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At least 217 records · Page 12Linked to original sources
PubMed2005

Identification of putative adhesin genes in shigatoxigenic Escherichia coli isolated from different sources.

Shiga toxin-producing Escherichia coli (STEC) is an important pathogen responsible for severe human intestinal and systemic infections. The bacterial factors required for colonization of the hosts are still not well defined. In this study, the prevalence of seven putative adhesive genes that are not encoded in the locus of enterocyte effacement (LEE) in 74 STEC strains isolated from humans (n=39), food (n=6), cattle (n=11), and pigs (n=18) was investigated by PCR. In addition, Shiga toxin (stx) and intimin (eaeA including alpha, beta, gamma, delta, epsilon, zeta variants) genes were tested. The most prevalent adhesin was that encoded by toxB gene (52 of 74 isolates; 70.3%). This marker was found in all 12 strains of O157:H7 serotype and in 23 of 32 (71.9%) isolates of the O157:NM serogroup. Moreover, this gene was also present in other 17 STEC of the non-O157 serogroup. The second most prevalent adhesin was that encoded by the lpfAO157/OI-154 gene (43 isolates; 58.1%). This marker was detected in LEE-positive strains of the O157 serogroup but also in 9 LEE-negative isolates of porcine origin. Several STEC isolates tested (42 strains; 56.7%) had the efa1 gene of the Efa1 putative adhesive marker. This adhesin was almost exclusively found among eaeA-positive strains recovered from humans, food and cattle. On the other hand, iha marker was detected either in LEE-positive (29 isolates) or LEE-negative (12 strains) STEC. Only two eaeA-negative strains had the saa putative adhesive gene. These results show that STEC strains may be able to express several putative adhesins. However, further studies are needed to evaluate the role of the genes identified in the present study in the pathogenesis of human infections.

Adhesins, Bacterial↗
PubMed2002

Cupressus lusitanica (Cupressaceae) leaf extract induces apoptosis in cancer cells.

A crude ethanolic extract of Cupressus lusitanica Mill. leaves demonstrate cytotoxicity in a panel of cancer cell lines. Cell death was due to apoptosis, as assessed by morphologic features (chromatin condensation and apoptotic bodies formation) and specific DNA fragmentation detected by in situ end-labeling of DNA breaks (TUNEL). The apoptotic cell death was induced timely in a dose-dependent manner. Despite the absence of changes in the expression levels of antiapoptotic protein Bcl-2, proapoptotic Bax protein variants omega and delta were increased. These results warrant further research of possible antitumor compounds in this plant.

Antineoplastic Agents↗
PubMed1999

The membrane affinities of the aliphatic amino acid side chains in an alpha-helical context are independent of membrane immersion depth.

Understanding, predicting, and designing the binding of peptides and proteins to bilayers require quantifying the intrinsic propensities of individual amino acid residues to bind membranes as a function of structural context and bilayer depth. A host-guest study was performed using the peptide host named helix5 in order to determine the membrane affinities of the aliphatic side chains both in an alpha-helical context and as a function of bilayer depth. Use of the alpha-helical host with a constrained geometry allowed the placement of guest sites at three different depths in bilayers and minimized secondary structural changes due to guest substitutions. Circular dichroism and electron paramagnetic resonance (EPR) were used to characterize the aqueous and bilayer-bound structures of the peptide variants. EPR was also used to measure the bilayer-water partition constants of the peptide variants, and the Delta DeltaGtr values (relative to Gly) of the aliphatic amino acid side chains were subsequently calculated. Surprisingly, the DeltaDeltaGtr values did not significantly vary as a function of the guest site depth in bilayers. In addition, the Delta DeltaGtr values determined in an alpha-helical context are reduced to approximately two-thirds of Delta DeltaGtr values determined in other studies for the bilayer-water and octanol-water partitioning of amino acid side chains in extended and unstructured hosts. Both the relative reduction in Delta DeltaGtr values in the context of an alpha-helical host and the invariance of Delta DeltaGtr values with respect to bilayer depth are consistent with the membrane affinities of the aliphatic residues being largely determined by the classical hydrophobic effect.

Amino Acid Sequence↗
PubMed2000

Cell type specificity in alternative splicing of the human mismatch repair gene hMSH2.

