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Severe Reduction (severe + reduction)
Selected AbstractsThresholds of economic damage by clover seed weevil (Apion fulvipes Geoff.) and lesser clover leaf weevil (Hypera nigrirostris Fab.) on white clover (Trifolium repens L.) seed cropsGRASS & FORAGE SCIENCE, Issue 4 2008L. M. Hansen Abstract Severe reductions in the seed yield of white clover can occur because of feeding by the white clover seed weevil Apion fulvipes and the lesser clover leaf weevil Hypera nigrirostris which together can reduce the seed yield by more than 0·50. From 2002 to 2006 five field experiments were carried out to investigate the relationship between the density of these two weevil species and seed yield of white clover. Damage caused by the weevils was calculated as the difference in the number of weevils and the difference in seed yield between the average of insecticide-treated and untreated plots. Loss of seed yield was expressed as a proportion of the seed yield in insecticide-treated plots, which allowed for a comparison between years as yields in insecticide-treated plots varied. A multiple regression approach was chosen in which proportional loss in seed yield was the response variable and the weevils A. fulvipes and H. nigrirostris were the independent variables. Data obtained from the experiments were used to construct the following threshold model of economic damage: [source] Homozygous type 2N R854W von Willebrand factor is poorly secreted and causes a severe von Willebrand disease phenotypeJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 9 2010G. CASTAMAN Summary.,Background:,von Willebrand disease (VWD) type Normandy (VWD 2N) is caused by mutations at the factor (F)VIII-binding site of von Willebrand factor (VWF), located in the D,and D3 domains on the N-terminus of mature VWF. The R854Q mutation is the most frequent cause of this phenotype. Objectives:,We report the characterization of a homozygous VWD 2N mutation, R854W, detected in a patient with a severe VWD phenotype. Methods:,The plasma VWF phenotype was studied, transient expression of recombinant mutant full-length VWF in 293 EBNA cells was performed, and the results were compared with those obtained with wild-type (WT) VWF. Furthermore, expression was also examined in HEK293 cells, which form Weibel,Palade body-like granules when transfected with WT VWF. Results:,The multimer analysis of plasma VWF showed the lack of the typical triplet structure, with the presence of the central band only, and a relative decrease in the high molecular mass multimers. Homozygous expression of recombinant R854W VWF resulted in normal amounts of cellular VWF, but with a severe reduction in secretion into the medium. Severe reductions in FVIII binding to R854W VWF, glycoprotein Ib binding activity and collagen binding of secreted W854 VWF was observed, and reproduced the phenotypic parameters of plasma VWF. In HEK293 cells, homozygous R854W VWF failed to form Weibel,Palade body-like granules. Conclusions:,Our results demonstrate that a homozygous R854W mutation in the D, domain of VWF induces impaired secretion and activity of the protein, thereby explaining the severe phenotype of the patient. [source] Physiological functions of glucose-inhibited neuronesACTA PHYSIOLOGICA, Issue 1 2009D. Burdakov Abstract Glucose-inhibited neurones are an integral part of neurocircuits regulating cognitive arousal, body weight and vital adaptive behaviours. Their firing is directly suppressed by extracellular glucose through poorly understood signalling cascades culminating in opening of post-synaptic K+ or possibly Cl, channels. In mammalian brains, two groups of glucose-inhibited neurones are best understood at present: neurones of the hypothalamic arcuate nucleus (ARC) that express peptide transmitters NPY and agouti-related peptide (AgRP) and neurones of the lateral hypothalamus (LH) that express peptide transmitters orexins/hypocretins. The activity of ARC NPY/AgRP neurones promotes food intake and suppresses energy expenditure, and their destruction causes a severe reduction in food intake and body weight. The physiological actions of ARC NPY/AgRP cells are mediated by projections to numerous hypothalamic areas, as well as extrahypothalamic sites such as the thalamus and ventral tegmental area. Orexin/hypocretin neurones of the LH are critical for normal wakefulness, energy expenditure and reward-seeking, and their destruction causes narcolepsy. Orexin actions are mediated by highly widespread central projections to virtually all brain areas except the cerebellum, including monosynaptic innervation of the cerebral cortex and autonomic pre-ganglionic neurones. There, orexins act on two specific G-protein-coupled receptors generally linked to neuronal excitation. In addition to sensing physiological changes in sugar levels, the firing of both NPY/AgRP and orexin neurones is inhibited by the ,satiety' hormone leptin and stimulated by the ,hunger' hormone ghrelin. Glucose-inhibited neurones are thus well placed to coordinate diverse brain states and behaviours based on energy levels. [source] Dan is required for normal morphogenesis and patterning in the developing chick inner earDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 1 2007Takahiro Yamanishi During vertebrate inner ear development, compartmentalization of the auditory and vestibular apparatuses along two axes depends on the patterning of transcription factors expressed in a region-specific