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Selected AbstractsCytoplasmic ,-catenin accumulation is a good prognostic marker in upper and lower gastrointestinal adenocarcinomasHISTOPATHOLOGY, Issue 1 2010Michael G A Norwood Norwood M G A, Bailey N, Nanji M, Gillies R S, Nicholson A, Ubhi S, Darnton J J, Steyn R S, Womack C, Hughes A, Hemingway D, Harrison R, Waters R & Jankowski J A (2010) Histopathology,57, 101,111 Cytoplasmic ,-catenin accumulation is a good prognostic marker in upper and lower gastrointestinal adenocarcinomas Aims:, ,-Catenin is an important molecule in cancer biology. Membranous ,-catenin enhances cellular differentiation and inhibits invasion by its action on E-cadherin. The aim was to ascertain whether the cellular expression of these molecules in colorectal and oesophageal cancer specimens is associated with survival in patients with gastrointestinal cancer. Methods and results:, Tumour samples from 149 patients undergoing resection for colorectal adenocarcinoma and 147 patients undergoing resection for oesophageal adenocarcinoma were retrospectively analysed using immunohistochemical techniques to assess ,-catenin expression. Increasing ,-catenin expression in the cytoplasm was associated with improved survival for colorectal cancer cases on both univariate (P = 0.003) and multivariate (P = 0.01) analysis. In addition, increased expression in the most recent cohort of oesophageal adenocarcinoma patients was associated with improved TNM staging (P = 0.007). Membrane expression was weakly associated with survival in colorectal cancer on univariate analysis (P = 0.09), but not on multivariate analysis (P = 0.21). Complete absence of ,-catenin expression at all three sites was associated with reduced 5-year survival in colorectal cancer. Conclusions:, This is one of the largest prognostic studies of ,-catenin in gastrointestinal adenocarcinoma. It shows that low levels of cytoplasmic ,-catenin expression are associated with reduced survival in patients with colorectal cancer as well as worse TNM staging in oesophageal adenocarcinoma (a recognized surrogate end-point for survival). We believe this is the first time that this has been reported. This finding should be tested prospectively in oncological trials to validate whether the presence of cytoplasmic ,-catenin could be used as a prognostic marker for less aggressive disease. [source] Zebrafish KLF4 is essential for anterior mesendoderm/pre-polster differentiation and hatchingDEVELOPMENTAL DYNAMICS, Issue 4 2005Melissa R. Gardiner Abstract Gene knockout studies of Krüppel-like factors (KLFs) in mice have shown essential roles in organogenesis. A screen for KLF family members in zebrafish identified many KLFs. One of these, zebrafish KLF4 (zKLF4) is the homologue of neptune, a Xenopus laevis KLF. zKLF4 is expressed from approximately 80% epiboly a patch of dorsal/anterior mesendodermal cells called the pre-polster and, subsequently, in the polster and hatching gland. Here we investigate the function of zKLF4 using morpholino-based antisense oligonucleotides. Knockdown of zKLF4 resulted in complete absence of hatching gland formation and subsequent hatching in zebrafish. In addition, there was early knockdown of expression of the pre-polster/anterior mesendoderm markers CatL, cap1, and BMP4. These results indicate zKLF4 is expressed within the pre-polster, an early mesendodermal site, and that it plays a critical role in the differentiation of these cells into hatching gland cells. Developmental Dynamics 234:992,996, 2005. © 2005 Wiley-Liss, Inc. [source] The obligate aerobic actinomycete Streptomyces coelicolor A3(2) survives extended periods of anaerobic stressENVIRONMENTAL MICROBIOLOGY, Issue 12 2007Geertje Van Keulen Summary The actinomycete Streptomyces coelicolor is an obligate aerobe that is found in soil and aqueous habitats. The levels of oxygen in these environments can vary considerably, which raises the question of how these bacteria survive during periods of anaerobiosis. Although S. coelicolor cannot grow in the complete absence of oxygen, we demonstrate here that it is capable of microaerobic growth and maintaining viability through several weeks of strict anaerobiosis. Both resting and germinated spores are able to survive abrupt exposure to anaerobiosis, which contrasts the situation with Mycobacterium species where gradual oxygen depletion is required to establish a latent state in which the bacterium is able to survive extended periods of anaerobiosis. Growth of S. coelicolor resumes immediately upon re-introduction of oxygen. Taken together these findings indicate that survival is not restricted to spores and suggest that the bacterium has evolved a mechanism to maintain viability and a membrane potential in the hyphal state. Furthermore, although we demonstrate that several members of the genus also survive long periods of anaerobic stress, one species, Streptomyces avermitilis, does not have this capacity and might represent a naturally occurring variant that is unable to adopt this survival strategy. [source] Application of toxicity identification evaluation to sediment in a highly contaminated water reservoir in southeastern BrazilENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2006Rosalina P. A. Araújo Abstract Rasgão Reservoir, located close to the Metropolitan region of São Paulo, Brazil, has been analyzed previously, and its sediment was found to be highly toxic, with high levels of metals and polycyclic aromatic hydrocarbons and a complete absence of benthic life. Polychlorinated biphenyls also were present, as was mutagenic activity, detected with the Salmonella/microsome assay. Because of the extremely complex mixture of contaminants in these sediments, a toxicity identification evaluation was performed on the pore water and elutriate using Ceriodaphnia dubia and Vibrio fischeri. Toxicity characterization, identification, and confirmation procedures were performed in one representative sample of the reservoir, and the results indicated that ammonia was the main cause of the toxicity detected with C. dubia in both sediment pore water and elutriate. Chemical analysis corroborated this observation by revealing un-ionized ammonia