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Complete Lack (complete + lack)
Selected AbstractsComplete lack of mitochondrial divergence between two species of NE Atlantic marine intertidal gastropodsJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 10 2009P. KEMPPAINEN Abstract Some mitochondrial introgression is common between closely related species, but distinct species rarely show substantial introgression in their entire distribution range. In this study, however, we report a complete lack of mitochondrial divergence between two sympatric species of flat periwinkles (Littorina fabalis and Littorina obtusata) which, based on previous allozyme studies, diverged approximately 1 Ma. We re-examined their species status using both morphology (morphometric analysis) and neutral genetic markers (microsatellites) and our results confirmed that these species are well separated. Despite this, the two species shared all common cytochrome-b haplotypes throughout their NE Atlantic distribution and no deep split between typical L. fabalis and L. obtusata haplotypes could be found. We suggest that incomplete lineage sorting explains most of the lack of mitochondrial divergence between these species. However, coalescent-based analyses and the sympatric sharing of unique haplotypes suggest that introgressive hybridization also has occurred. [source] Pursuing paradoxical proconvulsant prophylaxis for epileptogenesisEPILEPSIA, Issue 7 2009Caren Armstrong Summary There are essentially two potential treatment options for any acquired disorder: symptomatic or prophylactic. For acquired epilepsies that follow a variety of different brain insults, there remains a complete lack of prophylactic treatment options, whereas at the same time these epilepsies are notoriously resistant, once they have emerged, to symptomatic treatments with antiepileptic drugs. The development of prophylactic strategies is logistically challenging, both for basic researchers and clinicians. Nevertheless, cannabinoid-targeting drugs provide a very interesting example of a system within the central nervous system (CNS) that can have very different acute and long-term effects on hyperexcitability and seizures. In this review, we outline research on cannabinoids suggesting that although cannabinoid antagonists are acutely proconvulsant, they may have beneficial effects on long-term hyperexcitability following brain insults of multiple etiologies, making them promising candidates for further investigation as prophylactics against acquired epilepsy. We then discuss some of the implications of this finding on future attempts at prophylactic treatments, specifically, the very short window within which prevention may be possible, the possibility that traditional anticonvulsants may interfere with prophylactic strategies, and the importance of moving beyond anticonvulsants,even to proconvulsants,to find the ideal preventative strategy for acquired epilepsy. [source] Clinician stance in the treatment of chronic eating disordersEUROPEAN EATING DISORDERS REVIEW, Issue 6 2001Josie Geller Abstract Long-term outcome studies of anorexia nervosa have shown that a significant number of individuals do not fully recover from their eating disorder symptoms. Individuals who develop chronic eating disorders may express either strong ambivalence about symptom reduction or a complete lack of interest in change. As a result, clinicians can find this group particularly challenging. This report expands upon a treatment stance based on principles of Motivational Interviewing that addresses difficulties typically encountered in working with this population. The stance outlines a mission statement and specific clinician behaviours that promote engagement and alliance with this group, including the communication of beliefs that foster client self-acceptance, not making assumptions, being curious, active, and on the same side, and maximizing client responsibility for change. Copyright © 2001 John Wiley & Sons, Ltd and Eating Disorders Association. [source] The IFN regulatory factor 7-dependent type I IFN response is not essential for early resistance against murine cytomegalovirus infectionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2009Christian Steinberg Abstract IFN regulatory factor 7 (IRF7) has been described as the master regulator of type I IFN responses and has been shown to be critical for innate antiviral immunity in vivo. In addition to type I IFN, NK cell responses are involved in the control of viral replication during acute viral infection. To investigate the role of IRF7 in the context of a viral infection that induces a strong NK cell response, the murine cytomegalovirus (MCMV) infection model was used. WT, IRF7-deficient and IRF3/IRF7-double deficient mice were infected