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51.
Carolina V Morgante Patricia M Guimarães Andressa CQ Martins Ana CG Araújo Soraya CM Leal-Bertioli David J Bertioli Ana CM Brasileiro 《BMC research notes》2011,4(1):1-11
Background
Molecular genetic studies on rare tumour entities, such as bone tumours, often require the use of decalcified, formalin-fixed, paraffin-embedded tissue (dFFPE) samples. Regardless of which decalcification procedure is used, this introduces a vast breakdown of DNA that precludes the possibility of further molecular genetic testing. We set out to establish a robust protocol that would overcome these intrinsic hurdles for bone tumour research.Findings
The goal of our study was to establish a protocol, using a modified DNA isolation procedure and quality controls, to select decalcified samples suitable for array-CGH testing. Archival paraffin blocks were obtained from 9 different pathology departments throughout Europe, using different fixation, embedding and decalcification procedures, in order to preclude a bias for certain lab protocols. Isolated DNA samples were subjected to direct chemical labelling and enzymatic labelling systems and were hybridised on a high resolution oligonucleotide chip containing 44,000 reporter elements. Genomic alterations (gains and losses) were readily detected in most of the samples analysed. For example, both homozygous deletions of 0.6 Mb and high level of amplifications of 0.7 Mb were identified.Conclusions
We established a robust protocol for molecular genetic testing of dFFPE derived DNA, irrespective of fixation, decalcification or sample type used. This approach may greatly facilitate further genetic testing on rare tumour entities where archival decalcified, formalin fixed samples are the only source. 相似文献52.
R Simões WB Feitosa CM Mendes AC Nicacio FRO de Barros 《Biotechnic & histochemistry》2013,88(3):79-83
Sperm chromatin integrity is essential for accurate transmission of male genetic information, and normal sperm chromatin structure is important for fertilization. Protamine is a nuclear protein that plays a key role in sperm DNA integrity, because it is responsible for sperm DNA stability and packing until the paternal genome is delivered into the oocyte during fertilization. Our aim was to investigate protamine deficiency in sperm cells of Bos indicus bulls (Nelore) using chromomycin A3 (CMA3) staining. Frozen semen from 14 bulls were thawed, then fixed in Carnoy's solution. Smears were prepared and analyzed by microscopy. As a positive control of CMA3 staining, sperm from one bull was subjected to deprotamination of nuclei. The percentage of CMA3-positive bovine sperm did not vary among batches. Only two bulls showed a higher percentage of CMA3-positive sperm cells compared to the others. CMA3 is a simple and useful tool for detecting sperm protamine deficiency in bulls. 相似文献
53.
Mahdi Saatchi Mathew C McClure Stephanie D McKay Megan M Rolf JaeWoo Kim Jared E Decker Tasia M Taxis Richard H Chapple Holly R Ramey Sally L Northcutt Stewart Bauck Brent Woodward Jack CM Dekkers Rohan L Fernando Robert D Schnabel Dorian J Garrick Jeremy F Taylor 《遗传、选种与进化》2011,43(1):40
Background
Genomic selection is a recently developed technology that is beginning to revolutionize animal breeding. The objective of this study was to estimate marker effects to derive prediction equations for direct genomic values for 16 routinely recorded traits of American Angus beef cattle and quantify corresponding accuracies of prediction.Methods
Deregressed estimated breeding values were used as observations in a weighted analysis to derive direct genomic values for 3570 sires genotyped using the Illumina BovineSNP50 BeadChip. These bulls were clustered into five groups using K-means clustering on pedigree estimates of additive genetic relationships between animals, with the aim of increasing within-group and decreasing between-group relationships. All five combinations of four groups were used for model training, with cross-validation performed in the group not used in training. Bivariate animal models were used for each trait to estimate the genetic correlation between deregressed estimated breeding values and direct genomic values.Results
Accuracies of direct genomic values ranged from 0.22 to 0.69 for the studied traits, with an average of 0.44. Predictions were more accurate when animals within the validation group were more closely related to animals in the training set. When training and validation sets were formed by random allocation, the accuracies of direct genomic values ranged from 0.38 to 0.85, with an average of 0.65, reflecting the greater relationship between animals in training and validation. The accuracies of direct genomic values obtained from training on older animals and validating in younger animals were intermediate to the accuracies obtained from K-means clustering and random clustering for most traits. The genetic correlation between deregressed estimated breeding values and direct genomic values ranged from 0.15 to 0.80 for the traits studied.Conclusions
These results suggest that genomic estimates of genetic merit can be produced in beef cattle at a young age but the recurrent inclusion of genotyped sires in retraining analyses will be necessary to routinely produce for the industry the direct genomic values with the highest accuracy. 相似文献54.