manner. Although most of the patterning is regulated by extrinsic signals, it is not known how Nkx5.1 and Msx1 are patterned. We focus on Dan, the founding member of the Cerberus/Dan gene family that encodes BMP antagonists, and describe its function in morphogenesis and patterning. First, we confirmed that Dan is expressed in the dorso-medial region of the otic vesicle that corresponds to the presumptive endolymphatic duct and sac (ed/es). Second, we used siRNA knockdown to demonstrate that depletion of Dan induced both a severe reduction in the size of the ed/es and moderate deformities of the semicircular canals and cochlear duct. Depletion of Dan also caused suppression of Nkx5.1 in the dorso-lateral region, suppression of Msx1 in the dorso-medial region, and ectopic induction of Nkx5.1 and Msx1 in the ventro-medial region. Most of these phenotypes also appeared following misexpression of the constitutively active form of BMP receptor type Ib. Thus, Dan is required for the normal morphogenesis of the inner ear and, by inhibiting BMP signaling, for the patterning of the transcription factors Nkx5.1 and Msx1. [source] Impaired B-1 and B-2 B,cell development and atypical splenic B,cell structures in IL-7 receptor-deficient miceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2004Lena Erlandsson Abstract The cytokine IL-7 and its receptor are essential for normal B and T,lymphopoiesis. We have analyzed the role of this receptor in B,cell development throughout ontogeny in IL-7 receptor,,-deficient mice. We demonstrate that the IL-7 receptor becomes progressively more important with age. B,lymphopoiesis takes place, albeit at reduced levels, in fetal liver and bone marrow of young mice, but is arrested in adults. The outcome is a severe reduction, from an early age, in peripheral B,cells including follicular, marginal zone and B-1 B,cells as well as perturbed splenic B,cell structures, which are restored after adoptive transfer of normal spleen cells. We conclude that in the absence of the IL-7 receptor, the residual B,lymphopoiesis occurring early in ontogeny must be facilitated by another component, whereas the IL-7 receptor is the key factor in adults. The impairment of marginal zone and B-1 B,cells in IL-7 receptor- but not IL-7-deficient mice suggests non-redundant functions for the IL-7 receptor ligands, IL-7 and thymic stromal lymphopoietin. [source] Utp25p, a nucleolar Saccharomyces cerevisiae protein, interacts with U3 snoRNP subunits and affects processing of the 35S pre-rRNAFEBS JOURNAL, Issue 13 2010Mauricio B. Goldfeder In eukaryotes, pre-rRNA processing depends on a large number of nonribosomal trans -acting factors that form intriguingly organized complexes. Two intermediate complexes, pre-40S and pre-60S, are formed at the early stages of 35S pre-rRNA processing and give rise to the mature ribosome subunits. Each of these complexes contains specific pre-rRNAs, some ribosomal proteins and processing factors. The novel yeast protein Utp25p has previously been identified in the nucleolus, an indication that this protein could be involved in ribosome biogenesis. Here we show that Utp25p interacts with the SSU processome proteins Sas10p and Mpp10p, and affects 18S rRNA maturation. Depletion of Utp25p leads to accumulation of the pre-rRNA 35S and the aberrant rRNA 23S, and to a severe reduction in 40S ribosomal subunit levels. Our results indicate that Utp25p is a novel SSU processome subunit involved in pre-40S maturation. Structured digital abstract ,,MINT-7889901: SAS10 (uniprotkb:Q12136) physically interacts (MI:0915) with Utp25p (uniprotkb:P40498) by pull down (MI:0096) ,,MINT-7889915: NIP7 (uniprotkb:Q08962) physically interacts (MI:0915) with RRP43 (uniprotkb:P25359) by two hybrid (MI:0018) ,,MINT-7889852: Utp25p (uniprotkb:P40498) physically interacts (MI:0915) with MPP10 (uniprotkb:P47083) by two hybrid (MI:0018) ,,MINT-7890065: NOP1 (uniprotkb:P15646) and Utp25p (uniprotkb:P40498) colocalize (MI:0403) by fluorescence microscopy (MI:0416) ,,MINT-7889865: Utp25p (uniprotkb:P40498) physically interacts (MI:0915) with SAS10 (uniprotkb:Q12136) by two hybrid (MI:0018) [source] Effects of waterfowl and fish on submerged vegetation and macroinvertebratesFRESHWATER BIOLOGY, Issue 11 2002Ola Marklund SUMMARY 1. With the aim to assess the combined and separate effects of waterfowl and fish on submerged vegetation and macroinvertebrates, we performed a replicated selective exclosure study in a shallow, eutrophic lake in southern Sweden. Our results are presented together with a literature review of the effects of fish and waterfowl on macroinvertebrates and submerged vegetation. 2. Based on our experiment and on published data, we conclude that waterfowl normally will reduce submerged vegetation only at high waterfowl densities, at very low vegetation densities, or in the colonisation phase of the vegetation. 3. Further, we conclude that in shallow temperate eutrophic lakes, a naturally occurring mixed fish assemblage rarely reduces submerged vegetation. Unless the vegetation is very sparse, the risk of severe reduction of submerged vegetation as a result of waterfowl or fish grazing, should thereby be low. 4. Even relatively low densities of fish seem to reduce macroinvertebrate biomass, while a mixed waterfowl assemblage rarely has a significant effect on macroinvertebrate biomass. [source] Resprouting of the Mediterranean-type shrub Erica australis with modified lignotuber carbohydrate contentJOURNAL OF ECOLOGY, Issue 3 2003Alberto Cruz Summary 1The vigour of plant resprouting after fire may be driven by the amount of stored non-structural carbohydrates (NC). However, the extent to which NC reserves limit this response in woody plants has not been established. 