with MCMV. The systemic IFN-, response to MCMV was entirely dependent on IRF7, but independent of IRF3. However, peak IFN-, production during MCMV infection was not affected by the lack of IRF7 or both IRF7 and IRF3. Despite the complete lack of IFN-, production IRF7- and IRF3/IRF7-deficient mice were surprisingly efficient in controlling MCMV replication and were only modestly more susceptible to MCMV infection than WT mice. NK cell cytotoxicity was unimpaired and NK cell IFN-, production was enhanced in IRF7-deficient mice correlating with increased levels of bioactive IL-12. Owing to these compensatory mechanisms IRF7-dependent antiviral immune responses were not essential for resistance against acute MCMV infection in vivo. [source] Genetic diversity in Nordic and Baltic populations of Chondrostereum purpureum: a potential herbicide biocontrol agentFOREST PATHOLOGY, Issue 6 2008H. Vartiamäki Summary We analysed genetic variation in the natural populations of a potential herbicide biocontrol agent, Chondrostereum purpureum, in Nordic and Baltic countries using random amplified microsatellite markers. The results showed high genetic diversity among the populations of this fungus, but almost a complete lack of local differentiation. The results implicate that any local strain from the area can be used as a biocontrol agent without a fear of introducing new genotypes to treatment areas. [source] Sequential methods and group sequential designs for comparative clinical trialsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2003Véronique Sébille Abstract Comparative clinical trials are performed to assess whether a new treatment has superior efficacy than a placebo or a standard treatment (one-sided formulation) or whether two active treatments have different efficacies (two-sided formulation) in a given population. The reference approach is the single-stage design and the statistical test is performed after inclusion and evaluation of a predetermined sample size. In practice, the single-stage design is sometimes difficult to implement because of ethical concerns and/or economic reasons. Thus, specific early termination procedures have been developed to allow repeated statistical analyses to be performed on accumulating data and stop the trial as soon as the information is sufficient to conclude. Two main different approaches can be used. The first one is derived from strictly sequential methods and includes the sequential probability ratio test and the triangular test. The second one is derived from group sequential designs and includes Peto, Pocock, and O'Brien and Fleming methods, , and , spending functions, and one-parameter boundaries. We review all these methods and describe the bases on which they rely as well as their statistical properties. We also compare these methods and comment on their advantages and drawbacks. We present software packages which are available for the planning, monitoring and analysis of comparative clinical trials with these methods and discuss the practical problems encountered when using them. The latest versions of all these methods can offer substantial sample size reductions when compared with the single-stage design not only in the case of clear efficacy but also in the case of complete lack of efficacy of the new treatment. The software packages make their use quite simple. However, it has to be stressed that using these methods requires efficient logistics with real-time data monitoring and, apart from survival studies or long-term clinical trials with censored endpoints, is most appropriate when the endpoint is obtained quickly when compared with the recruitment rate. [source] Regulation of the activity of the transcription factor Runx2 by two homeobox proteins, Msx2 and Dlx5GENES TO CELLS, Issue 10 2001Kyoko Shirakabe Background Runx2, formerly called PEBP2,A or Cbfa1, is a transcription factor whose deletion causes a complete lack of ossification. It directly regulates the expression of osteoblast-specific genes through the osteoblast-specific cis -acting element found in the promoter region of these genes. Results In this study, we have found conditions in which induction of the expression of Runx2 is not accompanied by expression of an osteoblast-specific gene, osteocalcin in C2C12 cells. This finding suggests the existence of a repressor of the activity of Runx2. We have then found that the homeobox protein Msx2 is able to repress the transcription activity of Runx2 by interacting with it. Furthermore, our results have shown that the other homeobox protein Dlx5 has an activity which interferes with both abilities of Msx2 to interact with Runx2 and repress its transcription activity. It has previously been shown that a missense mutation of Msx2 (P148H) causes Boston-type craniosynostosis in