concentrations as high as 5.14 mg/L in pore water and 2.06 mg/L in elutriate. These high ammonia levels masked possible toxicity caused by other classes of compounds. The toxicity detected with V. fischeri decreased with the time of sample storage and was related to the organic fraction of the pore water and the elutriate, in which compounds such as benzothiazole and nonylphenol were detected. [source] Ultra-rapid opiate detoxification: from clinical applications to basic scienceADDICTION BIOLOGY, Issue 2 2003EMMANUEL STREEL Rapid or ultra-rapid opiate detoxification has become increasingly popular in both private and public addiction centres. These techniques seem to facilitate the transfer of opiate-dependent patients from opiate agonist to opiate antagonist. Despite the probable complex neuropharmacological aspects involved in these procedures, their development over nearly three decades is notable for the almost complete absence of clinically relevant animal studies. This paper discusses the historical background of this occurrence, and reviews the small number of animal studies that have been conducted. Many discussions and arguments about the techniques seem to underscore their true purpose, which is not "simply to detoxify" opiate-addicted patients but to initiate long-term management with naltrexone. For this reason, it may be better to conceptualize these techniques not as "rapid detoxification" but as "rapid antagonist induction". [source] The essential haematopoietic transcription factor Scl is also critical for neuronal developmentEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2006Cara K. Bradley Abstract The basic helix-loop-helix (bHLH) transcription factor Scl displays tissue-restricted expression and is critical for the establishment of the haematopoietic system; loss of Scl results in embryonic death due to absolute anaemia. Scl is also expressed in neurons of the mouse diencephalon, mesencephalon and metencephalon; however, its requirement in those sites remains to be determined. Here we report conditional deletion of Scl in neuronal precursor cells using the Cre/LoxP system. Neuronal-Scl deleted mice died prematurely, were growth retarded and exhibited an altered motor phenotype characterized by hyperactivity and circling. Moreover, ablation of Scl in the nervous system affected brain morphology with abnormal neuronal development in brain regions known to express Scl under normal circumstances; there was an almost complete absence of Scl-null neurons in the hindbrain and partial loss of Scl-null neurons in the thalamus and midbrain from early neurogenesis onwards. Our results demonstrate a crucial role for Scl in the development of Scl-expressing neurons, including ,-aminobutyric acid (GABA)ergic interneurons. Our study represents one of the first demonstrations of functional overlap of a single bHLH protein that regulates neural and haematopoietic cell development. This finding underlines Scl's critical function in cell fate determination of mesodermal as well as neuroectodermal tissues. [source] The Langerhans' cell-like cell lines XS52 and XS106 express mRNA for ciliary neurotrophic factor and neurotrophic factor 4/5EXPERIMENTAL DERMATOLOGY, Issue 9 2004K. Seiffert Neurotrophins are responsible for the survival and outgrowth of nerves within the peripheral and central nervous systems. These factors include brain-derived neurotrophic factor (BDNF), CNTF, NT 3, and NT4/5. We have previously shown that LCs lie in close proximity to nerves and that several neuropeptides regulate LC function, implying that nerves send regulatory signals to LCs. To evaluate the possibility that LC signal nerves by release of neurotrophins, we examined LC expression of neurotrophins by RT-PCR. To eliminate the possibility of contaminating keratinocytes in highly enriched LC preparations, we utilized the LC-like cell lines XS52 (BALB/c derived) and XS106 (A/J derived) for initial experiments. The RNA obtained was digested with DNase to ensure complete absence of genomic DNA. Several independent RT-PCRs revealed expression of bands of the expected size for CTNF and NT4/5, but not for BDNF and NT3 in XS106 and XS52 cells. In contrast, the transformed keratinocyte cell line PAM212 expressed BDNF, as well as CTNF and NT4/5. Preliminary experiments with purified LC confirm the expression of CTNF and NT4/5 and also show the expression of BDNF. However, we cannot be sure that BDNF expression is not due to keratinocyte contamination. We conclude that LCs may regulate nerve cells by the release of neurotrophic factors. [source] Uncoupling of rhythmic hypoglossal from phrenic activity in the ratEXPERIMENTAL PHYSIOLOGY, Issue 6 2004Walter M. St.-John During eupnoea, rhythmic motor activities of the hypoglossal, vagal and phrenic nerves are linked temporally. The inspiratory discharges of the hypoglossal and vagus motor neurones commence before the onset of the phrenic burst. The vagus nerve also discharges in expiration. Upon exposure to hypocapnia or hypothermia, the hypoglossal discharge became uncoupled from that of the phrenic nerve. This uncoupling was evidenced by variable times of onset of hypoglossal discharge before or after the onset of phrenic discharge, extra bursts of hypoglossal activity in neural expiration, or complete absence of any hypoglossal discharge during a respiratory cycle. No such changes were found for vagal discharge, which remained linked to the phrenic bursts. Intracellular recordings in the hypoglossal nucleus revealed that all changes in hypoglossal discharge were due to neuronal depolarization. These results add support to the conclusion that the brainstem control of respiratory-modulated hypoglossal activity differs from control of phrenic and vagal activity. These findings have implications for any studies in which activity of the hypoglossal nerve is used as the sole index of neural inspiration. Indeed, our results establish that hypoglossal discharge alone is an equivocal index of the pattern of overall ventilatory activity and that this is accentuated by hypercapnia and hypothermia. [source] Role of the N- and C-terminal regions of the PufX protein in the structural organization of the photosynthetic core complex of