2This study analyses the effects of modifying NC concentrations in the lignotuberous Mediterranean-type shrub Erica australis, on resprouting after experimental burning. A factorial experiment with two treatments (shade and burn) was carried out, with three levels per treatment. Plants were shaded (exposure to 100%, 50% or 20% of incident radiation for 1 year), following which they were clipped (control, no fire), or clipped and burned at one of two levels of severity. After this, they were allowed to resprout and grow for 2 years. 3Shading modified NC concentrations in the lignotuber, but not in the roots. Two years after burning, plants subjected to the greatest shading, which reduced their NC concentrations to 44% (sum of NC) or 19% (starch) of that of control plants, had suffered higher mortality after resprouting, had a significantly lower number of resprouts, of shorter length, and had produced lower biomass per plant than less shaded or unshaded plants. However, plants subjected to intermediate shade, which suffered a reduction in NC concentrations to 70% of that of control plants, did not differ in resprouting response from control plants. 4Burning caused more direct mortality, and a severe reduction in both number or biomass of resprouts, than just clipping. There were no significant shade × burning interaction effects. 5While reductions in NC may limit resprouting, such limitation may only occur when NC is reduced to much lower concentrations than caused by commonly experienced conditions. The role of NC reserves in limiting resprouting of lignotuberous, woody plants such as E. australis might therefore not be as important as is commonly assumed. [source] Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studiesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2006K.H. Alzoubi Abstract Nicotine alleviates cognitive impairment associated with a variety of health conditions. We examined the effect of chronic nicotine treatment on adult-onset hypothyroidism-induced impairment of learning and memory in rats. Hypothyroidism was induced by surgical removal of thyroid glands (thyroidectomy). One month later, chronic nicotine treatment (1 mg/kg sc, twice/day) was instituted for 4,6 weeks. Test of hippocampus-dependent spatial learning and memory in the radial arm water maze showed that hypothyroidism impaired learning as well as short-term and long-term memory retention. Chronic nicotine treatment reversed the hypothyroidism-induced learning and memory impairment. In normal rats, chronic nicotine treatment had no effect on learning and memory. Extracellular recordings from the CA1 region of anesthetized hypothyroid rats showed severe reduction of both early-phase and late-phase long-term potentiation (LTP) magnitude, which was reversed in nicotine-treated hypothyroid rats. These results show that chronic nicotine treatment prevents hypothyroidism-induced impairment of spatial cognition and LTP. © 2006 Wiley-Liss, Inc. [source] Homozygous type 2N R854W von Willebrand factor is poorly secreted and causes a severe von Willebrand disease phenotypeJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 9 2010G. CASTAMAN Summary.,Background:,von Willebrand disease (VWD) type Normandy (VWD 2N) is caused by mutations at the factor (F)VIII-binding site of von Willebrand factor (VWF), located in the D,and D3 domains on the N-terminus of mature VWF. The R854Q mutation is the most frequent cause of this phenotype. Objectives:,We report the characterization of a homozygous VWD 2N mutation, R854W, detected in a patient with a severe VWD phenotype. Methods:,The plasma VWF phenotype was studied, transient expression of recombinant mutant full-length VWF in 293 EBNA cells was performed, and the results were compared with those obtained with wild-type (WT) VWF. Furthermore, expression was also examined in HEK293 cells, which form Weibel,Palade body-like granules when transfected with WT VWF. Results:,The multimer analysis of plasma VWF showed the lack of the typical triplet structure, with the presence of the central band only, and a relative decrease in the high molecular mass multimers. Homozygous expression of recombinant R854W VWF resulted in normal amounts of cellular VWF, but with a severe reduction in secretion into the medium. Severe reductions in FVIII binding to R854W VWF, glycoprotein Ib binding activity and collagen binding of secreted W854 VWF was observed, and reproduced the phenotypic parameters of plasma VWF. In HEK293 cells, homozygous R854W VWF failed to form Weibel,Palade body-like granules. Conclusions:,Our results demonstrate that a homozygous R854W mutation in the D, domain of VWF induces impaired secretion and activity of the protein, thereby explaining the severe phenotype of the patient. [source] Population genetics of Galápagos land iguana (genus Conolophus) remnant populationsMOLECULAR ECOLOGY, Issue 23 2008ATHANASIA C. TZIKA Abstract The Galápagos land iguanas (genus Conolophus) have faced significant anthropogenic disturbances since the 17th century, leading to severe reduction of some populations and the extinction of others. Conservation activities, including the repatriation of captive-bred animals to depleted areas, have been ongoing since the late 1970s, but