humans. Interestingly, while this mutant form of Msx2 was able to bind to Runx2 and repress its activity, these abilities of Msx2 (P148H) were not subject to regulation by Dlx5. Conclusion These results suggest that regulation of the activity of Runx2 by Msx2 and Dlx5 plays an important role in the mammalian skull development. [source] The Nonchiral Bislactim Diethoxy Ether as a Highly Stereo-Inducing Synthon for Sterically Hindered, , -Branched , -Amino Acids: A Practical, Large-Scale Route to an Intermediate of the Novel Renin Inhibitor AliskirenHELVETICA CHIMICA ACTA, Issue 8 2003Richard Göschke The diastereoselective synthesis of the sterically hindered, , -branched , -amino acid derivative (2S,4S)- 24a and its N -[(tert -butoxy)carbonyl](Boc)-protected alcohol (2S,4S)- 19, both key intermediates of a novel class of nonpeptide renin inhibitors such as aliskiren (1), is described. Initially, the analogous methyl ester (2S,4S)- 17 was obtained by alkylation of the chiral Schöllkopf dihydropyrazine (R)- 12a with the dialkoxy-substituted alkyl bromide (R)- 11a, which proceeded with explicitly high diastereofacial selectivity (ds ,98%) to give (2S,5R,2,S)- 13a (Scheme,4), followed by mild acid hydrolysis and N -Boc protection (Scheme,5). Conversely, the complete lack of stereocontrol and poor yields for the reaction of (R)- 11a with the enantiomeric (S)- 12b suggested, in addition to the anticipated shielding effect by the iPr group at C(2) of the auxiliary, steric repulsion between the MeOC(6) and the bulky residues of (R)- 11a in the proposed transition state, which would strongly disfavor both the Si and Re attack of the electrophile (see Fig.). Based on this rationale, alkylation of the readily accessible achiral diethoxy-dihydropyrazine 21 with (R)- 11a was found to provide a 95,:,5 mixture of diastereoisomers (2S,2,S)- 22a and (2R,2,S)- 23a in high yield (Scheme,6), which afforded in two steps and after recrystallization enantiomerically pure (2S,4S)- 24a. Similarly, the stereochemical course for the alkylation reactions of the related alkyl bromides (S)- 28a and (R)- 28b with both (R)- 12a and (S)- 12b as well as with the achiral 21 was investigated (Schemes,7,9). The precursor bromides (R)- 11a, (S)- 11b, (R)- 28a, and (S)- 28b were efficiently synthesized via the diastereoselective alkylation of the Evans 3-isovaleroyloxazolidin-2-ones (R)- 7a and (S)- 7b either with bromide 6 or with benzyl chloromethyl ether, and subsequent standard transformations (Schemes,3 and 7). A practical and economical protocol of the preparation of (2S,4S)- 24a on a multi-100-g scale is given. This is the first report of the application of an achiral dihydropyrazine, i.e., in form of 21, as a highly stereo-inducing synthon providing rapid access to a N -protected , -branched , -amino acid with (2S) absolute configuration. [source] Complete lack of mitochondrial divergence between two species of NE Atlantic marine intertidal gastropodsJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 10 2009P. KEMPPAINEN Abstract Some mitochondrial introgression is common between closely related species, but distinct species rarely show substantial introgression in their entire distribution range. In this study, however, we report a complete lack of mitochondrial divergence between two sympatric species of flat periwinkles (Littorina fabalis and Littorina obtusata) which, based on previous allozyme studies, diverged approximately 1 Ma. We re-examined their species status using both morphology (morphometric analysis) and neutral genetic markers (microsatellites) and our results confirmed that these species are well separated. Despite this, the two species shared all common cytochrome-b haplotypes throughout their NE Atlantic distribution and no deep split between typical L. fabalis and L. obtusata haplotypes could be found. We suggest that incomplete lineage sorting explains most of the lack of mitochondrial divergence between these species. However, coalescent-based analyses and the sympatric sharing of unique haplotypes suggest that introgressive hybridization also has occurred. [source] An investigation of overeruption of posterior teeth with partial occlusal contactJOURNAL OF ORAL REHABILITATION, Issue 4 2007H. L. CRADDOCK Summary, The need and demand for replacement of missing posterior teeth may increase as the UK population is predicted to be at least partially dentate for life. Replacement with either fixed or removable prostheses may be indicated, and the tooth positional changes of adjacent or opposing teeth may require consideration. The objectives of this study are to: (1) Investigate the extent of overeruption associated with partially opposed posterior teeth; (2) Determine if overeruption is associated with tipping of the partially opposed tooth