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51.
Clark RM De Biase I Malykhina AP Al-Mahdawi S Pook M Bidichandani SI 《Human genetics》2007,120(5):633-640
Friedreich ataxia (FRDA) is caused by homozygosity for FXN alleles containing an expanded GAA triplet-repeat (GAA-TR) sequence. Patients have progressive neurodegeneration of the dorsal
root ganglia (DRG) and in later stages the cerebellum may be involved. The expanded GAA-TR sequence is unstable in somatic
cells in vivo, and although the mechanism of instability remains unknown, we hypothesized that age-dependent and tissue-specific
somatic instability may be a determinant of the progressive pathology involving DRG and cerebellum. We show that transgenic
mice containing the expanded GAA-TR sequence (190 or 82 triplets) in the context of the human FXN locus show tissue-specific and age-dependent somatic instability that is compatible with this hypothesis. Small pool PCR
analysis, which allows quantitative analysis of repeat instability by assaying individual transgenes in vivo, showed age-dependent
expansions specifically in the cerebellum and DRG. The (GAA)190 allele showed some instability by 2 months, progressed at about 0.3–0.4 triplets per week, resulting in a significant number
of expansions by 12 months. Repeat length was found to determine the age of onset of somatic instability, and the rate and
magnitude of mutation. Given the low level of cerebellar instability seen by others in multiple transgenic mice with expanded
CAG/CTG repeats, our data indicate that somatic instability of the GAA-TR sequence is likely mediated by unique tissue-specific
factors. This mouse model will serve as a useful tool to delineate the mechanism(s) of disease-specific somatic instability
in FRDA. 相似文献
52.
Najmabadi H Motazacker MM Garshasbi M Kahrizi K Tzschach A Chen W Behjati F Hadavi V Nieh SE Abedini SS Vazifehmand R Firouzabadi SG Jamali P Falah M Seifati SM Grüters A Lenzner S Jensen LR Rüschendorf F Kuss AW Ropers HH 《Human genetics》2007,121(1):43-48
Autosomal recessive gene defects are arguably the most important, but least studied genetic causes of severe cognitive dysfunction.
Homozygosity mapping in 78 consanguineous Iranian families with nonsyndromic autosomal recessive mental retardation (NS-ARMR)
has enabled us to determine the chromosomal localization of at least 8 novel gene loci for this condition. Our data suggest
that in the Iranian population NS-ARMR is very heterogeneous, and they argue against the existence of frequent gene defects
that account for more than a few percent of the cases.
Mohammad Mahdi Motazacker and Masoud Garshasbi have contributed equally to this work. 相似文献
53.
Sahar F. Deraz Martin Hedström Eva Nordberg Karlsson Sara Linse Ashraf A. Khalil Bo Mattiasson 《World journal of microbiology & biotechnology》2007,23(7):911-921
Lactobacillus acidophilus DSM 20079 is the producer of a novel bacteriocin termed acidocin D20079. In this paper, a partial sequence of this peptide
is determined, together with data on its secondary structure. A modification of the MRS-growth medium (replacing the detergent
Tween 80 with oleic acid), was shown to improve the production level of the peptide by one order of magnitude, as well as
to stabilize the activity level. Addition of a detergent (Tween 20, less interfering in mass spectrometric analysis), was
however necessary for solubilization of the purified acidocin D20079. Digestion of the peptide followed by de-novo sequencing
of generated fragments, allowed determination of a partial sequence consisting of 39 of the totally estimated 65 residues.
Acidocin D20079 has a high content of glycine residues, hydrophobic residues, and acidic residues. No modified amino acids
were found. Edman degradation, and C-terminal sequencing failed, suggesting that the peptide may be cyclic, and a novel member
of class IIc bacteriocins. Circular dichroism spectroscopy and secondary structure prediction showed random coil conformation
in aqueous solution, but secondary structure was induced in the presence of sodium-dodecyl sulfate. The data could be fitted
assuming 2–13% of the residues to be in α-helix and 23–27% of the residues to be in β-strand conformation. This indicates
that a membrane/membrane-mimicking hydrocarbon–water interface induces an active conformation. 相似文献
54.