genetic information has not been extensively incorporated. Here we use nine species-specific microsatellite loci of 703 land iguanas from the six islands where the species occur today to characterize the genetic diversity within, and the levels of genetic differentiation among, current populations as well as test previous hypotheses about accidental translocations associated with early conservation efforts. Our analyses indicate that (i) five populations of iguanas represent distinct conservation units (one of them being the recently discovered rosada form) and could warrant species status, (ii) some individuals from North Seymour previously assumed to be from the natural Baltra population appear related to both Isabela and Santa Cruz populations, and (iii) the five different management units exhibit considerably different levels of intrapopulation genetic diversity, with the Plaza Sur and Santa Fe populations particularly low. Although the initial captive breeding programmes, coupled with intensive efforts to eradicate introduced species, saved several land iguana populations from extinction, our molecular results provide objective data for improving continuing in situ species survival plans and population management for this spectacular and emblematic reptile. [source] Strain-specific regulation of intracellular Wolbachia density in multiply infected insectsMOLECULAR ECOLOGY, Issue 12 2003L. Mouton Abstract Vertically transmitted symbionts suffer a severe reduction in numbers when they pass through host generations, resulting in genetic homogeneity or even clonality of their populations. Wolbachia endosymbionts that induce cytoplasmic incompatibility in their hosts depart from this rule, because cytoplasmic incompatibility actively maintains multiple infection within hosts. Hosts and symbionts are thus probably under peculiar selective pressures that must shape the way intracellular bacterial populations are regulated. We studied the density and location of Wolbachia within adult Leptopilina heterotoma, a haplodiploid wasp that is parasitic on Drosophila and that is naturally infected with three Wolbachia strains, but for which we also obtained one simply infected and two doubly infected lines. Comparison of these four lines by quantitative polymerase chain reaction using a real-time detection system showed that total Wolbachia density varies according to the infection status of individuals, while the specific density of each Wolbachia strain remains constant regardless of the presence of other strains. This suggests that Wolbachia strains do not compete with one another within the same host individual, and that a strain-specific regulatory mechanism is operating. We discuss the regulatory mechanisms that are involved, and how this process might have evolved as a response to selective pressures acting on both partners. [source] Dinucleotide microsatellite primers designed for a critically endangered primate, the black lion tamarin (Leontopithecus chrysopygus)MOLECULAR ECOLOGY RESOURCES, Issue 2 2005BEATRIZ M. PEREZ-SWEENEY Abstract Black lion tamarin (BLT) monkeys (Leontopithecus chrysopygus) have suffered a severe reduction in their natural range and are consequently critically endangered. Because allozyme data showed very low levels of variation, it was not clear if these monkeys had much genetic diversity. We designed microsatellite primers for BLTs, and from them we identified nine polymorphic loci, seven of which were tested on golden lion tamarins (GLTs) (Leontopithecus rosalia). All of the seven polymorphic loci and two other monomorphic BLT loci were polymorphic in GLTs. The microsatellite markers identified here are directly applicable to ongoing lion tamarin population and conservation genetics studies. [source] Biological roles of translesion synthesis DNA polymerases in eubacteriaMOLECULAR MICROBIOLOGY, Issue 3 2010Dan I. Andersson Summary Biological systems are strongly selected to maintain the integrity of their genomes by prevention and repair of external and internal DNA damages. However, some types of DNA lesions persist and might block the replication apparatus. The universal existence of specialized translesion synthesis DNA polymerases (TLS polymerases) that can bypass such lesions in DNA implies that replication blockage is a general biological problem. We suggest that the primary function for which translesion synthesis polymerases are selected is to rescue cells from replication arrest at lesions in DNA, a situation that, if not amended, is likely to cause an immediate and severe reduction in cell fitness and survival. We will argue that the mutagenesis observed during translesion synthesis is an unavoidable secondary consequence of this primary function and not, as has been suggested, an evolved mechanism to increase mutation rates in response to various stresses. Finally, we will discuss recent data on additional roles for translesion synthesis polymerases in the formation of spontaneous deletions and in transcription-coupled TLS, where the coupling of transcription to TLS is proposed to allow the rescue of the transcription machinery arrested at DNA lesions. [source] Loss of surface EWI-2 on CD9 null oocytesMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 7 2009Zhi-Yong He CD9, a member of the tetraspanin family, associates with a variety of other proteins to form the tetraspanin web. CD9 forms direct and relatively stable associations with the immunoglobulin superfamily proteins EWI-2 and