and examine the extent of tip. Ninety-one patients with either partially or completely unopposed posterior teeth were included in the study. For each group the extent of overeruption of the tooth was measured. Differences in the extent of overeruption and tipping were analysed. Correlations between the presence of partial tooth contact and the extent of overeruption and degree of tipping of the unopposed tooth were analysed. There was no significant difference in the extent of overeruption between the unopposed and partially opposed groups. The partially opposed teeth displayed a greater degree of tipping than the unopposed group. There was no significant correlation between the extent of overeruption and the degree of tipping, nor between the extent of overeruption and the presence of partial tooth contact. There was, a significant correlation between the degree of tooth tip and the presence of partial tooth contact. (1) Partial tooth contact does not appear to prevent or reduce overeruption; (2) Partially opposed teeth show an increased degree of tip relative to teeth with complete lack of occlusal contact. The findings suggest that partial tooth contact should not be relied on clinically to maintain vertical tooth position. [source] Copper-mediated reversal of defective laccase in a ,vph1 avirulent mutant of Cryptococcus neoformansMOLECULAR MICROBIOLOGY, Issue 4 2003Xudong Zhu Summary Previous studies have shown that a ,vph1 Cryptococcus neoformans mutant defective in vesicular acidification lacked several important virulence factors including a copper-containing laccase and was avirulent in a mouse model. In the present studies, we characterized laccase transcription and protein production to obtain insights into the mechanism of the vph1 mutation in this pathogen. Although transcription and protein expression were somewhat reduced, laccase protein was found to be successfully translated and correctly targeted to the cell wall in the ,vph1 mutant as shown by Western blot and immuno-electron microscopy, despite a complete lack of laccase activity. Laccase activity was substantially restored in metabolically active ,vph1 cells at 30°C by addition of 100 µM copper sulphate. This restoration by copper was found to occur through both transcriptional and post-translational mechanisms. Laccase transcriptional induction by copper was found to be dependent on enhancer region II within the 5,-untranslated region of CNLAC1. Copper was also found to restore partial activity to ,vph1 cells at 0°C, suggesting that cell wall laccase was expressed in the mutant as an apo-enzyme. Apo-laccase restoration by copper was found to be facilitated by an acidic environment, consistent with a role for the vacuolar (H+)-ATPase proton pump in copper assembly of laccase in C. neoformans. [source] Magnaporthe oryzae isolates causing gray leaf spot of perennial ryegrass possess a functional copy of the AVR1-CO39 avirulence geneMOLECULAR PLANT PATHOLOGY, Issue 3 2006REBECCA PEYYALA SUMMARY Gray leaf spot of perennial ryegrass (Lolium perenne) is a severe foliar disease caused by the ascomycete fungus Magnaporthe oryzae (formerly known as Magnaporthe grisea). Control of gray leaf spot is completely dependent on the use of fungicides because currently available perennial ryegrass cultivars lack genetic resistance to this disease. M. oryzae isolates from perennial ryegrass (prg) were unable to cause disease on rice cultivars CO39 and 51583, and instead triggered a hypersensitive response. Southern hybridization analysis of DNA from over 50 gray leaf spot isolates revealed that all of them contain sequences corresponding to AVR1-CO39, a host specificity gene that confers avirulence to rice cultivar CO39, which carries the corresponding resistance gene Pi-CO39(t). There was also an almost complete lack of restriction site polymorphism at the avirulence locus. Cloning and sequencing of the AVR1-CO39 gene (AVR1-CO39Lp) from 16 different gray leaf spot isolates revealed just two point mutations, both of which were located upstream of the predicted open reading frame. When an AVR1-CO39Lp gene copy was transferred into ML33, a rice pathogenic isolate that is highly virulent to rice cultivar CO39, the transformants were unable to cause disease on CO39 but retained their virulence to 51583, a rice cultivar that lacks Pi-CO39(t). These data demonstrate that the AVR1-CO39 gene in the gray leaf spot pathogens is functional, and suggest that interaction of AVR1-CO39Lp and Pi-CO39(t) is responsible, at least in part, for the host specificity expressed on CO39. This indicates that it may be possible to use the Pi-CO39(t) resistance gene as part of a transgenic strategy to complement the current deficiency of gray leaf spot resistance in prg. Furthermore, our data indicate that, if