Rhodobacter sphaeroidesFEBS JOURNAL, Issue 7 2002Francesco Francia The core complex of Rhodobacter sphaeroides is formed by the association of the light-harvesting antenna 1 (LH1) and the reaction center (RC). The PufX protein is essential for photosynthetic growth; it is located within the core in a 1 : 1 stoichiometry with the RC. PufX is required for a fast ubiquinol exchange between the QB site of the RC and the Qo site of the cytochrome bc1 complex. In vivo the LH1,PufX,RC complex is assembled in a dimeric form, where PufX is involved as a structural organizer. We have modified the PufX protein at the N and the C-terminus with progressive deletions. The nine mutants obtained have been characterized for their ability for photosynthetic growth, the insertion of PufX in the core LH1,RC complex, the stability of the dimers and the kinetics of flash-induced reduction of cytochrome b561 of the cytochrome bc1 complex. Deletion of 18 residues at the N-terminus destabilizes the dimer in vitro without preventing photosynthetic growth. The dimer (or a stable dimer) does not seem to be a necessary requisite for the photosynthetic phenotype. Partial C-terminal deletions impede the insertion of PufX, while the complete absence of the C-terminus leads to the insertion of a PufX protein composed of only its first 53 residues and does not affect the photosynthetic growth of the bacterium. Overall, the results point to a complex role of the N and C domains in the structural organization of the core complex; the N-terminus is suggested to be responsible mainly for dimerization, while the C-terminus is thought to be involved mainly in PufX assembly. [source] slowmo is required for Drosophila germline proliferationGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 2 2007Simon Reeve Abstract Null mutations in the Drosophila gene, slowmo (slmo), result in reduced mobility and lethality in first-instar larvae. Slowmo encodes a mitochondrial protein of unknown function, as do the two other homologs found in Drosophila. Here, we have studied a hypomorphic P-element allele of slmo demonstrating its effects on germline divisions in both testes and ovaries. Using in situ studies, enhancer-trap activity, and promoter fusions, we have shown that slmo expression in testes is found in the somatic cyst cells (SCC). The hypomorphic allele for Slmo revealed apoptotic loss of germline cells in the larval germline, culminating in a complete absence of the germline in adult flies. In females, a similar degeneration of the germarium is observed, while reporter gene expression is found in both germline and somatic cells. Using a null mutation in female germline clones, we find slmo is dispensable from the germline cells. Our results suggest that Slowmo is not required in germline cells directly, but is required in SCCs responsible for maintaining germline survival in both sexes. genesis 45:66,75, 2007. © 2007 Wiley-Liss, Inc. [source] Floxed allele for conditional inactivation of the GABAB(1) geneGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 3 2004Corinne Haller Abstract GABAB receptors are the G-protein-coupled receptors for the neurotransmitter GABA. GABAB receptors are broadly expressed in the nervous system. Their complete absence in mice causes premature lethality or,when mice are viable,epilepsy, impaired memory, hyperalgesia, hypothermia, and hyperactivity. A spatially and temporally restricted loss of GABAB function would allow addressing how the absence of GABAB receptors leads to these diverse phenotypes. To permit a conditional gene inactivation, we flanked critical exons of the GABAB(1) gene with lox511 sites. GABAB(1)lox511/lox511 mice exhibit normal levels of GABAB(1) protein, are fertile, and do not display any behavioral phenotype. We crossed GABAB(1)lox511/lox511 with Cre-deleter mice to produce mice with an unrestricted GABAB receptor elimination. These GABAB(1),/, mice no longer synthesize GABAB(1) protein and exhibit the expected behavioral abnormalities. The conditional GABAB(1) allele described here is therefore suitable for generating mice with a site- and time-specific loss of GABAB function. genesis 40:125,130, 2004. © 2004 Wiley-Liss, Inc. [source] Cell cycle effects resulting from inhibition of hepatocyte growth factor and its receptor c-Met in regenerating rat livers by RNA interference,HEPATOLOGY, Issue 6 2007Shirish Paranjpe Hepatocyte growth factor (HGF) and its receptor c-Met are involved in liver regeneration. The role of HGF and c-Met in liver regeneration in rat following two-thirds partial hepatectomy (PHx) was investigated using RNA interference to silence HGF and c-Met in separate experiments. A mixture of 2 c-Met-specific short hairpin RNA (ShRNA) sequences, ShM1 and ShM2, and 3 HGF-specific ShRNA, ShH1, ShH3, and ShH4, were complexed with linear polyethylenimine. Rats were injected with the ShRNA/PEI complex 24 hours before and at the time of PHx. A mismatch and a scrambled ShRNA served as negative controls. ShRNA treatment resulted in suppression of c-Met and HGF mRNA and protein compared with that in controls. The regenerative response was assessed by PCNA, mitotic index, and BrdU labeling. Treatment with the ShHGF mixture resulted in moderate suppression of hepatocyte proliferation. Immunohistochemical analysis revealed severe suppression of incorporation of BrdU and complete absence of mitosis in rats treated with ShMet 24 hours after PHx compared with that in controls. Gene array analyses indicated abnormal expression patterns in many cell-cycle- and apoptosis-related genes. The active form of caspase 3 was seen to increase in ShMet-treated rats. The TUNEL assay indicated a slight increase in apoptosis in ShMet-treated rats compared with that in controls. Conclusion: The data indicated that in vivo silencing of c-Met and HGF mRNA by RNA interference in normal rats results in suppression of mRNA and protein, which had a measurable effect on proliferation kinetics associated with liver regeneration. (HEPATOLOGY 2007.) [source] Mutational spectrum of the NF2 gene: a meta-analysis of 12 years of research and diagnostic laboratory findings,,HUMAN MUTATION, Issue 1 2007Iris Ahronowitz Abstract The NF2 tumor suppressor gene on