repeats genetic recombination and the pathogenesis of genetic disorders

Ngày tải lên: 16/03/2014, 03:20

... levels of risk to SLE There is an approximately twofold increase in the level of risk between carriers of the highest and lowest risk haplotypes Second, candidate genes from a region of LD can ... critical, as the region of LD surrounding the associated SNP often contains more than one gene (although often there is one likely candidate gene from the known biology) A region of LD includes ... insertion/deletion variant of exon 6, and a variant in a conserved poly(A)+ signal sequence that alters the length of the 3’ untranslated region and stability of IRF5 mRNAs [30] Haplotypes of these three variants...

Ngày tải lên: 09/08/2014, 20:21

... an early ‘southern-route’ originated from the Horn of Africa, crossed the mouth of the Red Sea into the Arabian Peninsula, and subsequently migrated into India, Southeast Asia, and Australia ... ∂a∂i at the same time, we fixed the parameters of the out -of- Africa epoch (N Af , N B , T Af , and TB) in the model based on the parameters estimated from the three-population model with the highest ... contributions JX, LJ, and FY conceived and designed the study JX, WSW, YH, CH, and FY performed the analysis and wrote the manuscript AS and DM generated sequencing data and performed the validation...

Ngày tải lên: 09/08/2014, 22:23

... correlated with their physical size (Figure 3) Comparison of the genetic maps of T b gambiense and T b brucei and the physical map of T b brucei The linkage groups of the STIB 386 genetic map comprise ... between the two strains focused outside the gene-rich coding region (in the sub-telomeres) and therefore not covered by the genetic map The genetic distances in the map reflect the number of recombination ... compare the position of markers in the physical map of T b brucei and the genetic map of T b gam- Marker segregation proportions The availability of segregation data across the length of each...

Ngày tải lên: 14/08/2014, 20:22

... double-strand breaks (DSBs) A single-strand overhang is formed by exonuclease activity and invades the homologous doublestranded region of the other allele These steps of homology search and recombination ... [8] The heterodimeric complex of Hop2 and Mnd1 stimulates strand exchange of Lim15/Dmc1 [9–11] The meiosis-specific proteins Mei5 and Sae3 form a complex with Lim15/Dmc1 and are necessary for the ... on the naked DNA to restore the nucleosome structure (Fig 4C) Because of the various interactions of Lim15/Dmc1–CAF-1–PCNA, we suggest that they act in multiple ways at the site of meiotic recombination...

Ngày tải lên: 07/03/2014, 05:20

... proliferation and blocking apoptosis in the pathogenesis of RA Results GM-CSF induces the proliferation of MH7A cells and the expression of MLN51 Our recent study has shown that GM-CSF is involved in the ... is upregulated in the FLSs of RA patients, and is enhanced days after GM-CSF treatment [7] In the present experiments, we assessed the dose and time kinetics of the effects of GM-CSF on MLN51 ... left untreated The cells were harvested and assessed by western blot analysis for the expression of MLN5 1and FLIP proliferation of RA FLSs through the upregulation of MLN51 [7] In the present study,...

Ngày tải lên: 23/03/2014, 07:20

... enhances activation of eosinophils in EoE specifically Page of The increased global expression of bFGF led to the investigation of the local expression bFGF of the esophageal biopsies of the subjects ... subsets and can be found in a variety of tissues, including epithelial and mesenchymal tissue [20] bFGF increases the half-life of cells and could possibly increase the overall lifetime of the eosinophil ... essential to the transcription of ERK [18] and ERK feeds into the eotaxin-3 pathway, potentially further activating the eosinophil and improving its sensitivity and migration towards eotaxin in the esophageal...

Ngày tải lên: 08/08/2014, 21:20

... high levels of C5a in SF [21] and correlation of the levels of C5a with the number of neutrophils present in the SF of patients with RA [22] More direct evidence for the role of the complement ... although the relative contributions and the hierarchy of these two pathways in the manifestation of disease are still unclear In FcγR−/− mice, in which the surface expression of FcγRI and FcγRIII ... and because the bound IgGs are able to bind C3b and prevent the binding of the complement regulatory plasma proteins factor I and factor H, formation of the C3 convertase is possible The chemotactic...

Ngày tải lên: 09/08/2014, 06:23

... secretion of Simultaneous application of TNF-α and IFN-γ to endothelial cells causes an increase in NPY, upregulation of the Y5 receptor, and complete loss of the Y2 receptor, together with an ... maintained and exacerbated by the activity of DPPIV Nevertheless, in two mouse models of inflammatory arthritis, the severity of joint damage correlated directly with levels of SDF-1α where the efficacy ... measured This is complicated further by a lack of understanding of the breadth of substrate and inhibitor specificities for the DASH family This is illustrated well by the CD26-knockout mouse that...

Ngày tải lên: 09/08/2014, 07:20

... Yudoh and colleagues [1] further analyzed the role of HIF-1 in chondrocytic energy generation, matrix synthesis and cell survival During hypoxic and normoxic conditions, functional inactivation of ... chondrocytes [11] Conclusion The results provided in the study by Yudoh and colleagues and previous reports by us and other groups strongly support the notion that HIF-1 is of pivotal importance in ... expression of hypoxia-inducible factor (HIF)-1a in articular chondrocytes: involvement of HIF1a in the pathogenesis of osteoarthritis Arthritis Res Ther 2005, 7:R904-R914 Silver IA: Measurement of pH and...