Pi-CO39(t) can function in prg, the resistance provided should be broadly effective against a large proportion of the gray leaf spot pathogen population. [source] Where is the radiation edge in magnetized black hole accretion discs?MONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 1 2008Kris Beckwith ABSTRACT General relativistic (GR) magnetohydrodynamic (MHD) simulations of black hole accretion find significant magnetic stresses near and inside the innermost stable circular orbit (ISCO), suggesting that such flows could radiate in a manner noticeably different from the prediction of the standard model, which assumes that there are no stresses in that region. We provide estimates of how phenomenologically interesting parameters like the ,radiation edge', the innermost ring of the disc from which substantial thermal radiation escapes to infinity, may be altered by stresses near the ISCO. These estimates are based on data from a large number of three-dimensional GRMHD simulations combined with GR ray tracing. For slowly spinning black holes (a/M < 0.9), the radiation edge lies well inside where the standard model predicts, particularly when the system is viewed at high inclination. For more rapidly spinning black holes, the contrast is smaller. At fixed total luminosity, the characteristic temperature of the accretion flow increases between a factor of 1.2 and 2.4 over that predicted by the standard model, whilst at fixed mass accretion rate, there is a corresponding enhancement of the accretion luminosity which may be anywhere from tens of per cent to order unity. When all these considerations are combined, we find that, for fixed black hole mass, luminosity and inclination angle, our uncertainty in the characteristic temperature of the radiation reaching distant observers due to uncertainty in dissipation profile (around a factor of 3) is greater than the uncertainty due to a complete lack of knowledge of the black hole's spin (around a factor of 2) and furthermore that spin estimates based on the stress-free inner boundary condition provide an upper limit to a/M. [source] Pleomorphic xanthoastrocytoma with anaplastic features presenting without GFAP immunoreactivity: Implications for differential diagnosisNEUROPATHOLOGY, Issue 3 2005Ellen Gelpi Pleomorphic xanthoastrocytoma (PXA) is an uncommon, usually low-grade, astrocytic tumor. Characteristic histological features include tumor cell pleomorphism and lipidization of tumor cells. Albeit prognosis in PXA is generally good, cases with histological signs of anaplasia have been observed. In these cases, the differential diagnosis needs to exclude other malignancies, for example, glioblastoma or malignant fibrous histiocytoma. Immunocytochemical detection of GFAP may support exclusion of non-glial neoplasms resembling PXA. However, GFAP expression in PXA may be faint or focal, although complete lack of GFAP has not been described. A 43-year-old woman was operated on for a left occipital parasagital tumor attached to the dura. Histopathology showed a pleomorphic tumor with moderate mitotic activity and necrosis, lack of GFAP immunoreactivity and ultrastructural detection of premelanosome-like structures. These features led to the tentative diagnosis of amelanotic melanoma, and the patient was irradiated. Three years later she had local tumor recurrence and underwent another operation. The recurrent tumor showed similar plain histology as the first specimen. In contrast, anti-GFAP immunoreactivity was now detectable in pleomorphic tumor cells. Anti-GFAP staining of the first biopsy was repeated using monoclonal and polyclonal antibodies in combination with prolonged tissue pretreatment. Focal GFAP staining of tumor cells was now achieved. We conclude that non-standard GFAP staining protocols may enhance sensitivity and thus lead to detection of a low level of GFAP expression in tumor specimens, in which PXA is considered in the differential diagnosis. This may avoid misleading diagnostic considerations that impact on postoperative patient management. [source] Optometrists' examination and referral practices for patients presenting with flashes and floatersOPHTHALMIC AND PHYSIOLOGICAL OPTICS, Issue 3 2002A. Alwitry Introduction:,Patients experiencing flashes and floaters commonly present to their optometrist. Some of these patients may have significant pathology, yet there is a great deal of variability with regard to examination technique and referral practice. Methods:,A questionnaire survey was undertaken to determine the current management of patients presenting to their optometrist with flashes and floaters. All practising community optometrists within Southern Derbyshire received a questionnaire and 74 (56.9%) completed replies were received. Results:,Optometrists estimated