate followed by the cleavage of the mono-substituent CC bond and concurrent formation of an ion-molecule complex. This unique mechanism has been scrutinized by examining some deuterated molecules and a series of structurally related model compounds. This finding provides a convenient mean to generate C6H, a reactive intermediate of considerable interest, for further physical or chemical investigation. Further studies indicate that the occurrence of C6H in liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) appears to be a rather common phenomenon for many compounds that contain ,benzoyl-type' moieties. Hence, the observation of the C6H ion in LC/ESI-MS/MS can be used as an informative fragmentation pathway which should facilitate the identification of a great number of compounds containing the ,benzoyl-type' and similar structural features. These compounds are frequently present in food and pharmaceutical products as leachable impurities that require strict control and rapid elucidation of their identities. Copyright © 2010 John Wiley & Sons, Ltd. [source] Contralateral Incipient Posterior Canal Benign Positional Paroxysmal Vertigo: Complication After Epley ManeuverTHE LARYNGOSCOPE, Issue 11 2008Annabelle C. Leong BSc MRCS Abstract Background: Particle repositioning procedures give consistent results for the treatment of benign positional paroxysmal vertigo (BPPV). However, little consideration has been given to the possibilities of bilateral disease. Objective/Hypothesis: To report contralateral symptoms and signs suggestive of revealed or incipient BPPV as a complication of Epley maneuver. Study Design: A prospective cohort of 198 cases over a period of 11 years. Results: Ten (5.0%) developed contralateral symptoms and signs suggestive of revealed or incipient posterior canal BPPV within 2 weeks of treatment. Conclusion: This novel observation has not been previously described and may influence the strategy for future management of patients with BPPV. Particle repositioning maneuvers for the previously asymptomatic contralateral ear may need to be considered in a subset of patients with posterior canal BPPV who suffer contralateral symptoms after undergoing treatment for the original ear. [source] Apoptosis and Phagocytosis of Tissue-Dwelling Eosinophils in Sinonasal Polyps,THE LARYNGOSCOPE, Issue 1 2000Åke Davidsson MD Abstract Objective: Sinonasal polyps contain numerous tissue-dwelling eosinophils, but the mechanisms causing their accumulation, functional activities, and resolution are largely unknown. Study Design: Nasal polyp tissue from 14 patients was evaluated for cellular expression of CD95, CD68, and Annexin-V, for the degree of apoptosis, and for phagocytosis of eosinophils. Material and Methods: Histological sections were immunostained as single stains for CD95, CD68, and Annexin-V, and as an immunostaining for CD68 combined with a modified Vital New Red staining. The latter staining is specific for eosinophils. Other sections were stained by terminal d-UTP nick end labeling (TUNEL) assay and routinely stained for H&E. Evaluation of the amount of stained cells was performed by counting the average number in 10 randomly chosen high-power fields. The TUNEL positivity was in all cases confirmed with apoptotic morphology. Results: The inflammatory infiltrate consisted of numerous eosinophils but also a considerable amount of lymphocytes, mast cells, and macrophage-like CD68+ cells. CD95 was frequently expressed on eosinophils, on numerous other inflammatory cells, and also on morphologically apoptotic cells. Annexin-V-positive eosinophils were not as frequent as CD95+ cells, but numerous Annexin-V-positive eosinophils were found. CD68+ cells approximately equalled the number of eosinophils. The number of cells phagocytosing eosinophils varied between polyps. Apoptosis of eosinophils (as evaluated by TUNEL combined with apoptotic morphology) was a common finding in six of the polyps. Conclusions: Previous in vitro and ex vivo findings of CD95 on eosinophils are now supported by demonstration of CD95 on eosinophils in this in vivo study. This investigation revealed a switch of the membrane-bound phosphatidylserine of apoptotic cells, which is a novel observation. The study has demonstrated apoptosis of tissue-dwelling eosinophils, and that CD68+ macrophage-like cells phagocytose eosinophils within the sinonasal polyps. [source] In vivo and in vitro analysis of the vasculogenic potential of avian proepicardial and epicardial cells,DEVELOPMENTAL DYNAMICS, Issue 4 2006Juan A. Guadix Abstract Coronary vessel formation is a special case in the context of embryonic vascular development. A major part of the coronary cellular precursors (endothelial, smooth muscle, and fibroblastic cells) derive from the