Aghamohamadi Elham Asri † Nastaran Odak Aylin Rostami-Nejad Mohammad Chaleshi Vahid Hajinabi Yasaman Eslami Maryam Mohammadian Haftcheshmeh Saeed Gholam-Mostafaei Fahimeh Sadat Asadzadeh-Aghdaei Hamid Masotti Andrea Zali Mohammad Reza 《Molecular biology reports》2022,49(7):6085-6091
Molecular Biology Reports - Celiac disease (CeD) and inflammatory bowel disease (IBD) are accompanied by impaired immune responses. To study the immune regulation of these diseases, we evaluated... 相似文献
55.
56.
Anderson KS Sibani S Wallstrom G Qiu J Mendoza EA Raphael J Hainsworth E Montor WR Wong J Park JG Lokko N Logvinenko T Ramachandran N Godwin AK Marks J Engstrom P Labaer J 《Journal of proteome research》2011,10(1):85-96
Cancer patients spontaneously generate autoantibodies (AAb) to tumor-derived proteins. To detect AAb, we have probed novel high-density custom protein microarrays (NAPPA) expressing 4988 candidate tumor antigens with sera from patients with early stage breast cancer (IBC), and bound IgG was measured. We used a three-phase serial screening approach. First, a prescreen was performed to eliminate uninformative antigens. Sera from stage I-III IBC (n = 53) and healthy women (n = 53) were screened for AAb to all 4988 protein antigens. Antigens were selected if the 95th percentile of signal of cases and controls were significantly different (p < 0.05) and if the number of cases with signals above the 95th percentile of controls was significant (p < 0.05). These 761 antigens were screened using an independent set of IBC sera (n = 51) and sera from women with benign breast disease (BBD) (n = 39). From these, 119 antigens had a partial area under the ROC curve (p < 0.05), with sensitivities ranging from 9-40% at >91% specificity. Twenty-eight of these antigens were confirmed using an independent serum cohort (n = 51 cases/38 controls, p < 0.05). Using all 28 AAb, a classifier was identified with a sensitivity of 80.8% and a specificity of 61.6% (AUC = 0.756). These are potential biomarkers for the early detection of breast cancer. 相似文献
57.
Micropatterning techniques provide direct control over the spatial organization of cells at the sub-mm scale. Regulation of these spatial parameters is important for controlling cell fate and cell function. While micropatterning has proved a powerful technique for understanding the impact of cell organization on cell behaviour, current methods for micropatterning cells require complex, specialized equipment that is not readily accessible in most biological and bioengineering laboratories. In addition, currently available methods require significant protocol optimization to ensure reliable and reproducible patterning. The inaccessibility of current methods has severely limited the widespread use of micropatterning as a tool in both biology and tissue engineering laboratories. Here we present a simple, cheap, and fast method to micropattern mammalian cells into stripes and circular patterns using Parafilm?, a common material found in most biology and bioengineering laboratories. Our method does not require any specialized equipment and does not require significant method optimization to ensure reproducible patterning. Although our method is limited to simple patterns, these geometries are sufficient for addressing a wide range of biological problems. Specifically, we demonstrate i) that using our Parafilm? insert method we can pattern and co-pattern ARPE-19 and MDCK epithelial cells into circular and stripe micropatterns in tissue culture polystyrene (TCPS) wells and on glass slides, ii) that we can contain cells in the desired patterns for more than one month and iii) that upon removal of the Parafilm? insert we can release the cells from the containment pattern and allow cell migration outward from the original pattern. We also demonstrate that we can exploit this confinement release feature to conduct an epithelial cell wound healing assay. This novel micropatterning method provides a reliable and accessible tool with the flexibility to address a wide range of biological and engineering problems that require control over the spatial and temporal organization of cells. 相似文献
58.