chromosome 22 is a member of the protein 4.1 family of cytoskeletal elements. A number of single- and multiple-tumor phenotypes have been linked to alterations of NF2 since its characterization in 1993. We present a meta-analysis of 967 constitutional and somatic NF2 alterations from 93 published reports, along with 59 additional unpublished events identified in our laboratory and 115 alterations identified in clinical samples submitted to the Massachusetts General Hospital (MGH) Neurogenetics DNA Diagnostic Laboratory. In total, these sources defined 1,070 small genetic changes detected primarily by exon scanning, 42 intragenic changes of one whole exon or larger, and 29 whole gene deletions and gross chromosomal rearrangements. Constitutional single-exon events (N=422) were significantly more likely to be nonsense or splice site changes than somatic events (N=533), which favored frameshift changes (,2 test; P<0.001). Somatic events also differed markedly between tumors of different pathology, most significantly in the tendency of somatic events in meningiomas to lie within the 5, FERM domain of the transcript (Fisher's exact test; P<0.01 in comparison to schwannomas) with a complete absence of mutations in exons 14 and 15. There was no statistically significant difference in mutation type or exon distribution between published constitutional events and those found by the clinical laboratory. Less than 10% of all published and unpublished small alterations are nontruncating (N=63) and these changes are clustered in exons 2 and 3, suggesting that this region may be especially crucial to tumor suppressor activity in the protein. Hum Mutat 28(1), 1,12, 2007. Published 2006 Wiley-Liss, Inc. [source] Deletion hotspot in the argininosuccinate lyase gene: association with topoisomerase II and DNA polymerase , sites ,HUMAN MUTATION, Issue 11 2006John Christodoulou Abstract Molecular analysis of argininosuccinate lyase (ASAL) deficiency has led to the identification of a deletion hotspot in the ASL gene. Six individuals with ASAL deficiency had alleles that led to a complete absence of exon 13 from the ASL mRNA; each had a partial deletion of exon 13 in the genomic DNA. In all six patients, the deletions begin 18 bp upstream of the 3, end of exon 13. In four cases, the deletions were 13 bp in length, and ended within exon 13, whereas in two other patients the deletions were 25 bp and extended into intron 13. The sequence at which these deletions begin overlaps both a putative topoisomerase II recognition site and a DNA polymerase , mutation/frameshift site. Moreover, the topoisomerase II cut site is situated precisely at the beginning of the deletions, which are flanked by small (2- and 3-bp) direct repeats. We note that a similar concurrence of these two putative enzyme sites can be found in a number of other deletion sites in the human genome, most notably the ,F508 deletion in the CFTR gene. These findings suggest that the joint presence of these two enzyme sites represents a DNA sequence context that may favor the occurrence of small deletions. Hum Mutat 27(11), 1065,1071, 2006. © 2006 Wiley-Liss, Inc. [source] Modelling stream flow for use in ecological studies in a large, arid zone river, central AustraliaHYDROLOGICAL PROCESSES, Issue 6 2005Justin F. Costelloe Abstract Australian arid zone ephemeral rivers are typically unregulated and maintain a high level of biodiversity and ecological health. Understanding the ecosystem functions of these rivers requires an understanding of their hydrology. These rivers are typified by highly variable hydrological regimes and a paucity, often a complete absence, of hydrological data to describe these flow regimes. A daily time-step, grid-based, conceptual rainfall,runoff model was developed for the previously uninstrumented Neales River in the arid zone of northern South Australia. Hourly, logged stage data provided a record of stream-flow events in the river system. In conjunction with opportunistic gaugings of stream-flow events, these data were used in the calibration of the model. The poorly constrained spatial variability of rainfall distribution and catchment characteristics (e.g. storage depths) limited the accuracy of the model in replicating the absolute magnitudes and volumes of stream-flow events. In particular, small but ecologically important flow events were poorly modelled. Model performance was improved by the application of catchment-wide processes replicating quick runoff from high intensity rainfall and improving the area inundated versus discharge relationship in the channel sections of the model. Representing areas of high and low soil moisture storage depths in the hillslope areas of the catchment also improved the model performance. The need for some explicit representation of the spatial variability of catchment characteristics (e.g. channel/floodplain, low storage hillslope and high storage hillslope) to effectively model the range of stream-flow events makes the development of relatively complex rainfall,runoff models necessary for multisite ecological studies in large, ungauged arid zone catchments. Grid-based conceptual models provide a good balance between providing the capacity to easily define land types with differing rainfall,runoff responses, flexibility in defining data output points and a parsimonious water-balance,routing model. Copyright © 2004 John Wiley & Sons, Ltd. [source] Predicting the population consequences of human disturbance for Ringed Plovers Charadrius hiaticula: a game theory approachIBIS, Issue 2007DURWYN LILEY Human disturbance and its potential impacts upon bird populations are currently topical and contentious issues for conservationists. Although many studies have revealed a behavioural impact, or even direct effect on breeding success or survival, these cannot usually be extended to predict the impact on population size. Here we present a population model that allows predictions of the effect that changes in human numbers, visiting a 9-km-long section of the coastline, may have upon the size of a Ringed Plover Charadrius hiaticula population. Human disturbance affects Ringed Plovers in our study area through birds avoiding areas of high disturbance and, in