Human non-polyposis colorectal cancer is caused by germline mutations in the DNA mismatch repair genes hMSH2 and hMHL1. Several alternatively spliced mRNA species of these genes are present in peripheral blood lymphocytes of normal individuals, which can confound RT-PCR based techniques of mutation detection. Using RT-PCR, we compared the pattern of alternative splicing in whole peripheral blood lymphocytes (PBLs), separated T and B cells, lymphoblastoid cell lines (LCLs) from the same individuals, and a variety of tissues. Alternatively spliced forms of hMLH1 lacking exons 9/10, 10/11 and 9/10/11 were found to have similar patterns of expression in T cells, B cells, and LCLs. By contrast, a subset of hMSH2 transcripts, some of which were produced by utilisation of novel splicing motifs, were generally expressed in T but not in B cells. LCLs derived from the same blood samples showed no expression of any hMSH2 splicing variants. The hMSH2 delta ex13 transcript, while absent from LCLs, was expressed in whole PBLs and both T and B cell fractions. This transcript was furthermore largely undetectable in tissues other than mononuclear blood cells. These data provide evidence for tissue specificity in the regulation of alternative splicing in hMSH2. In particular we show that LCLs generally do not express alternatively spliced forms of hMSH2 mRNA and are thus suited for RT-PCR based mutation screening in that gene.

Alternative Splicing↗
PubMed1987

Stable expression of recombinant factor VIII molecules using a bovine papillomavirus vector.

The bleeding disorder in hemophilia A results from a deficiency or abnormality of Factor VIII (FVIII), a member of the coagulation cascade. FVIII is a large glycoprotein (approximately 350,000 daltons) that is activated by a series of proteolytic cleavages. During activation, a large internal domain (B domain) is removed, resulting in an active complex comprised of the amino and carboxyl subunits of the parental molecule. Using a bovine papillomavirus expression vector system, we have established stable, genetically engineered cell lines harboring either full-length FVIII cDNA or variant FVIII cDNA (delta FVIII), the latter containing an extensive deletion in the region encoding the B domain. We demonstrate that the two recombinant FVIII molecules manifest the biological attributes of native FVIII. Relative to full-length FVIII transformants, cells harboring delta FVIII cDNA are five to eight times more efficient in expressing coagulant activity. This difference is due to a post-transcriptional event.

Bovine papillomavirus 1↗
PubMed2006

Dynamic properties in a family of competitive growing models.

The properties of a wide variety of growing models, generically called X-RD, involving the deposition of particles according to competitive processes, such that a particle is attached to the aggregate with probability p following the mechanisms of a generic model X that provides the correlations and at random [random deposition (RD)] with probability (1-p), are studied by means of numerical simulations and analytic developments. The study comprises the following X models: Ballistic deposition, random deposition with surface relaxation, Das Sarma-Tamboronea, Kim-Kosterlitz, Lai-Das Sarma, Wolf-Villain, large curvature, and three additional models that are variants of the ballistic deposition model. It is shown that after a growing regime, the interface width becomes saturated at a crossover time (tx2) that, by fixing the sample size, scales with p according to tx2(p) proportional variant p-y (P>0), where is an exponent. Also, the interface width at saturation (Wsat) scales as Wsat(p) proportional variant p-delta (p>0), where delta is another exponent. It is proved that, in any dimension, the exponents delta and y obey the following relationship: delta=y beta RD, where beta RD=1/2 is the growing exponent for RD. Furthermore, both exponents exhibit universality in the p --> 0 limit. By mapping the behavior of the average height difference of two neighboring sites in discrete models of type X-RD and two kinds of random walks, we have determined the exact value of the exponent delta. When the height difference between two neighbouring sites corresponds to a random walk that after walking steps returns to a distance from its initial position that is proportional to the maximum distance reached (random walk of type A), one has delta=1/2. On the other hand, when the height difference between two neighboring sites corresponds to a random walk that after steps moves steps towards the initial position (random walk of type B), one has delta=1. Finally, by linking four well-established universality classes (namely Edwards-Wilkinson, Kardar-Parisi-Zhang, linear [molecular beam epitaxy (MBE)] and nonlinear MBE) with the properties of type A and B of random walks, eight different stochastic equations for all the competitive models studied are derived.

Animals↗
PubMed2004

Variants of U1 small nuclear RNA assemble into spliceosomal complexes.

In this study, the existence of additional U1 snRNA variants in the posterior silk gland of the Bombyx mori Nistari strain from India was investigated. Three new U1 variants were detected. One of the new isoforms (U1 SG1) was found to be preferentially assembled into high molecular weight spliceosomal complexes in comparison with the total cellular lysate RNA control. Structural and nucleotide differences were examined in these new isoforms and compared with the previously reported U1 variants. Free energy (Delta G) values for the entire U1 snRNA secondary structures as well as the individual stem/loops (I, II, III and IV) domains of the isoforms were estimated to determine their structural stability.