EWI-F. Deletion of the Cd9 gene results in female infertility since Cd9 null mice produce oocytes that fail to fuse. It is thought that the absence of CD9 causes the inability of the oocytes to fuse. In this study, we report that the expression level of EWI-2 on the Cd9,/, oocyte surface is <10% of the wild-type level. Hence, the severe reduction in EWI-2 activity may be responsible for the loss of fusion ability. An entirely different mutant of CD9, not a deletion but a depalmitoylated construct, does not affect in vivo female fertility suggesting that the palmitate modification of CD9 is not essential for its putative fusion function. Additionally, the level of EWI-2 on the surface of the oocytes from these females was comparable to the EWI-2 level on wild-type oocytes. We also found that soluble, recombinant EWI-2 binds preferentially to acrosome-reacted sperm but the bound EWI-2 does not inhibit sperm,oocyte fusion. Overall, the results indicate that deletion of CD9, which is known to have multiple associations, may have pleiotropic effects on function that will require further dissection. Mol. Reprod. Dev. 76: 629,636, 2009. © 2008 Wiley-Liss, Inc. [source] Increased recombination frequency showing evidence of loss of interference is associated with abnormal testicular histopathologyMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2003Susannah Varmuza Abstract Nondisjunction leading to aneuploid gametes has been linked genetically to both increases and decreases in recombination frequency on the aneuploid chromosome. In the present study, we present physical evidence of increased frequency of recombination nodules as measured by Mut-S-like homologue-1 (MLH1) foci on pachytene chromosomes from sterile male mice homozygous for a mutation in the protein phosphatase 1c, (PP1c,) gene. The pattern of elevated recombination frequency in PP1c, mutant spermatocytes is consistent with a loss of interference. Previous studies demonstrated: (1) spermiogenesis is impaired starting at step 8 with a severe reduction in elongating and condensed spermatids; (2) spermatids and sperm exhibit elevated rates of DNA fragmentation; and (3) haploid gametes exhibit elevated levels of aneuploidy. Morphometric analysis of developing testes revealed that the first wave of meiosis proceeds at a normal rate in mutant testes, a surprising result given that the PP1 inhibitor okadaic acid has been shown to accelerate progression of spermatocytes from pachytene to the first meiotic division (MI). Evidence of abnormal testicular histopathology is apparent at 3 weeks, before the appearance of haploid gametes, eliminating the possibility that the mutant phenotype is caused by the presence of abnormal spermatids, but coincident with the appearance of the first set of mid to late pachytene spermatocytes. These observations lead us to conclude that the PP1c, mutation causes a complex phenotype, including subtle adverse effects on meiosis, possibly mediated by defective signaling between germ cells and Sertoli cells. Mol. Reprod. Dev. 64: 499,506, 2003. © 2003 Wiley-Liss, Inc. [source] Melt strength of calcium carbonate filled polypropylene meltsPOLYMER INTERNATIONAL, Issue 12 2002Nhol Kao Abstract This paper investigates the extensional rheology (through melt strength measurement) of calcium carbonate (CaCO3) filled polypropylene (PP) melts. Different concentrations of CaCO3 filled PP were produced by mixing two master batches of pure PP and 70,wt% CaCO3 filled PP in required proportions in a counter-rotating twin-screw extruder. It was found that the melt strength of the CaCO3,PP melts was independent of CaCO3 concentrations up to 25,vol%. Further increase in CaCO3 concentration led to a severe reduction of melt strength. © 2002 Society of Chemical Industry [source] Strong decrease in lignin content without significant alteration of plant development is induced by simultaneous down-regulation of cinnamoyl CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD) in tobacco plantsTHE PLANT JOURNAL, Issue 3 2001Matthieu Chabannes Summary Different transgenic tobacco lines down-regulated for either one or two enzymes of the monolignol pathway were compared for their lignin content and composition, and developmental patterns. The comparison concerned CCR and CAD down-regulated lines (homozygous or heterozygous for the transgene) and the hybrids resulting from the crossing of transgenic lines individually altered for CCR or CAD activities. Surprisingly, the crosses containing only one allele of each antisense transgene, exhibit a dramatic reduction of lignin content similar to the CCR down-regulated parent but, in contrast to this transgenic line, display a normal phenotype and only slight alterations of the shape of the vessels. Qualitatively the lignin of the double transformant displays characteristics more like the wild type control than either of the other transgenics. In the transgenics with a low lignin content, the transformations induced other biochemical changes involving polysaccharides, phenolic components of the cell wall and also soluble phenolics. These results show that the ectopic expression of a specific transgene may have a different impact depending on the genetic background and suggest that the two transgenes present in the crosses may operate synergistically to reduce the lignin content. In addition, these data confirm that plants with a severe reduction in lignin content may undergo normal development at least in controlled