proepicardium and the epicardium in what can be regarded as a late event of angioblastic and smooth muscle cell differentiation. Thus, coronary morphogenesis is dependent on the epithelial,mesenchymal transformation of the proepicardium and the epicardium. In this study, we present several novel observations about the process of coronary vasculogenesis in avian embryos, namely: (1) The proepicardium displays a high vasculogenic potential, both in vivo (as shown by heterotopic transplants) and in vitro, which is modulated by vascular endothelial growth factor (VEGF) and basic fibroblast growth factor signals; (2) Proepicardial and epicardial cells co-express receptors for platelet-derived growth factor-BB and VEGF; (3) Coronary angioblasts (found all through the epicardial, subepicardial, and compact myocardial layers) express the Wilms' tumor associated transcription factor and the retinoic acid-synthesizing enzyme retinaldehyde-dehydrogenase-2, two markers of the coelomic epithelium involved in coronary endothelium development. All these results contribute to the development of our knowledge on the vascular potential of proepicardial/epicardial cells, the existent interrelationships between the differentiating coronary cell lineages, and the molecular mechanisms involved in the regulation of coronary morphogenesis. Developmental Dynamics 235:1014,1026, 2006. © 2006 Wiley-Liss, Inc. [source] Behavioural and psychological syndromes in Alzheimer's diseaseINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 11 2004A. Mirakhur Abstract Objectives The origins of behavioural and psychological symptoms of dementia are still poorly understood. By focusing on piecemeal behaviours as opposed to more robust syndrome change valid biological correlates may be overlooked. Our understanding of BPSD via the identification of neuropsychiatric syndromes. Methods We recruited 435 subjects from old age psychiatry and elderly care memory outpatient clinics fulfilling the criteria for diagnosis of probable Alzheimer's disease. Behavioural and psychological symptoms were assessed using the Neuropsychiatric Inventory. Principal components factor analysis was carried out on the composite scores of the 12 symptom domains to identify behavioural syndromes (factors). Results were confirmed by performing three different rotations: Varimax, Equamax and Quartimax. Results Four factors were identified (which accounted for 57% of the variance): ,affect' factor,depression/dysphoria, anxiety, irritability/lability and agitation/aggression; ,physical behaviour' factor,apathy, aberrant motor behaviour, sleep disturbance and appetite/eating disturbance; ,psychosis' factor,delusions and hallucinations; ,hypomania' factor,disinhibition and elation/euphoria. These groups were unchanged when different methods of rotation were used. Conclusions We report novel observations that agitation/aggression/irritability cluster within a depressive symptom factor and apathy is found within a physical behaviour factor. Copyright © 2004 John Wiley & Sons, Ltd. [source] ApcMin/+ mouse model of colon cancer: Gene expression profiling in tumorsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2004Daniel Leclerc Abstract The ApcMin/+ mouse is a popular animal model for studies of human colon cancer, but the molecular changes associated with neoplasia in this system have only been partially characterized. Our aim was to identify novel genes involved in tumorigenesis in this model. RNA from intestinal adenomas and from pre-neoplastic small intestine were prepared from six ApcMin/+ mice. The tumor transcriptomes were analyzed with high-density oligonucleotide microarrays representing ,12,000 probe sets; we compared their profiles with those of matched pre-neoplastic intestine. Stringent analysis revealed reproducible changes for 98 probe sets representing 90 genes, including novel observations regarding 50 genes whose involvement in this mouse model has never been reported. In addition to the expected changes in growth regulatory genes, the altered gene products could be assigned to four functional groupings that should enhance tumorigenesis: metabolic changes that would result in a high rate of glycolysis, alterations in enzymes involved in reactive oxygen species or carcinogen metabolism, cytoskeletal elements, and proteins involved in tumor invasion or angiogenesis. A fifth group consisted of expression changes that might restrict tumor progression, suggesting that the adenomatous state reflects a balance of pro- and anti-tumorigenic factors. Since many of the altered genes had not previously been reported to be involved in any tumorigenic processes, our observations provide a host of new candidates for potential modulation to prevent or treat intestinal neoplasia. Supplementary