addition, through the accidental trampling of a small number of nests by people walking on the beach. Using the level of human disturbance and habitat variables (which define territory quality) it is possible to predict which areas of beach are occupied and therefore the sites available to the population. Breeding success, for a given area of beach, can be predicted from habitat data. Incorporating known, density-independent, adult mortality allows the equilibrium population size to be predicted. This provides a model that predicts population size. This model is then used to predict the population that the site would support with different, hypothetical, levels of disturbance. If nest loss from human activity was prevented, for example by fencing nests, we predict the Plover population size would increase by 8%. A complete absence of human disturbance would cause a population increase of 85%. If the numbers of people were to double, we predict the population would decrease by 23%. [source] Abortive activation precedes functional deletion of CD8+ T cells following encounter with self-antigens expressed by resting B cells in vivoIMMUNOLOGY, Issue 1 2006Joanne M. Fraser Summary InsHA mice express the haemagglutinin (HA) protein from influenza virus A/PR/8 H1N1 (PR8) as a self antigen on pancreatic islet , cells. We have utilized these mice to investigate the ability of resting B cells expressing Kd to induce self-tolerance among naive KdHA-specific clone 4 CD8+ T cells. Adoptive transfer of KdHA-peptide-pulsed resting B cells into clone 4,InsHA recipients resulted in the activation and proliferation of clone 4 CD8+ T cells throughout the peripheral lymphoid tissues. Significantly, proliferation was not associated with the acquisition of T cell effector function; as evidenced by a lack of interferon-, production and the complete absence of any autoimmune pathology even after immunization of recipient mice with PR8. These data demonstrate that resting B cells pulsed with self-epitopes can induce abortive activation of potentially self-reactive naive CD8+ T cells resulting in their functional deletion from the peripheral T-cell repertoire in the absence of any associated autoimmunity. [source] An unusual distribution of the kdr gene among populations of Anopheles gambiae on the island of Bioko, Equatorial GuineaINSECT MOLECULAR BIOLOGY, Issue 6 2005L. J. Reimer Abstract In West Africa, Anopheles gambiae exists in discrete subpopulations known as the M and S molecular forms. Although these forms occur in sympatry, pyrethroid knock-down resistance (kdr) is strongly associated with the S molecular form. On the island of Bioko, Equatorial Guinea we found high frequencies of the kdr mutation in M form individuals (55.8%) and a complete absence of kdr in the S form. We also report the absence of the kdr allele in M and S specimens from the harbour town of Tiko in Cameroon, representing the nearest continental population to Bioko. The kdr allele had previously been reported as absent in populations of An. gambiae on Bioko. Contrary to earlier reports, sequencing of intron-1 of this sodium channel gene revealed no fixed differences between M form resistant and susceptible individuals. The mutation may have recently arisen independently in the M form on Bioko due to recent and intensive pyrethroid application. [source] Semi-coupled air/water immersed boundary approach for curvilinear dynamic overset grids with application to ship hydrodynamicsINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN FLUIDS, Issue 6 2008Juntao Huang Abstract For many problems in ship hydrodynamics, the effects of air flow on the water flow are negligible (the frequently called free surface conditions), but the air flow around the ship is still of interest. A method is presented where the water flow is decoupled from the air solution, but the air flow uses the unsteady water flow as a boundary condition. The authors call this a semi-coupled air/water flow approach. The method can be divided into two steps. At each time step the free surface water flow is computed first with a single-phase method assuming constant pressure and zero stress on the interface. The second step is to compute the air flow assuming the free surface as a moving immersed boundary (IB). The IB method developed for Cartesian grids (Annu. Rev. Fluid Mech. 2005; 37:239,261) is extended to curvilinear grids, where no-slip and continuity conditions are used to enforce velocity and pressure boundary conditions for the air flow. The forcing points close to the IB can be computed and corrected under a sharp interface condition, which makes the computation very stable. The overset implementation is similar to that of the single-phase solver (Comput. Fluids 2007; 36:1415,1433), with the difference that points in water are set as IB points even if they are fringe points. Pressure,velocity coupling through pressure implicit with splitting of operators or projection methods is used for water computations, and a projection method is used for the air. The method on each fluid is a single-phase method, thus avoiding ill-conditioned numerical systems caused by large differences of fluid properties between air and water. The computation is only slightly slower than the single-phase version, with complete absence of spurious velocity oscillations near the free surface, frequently present in fully coupled approaches. Validations are performed for laminar Couette flow over a wavy boundary by comparing with the analytical solution, and for the surface combatant model David Taylor Model Basin (DTMB) 5512 by comparing with Experimental Fluid Dynamics (EFD) and the results of two-phase level set computations. Complex flow computations are demonstrated for the ONR Tumblehome DTMB 5613 with superstructure subject to waves and wind, including 6DOF motions and broaching in SS7 irregular waves and wind. Copyright © 2008 John Wiley & Sons, Ltd. [source] A to G transitions at 260, 386 and 437 in DAZL gene are not associated with spermatogenic failure in Indian populationINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 5 2006K. Thangaraj Summary The autosomal DAZL (Deleted-in- Azoospermic- Like) gene, mapped to the short arm of the