that an average of 14 patients per month per optometrist presented with symptoms of flashes and/or floaters. Mydriasis was utilised routinely for examination in approximately half of the patients. Mean relative confidence was 2.0 at identifying a vitreous haemorrhage and 6.5 for vitreous pigment (complete confidence = 0, complete lack of confidence = 10). Eight percent of responders were unfamiliar with the clinical sign of vitreous pigment, and 17% identifying this sign did not refer all such patients to the hospital services. Conclusions:,Patients presenting to their optometrists with flashes and/or floaters make up a sizeable part of the community optometrist's workload and the management of these patients is highly variable. A large proportion of these patients are examined without mydriasis, even in the presence of various risk factors for retinal detachment. There is a relative lack of confidence amongst optometrists with regards the detection of vitreous pigment and the prognostic implications of this finding. Educational measures such as study days may help the level of understanding and heighten the appreciation of the implications of flashes and floaters and the various clinical signs encountered. [source] Atrial Activation Occurring Immediately after Successful Cardioversion of Atrial FibrillationPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 1 2008ARTURO MARTÍN PEŃATO MOLINA M.D. Background and Objective: Electrical defibrillation is very effective in interrupting atrial fibrillation (AF). However, its mechanism is not completely understood. We report our observations in patients subjected to external electriocardioversion (ECV) of atrial fibrillation and contrast them with recent theories about defibrillation mechanism. Methods: In 13 consecutive patients transthoracic electrical cardioversion for AF was performed during an electrophysiological study (11 monophasic -200,360 J- and 9 biphasic shocks -50,150 J-). About 10,16 electrograms were obtained with multipolar catheters recording right atrium, coronary sinus, and right pulmonary artery. AF was defined by interelectrogram intervals and changing sequences among recordings, indicating complete lack of organization. We evaluated the presence of propagated activations immediately (<300 ms) after successful shocks (,1 discrete electrogram in all recordings). In unsuccessful shocks we evaluated changes in electrogram morphology (discrete/fragmented) and interelectrogram intervals before and after defibrillation. Results: About 16/20 shocks terminated AF. In 6/16 one or two cycles of atrial activation were recorded just after the shock and before AF ended. In 10/16 AF was interrupted immediately after the shock. 4/20 shocks did not interrupt the arrhythmia. After these shocks, transient organization of recorded activity with longer interelectrogram cycle length and disappearance of fragmented activity were transiently observed. Conclusion: Our clinical findings in atrial defibrillation in vivo reproduce experimental data that show myocardial activations early after successful direct current shocks. These observations suggest that successful defibrillation depends not only on the immediate effects of the shock, but also on transient effects on electrophysiological properties of the myocardium, capable of interrupting persistent or reinitiated activations. [source] UV Exposure, Genetic Targets in Melanocytic Tumors and Transgenic Mouse Models,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2005Frank R. de Gruijl ABSTRACT The genetic changes and corruption of kinase activity in melanomas appear to revolve around a central axis: mitogenic signaling along the RAS pathway down to transcription regulation by pRB. Epidemiological studies point to the importance of ultraviolet (UV) radiation in the etiology of melanoma, but where and how UV radiation is targeted to contribute to the oncogenic signaling remains obscure. Animal models of melanoma genesis could serve to clarify this issue, but many of these models are not responsive to UV exposure. Most interesting advances have been made by using transgenic mice that carry genetic defects that are known to be relevant to human melanoma: specifically, dysfunction in the tumor suppressive action of p161NK4a or a receptor tyrosine kinase/RAS pathway, that is constitutively activated in melanocytes. The latter types of mice appear to be most responsive to (neonatal) UV exposure. Whether this is due to a general increase in target cells by melanocytosis and a paucity or complete lack of pigment, or a possible UV-induced response of the promoter,enhancer of the transgene or a genuinely independent and additional genetic alteration caused by UV exposure needs to be established. Importantly, the full effect of UV radiation needs