59.
Campan M Moffitt M Houshdaran S Shen H Widschwendter M Daxenbichler G Long T Marth C Laird-Offringa IA Press MF Dubeau L Siegmund KD Wu AH Groshen S Chandavarkar U Roman LD Berchuck A Pearce CL Laird PW 《PloS one》2011,6(12):e28141
Background
The identification of sensitive biomarkers for the detection of ovarian cancer is of high clinical relevance for early detection and/or monitoring of disease recurrence. We developed a systematic multi-step biomarker discovery and verification strategy to identify candidate DNA methylation markers for the blood-based detection of ovarian cancer.Methodology/Principal Findings
We used the Illumina Infinium platform to analyze the DNA methylation status of 27,578 CpG sites in 41 ovarian tumors. We employed a marker selection strategy that emphasized sensitivity by requiring consistency of methylation across tumors, while achieving specificity by excluding markers with methylation in control leukocyte or serum DNA. Our verification strategy involved testing the ability of identified markers to monitor disease burden in serially collected serum samples from ovarian cancer patients who had undergone surgical tumor resection compared to CA-125 levels.We identified one marker, IFFO1 promoter methylation (IFFO1-M), that is frequently methylated in ovarian tumors and that is rarely detected in the blood of normal controls. When tested in 127 serially collected sera from ovarian cancer patients, IFFO1-M showed post-resection kinetics significantly correlated with serum CA-125 measurements in six out of 16 patients.Conclusions/Significance
We implemented an effective marker screening and verification strategy, leading to the identification of IFFO1-M as a blood-based candidate marker for sensitive detection of ovarian cancer. Serum levels of IFFO1-M displayed post-resection kinetics consistent with a reflection of disease burden. We anticipate that IFFO1-M and other candidate markers emerging from this marker development pipeline may provide disease detection capabilities that complement existing biomarkers. 相似文献60.
Kayser M Lao O Anslinger K Augustin C Bargel G Edelmann J Elias S Heinrich M Henke J Henke L Hohoff C Illing A Jonkisz A Kuzniar P Lebioda A Lessig R Lewicki S Maciejewska A Monies DM Pawłowski R Poetsch M Schmid D Schmidt U Schneider PM Stradmann-Bellinghausen B Szibor R Wegener R Wozniak M Zoledziewska M Roewer L Dobosz T Ploski R 《Human genetics》2005,117(5):428-443
To test for human population substructure and to investigate human population history we have analysed Y-chromosome diversity using seven microsatellites (Y-STRs) and ten binary markers (Y-SNPs) in samples from eight regionally distributed populations from Poland (n=913) and 11 from Germany (n=1,215). Based on data from both Y-chromosome marker systems, which we found to be highly correlated (r=0.96), and using spatial analysis of the molecular variance (SAMOVA), we revealed statistically significant support for two groups of populations: (1) all Polish populations and (2) all German populations. By means of analysis of the molecular variance (AMOVA) we observed a large and statistically significant proportion of 14% (for Y-SNPs) and 15% (for Y-STRs) of the respective total genetic variation being explained between both countries. The same population differentiation was detected using Monmoniers algorithm, with a resulting genetic border between Poland and Germany that closely resembles the course of the political border between both countries. The observed genetic differentiation was mainly, but not exclusively, due to the frequency distribution of two Y-SNP haplogroups and their associated Y-STR haplotypes: R1a1*, most frequent in Poland, and R1*(xR1a1), most frequent in Germany. We suggest here that the pronounced population differentiation between the two geographically neighbouring countries, Poland and Germany, is the consequence of very recent events in human population history, namely the forced human resettlement of many millions of Germans and Poles during and, especially, shortly after World War II. In addition, our findings have consequences for the forensic application of Y-chromosome markers, strongly supporting the implementation of population substructure into forensic Y chromosome databases, and also for genetic association studies. 相似文献