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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.
The discovery of potent, selective, and orally bioavailable hNK1 antagonists derived from pyrrolidine 总被引:2,自引:0,他引:2
Lin P Chang L Devita RJ Young JR Eid R Tong X Zheng S Ball RG Tsou NN Chicchi GG Kurtz MM Tsao KL Wheeldon A Carlson EJ Eng W Burns HD Hargreaves RJ Mills SG 《Bioorganic & medicinal chemistry letters》2007,17(18):5191-5198
SAR studies on amides, ureas, and vinylogous amides derived from pyrrolidine led to the discovery of several potent hNK(1) antagonists. One particular vinylogous amide (45b) had excellent potency, selectivity, pharmacokinetic profile, and functional activity in vivo. An in vivo rhesus macaque brain receptor occupancy PET study for compound 45b revealed an estimated Occ(90) approximately 300 ng/ml. 相似文献
55.
Paul Eid 《Ethnic and racial studies》2015,38(11):1902-1917
In the past decade, the hijab has increasingly come to be regarded in the West as an unambiguous symbol of female oppression. Such an orientalist framework rests upon a feminist rhetoric using gender equality as a vehicle for the racialization of Muslims. Correlatively, from the 1970s onwards, conservative Islamist movements have converted the hijab into a natural(ized) symbol of cultural resistance to Western imperialism. In this context, what room is left to Muslim women's agency in the production of the social meanings embedded in veil wearing? I explore this issue by presenting the findings of an interview-based research with veiled and non-veiled high school Muslim female teens in Montreal (Quebec). I show that, although these teenagers have much leeway to bypass and subvert the dominant framings of veil wearing, one should not overestimate their capacity to disrupt the dominant gendered religious framework through which this practice is socially construed. 相似文献
56.
57.
Kassab SE Hegazy GH Eid NM Amin KM El-Gendy AA 《Nucleosides, nucleotides & nucleic acids》2011,30(11):991-998
A series of new 9-glycosyl-4,9-dihydropyrano[3,4-b]indole-1(3H)-ones 3 was synthesized in moderate to low yields. 4,9-Dihydropyrano[3,4-b]indole-1(3H)-ones (1) were coupled with different acetobromoglycopyranoses 2 in refluxing toluene in the presence of silver oxide to afford one coupling product of the respective N-glycosides. α-L-Arabinopyranosides 3j and 3m were the most active glycosides among the tested compounds against certain Gram positive and Gram negative bacterial strains. 相似文献
58.
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
59.
60.
Cassado Ados A de Albuquerque JA Sardinha LR Buzzo Cde L Faustino L Nascimento R Ghosn EE Lima MR Alvarez JM Bortoluci KR 《PloS one》2011,6(7):e22141
The peritoneal cavity (PerC) is a singular compartment where many cell populations reside and interact. Despite the widely adopted experimental approach of intraperitoneal (i.p.) inoculation, little is known about the behavior of the different cell populations within the PerC. To evaluate the dynamics of peritoneal macrophage (MØ) subsets, namely small peritoneal MØ (SPM) and large peritoneal MØ (LPM), in response to infectious stimuli, C57BL/6 mice were injected i.p. with zymosan or Trypanosoma cruzi. These conditions resulted in the marked modification of the PerC myelo-monocytic compartment characterized by the disappearance of LPM and the accumulation of SPM and monocytes. In parallel, adherent cells isolated from stimulated PerC displayed reduced staining for β-galactosidase, a biomarker for senescence. Further, the adherent cells showed increased nitric oxide (NO) and higher frequency of IL-12-producing cells in response to subsequent LPS and IFN-γ stimulation. Among myelo-monocytic cells, SPM rather than LPM or monocytes, appear to be the central effectors of the activated PerC; they display higher phagocytic activity and are the main source of IL-12. Thus, our data provide a first demonstration of the consequences of the dynamics between peritoneal MØ subpopulations by showing that substitution of LPM by a robust SPM and monocytes in response to infectious stimuli greatly improves PerC effector activity. 相似文献