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81.
82.
Each microspore of the onion Allium fistulosum (n=8) has 8 chromosomes. It is shown that in the microspore the 8 centromeres aggregate to form 2 or 3 centromeric structures. Subsequently, at early mitotic prophase, these aggregates are resolved into 8 separate centromeres and each becomes structurally double. After mitosis the pollen grain contains 2 nuclei, each with 8 separate and distinct centromeres, clustered at the nuclear envelope. As interphase progresses the centromeres of the vegetative nucleus are no longer at the nuclear envelope and they aggregate into 3 or 4 centromeric masses. In the generative nucleus there is less movement. The interphase centromere movements occur in the absence of microtubules. The centromeres range in size from about 0.10 to 0.17 m3 with an average of 0.14 m3 per centromere. 相似文献
83.
Carr PA Wang HH Sterling B Isaacs FJ Lajoie MJ Xu G Church GM Jacobson JM 《Nucleic acids research》2012,40(17):e132
Genome-scale engineering of living organisms requires precise and economical methods to efficiently modify many loci within chromosomes. One such example is the directed integration of chemically synthesized single-stranded deoxyribonucleic acid (oligonucleotides) into the chromosome of Escherichia coli during replication. Herein, we present a general co-selection strategy in multiplex genome engineering that yields highly modified cells. We demonstrate that disparate sites throughout the genome can be easily modified simultaneously by leveraging selectable markers within 500 kb of the target sites. We apply this technique to the modification of 80 sites in the E. coli genome. 相似文献
84.
Elshorbagy AK Church C Valdivia-Garcia M Smith AD Refsum H Cox R 《The Journal of nutritional biochemistry》2012,23(4):332-340
Plasma total cysteine (tCys) is strongly and independently associated with obesity in large human cohorts, but whether the association is causal is unknown. Dietary cyst(e)ine increases weight gain in some rodent models. We investigated the body composition, metabolic rate and metabolic phenotype of mature C3H/HeH mice assigned to low-cystine (LC) or high-cystine (HC) diets for 12 weeks.Compared to LC mice, HC mice gained more weight (P=.004 for 12-week weight gain %), with increased fat mass and lean mass, and lowered O2 consumption and CO2 production by calorimetry. The HC mice had 30% increase in intestinal fat/body weight % (P=.003) and ~twofold elevated hepatic triglycerides (P=.046), with increased expression of hepatic lipogenic factors, peroxisome proliferator-activated receptor-γ and sterol regulatory element binding protein-1. Gene expression of both basal and catecholamine-stimulated lipolytic enzymes, adipose triglyceride lipase and hormone-sensitive lipase was inhibited in HC mice adipose tissue. The HC mice also had elevated fasting glucose (7.0 vs. 4.5 mmol/L, P<.001) and a greater area under the curve (P<.001) in intraperitoneal glucose tolerance tests, with enhanced expression of the negative regulator of insulin signaling, protein tyrosine phosphatase-1B, in liver and adipose tissue.Overall, high cystine intake promotes adiposity and an adverse metabolic phenotype in mice, indicating that the positive association of plasma tCys with obesity in humans may be causal. 相似文献
85.
Fang G Haznadar M Wang W Yu H Steinbach M Church TR Oetting WS Van Ness B Kumar V 《PloS one》2012,7(4):e33531
There has been increased interest in discovering combinations of single-nucleotide polymorphisms (SNPs) that are strongly associated with a phenotype even if each SNP has little individual effect. Efficient approaches have been proposed for searching two-locus combinations from genome-wide datasets. However, for high-order combinations, existing methods either adopt a brute-force search which only handles a small number of SNPs (up to few hundreds), or use heuristic search that may miss informative combinations. In addition, existing approaches lack statistical power because of the use of statistics with high degrees-of-freedom and the huge number of hypotheses tested during combinatorial search. Due to these challenges, functional interactions in high-order combinations have not been systematically explored. We leverage discriminative-pattern-mining algorithms from the data-mining community to search for high-order combinations in case-control datasets. The substantially improved efficiency and scalability demonstrated on synthetic and real datasets with several thousands of SNPs allows the study of several important mathematical and statistical properties of SNP combinations with order as high as eleven. We further explore functional interactions in high-order combinations and reveal a general connection between the increase in discriminative power of a combination over its subsets and the functional coherence among the genes comprising the combination, supported by multiple datasets. Finally, we study several significant high-order combinations discovered from a lung-cancer dataset and a kidney-transplant-rejection dataset in detail to provide novel insights on the complex diseases. Interestingly, many of these associations involve combinations of common variations that occur in small fractions of population. Thus, our approach is an alternative methodology for exploring the genetics of rare diseases for which the current focus is on individually rare variations. 相似文献
86.