Caitlyn E Abell Jack CM Dekkers Max F Rothschild John W Mabry Kenneth J Stalder 《遗传、选种与进化》2014,46(1):32
Background
Determining an animal’s genetic merit using genomic information can improve estimated breeding value (EBV) accuracy; however, the magnitude of the accuracy improvement must be large enough to recover the costs associated with implementing genome-enabled selection. One way to reduce costs is to genotype nucleus herd selection candidates using a low-density chip and to use high-density chip genotyping for animals that are used as parents in the nucleus breeding herd. The objective of this study was to develop a tool to estimate the cost structure associated with incorporating genome-enabled selection into multi-level commercial breeding programs.Results
For the purpose of this deterministic study, it was assumed that a commercial pig is created from a terminal line sire and a dam that is a cross between two maternal lines. It was also assumed that all male and female selection candidates from the 1000 sow maternal line nucleus herds were genotyped at low density and all animals used for breeding at high density. With the assumptions used in this analysis, it was estimated that genome-enabled selection costs for a maternal line would be approximately US$0.082 per weaned pig in the commercial production system. A total of US$0.164 per weaned pig is needed to incorporate genome-enabled selection into the two maternal lines. Similarly, for a 600 sow terminal line nucleus herd and genotyping only male selection candidates with the low-density panel, the cost per weaned pig in the commercial herd was estimated to be US$0.044. This means that US$0.21 per weaned pig produced at the commercial level and sired by boars obtained from the nucleus herd breeding program needs to be added to the genetic merit value in order to break even on the additional cost required when genome-enabled selection is used in both maternal lines and the terminal line.Conclusions
By modifying the input values, such as herd size and genotyping strategy, a flexible spreadsheet tool developed from this work can be used to estimate the additional costs associated with genome-enabled selection. This tool will aid breeders in estimating the economic viability of incorporating genome-enabled selection into their specific breeding program. 相似文献55.
Tom?PMM?VluggenEmail author Jolanda?CM?van Haastregt Jeanine?A?Verbunt Elly?JM?Keijsers Jos?MGA?Schols 《BMC neurology》2012,12(1):164
Background
Stroke is one of the major causes of loss of independence, decreased quality of life and mortality among elderly people. About half of the elderly stroke patients discharged after rehabilitation in a nursing home still experience serious impairments in daily functioning one year post stroke, which can lead to difficulties in picking up and managing their social life. The aim of this study is to evaluate the effectiveness and feasibility of a new multidisciplinary transmural rehabilitation programme for older stroke patients.Methods
A two group multicentre randomised controlled trial is used to evaluate the effects of the rehabilitation programme. The programme consists of three care modules: 1) neurorehabilitation treatment for elderly stroke patients; 2) empowerment training for patient and informal caregiver; and 3) stroke education for patient and informal caregiver. The total programme has a duration of between two and six months, depending on the individual problems of the patient and informal caregiver. The control group receives usual care in the nursing home and after discharge.Patients aged 65 years and over are eligible for study participation when they are admitted to a geriatric rehabilitation unit in a nursing home due to a recent stroke and are expected to be able to return to their original home environment after discharge. Data are gathered by face-to-face interviews, self-administered questionnaires, focus groups and registration forms. Primary outcomes for patients are activity level after stroke, functional dependence, perceived quality of life and social participation. Outcomes for informal caregivers are perceived care burden, objective care burden, quality of life and perceived health. Outcome measures of the process evaluation are implementation fidelity, programme deliverance and the opinion of the stroke professionals, patients and informal caregivers about the programme. Outcome measures of the economic evaluation are the healthcare utilisation and associated costs. Data are collected at baseline, and after six and 12 months. The first results of the study will be expected in 2014.Trial registration
International Standard Randomised Controlled Trial Register Number ISRCTN62286281, The Dutch Trial Register NTR241256.
CM Galmarini A Kertesz R Oliva J Porta F C Galmarini 《Cancer immunology, immunotherapy : CII》1998,15(4):282-285
Bone metastasis in the hand is rare. The etiology is quite different from that of metastasis to other bones; bronchogenic
carcinoma is by far the most frequent case. Distal phalanges are mainly involved with irregular osteolysis and cortical destruction.
Differential diagnosis of phalangeal metastasis includes osteomyelitis, rheumatoid arthritis and gout. The prognosis is always
that of metastatic bronchial cancer with an average survival of three months. Treatment may involve distal digital amputation
or antalgic radiotherapy. A case of bronchogenic carcinoma with metastasis to the thumb is presented. The metastasis was located
in the distal phalanx of the left thumb. The primary tumor was located in the lung. Treatment consisted of amputation. The
overall survival was five months. 相似文献
57.