to be ascertained in mice with different pigmentation by varying the wavelengths, UV-B versus UV-A1, and the exposure schedules, i.e. neonatal versus adult and chronic versus intermittent overexposure. Intermittent UV-B overexposure deserves special attention because it most strongly evokes proliferative responses in melanocytes. [source] Determination of physical behaviour of feed pellets in Mediterranean waterAQUACULTURE RESEARCH, Issue 2 2006Paolo Vassallo Abstract Settled uneaten feed causes the most intense impact under sea cages, and settling velocity of the feed pellets represents a key parameter for waste dispersion models. Even if some data about physical properties of feed pellets have been published in the framework of salmonid rearing, there is a complete lack of information related to the Mediterranean Sea, as regards typical values of temperature, salinity and feed composition for Gilthead Sea Bream (Sparus aurata L.) and Sea Bass (Dicentrarchus labrax L.). In this study we try to fill this lack, determining dimensions, water adsorption properties, floating times and settling velocities of a typical growing sequence of pellets for the species mentioned above, under defined laboratory conditions reproducing Mediterranean Sea water. The settling velocity increases with pellet size from 0.087, for the smallest pellet (3 mm), to 0.144 m s,1, for the 5 mm pellet. The biggest extruded pellet (6 mm) falls slower (0.088 m s,1). The floating time before pellet's fall is found to be a critical parameter in determining settling velocity. The latter depends on pellet's size, water temperature and salinity. The examined pellets reach a 42% of weight increase after 10 min of immersion, while no appreciable dimension change is observed. Our results are in part different from previous ones and could play a role in evaluating and modelling Mediterranean aquaculture environmental impact. [source] Caveolin-1 is expressed on multipotent cells of hair follicles and might be involved in their resistance to chemotherapyBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2005S. Selleri Summary Background, Caveolin-1 is the principal protein that composes caveolae, which are vesicular invaginations present on the plasma membrane of different cell types. Caveolae are involved in a variety of cellular functions including regulation of proliferation rate and resistance to chemotherapeutic drugs. Chemotherapy frequently induces alopecia which is reversible most probably due to the low proliferative rate of hair follicle stem cells and due to the expression of proteins which confer resistance. Objectives, Using a specific animal model and immunohistochemistry, we analysed the expression of both caveolin-1 and the cell proliferation marker ,-catenin, at different stages of the hair follicle cycle, both before and after doxorubicin (DXR) -induced alopecia. Methods, Seven-week-old C57BL/6 mice were depilated in order to synchronize hair follicle cycle in the anagen phase. Chemotherapy with DXR 15 mg kg,1 was used to induce alopecia. Control and treated mice were then sacrificed at precise time points and caveolin-1 expression in hairs at different stages of the cycle were analysed by immunohistochemistry. By double immunofluorescence, colocalization of caveolin-1 and cytokeratin-15 was confirmed in the bulge region. The state of proliferation of cells composing hair follicle was assessed by ,-catenin immunohistochemistry. Results, Caveolin-1 was expressed by the cells of the bulge area, the multipotent compartment of the hair follicle, during all phases of growth (anagen), regression (catagen) and resting (telogen). During the anagen phases, nuclear ,-catenin labelling was not observed in bulge cells, but rather in the deeper portion of the follicle. Damaged hair follicles from DXR-treated mice presented bulge cells which still expressed caveolin-1, suggesting that this protein might play a role in their drug resistance. As expected, no ,-catenin nuclear staining was detectable in DXR-treated hair follicles, indicating the complete lack of proliferative processes. The differential localization of caveolin-1 and ,-catenin suggests that the mutually exclusive expression of these proteins is useful for correct hair regrowth, whether during the physiological cycle or after chemotherapy-induced alopecia. Conclusions, Expression of caveolin-1 within the multipotent cell compartment of the hair follicle can explain the resistance of bulge cells to many chemotherapeutics, suggested by the reversibility of chemotherapy-induced alopecia. [source] ADME Investigations of Unnatural Peptides: Distribution of a 14C-Labeled ,,3 -Octaarginine in RatsCHEMISTRY & BIODIVERSITY, Issue 7 2007Markus Weiss Abstract The highly positively charged, cell-penetrating ,,3 -octaarginine has been prepared with a radioactive label by acetylation at the N-terminus with a doubly 14C-labeled acetyl group (14CH314CO). With the radioactive compound, an ADME study (Absorption, Distribution, Metabolism, Excretion) was performed in male rats following an intravenous or oral dose of 1,mg/kg. Sampling was carried out after periods ranging from 5,min to 4,d or 7,d for blood/excretia and quantitative whole-body autoradioluminography (QWBA), respectively. After p.o. dosing, no systemic exposure to peptide-related radioactivity was observed, and the dose was completely excreted in the feces within 24,h suggesting the absence of relevant absorption; less than 3% of the i.v. dose was excreted from the animals within 4,d. Blood levels, after i.v. dosing, dropped within 4,d to less than 2% of Cmax and decreased afterwards only very slowly. No metabolites were observed in the systemic circulation. QWBA Data indicated that the distribution of the acetyl- , -octaarginine-related radioactivity in the organs and tissues shifted over time. Notably, after 7,d, the highest concentration was measured in the lymph nodes, and the largest amount was found in the liver. A comparison with the results of two previous ADME investigations of , -peptides (cf. Table,1) reveals that the distribution of the compounds within the animals is structure-dependent, and that there is a full range from oral availability with rather rapid excretion (of a tetrapeptide) to essentially complete lack of both oral absorption and excretion after i.v. administration (of a highly charged octapeptide). A discussion is presented about the in vivo stability and ,drug-ability' of peptides. In general, , -peptides bearing proteinogenic side chains are compared with peptides consisting entirely of D - , -amino acid residues (the enantiomers of the ,natural' building blocks), and suggestions are made regarding a possible focus of future biomedical investigations with , -peptides. [source] Constitutive deficiency in DNA mismatch repairCLINICAL GENETICS, Issue 6 2007KEA Felton Mutations in the DNA mismatch repair (MMR) genes are associated with the inheritance of hereditary non-polyposis colorectal cancer, also known as Lynch syndrome, a cancer syndrome with an average age at onset of 44. Individuals presenting with colorectal cancer are diagnosed with Lynch I, whereas individuals who present with extra-colonic tumors (such as endometrial, stomach, etc.) are identified as patients with Lynch syndrome II. Recently, 30 families have been reported with inheritance of biallelic mutations in the MMR genes. Here we summarize the phenotype of individuals with inheritance of homozygous or compound heterozygous mutations in the MMR genes that result in a complete lack of protein or greatly compromised protein function. In contrast to individuals with Lynch syndrome I and II, individuals with no MMR function present with childhood onset of hematological and brain malignancies, whereas residual MMR function can also result in gastrointestinal cancers and an age of onset in the second to fourth decade. Individuals with biallelic MMR mutations often present with café-au-lait spots, regardless of the level of MMR function remaining. Thus, the inheritance of two MMR gene mutations is a separate entity from Lynch I or II or the subtypes Turcot and Muir,Torre. [source] Constitutive deficiency in DNA mismatch repair: is it time for Lynch III?CLINICAL GENETICS, Issue 6 2007KEA Felton Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome types I and II, and the related subtypes Turcot and Muir,Torre syndrome, have all been associated with inheritance of germ line mutations in the DNA mismatch repair (MMR) genes. Fifty individuals have recently been identified with an early onset of a different spectrum of cancers associated with inheritance of two MMR mutations , resulting either in a constitutive loss of MMR function, or greatly impaired MMR function. In contrast to Lynch I and II individuals, individuals with inheritance of homozygous or compound heterozygous mutations in the MMR genes that result in a complete lack of protein, present with hematological and brain malignancies in the first decade of life. Biallelic mutations with compromised but residual protein function present with a broader spectrum of cancers (brain, hematological or gastrointestinal) in the second to fourth decades of life. We propose that inheritance of two MMR mutations in an individual and the unique tumor spectrum that occurs with an early onset should be defined separately from Lynch syndrome I and II, or the subtypes Turcot and Muir,Torre. We suggest Lynch III as an appropriate name for identifying individuals with constitutively compromised MMR associated with biallelic mutations. [source] | |||||||||||||||||||