conditions. [source] Tubulitis and Epithelial Cell Alterations in Mouse Kidney Transplant Rejection Are Independent of CD103, Perforin or Granzymes A/BAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2006G. Einecke One of the defining lesions of kidney allograft rejection is epithelial deterioration and invasion by inflammatory cells (tubulitis). We examined epithelial changes and their relationship to effector T cells and to CD103/E-cadherin interactions in mouse kidney allografts. Rejecting allografts showed interstitial mononuclear infiltration from day 5. Loss of epithelial mass, estimated by tubular surface area, and tubulitis were minimal through day 7 and severe by day 21. Tubules in day 21 allografts manifested severe reduction of E-cadherin and Ksp-cadherin by immunostaining with redistribution to the apical membrane, indicating loss of polarity. By flow cytometry T cells isolated from allografts were 25% CD103+. Laser capture microdissection and RT-PCR showed increased CD103 mRNA in the interstitium and tubules. However, allografts in hosts lacking CD103 developed tubulitis, cadherin loss, and epithelial deterioration similar to wild-type hosts. The loss of cadherins and epithelial mass was also independent of perforin and granzymes A and B. Thus rejection is characterized by severe tubular deterioration associated with CD103+ T cells but not mediated by CD103/cadherin interactions or granzyme-perforin cytotoxic mechanisms. We suggest that alloimmune effector T cells mediate epithelial injury by contact-independent mechanisms related to delayed type hypersensitivity, followed by invasion of the altered epithelium to produce tubulitis. [source] Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophyANNALS OF NEUROLOGY, Issue 5 2006Caroline Godfrey BSc Objective Defects in glycosylation of ,-dystroglycan are associated with several forms of muscular dystrophy, often characterized by congenital onset and severe structural brain involvement, collectively known as dystroglycanopathies. Six causative genes have been identified in these disorders including fukutin. Mutations in fukutin cause Fukuyama congenital muscular dystrophy. This is the second most common form of muscular dystrophy in Japan and is invariably associated with mental retardation and structural brain defects. The aim of this study was to determine the genetic defect in two white families with a dystroglycanopathy. Methods The six genes responsible for dystroglycanopathies were studied in three children with a severe reduction of ,-dystroglycan in skeletal muscle. Results We identified pathogenic fukutin mutations in these two families. Affected children had normal intelligence and brain structure and shared a limb girdle muscular dystrophy (LGMD) phenotype, had marked elevation of serum creatine kinase, and were all ambulant with remarkable steroid responsiveness. Interpretation Our data suggest that fukutin mutations occur outside Japan and can be associated with much milder phenotypes than Fukuyama congenital muscular dystrophy. These findings significantly expand the spectrum of phenotypes associated with fukutin mutations to include this novel form of limb girdle muscular dystrophy that we propose to name LGMD2L. Ann Neurol 2006 [source] Decreased lymphatic vessel counts in patients with systemic sclerosis: Association with fingertip ulcersARTHRITIS & RHEUMATISM, Issue 5 2010Alfiya Akhmetshina Objective Systemic sclerosis (SSc) is a connective tissue disease that is characterized by microvascular disease and tissue fibrosis. Progressive loss and irregular architecture of the small blood vessels are well characterized, but the potential involvement of the lymphatic vessel system has not been analyzed directly in SSc. This study was undertaken to assess whether the lymphatic vascular system is affected in SSc, and whether changes to the lymphatic vessels are associated with dystrophic changes and tissue damage in patients with SSc. Methods Lymphatic endothelial cells in skin biopsy samples from patients with SSc and age- and sex-matched healthy volunteers were identified by staining for podoplanin and prox-1, both of which are specifically expressed in lymphatic endothelial cells but not in blood vascular endothelial cells. CD31 was used as a pan,endothelial cell marker. Statistical analyses were performed using Kruskal-Wallis, Mann-Whitney U, and Spearman's rank correlation tests. Results The numbers of podoplanin- and prox-1,positive lymphatic vessels were significantly reduced in patients with SSc as compared with healthy individuals. The number of podoplanin-positive lymphatic precollector vessels was significantly lower in SSc patients with fingertip ulcers than in SSc patients without ulcers. Moreover, the number of lymphatic vessels correlated inversely with the number of fingertip ulcers at the time of biopsy and with the number of fingertip ulcers per year. The inverse correlation between lymphatic precollector vessel counts and fingertip ulcers remained significant after statistical adjustment for the blood vessel count, age, and modified Rodnan skin thickness score. Conclusion These results demonstrate a severe reduction in the number of lymphatic capillaries and lymphatic precollector vessels in patients with SSc. Patients with decreased lymphatic vessel counts may be at particularly high risk of developing fingertip ulcers. [source] Comparative Assessment of Coagulation Changes Induced by Two Different Types of Heart,Lung MachineARTIFICIAL ORGANS, Issue 