58.
Rens W O'Brien PC Grützner F Clarke O Graphodatskaya D Tsend-Ayush E Trifonov VA Skelton H Wallis MC Johnston S Veyrunes F Graves JA Ferguson-Smith MA 《Genome biology》2007,8(11):R243-21
Background
Sex-determining systems have evolved independently in vertebrates. Placental mammals and marsupials have an XY system, birds have a ZW system. Reptiles and amphibians have different systems, including temperature-dependent sex determination, and XY and ZW systems that differ in origin from birds and placental mammals. Monotremes diverged early in mammalian evolution, just after the mammalian clade diverged from the sauropsid clade. Our previous studies showed that male platypus has five X and five Y chromosomes, no SRY, and DMRT1 on an X chromosome. In order to investigate monotreme sex chromosome evolution, we performed a comparative study of platypus and echidna by chromosome painting and comparative gene mapping.Results
Chromosome painting reveals a meiotic chain of nine sex chromosomes in the male echidna and establishes their order in the chain. Two of those differ from those in the platypus, three of the platypus sex chromosomes differ from those of the echidna and the order of several chromosomes is rearranged. Comparative gene mapping shows that, in addition to bird autosome regions, regions of bird Z chromosomes are homologous to regions in four platypus X chromosomes, that is, X1, X2, X3, X5, and in chromosome Y1.Conclusion
Monotreme sex chromosomes are easiest to explain on the hypothesis that autosomes were added sequentially to the translocation chain, with the final additions after platypus and echidna divergence. Genome sequencing and contig anchoring show no homology yet between platypus and therian Xs; thus, monotremes have a unique XY sex chromosome system that shares some homology with the avian Z. 相似文献59.
Background
Genomic selection is an appealing method to select purebreds for crossbred performance. In the case of crossbred records, single nucleotide polymorphism (SNP) effects can be estimated using an additive model or a breed-specific allele model. In most studies, additive gene action is assumed. However, dominance is the likely genetic basis of heterosis. Advantages of incorporating dominance in genomic selection were investigated in a two-way crossbreeding program for a trait with different magnitudes of dominance. Training was carried out only once in the simulation.Results
When the dominance variance and heterosis were large and overdominance was present, a dominance model including both additive and dominance SNP effects gave substantially greater cumulative response to selection than the additive model. Extra response was the result of an increase in heterosis but at a cost of reduced purebred performance. When the dominance variance and heterosis were realistic but with overdominance, the advantage of the dominance model decreased but was still significant. When overdominance was absent, the dominance model was slightly favored over the additive model, but the difference in response between the models increased as the number of quantitative trait loci increased. This reveals the importance of exploiting dominance even in the absence of overdominance. When there was no dominance, response to selection for the dominance model was as high as for the additive model, indicating robustness of the dominance model. The breed-specific allele model was inferior to the dominance model in all cases and to the additive model except when the dominance variance and heterosis were large and with overdominance. However, the advantage of the dominance model over the breed-specific allele model may decrease as differences in linkage disequilibrium between the breeds increase. Retraining is expected to reduce the advantage of the dominance model over the alternatives, because in general, the advantage becomes important only after five or six generations post-training.Conclusion
Under dominance and without retraining, genomic selection based on the dominance model is superior to the additive model and the breed-specific allele model to maximize crossbred performance through purebred selection. 相似文献60.
Ashley L. Marcinkiewicz Alan P. Dupuis Maxime Zamba‐Campero Nancy Nowak Peter Kraiczy Sanjay Ram Laura D. Kramer Yi‐Pin Lin 《Cellular microbiology》2019,21(2)
Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common vector‐borne disease in the United States and Europe. The spirochetes are transmitted from mammalian and avian reservoir hosts to humans via ticks. Following tick bites, spirochetes colonize the host skin and then disseminate haematogenously to various organs, a process that requires this pathogen to evade host complement, an innate immune defence system. CspZ, a spirochete surface protein, facilitates resistance to complement‐mediated killing in vitro by binding to the complement regulator, factor H (FH). Low expression levels of CspZ in spirochetes cultivated in vitro or during initiation of infection in vivo have been a major hurdle in delineating the role of this protein in pathogenesis. Here, we show that treatment of B. burgdorferi with human blood induces CspZ production and enhances resistance to complement. By contrast, a cspZ‐deficient mutant and a strain that expressed an FH‐nonbinding CspZ variant were impaired in their ability to cause bacteraemia and colonize tissues of mice or quail; virulence of these mutants was however restored in complement C3‐deficient mice. These novel findings suggest that FH binding to CspZ facilitates B. burgdorferi complement evasion in vivo and promotes systemic infection in vertebrate hosts. 相似文献