material for this article can be found at http://www.mrw.interscience.wiley.com/suppmat/0730-2312/suppmat/v93.html. © 2004 Wiley-Liss, Inc. [source] Intracellular redistribution and modification of proteins of the Mre11/Rad50/Nbs1 DNA repair complex following irradiation and heat-shockJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2004Joshua D. Seno Mre11, Rad50, and Nbs1form a tight complex which is homogeneously distributed throughout the nuclei of mammalian cells. However, after irradiation, the Mre11/Rad50/Nbs1 (M/R/N) complex rapidly migrates to sites of double strand breaks (DSBs), forming foci which remain until DSB repair is complete. Mre11 and Rad50 play direct roles in DSB repair, while Nbs1 appears to be involved in damage signaling. Hyperthermia sensitizes mammalian cells to ionizing radiation. Radiosensitization by heat shock is believed to be mediated by an inhibition of DSB repair. While the mechanism of inhibition of repair by heat shock remains to be elucidated, recent reports suggest that the M/R/N complex may be a target for inhibition of DSB repair and radiosensitization by heat. We now demonstrate that when human U-1 melanoma cells are heated at 42.5 or 45.5°C, Mre11, Rad50, and Nbs1 are rapidly translocated from the nucleus to the cytoplasm. Interestingly, when cells were exposed to ionizing radiation (12 Gy of X-rays) prior to heat treatment, the extent and kinetics of translocation were increased when nuclear and cytoplasmic fractions of protein were analyzed immediately after treatment. The kinetics of the translocation and subsequent relocalization back into the nucleus when cells were incubated at 37°C from 30 min to 7 h following treatment were different for each protein, which suggests that the proteins redistribute independently. However, a significant fraction of the translocated proteins exist as a triple complex in the cytoplasm. Treatment with leptomycin B (LMB) inhibits the translocation of Mre11, Rad50, and Nbs1 to the cytoplasm, leading us to speculate that the relocalization of the proteins to the cytoplasm occurs via CRM1-mediated nuclear export. In addition, while Nbs1 is rapidly phosphorylated in the nuclei of irradiated cells and is critical for a normal DNA damage response, we have found that Nbs1 is rapidly phosphorylated in the cytoplasm, but not in the nucleus, of heated irradiated cells. The phosphorylation of cytoplasmic Nbs1, which cannot be inhibited by wortmannin, appears to be a unique post-translational modification in heated, irradiated cells, and coupled with our novel observations that Mre11, Rad50, and Nbs1 translocate to the cytoplasm, lend further support for a role of the M/R/N complex in thermal radiosensitization and inhibition of DSB repair. J. Cell. Physiol. 199: 157,170, 2004© 2004 Wiley-Liss, Inc. [source] Peroxisome proliferator-activated receptor-, agonist fenofibrate regulates IL-12 family cytokine expression in the CNS: relevance to multiple sclerosisJOURNAL OF NEUROCHEMISTRY, Issue 5 2007Jihong Xu Abstract The interleukin-12 (IL-12) family of cytokines which includes IL-12, IL-23, and IL-27 play critical roles in T cell differentiation and are important modulators of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Previously, we demonstrated that peroxisome proliferator-activated receptor (PPAR) -, agonists suppress the development of EAE. The present studies demonstrated that the PPAR-, agonist fenofibrate inhibited the secretion of IL-12p40, IL-12p70 (p35/p40), IL-23 (p19/p40), and IL-27p28 by lipopolysaccharide-stimulated microglia. The cytokines interferon-, and tumor necrosis factor-, also stimulated IL-12 p40 and IL-27 p28 expression by microglia, which was suppressed by fenofibrate. Furthermore, fenofibrate inhibited microglial expression of CD14 which plays a critical role in TLR signaling, suggesting a mechanism by which this PPAR-, agonist regulates the production of these pro-inflammatory molecules. In addition, fenofibrate suppressed the secretion of IL-12p40, IL-23, and IL-27p28 by lipopolysaccharide-stimulated astrocytes. Importantly, fenofibrate suppression of EAE was associated with decreased expression of IL-12 family cytokine mRNAs as well as mRNAs encoding TLR4, CD14, and MyD88 known to play critical roles in MyD88-dependent TLR signaling. These novel observations suggest that PPAR-, agonists including fenofibrate may modulate the development of EAE, at least in part, by suppressing the production of IL-12 family cytokines and MyD88-dependent signaling. [source] Visceral sensation and colitis: inflammation and hypersensitivity do not always go hand in handNEUROGASTROENTEROLOGY & MOTILITY, Issue 2 2006K. A. Sharkey Abstract, Visceral sensitivity and inflammation are discussed in relation to novel observations