Animals↗
PubMed2005

Expression of phosphatidylserine (PS) on wild-type and Gerbich variant erythrocytes following glycophorin-C (GPC) ligation.

Glycophorin-C (GPC) is a 40 kDa glycoprotein expressed on erythrocytes and is a receptor for the malarial parasite Plasmodium falciparum to invade these cells. A link between GPC binding (ligation) and phosphatidylserine (PS) expression on erythrocytes has been suggested by its appearance on P. falciparum-infected erythrocytes. Phosphatidylserine expression has also been shown to be a marker of cellular death in a number of biological pathways including some in erythrocytes. Using Annexin V binding, we demonstrated that ligation of GPC with mouse mAb (BRIC-10) induced PS expression on normal erythrocytes. Phosphatidylserine exposure was prevented following tryptic digestion of intact erythrocytes. In addition, GPC variant phenotypes Yus (Delta exon 2) and Gerbich (Delta exon 3), which express a truncated extracellular domain, did not express PS following BRIC-10 binding, whereas PS was exposed on Ls(a) erythrocytes (duplication of exon 3). GPC ligation was also shown to result in a concomitant loss of erythrocyte viability in wild-type erythrocytes after 24 h in vitro. These results identify a potential pathway linking GPC to PS exposure on erythrocytes that may have a role in regulating red cell turnover. Further characterization of this pathway may also identify new targets for the treatment of P. falciparum malaria.

Adult↗
PubMed2003

Haplo-insufficiency of BRCA1 in sporadic breast cancer.

Copy number deletions and loss of heterozygosity of the BRCA1 gene have been frequently reported in sporadic breast cancer. We studied their relationship with BRCA1 gene expression (the haplo-insufficiency hypothesis) with real-time quantitative reverse transcription-PCR. Expression levels of both full-length and BRCA1-Delta 11b splice variant mRNA were studied, and they showed strong correlation (Pearson r = 0.89). Copy number deletion of BRCA1, found in 45% (27 of 60) of the sporadic breast tumors, was associated with ErbB2 oncogene amplification (P = 0.001) and DNA aneuploidy (P = 0.037), but not with stage, grade, or hormone receptor status. The presence of BRCA1 copy number deletion associated significantly with low levels of full-length BRCA1 mRNA (P < 0.0001). The BRCA1 promoter hypermethylation, found in 6 of 53 tumors (11%) by methylation-specific PCR, was also correlated with low BRCA1 expression (P = 0.005). In statistical multiple regression analysis, decreased expression of BRCA1 mRNA showed strongest association with BRCA1 copy number deletion (P < 0.0001) but was also significantly linked to negative progesterone receptor status (P = 0.02) and BRCA1 promoter hypermethylation (P = 0.041). These findings demonstrate that deletion of the BRCA1 gene copies results in haplo-insufficiency, i.e., decreased BRCA1 mRNA expression. This, in turn, suggests that the BRCA1 gene might have a tumor suppressor function also in sporadic breast cancer.

Breast Neoplasms↗
PubMed1991

Protein engineering of novel plasminogen activators with increased thrombolytic potency in rabbits relative to activase.

Human tissue-type plasminogen activator (t-PA) is a glycoprotein used currently in thrombolytic therapy for patients with acute myocardial infarction. Due to its rapid rate of clearance from the circulation, continuous intravenous administration of approximately 100 mg over 3 h is recommended. We have previously characterized novel thrombolytic variant forms of t-PA which offer the potential of administration by bolus injection and reduced dosage due to their slower rates of clearance, relative to t-PA. This study was undertaken to quantitatively compare the pharmacokinetics, thrombolytic activity, and hemostatic effects of two of these variant forms, called delta FE1X and delta FE3X plasminogen activator (PA), with commercially available recombinant t-PA (Activase). These evaluations were performed in rabbits after bolus intravenous injection of the proteins. Following injection of 0.25 mg of protein/kg of body weight, the rates of clearance for delta FE3X and delta FE1X PA antigen were decreased approximately 9- and 18-fold, respectively, relative to Activase. Plasma plasminogen activator activity was also measured and the rates of clearance of delta FE3X and delta FE1X PA activity were similarly decreased by approximately 9- and 22-fold, respectively, relative to Activase. To quantitate thrombolytic activity we used the rabbit jugular vein thrombosis model and demonstrated that approximately 50% thrombolysis was achieved with delta FE1X and delta FE3X PA at approximately an 8.6- and 3-fold lower dose than Activase, respectively. No major differences in fibrinogen and alpha 2-antiplasmin depletion were observed among the agents at doses required to produce 50% thrombolysis, indicating similarities in fibrin specificities among these agents. These results demonstrate a reciprocal relationship between thrombolysis and rate of clearance for these thrombolytic proteins. The 8.6-fold increase in potency of delta FE1X PA relative to Activase supports the future clinical testing of this novel engineered protein as a thrombolytic agent.