human chromosome 3, is the precursor for the Y-chromosomal DAZ cluster, which encodes for putative RNA-binding proteins. Mutations in the DAZL have been reported to be associated with spermatogenic failure in Taiwanese population but not in Caucasians. As there was no study on Indian populations, we have analysed the entire coding sequences of exons 2 and 3 of DAZL in a total of 1010 men from Indian subcontinent, including 660 infertile men with 598 non-obstructive azoospermia, 62 severe oligozoospermia and 350 normozoospermic fertile control men, to investigate whether mutation(s) in the DAZL is associated with male infertility. Interestingly, none of our samples (1010) showed A386G (T54A) mutation, which was found to be associated with spermatogenic failure in Taiwanese population. In contrast, A260G (T12A) mutation was observed in both infertile and normozoospermic fertile control men, without any significant association with infertile groups (,2 = 0.342; p = 0.556). Similarly, we have found a novel A437G (I71V) mutation, which is also present in both infertile and normozoospermic fertile control men without any significant difference (,2 = 0.476; p = 0.490). Our study clearly demonstrates the complete absence of the A386G (T54A) mutation in Indian subcontinent and the other two mutations , A260G (T12A) and A437G (I71V) , observed are polymorpic. Therefore, we conclude that these mutations in the DAZL gene are not associated with male infertility in Indian subcontinent. [source] Heterogeneity in the granulomatous response to mycobacterial infection in patients with defined genetic mutations in the interleukin 12-dependent interferon-gamma production pathwayINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 1 2002D. A. LAMMAS Summary Patients with genetic lesions in the Type-1 cytokine/cytokine receptor pathway exhibit a selective susceptibility to severe infections with poorly pathogenic mycobacteria and non-typhi salmonella spp. These experiments of nature demonstrate that IL-12-dependent IFN, production is critical for granuloma formation and therefore host immunity against such pathogens. The essential role of granuloma formation for protective immunity to these organisms is emphasized by the differing granuloma forming capabilities and resultant clinical sequelae observed in these patients which seems to reflect their ability to produce or respond to IFN, (Fig. 9). At one pole of this spectrum, represented by the complete IFN,R1/2 deficient patients, there is a complete absence of mature granuloma formation, whereas with the less severe mutations (i.e. partial IFN,R1/2, complete IL-12p40 and complete IL-12R,1 deficiency), granuloma formation is very heterogenous with wide variations in composition being observed. This suggests that in the latter individuals, who produce partial but suboptimal IFN, responses, other influences, including pathogen virulence and host genotype may also affect the type and scale of the cellular response elicited. Figure 9. ,Spectrum of genetic susceptibility to intracellular bacteria. At one pole of this spectrum complete IFN,R deficiencies are found; at the other pole are healthy resistant individuals. Partial IFN,R1 deficiencies, and complete IL-12R,1 and IL-12p40 deficiencies can be positioned in between, albeit closer to the former end of the spectrum, with clinical outcome also depending on pathogen virulence and host compensatory immune mechanism(s). Abbreviations: IFN,R , interferon gamma receptor, IL-12R,1 , interleukin 12 receptor-1 (modified from Ottenhoff et al. (1998)). [source] Positive Regulation of Adult Bone Formation by Osteoblast-Specific Transcription Factor Osterix,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2009Wook-Young Baek Abstract Osterix (Osx) is essential for osteoblast differentiation and bone formation, because mice lacking Osx die within 1 h of birth with a complete absence of intramembranous and endochondral bone formation. Perinatal lethality caused by the disruption of the Osx gene prevents studies of the role of Osx in bones that are growing or already formed. Here, the function of Osx was examined in adult bones using the time- and site-specific Cre/loxP system. Osx was inactivated in all osteoblasts by Col1a1-Cre with the activity of Cre recombinase under the control of the 2.3-kb collagen promoter. Even though no bone defects were observed in newborn mice, Osx inactivation with 2.3-kb Col1a1-Cre exhibited osteopenia phenotypes in growing mice. BMD and bone-forming rate were decreased in lumbar vertebra, and the cortical bone of the long bones was thinner and more porous with reduced bone length. The trabecular bones were increased, but they were immature or premature. The expression of early marker genes for osteoblast differentiation such as Runx2, osteopontin, and alkaline phosphatase was markedly increased, but the late marker gene, osteocalcin, was decreased. However, no functional defects were found in osteoclasts. In summary, Osx inactivation in growing bones delayed osteoblast maturation, causing an accumulation of immature osteoblasts and reducing osteoblast function for bone formation, without apparent defects in bone resorption. These findings suggest a significant role of Osx in positively regulating osteoblast differentiation and bone formation in adult bone. [source] Prenatal identification of isolated bilateral radial dysplasiaJOURNAL OF CLINICAL ULTRASOUND, Issue 3 2009Alfredo Mancuso Abstract Radial aplasia or hypoplasia is characterized by complete or partial absence of the radius and/or radial ray structure occurring in 1:30,000 live births. It may be unilateral or bilateral of varying severity, and may be isolated or associated with other anomalies. We report an unusual case of isolated radial aplasia at 20 weeks' gestation with complete absence of the right radius and thumb associated with marked hypoplasia of the left radius. The intrauterine 2- and 3-dimensional findings, postnatal radiographic evaluation, and autopsy results are reported. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2009 [source] Mid-dermal elastolysis preceded by acute neutrophilic dermatosisJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2004Kevan G. Lewis Background:, Mid-dermal elastolysis is a rare idiopathic elastic tissue disorder that is characterized by localized patches of finely wrinkled skin and a ,band-like' loss of elastic tissue in the mid-reticular dermis. Lesions may be preceded by erythema and/or urticaria, and histological examination of inflamed lesional skin may demonstrate lymphohistiocytic dermal infiltration. Case report:, We report a case of mid-dermal elastolysis in a 31-year-old woman who developed multiple erythematous and urticarial plaques on the arms and trunk. Histologic examination of a representative lesion revealed a neutrophilic infiltrate and a normal pattern of elastic tissue. Several months later, the erythema and urticaria was noted to have resolved, leaving soft, pendulous plaques with overlying finely wrinkled skin. A follow-up biopsy at this time showed minimal lymphocytic inflammation but almost complete absence of elastic tissue in the mid-reticular dermis. Conclusions:, To our knowledge, acute neutrophilic dermatosis resulting in mid-dermal elastolysis has not been previously described. This observation lends support to an emerging theory that the pathogenesis of mid-dermal elastolysis may be inflammatory. [source] Expression of stratum corneum chymotryptic enzyme in ichthyoses and squamoproliferative processesJOURNAL OF CUTANEOUS PATHOLOGY, Issue 6 2003Brad Johnson Objective:, Stratum corneum chymotryptic enzyme (SCCE) is a serine protease, which is thought to play a role in the desquamation of skin via the proteolysis of desmosomes in the stratum corneum. The objective of this study was to investigate the expression of SCCE in ichthyoses and squamoproliferative processes, conditions in which the shedding and replacement of epidermal cells is disrupted. Design:, Tissue samples from cases of Netherton's syndrome, congenital ichthyosiform erythroderma, ichthyosis vulgaris, actinic keratosis, squamous cell carcinoma in situ, and invasive squamous cell carcinoma were examined for expression of SCCE using immunohistochemistry. Main outcome measures:, The slides were qualitatively analyzed for the expression of SCCE by a certified dermatopathologist. Results:, In all disease states, we found that the expression of SCCE was absent in areas of parakeratotic stratum corneum of normal thickness. In areas of mixed orthokeratosis and parakeratosis where the stratum corneum was greatly thickened as might correspond clinically to a cutaneous horn, SCCE staining was either absent or focally aggregated without regard to orthokeratosis or parakeratosis. Of note, complete absence of SCCE expression was not observed in any of the cases of ichthyosis examined, nor was there increased expression of SCCE in the atypical cells of the squamoproliferative disorders. Conclusions:, These results suggest that SCCE is abnormally expressed in skin where epidermal cell kinetics are disrupted due to inherited and acquired defects. Further investigation is needed to determine causality between the abnormal expression of SCCE and the altered cell kinetics in these diseases. [source] Anti-aging activity of the Ink4/Arf locusAGING CELL, Issue 2 2009Ander Matheu Summary The proteins encoded by the Ink4/Arf locus, p16Ink4a, p19Arf and p15Ink4b are major tumour suppressors that oppose aberrant mitogenic signals. The expression levels of the locus are progressively increased during aging and genome-wide association studies have linked the locus to a number of aging-associated diseases and frailty in humans. However, direct measurement of the global impact of the Ink4/Arf locus on organismal aging and longevity was lacking. In this work, we have examined the fertility, cancer susceptibility, aging and longevity of mice genetically modified to carry one (Ink4/Arf -tg) or two (Ink4/Arf -tg/tg) intact additional copies of the locus. First, increased gene dosage of Ink4/Arf impairs the production of male germ cells, and in the case of Ink4/Arf -tg/tg mice results in a Sertoli cell-only-like syndrome and a complete absence of sperm. Regarding cancer, there is a lower incidence of aging-associated cancer proportional to the Ink4/Arf gene dosage. Interestingly, increased Ink4/Arf gene dosage resulted in lower scores in aging markers and in extended median longevity. The increased survival was also observed in cancer-free mice indicating that cancer protection and delayed aging are separable activities of the Ink4/Arf locus. In contrast to these results, mice carrying one or two additional copies of the p53 gene (p53 -tg and p53 -tg/tg) had a normal longevity despite their increased cancer protection. We conclude that the Ink4/Arf locus has a global anti-aging effect, probably by favouring quiescence and preventing unnecessary proliferation. [source] Architecture of the nervous system in mystacocarida (Arthropoda, crustacea),An immunohistochemical study and 3D reconstructionJOURNAL OF MORPHOLOGY, Issue 2 2010Georg Brenneis Abstract Mystacocarida is a species-poor group of minute crustaceans with unclear phylogenetic affinities. Previous studies have highlighted the putative "primitiveness" of several mystacocarid features, including the architecture of the nervous system. Recent studies on arthropod neuroarchitecture have provided a wealth of characters valuable for phylogenetic reconstructions. To permit and facilitate comparison with these data, we used immunohistochemical labeling (against acetylated ,-tubulin, serotonin and FMRFamide) on the mystacocarid Derocheilocaris remanei, analyzing it with confocal laser-scanning microscopy and 3D reconstruction. The mystacocarid brain is fairly elongated, exhibiting a complicated stereotypic arrangement of neurite bundles. However, none of the applied markers provided evidence of structured neuropils such as a central body or olfactory glomeruli. A completely fused subesophageal ganglion is not present, all segmental soma clusters of the respective neuromeres still being delimitable. The distinct mandibular commissure comprises neurite bundles from more anterior regions, leading us to propose that it may have fused with an ancestral posterior tritocerebral commissure. The postcephalic ventral nervous system displays a typical ladder-like structure with separated