BM Zamft AH Marblestone K Kording D Schmidt D Martin-Alarcon K Tyo ES Boyden G Church 《PloS one》2012,7(8):e43876
High-throughput recording of signals embedded within inaccessible micro-environments is a technological challenge. The ideal recording device would be a nanoscale machine capable of quantitatively transducing a wide range of variables into a molecular recording medium suitable for long-term storage and facile readout in the form of digital data. We have recently proposed such a device, in which cation concentrations modulate the misincorporation rate of a DNA polymerase (DNAP) on a known template, allowing DNA sequences to encode information about the local cation concentration. In this work we quantify the cation sensitivity of DNAP misincorporation rates, making possible the indirect readout of cation concentration by DNA sequencing. Using multiplexed deep sequencing, we quantify the misincorporation properties of two DNA polymerases - Dpo4 and Klenow exo(-) - obtaining the probability and base selectivity of misincorporation at all positions within the template. We find that Dpo4 acts as a DNA recording device for Mn(2+) with a misincorporation rate gain of ~2%/mM. This modulation of misincorporation rate is selective to the template base: the probability of misincorporation on template T by Dpo4 increases >50-fold over the range tested, while the other template bases are affected less strongly. Furthermore, cation concentrations act as scaling factors for misincorporation: on a given template base, Mn(2+) and Mg(2+) change the overall misincorporation rate but do not alter the relative frequencies of incoming misincorporated nucleotides. Characterization of the ion dependence of DNAP misincorporation serves as the first step towards repurposing it as a molecular recording device. 相似文献
87.
Multiplex automated genome engineering (MAGE) uses short oligonucleotides to scarlessly modify genomes; however, insertions >10 bases are still inefficient but can be improved substantially by selection of highly modified chromosomes. Here we describe 'coselection' MAGE (CoS-MAGE) to optimize biosynthesis of aromatic amino acid derivatives by combinatorially inserting multiple T7 promoters simultaneously into 12 genomic operons. Promoter libraries can be quickly generated to study gain-of-function epistatic interactions in gene networks. 相似文献
88.
89.
Boyle PM Burrill DR Inniss MC Agapakis CM Deardon A Dewerd JG Gedeon MA Quinn JY Paull ML Raman AM Theilmann MR Wang L Winn JC Medvedik O Schellenberg K Haynes KA Viel A Brenner TJ Church GM Shah JV Silver PA 《Journal of biological engineering》2012,6(1):8
ABSTRACT: BACKGROUND: Plant biotechnology can be leveraged to produce food, fuel, medicine, and materials. Standardized methods advocated by the synthetic biology community can accelerate the plant design cycle, ultimately making plant engineering more widely accessible to bioengineers who can contribute diverse creative input to the design process. RESULTS: This paper presents work done largely by undergraduate students participating in the 2010 International Genetically Engineered Machines (iGEM) competition. Described here is a framework for engineering the model plant Arabidopsis thaliana with standardized, BioBrick compatible vectors and parts available through the Registry of Standard Biological Parts (www.partsregistry.org). This system was used to engineer a proof-of-concept plant that exogenously expresses the taste-inverting protein miraculin. CONCLUSIONS: Our work is intended to encourage future iGEM teams and other synthetic biologists to use plants as a genetic chassis. Our workflow simplifies the use of standardized parts in plant systems, allowing the construction and expression of heterologous genes in plants within the timeframe allotted for typical iGEM projects. 相似文献
90.
Gonadectomy not only affects hormonal homeostasis but also alters the turnover of different components of the extracellular matrix in urogenital tissues. Collagen is an important component of the bladder and urethral walls and thus crucial for the mechanical properties of normal lower urinary tract (LUT) functions. This study aimed at investigating the possibility of differences in the proportion of collagen and muscle tissues in the LUT of intact and gonadectomised male and female dogs. Twenty clinically healthy dogs were used including 10 sexually intact dogs (5 males, 5 anoestrus females) and 10 gonadectomised dogs (4 males and 6 females). Four regions of the LUT, i.e. body and neck of the bladder as well as proximal and distal urethra were collected. The tissue sections were stained with Masson's Trichrome. Quantitative evaluation of the blue-stained area for collagen and red-counterstained area for muscle was performed using colour image analysis. The relative proportion of collagen and muscle significantly differed with the gonadal status, the gender and the region. Overall, gonadectomised dogs had a higher (P < 0.001) proportion of collagen and consequently a lower (P < 0.001) proportion of muscle than intact dogs. Regardless of gonadal statuses, females had a higher (P < 0.05) proportion of collagen and a lower (P < 0.05) proportion of muscle tissues than males. Gender differences were found in all four regions of the LUT in intact dogs but only in proximal urethra in gonadectomised dogs where spayed females had a higher (P < 0.05) proportion of collagen and less muscle (P < 0.05). Regional differences were observed in females; a higher proportion of collagen and therefore less muscle were found in the urethra compared with the bladder. Proportional differences in collagen and muscle between intact and gonadectomised animals suggest a relation of different hormonal statuses to structural changes in the canine LUT. Excessive collagen deposits and less muscular volume may impair structural and functional integrity of the LUT which may associate with the development of post-neutering urinary incontinence in the dog. 相似文献