Ngày tải lên: 09/08/2014, 07:20

... stages of OA Materials and methods Sources of tissues Aborted human embryos were obtained according to the regulations of the Ethics Committee of the Medical Faculty of the University of Göttingen, ... to the OA grades (I – IV) proposed by Collins and McElligott [31] in the case of the 12 patients and classified as age-dependent healthy in the case of the control cartilage samples None of the ... B.Sc., for editing the manuscript and the Medical Faculty of the University of Göttingen for grants to NM Parts of the work were taken from the doctoral theses of TSC and MK References Hedbom E, Antonsson...

Ngày tải lên: 09/08/2014, 07:20

... coordination and the writing of this manuscript, and also for interpretation and discussion of the data JJ, YEC and YJ performed most of the studies and were responsible for the execution of most of the ... factors in the SFs are involved in the proliferation of RA FLSs, and whether the factors have a role in the expression of MLN51 We determined the growth kinetics of FLSs at different passages and SFtreated ... by radiography of the hand, and all satisfied the diagnostic criteria of the American College of Rheumatology (formerly the American Rheumatism Association) for the classification of RA [16] RA...

Ngày tải lên: 09/08/2014, 08:23

... the normal expression and function of MMPs There are reports of other staphylococcal virulence factors associated with the pathogenesis and severity of SA [43-45] Whether these virulence factors ... to augment the risk of infection in patients with RA The reasons for the predominance of S aureus in SA and the mechanisms of pathogenecity are not yet fully understood The synovium of patients ... down the possible candidates to molecular-weight groups of the range of >30 to 50 based on our experiments using Centricon filtration of the culture supernatants Because the molecular weight of the...

Ngày tải lên: 09/08/2014, 08:23

... expression and protein levels of the MMPs are often found to be accompanied by increases in the levels of one or more of the TIMPs It is therefore not obvious what can be the net result of these opposing ... complex deposition and compromising the physical integrity of the membrane Central to the pathogenesis of lupus is continuous activation and proliferation of B-lymphocytes and T-lymphocytes with ... complicated by the many levels of regulation of proteinase activity Also, there is an emerging appreciation of considerable functional divergence of both MMPs and their regulators, particularly the tissue...

Ngày tải lên: 09/08/2014, 13:22

... degenerate NP cells as well as the effect of IL-1β and TNF-α on cytokine gene expression and the expression of the associated receptors and endogenous antagonists There Page of 10 (page number not for ... carried out the remainder of the experimental work AJF helped to secure funding and contributed to the preparation of the final manuscript JAH conceived and designed the study, secured funding and co-wrote ... centrifugation and the RNA was extracted using TRIzol™ and PureLink columns in accordance with the instructions of the manufacturer (Invitrogen Corporation) To prevent any DNA contamination of the RNA, the...

Ngày tải lên: 09/08/2014, 14:20

... CCL20, a ligand for CCR6, CCL19 and CCL21, ligands for CCR7, and CXCL12, a ligand for CXCR4 First, we analyzed the effects the chemokines on migration of peripheral blood B cells Each of the four ... peripheral B cells of both normals and subjects with RA, and CXCL12 enhanced the expression of ICOSL on both normal and RA B cells In contrast, the effect of CCL20, CCL19 and CCL21 was not significant ... migration of both CD27- and CD27+ B cells (Figure 3a) However, the migration induced by CCL21 was most prominent Comparison of the migratory effects of the chemokines on peripheral blood CD27- and...

Ngày tải lên: 09/08/2014, 14:22

... motifs such as, in the case of CACTA elements, terminal inverted repeats (Figure 1) [21] and, in the case of Helitrons, palindromes and the identification of tandem arrays of elements (Figure ... outputs from BLASTN (e-value < 0.00001 and >20% of the length of the query) and RepeatMasker (RM; >50 bp in length, >70% similarity, and >20% of the length of the query), respectively Families with ... contributions SS, ML, and EP conceived of the study SS and EP carried out the bioinformatic analysis SS conceived of and SS and EC carried out the experimental work SS performed the molecular and statistical...

Ngày tải lên: 09/08/2014, 20:21

... used to clone the gene encoding the mouse Flt3 ligand (FL) [13] The mouse FL cDNA was then used to clone the human FL gene [14] The mouse and human FL genes encode proteins of 231 and 235 amino ... improved by the development of effective chemotherapy in the 1970s and subsequently improved by the development of hematopoietic stem cell transplantation therapy in the 1980s However, the clinical ... through the phosphorylation of FOXO3a leading to suppression of its function, thereby promoting the survival and proliferation of AML cells [54] FLT3-ITD is also known to inhibit the expression and...

Ngày tải lên: 10/08/2014, 21:23

... stress and TCRζ expression in RA T cells the possible role of NO Reduced GSH levels may contribute to the hyporesponsiveness of T cells from synovial fluid of RA patients [59,60] The expression of the ... [13] A central event in the antigen-specific interaction of T  cells with antigen-presenting cells is the formation of the immunological synapse, in which the TCR complex and the adhesion receptor ... Overexpression of eNOS was associated with increased phosphorylation of the CD3ζ chain, ZAP-70, and extracellular signal-regulated kinases, and increased IFN-γ synthesis, but reduced production of IL-2 These...

Ngày tải lên: 12/08/2014, 14:22

... which are responsible for the production of IL-5 and other cytokines that promote the development of eosinophilia On the basis of our current knowledge of the differentiation of IL-5-producing TH2-like ... of Fas Co-culturing of T cells with IL-4 downregulates Fas expression on the cell surface The expression of IL-4 in the asthmatic lung and the secondary lack of Fas expression might explain the ... the third section of the AQLQ (Asthma Quality of Life Questionnaire, showing a patient’s perception of general health and physical functioning) worsened in the placebo group and improved in the...

Ngày tải lên: 12/08/2014, 18:20