1 2010Niels Rahe-Meyer Abstract The cardiopulmonary bypass (CPB) used in heart surgery has a deleterious effect on hemostasis. The aim of our study was to assess by means of standard laboratory and point-of-care methods changes induced by CPB in coagulation parameters, particularly in platelet function, and to determine whether these changes differ depending on the type of heart,lung machine (HLM) used: minimal extracorporeal circulation system (MECC) and standard HLM. The study enrolled 88 patients scheduled for coronary artery bypass surgery performed on pump. Forty-four interventions were performed with MECC and 44 with standard HLM. Blood was sampled preoperatively, after 30 min on CPB, after weaning from CPB, and 24 h postoperatively. Coagulation and platelet function were assessed using multiple electrode aggregometry (MEA), rotation thromboelastometry, as well as standard laboratory tests. Rotation thromboelastometry and standard laboratory reflected significantly impaired hemostasis after weaning from CPB but no significant differences between the two groups at different time points. Aggregation decreased significantly in both groups as early as 30 min after the institution of CPB (P < 0.05, Mann,Whitney U -test) and recovered within the first 24 h postoperatively, without reaching the preoperative level. Intraoperatively, aggregometry values reflected a significantly more severe reduction of platelet function in standard HLM group than in the MECC group (P < 0.01, ProcMixed test). Our findings suggest that MEA and thromboelastometry reflect impairment of coagulation in cardiac surgery performed on different types of HLM and that platelet function is less affected by MECC than by standard HLM. [source] Effects of cover reduction on mulgara Dasycercus cristicauda (Marsupialia: Dasyuridae), rodent and invertebrate populations in central Australia: Implications for land managementAUSTRAL ECOLOGY, Issue 6 2003PIP MASTERS Abstract This study investigates the effect of cover reduction on the mulgara, Dasycercus cristicauda, a small marsupial classified as vulnerable to extinction, which occurs in areas of central Australia dominated by hummock grasslands. Loss or degradation of spinifex has been implicated in population declines of this species previously, but the importance of cover in maintaining quality habitat remains speculative. To determine the effect on D. cristicauda of cover reduction, caused by the harvesting of spinifex, we monitored population changes and changes in prey resources (rodents and invertebrates) before and after spinifex harvesting took place at a site near the Ayers Rock Resort, Northern Territory, Australia. Ten plots, each of 8.75 ha, were established and sampled from May 1994 to October 1995. Harvesting took place on five plots in August 1994, which reduced spinifex cover from 46 to 21% and the amount of spinifex >0.25 m high from 42 to 2%. Harvesting did not significantly affect the number of D. cristicauda known to be alive or captured despite other studies indicating that cover is an important habitat attribute. There was also no evidence that cover reduction impacted on the biomass of the invertebrate food resources. However, there was a significant reduction in the number of rodents captured. The lack of a response to cover reduction by D. cristicauda is possibly because the cover of Triodia remained high enough (above 15%) to sustain animals, and harvested areas were relatively small. This study therefore suggests that D. cristicauda can tolerate a moderate local reduction in cover of its preferred habitat. However, it remains possible that other land use practices that cause severe reduction of cover (including clearing for mining or fire prevention, grazing which may result in spinifex reduction through trampling, and fire management) will have more dramatic effects on D. cristicauda. Evaluation of such effects should be a priority for future research. [source] 4125: Phenotypic variability in association with mutation in RDS/peripherinACTA OPHTHALMOLOGICA, Issue 2010GE HOLDER Purpose To report the clinical and electrophysiological findings associated with autosomal dominant maculopathy caused by mutations in Rds/peripherin. Methods Fifty three individuals with autosomal dominant macular dystrophy and a confirmed molecular diagnosis of Rds/peripherin mutation were ascertained between January 2002 and December 2008. International-standard pattern and full-field electroretinograms (PERG; ERG) were performed in 38 cases. Electro-oculograms (EOG) were performed in 25 cases. Results Fourteen different mutations were identified in the Rds/peripherin gene; 4 of which were novel. Twenty four (45%) patients had the common p.Arg172 Trp allele. The mean age at the time of first symptoms and at diagnosis was 35.0+/- 2.4 and 47.1 +/- 1.5 years old [SEM] respectively. Mean LogMAR visual acuity at presentation was 0.5+/- 0.08 [SEM]. Fundus phenotypes included central atrophy (19 cases), pattern dystrophy (10 cases), maculopathy with flecks (5 cases), and adult vitellifom dystrophy (4 cases). Pattern ERG P50 reduction was seen in 75 of 76 eyes; the majority having undetectable or residual responses, including some cases with preserved visual acuity. ERG ranged from normal to severe reduction in both cone and rod driven responses and were not predictable either from the fundus appearance or from the specific mutation in Rds/peripherin; on addition, marked intra-familial variation could be noted. Conclusion