ganglia which bears some resemblance to larval stages in other crustaceans. Ganglia and commissures are also present in the first three limbless "abdominal" segments, which casts doubt on the notion of a clear-cut distinction between thorax and abdomen. An unpaired longitudinal median neurite bundle is present and discussed as a potential tetraconate autapomorphy. Additionally, a paired latero-longitudinal neurite bundle extends along the trunk. It is connected to the intersegmental nerves and most likely fulfils neurohemal functions. We report the complete absence of serotonin-ir neurons in the ventral nervous system, which is a unique condition in arthropods and herein interpreted as a derived character. J. Morphol., 2010. © 2009 Wiley-Liss, Inc. [source] Economic crisis and challenges for the Greek healthcare system: the emergent role of nursing managementJOURNAL OF NURSING MANAGEMENT, Issue 5 2010VENETIA NOTARA MSc notara v., koupidis s.a., vaga e. & grammatikopoulos i.a. (2010) Journal of Nursing Management18, 501,504 Economic crisis and challenges for the Greek healthcare system: the emergent role of nursing management Background, Despite several reform efforts, the Greek health care system still faces problems related to misdistribution of trained health staff and finance between geographical areas. Aim, The objectives of the present study were to describe the current situation of the delivery of the healthcare service in Greece, to explore the basic implications of the economic crisis from a nursing management perspective and to examine future practices opening a debate in policy developments. Key issue, The principal finding of this study was the serious shortage of trained nurses, the imbalances in nursing personnel, an excess of doctors and the complete absence of a Primary Healthcare System in civil areas provided by general doctors. Conclusion, It is important that health care policy makers become aware and seriously consider rearranging the Health Care System to become more effective and efficient for the population (client). Special attention should be paid to strengthening areas such as primary health care, public health and health promotion in the direction of minimizing the demand of hospital services. Implications for nursing management, Any implementation of major health care reforms should consider seriously the role of the nursing management which formulates the substantial link between the health services and the patient. [source] 3 Phylogenetic affinity of the palmelloid green algae, verdigellas and palmophyllum (chlorophyta), based on analyses of nuclear-encoded small subunit rDNA sequencesJOURNAL OF PHYCOLOGY, Issue 2003M. P. Ashworth Palmophyllum, Verdigellas and Palmoclathrus are marine palmelloid green algae with morphologies ranging from closely adherent crusts, peltate discs, to upright branched thalli. Thalli of these taxa are comprised of small spherical cells embedded within a dense mucilaginous matrix. Taxonomic affinities of these palmelloid genera, however, has remained uncertain. Previous studies of Palmophyllum and Verdigellas classified these algae within the Palmellaceae, but the complete absence of data regarding reproduction have blurred ordinal designations. Generally, these algae have been classified as members of the Tetrasporales within the class Chlorophyceae, but the Chlorococcales has also been proposed. Global analyses of eukaryotic nuclear-encoded small subunit rDNA sequences based on parsimony (MP), neighbor joining (NJ) and likelihood (ML) methods confirm the placement of Palmophyllum and Verdigellas as a monophyletic group within the Chlorophyta, but class and ordinal affinities were not clearly resolved. ML suggested that Verdigellas and Palmophyllum are members of a clade with coccoid prasinophyte algae at the base of the Chlorophyta, while NJ and ML suggested that the palmelloid genera formed a basal lineage of the Viridiplantae. A consistent feature of all analyses, however, is that Verdigellas and Palmophyllum did not group with the chlorophycean orders, Tetrasporales or Chlorococcales. Results will be discussed in the context of taxonomy, character evolution, and implications for green plant evolution. (Supported in part by NSF grants DEB-0128952 to MWF, DEB-0129030 to MAB, and DEB-0128977 to FWZ) [source] ROSS SYNDROME: CLINICAL AND LABORATORY EVALUATION OF TWO CASESJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2000G. De Joanna We describe two males, aged 41 and 55, come to our observation complaining of heat intolerance, abnormal increase in body temperature with minimal exercising, reduced sweating and, generalized fatigability; one of them had distal paresthesias. Neurologic evaluation showed bilateral Adie's tonic pupil and an absence of deep-tendon jerks. A diagnosis of Ross' Syndrome was advanced. Autonomic tests, nerve conduction study, H-reflex, computerized termoregulatory and pain thresholds, laser CO2 cortical evoked potentials, and skin biopsy were performed. One of them performed a histamine test and hand photopletismography resulted positive for sympathetic impairment, and pilocarpine pupil test that showed a parasympathetic denervation hypersensitivity. The following tests gave the same results in both patients: parasympathetic and most sympathetic tests were normal. Sympathetic skin response was absent and Minor test showed an almost complete absence of sweating. Sweating was possible only in two or three small areas. Positive pilocarpine test suggested a postganglionic involvement of sympathetic nervous system. Sensitive and motor nerve conduction velocities were normal, while H-reflex was not detectable. Termoregulatory and pain thresholds were abnormal. Laser CO2 cortical evoked potentials showed the absence of C fibre potentials, whereas A-, fibres response was abnormal in one of them. Hairy skin biopsy showed a definite reduction of sweat glands and of small vessel innervation; glabrous skin biopsy performed in one of them showed a reduced number of Meissner corpuscles. These findings suggest that in Ross' Syndrome the degenerative process can involve, besides the autonomic fibres, myelinated somatosensory fibres also. [source] | ||||||||||||||||||||||