Animals↗
PubMed1997

Thermal denaturation of iso-1-cytochrome c variants: comparison with solvent denaturation.

Thermal denaturation studies as a function of pH were carried out on wild-type iso-1-cytochrome c and three variants of this protein at the solvent-exposed position 73 of the sequence. By examining the enthalpy and Tm at various pH values, the heat capacity increment (delta Cp), which is dominated by the degree of change in nonpolar hydration upon protein unfolding, was found for the wild type where lysine 73 is normally present and for three variants. For the Trp 73 variant, the delta Cp value (1.15 +/- 0.17 kcal/mol K) decreased slightly relative to wild-type iso-1-cytochrome c (1.40 +/- 0.06 kcal/mol K), while for the Ile 73 (1.65 +/- 0.07 kcal/mol K) and the Val 73 (1.50 +/- 0.06 kcal/mol K) variants, delta Cp increased slightly. In previous studies, the Trp 73, Ile 73, and Val 73 variants have been shown to have decreased m-values in guanidine hydrochloride denaturations relative to the wild-type protein (Hermann L, Bowler BE, Dong A, Caughey WS. 1995. The effects of hydrophilic to hydrophobic surface mutations on the denatured state of iso-1-cytochrome c: Investigation of aliphatic residues. Biochemistry 34:3040-3047). Both the m-value and delta Cp are related to the change in solvent exposure upon unfolding and other investigators have shown a correlation exists between these two parameters. However, for this subset of variants of iso-1-cytochrome c, a lack of correlation exists which implies that there may be basic differences between the guanidine hydrochloride and thermal denaturations of this protein. Spectroscopic data are consistent with different denatured states for thermal and guanidine hydrochloride unfolding. The different response of m-values and delta Cp for these variants will be discussed in this context.

Circular Dichroism↗
PubMed1993

Conformational stability of the DNA-binding histone-like protein, HBsu, from Bacillus subtilis, and of the four HBsu variants [F29W], [F47W], [F50W] and [F79W].

From denaturation studies with urea a free energy delta GuH2O of unfolding of 49.8 kJ.mol-1 at 25C was calculated for the histone-like DNA-binding protein HBsu from Bacillus subtilis. Unfolding was monitored by circular dichroism measurements observing the changes of the molar mean residue ellipticity [theta] at 222 nm. For the calculation of delta Gu a two-state model of unfolding, i.e. the unfolding of native dimers into unfolded monomers, was applied. The validity of this model in high ionic strength buffer was proven by measurements at different protein concentrations yielding the same delta Gu values. Four HBsu variants, each carrying one single point mutation ([F29W], [F47W], [F50W] and [F79W]) were analysed with respect to their stability against unfolding at increasing temperatures and urea concentrations. The delta Gu values of mutants were calculated using the two-state model and show a reduced stability of the variants [F29W], [F47W], [F50W] and [F79W] in comparison to the wild type HBsu with delta delta Gu values of -9.2 kJ.mol-1, -7.5 kJ.mol-1, -5.9 kJ.mol-1, and -7.5 kJ.mol-1, respectively. Similar delta delta Gu values were obtained for the HBsu mutant proteins by thermal unfolding experiments.

Bacillus subtilis↗
PubMed2001

Four PSM/SH2-B alternative splice variants and their differential roles in mitogenesis.