Mutations in the Rds/peripherin gene result in a wide variety of fundus and functional phenotypes. The same mutation can result in profoundly different phenotypes, even within family members. [source] Molecular and clinical consequences of novel mutations in the arylsulfatase A geneCLINICAL GENETICS, Issue 1 2009ugowska Metachromatic leukodystrophy (MLD), a severe neurodegenerative metabolic disorder, is caused by deficient activity of arylsulfatase A (ARSA; EC 3.1.6.8), which leads to a progressive demyelinating process in central and peripheral nervous systems. In this study, a DNA sequence analysis was performed on six Polish patients with different types of MLD. Six novel mutations were identified: one nonsense (p.R114X), three missense (p.G122C, p.G293C, p.C493F) and two frameshift mutations (g.445_446dupG and g.2590_2591dupC). Substitutions p.G293C and p.C493F and duplication g.445_446dupG caused a severe reduction of enzyme activity in transient transfection experiments on mammalian cells (less than 1% of wild-type (WT) ARSA activity). Duplication 2590_2591dupC preserved low-residual ARSA activity (10% of WT ARSA). In summary, the novel MLD-causing mutations in the exons 2, 5 and even in 8 of the ARSA gene described here can be classified as severe type 0, leading in homozygosity to the late infantile form MLD. Growth retardation, delayed motor development, gait disturbances, tonic,clonic seizures and non-epileptic muscle spasms were the first onset symptoms in patients with late infantile form of MLD. In individual with juvenile type MLD gait disturbances evidenced the onset of the disease, while in a patient with late juvenile MLD, difficulties at school were displayed. [source] TARPs ,-2 and ,-7 are essential for AMPA receptor expression in the cerebellumEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2010Maya Yamazaki Abstract The ,-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors require auxiliary subunits termed transmembrane AMPA receptor regulatory proteins (TARPs), which promote receptor trafficking to the cell surface and synapses and modulate channel pharmacology and gating. Of six TARPs, ,-2 and ,-7 are the two major TARPs expressed in the cerebellum. In the present study, we pursued their roles in synaptic expression of cerebellar AMPA receptors. In the cerebellar cortex, ,-2 and ,-7 were preferentially localized at various asymmetrical synapses. Using quantitative Western blot and immunofluorescence, we found severe reductions in GluA2 and GluA3 and mild reduction in GluA4 in ,-2-knockout (KO) cerebellum, whereas GluA1 and GluA4 were moderately reduced in ,-7-KO cerebellum. GluA2, GluA3 and GluA4 were further reduced in ,-2/,-7 double-KO (DKO) cerebellum. The large losses of GluA2 and GluA3 in ,-2-KO mice and further reductions in DKO mice were confirmed at all asymmetrical synapses examined with postembedding immunogold. Most notably, the GluA2 level in the postsynaptic density fraction, GluA2 labeling density at parallel fiber,Purkinje cell synapses, and AMPA receptor-mediated currents at climbing fiber,Purkinje cell synapses were all reduced to approximately 10% of the wild-type levels in DKO mice. On the other hand, the reduction in GluA4 in ,-7-KO granular layer reflected its loss at mossy fiber,granule cell synapses, whereas that of GluA1 and GluA4 in ,-7-KO molecular layer was caused, at least partly, by their loss in Bergmann glia. Therefore, ,-2 and ,-7 cooperatively promote synaptic expression of cerebellar AMPA receptors, and the latter also promotes glial expression. [source] Waterlogging tolerance in the tribe Triticeae: the adventitious roots of Critesion marinum have a relatively high porosity and a barrier to radial oxygen lossPLANT CELL & ENVIRONMENT, Issue 6 2001M. P. Mcdonald Abstract Nine species from the tribe Triticeae , three crop, three pasture and three ,wild' wetland species , were evaluated for tolerance to growth in stagnant deoxygenated nutrient solution and also for traits that enhance longitudinal O2 movement within the roots. Critesion marinum (syn. Hordeum marinum) was the only species evaluated that had a strong barrier to radial O2 loss (ROL) in the basal regions of its adventitious roots. Barriers to ROL have previously been documented in roots of several wetland species, although not in any close relatives of dryland crop species. Moreover, the porosity in adventitious roots of C. marinum was relatively high: 14% and 25% in plants grown in aerated and stagnant solutions, respectively. The porosity of C. marinum roots in the aerated solution was 1·8,5·4-fold greater, and in the stagnant solution 1·2,2·8-fold greater, than in the eight other species when grown under the same conditions. These traits presumably contributed to C. marinum having a 1·4,3 times greater adventitious root length than the other species when grown in deoxygenated stagnant nutrient solution or in waterlogged soil. The length of the adventitious roots and ROL profiles of C. marinum grown in waterlogged soil were comparable to those of the extremely waterlogging-tolerant species Echinochloa crus-galli L. (P. Beauv.). The superior tolerance of C. marinum, as compared to Hordeum vulgare (the closest cultivated relative), was confirmed in pots of soil waterlogged for 21 d; H. vulgare suffered severe reductions in shoot and adventitious root dry mass (81% and 67%, respectively), whereas C. marinum shoot mass was only reduced by 38% and adventitious root mass was not affected. [source] |