in the current issue of the Journal by Larsson and her colleagues. This paper shows that neither acute nor chronic intestinal inflammation initiated by dextran sodium sulfate is associated with an increase in visceral sensitivity to balloon distension in mice. These findings are discussed in the context of recent work highlighting the role of mast cells, the induction of endogenous antinociceptive pathways and the role of altered bacterial flora in visceral hypersensitivity. [source] Enteric nervous system disorders: genetic and molecular insights for the neurogastroenterologistNEUROGASTROENTEROLOGY & MOTILITY, Issue 4 2001M. Camilleri The goals of this review are to summarize some of the novel observations on the genetic and molecular basis of enteric nervous system disorders, with particular emphasis on the relevance of these observations to the practicising neurogastroenterologist. In the last two decades, there has been a greater understanding of genetic loci involved in congenital forms of pseudo-obstruction and Hirschsprung's disease; and the contribution of endothelins and nuclear transcription factors to the development of the enteric nervous system. In addition, clarification of the molecules involved in the activation of the peristaltic reflex, the disorders of the interstitial cells of Cajal, the clinical manifestations of mitochondrial cytopathies affecting the gut, and the application of neurotrophic factors for disorders of colonic function have impacted on practical management of patients with gut dysmotility. [source] Diffusion-weighted MRI measurements on stroke patients reveal water-exchange mechanisms in sub-acute ischaemic lesionsNMR IN BIOMEDICINE, Issue 6 2009J. Lätt Abstract The aim of this study was to investigate the diffusion time dependence of signal- versus - b curves obtained from diffusion-weighted magnetic resonance imaging (DW-MRI) of sub-acute ischaemic lesions in stroke patients. In this case series study, 16 patients with sub-acute ischaemic stroke were examined with DW-MRI using two different diffusion times (60 and 260,ms). Nine of these patients showed sufficiently large lesions without artefacts to merit further analysis. The signal- versus - b curves from the lesions were plotted and analysed using a two-compartment model including compartmental exchange. To validate the model and to aid the interpretation of the estimated model parameters, Monte Carlo simulations were performed. In eight cases, the plotted signal- versus - b curves, obtained from the lesions, showed a signal,curve split-up when data for the two diffusion times were compared, revealing effects of compartmental water exchange. For one of the patients, parametric maps were generated based on the extracted model parameters. These novel observations suggest that water exchange between different water pools is measurable and thus potentially useful for clinical assessment. The information can improve the understanding of the relationship between the DW-MRI signal intensity and the microstructural properties of the lesions. Copyright © 2009 John Wiley & Sons, Ltd. [source] 3D seismic technology: the geological ,Hubble'BASIN RESEARCH, Issue 1 2005Joe Cartwright The proliferation of three-dimensional (3D) seismic technology is one of the most exciting developments in the Earth Sciences over the past century. 3D reflection seismic data provide interpreters with the ability to map structures and stratigraphic features in 3D detail to a resolution of a few tens of metres over thousands of square kilometres. It is a geological ,Hubble', whose resolving power has already yielded some fascinating (and surprising) insights and will continue to provide a major stimulus for research into geological processes and products for many decades to come. Academic and other research institutions have a major role to play in the use of this data by exploiting the enormous volume of geological information contained in 3D seismic surveys. This paper reviews some of the recent advances in basin analysis made using the medium of 3D seismic data, focusing on the fields of structural and sedimentary geology, fluid,rock interactions and igneous geology. It is noted that the increased resolution of the 3D seismic method provided the essential catalyst necessary to stimulate novel observations and discover new geological structures such as mud diapir feeders, km-long gas blow-out pipes, giant pockmarks and sandstone intrusions, and to capture the spatial variability of diagenetic fronts. The UKs first impact crater was also discovered using 3D seismic data. The potential for future developments in this field of geophysical interpretation is considerable, and we anticipate that new discoveries will be made in many years to come. [source] |