An SH2 domain originally termed SH2-B had been identified as a direct cellular binding target of a number of mostly mitogenic receptors. The complete cellular protein, termed PSM, and respective sequence variants share additional Pro-rich and PH regions, as well as similarities with APS and Lnk. A role of these mediators has been implicated in signaling pathways found downstream of growth hormone receptor and receptor tyrosine kinases, including the insulin, insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), nerve growth factor, hepatocyte growth factor, and fibroblast growth factor receptors. As a result of this report a total of four PSM/SH2-B sequence variants termed alpha, beta, gamma, and delta have now been identified in the mouse and have been compared with the available rat and human sequences. Variant differences are based on alternative splicing and define distinct last exons 7, 8, and 9 that result in reading frameshifts and unique carboxyl-terminal amino acid sequences. Variant sequences have been identified from cDNA libraries and directly by reverse transcription-polymerase chain reaction. Sequence analysis predicts four distinctly sized protein products that have been demonstrated after cDNA expression. All were found phosphorylated on tyrosine specifically in response to IGF-I and PDGF stimulation. cDNA expression of the four variants caused variant-dependent levels of stimulation of IGF-I- and PDGF-induced mitogenesis. The most pronounced increase in mitogenesis was consistently observed for the gamma variant followed by delta, alpha, and beta with decreasing responses. In contrast, the mitogenic response to epidermal growth factor consistently remained unaffected. The variants are expressed in most mouse tissues, typically, most strongly in pairs of alpha and delta or beta and gamma. Our findings implicate differential roles of the PSM/SH2-B splice variants in specific mitogenic signaling pathways.

Adaptor Proteins, Signal Transducing↗
PubMed1996

A protein AA-variant derived from a novel serum AA protein, SAA1 delta, in an individual from Papua New Guinea.

A major protein AA amyloid protein was purified and characterised from a Papua New Guinnean individual. This AA protein differed from all previously characterised SAA variants by the combination of Ala52, Val57, Asn60, Phe68, Phe69 and Gly72. Since the prevalence of AA-amyloidosis is unusually high in Papua New Guinea this AAdelta must originate from a novel SAAdelta which may represent a particularly amyloidogenic variant.

Adult↗
PubMed2003

A novel alternative spliced chondrolectin isoform lacking the transmembrane domain is expressed during T cell maturation.

Chondrolectin (CHODL) is a novel type I transmembrane protein containing one carbohydrate recognition domain (CRD) of C-type lectins. Recently, data base searching revealed a variant of CHODL (AK022689) with a different 5' leader sequence derived from a new putative upstream alternative promoter (P2). The P2 promoter gives rise to at least three additional alternatively spliced isoforms, designated as CHODLf, CHODLf Delta E, and CHODL Delta E. Of all variants, the alternative exon E-splicing isoforms (CHODLf Delta E/CHODL Delta E) are expressed exclusively in the T lymphocyte lineage and are regulated during T lymphopoiesis. Peripheral T lymphocytes demonstrated a unique exon E-splicing pattern in comparison with end maturation stage thymocytes, suggesting its association with the post-thymic maturation of T cells. Since exon E encodes the transmembrane domain of CHODL, the exon E-skipping variant results in a non-transmembrane domain-containing isoform (CHODLf Delta E/CHODL Delta E) terminating in the QDEL sequence, thus suggesting different functional attributes of CHODL isoforms during the development of T cells. Double label immunofluoresence experiments demonstrated that the transmembrane-containing isoform (CHODLf) colocalizes with rBet1 to the endoplasmic reticulum-Golgi apparatus. In summary, this study describes the molecular characterization of novel members of the chondrolectin family associated with T cell maturation and a subcellular localization of CHODLf in the endoplasmic reticulum-Golgi apparatus.

Alternative Splicing↗
PubMed1991

[Hepatitis B and delta infections in patients with tuberculosis].

Clinical variants of the course and outcomes of HBV and delta infections have been studied in pulmonary tuberculosis patients in the general structure of 1465 patients who were treated for hepatitis B. Enzyme immunoassay and radioimmunoassays were used to study the detection rate of contamination markers HBV activity and delta-virus replication in 437 pulmonary tuberculosis patients. Viruses were found to be predisposed to prolonged persistence and wide spread among tuberculosis patients.

Biomarkers↗
PubMedDate not supplied

cAMP-dependent protein kinase, but not the cGMP-dependent enzyme, rapidly phosphorylates delta-CREB, and a synthetic delta-CREB peptide.

Phosphorylation of the cAMP response element binding protein (CREB) by the catalytic subunit of cAMP-dependent protein kinase (cAK) has been implicated in the cAMP-dependent stimulation of gene transcription. delta-CREB, a spliced variant of CREB, and CREBtide (KRREILSRRPSYR), a synthetic peptide based on the phosphorylation sequence in delta-CREB, were tested as substrates of cAK. Phosphorylation of delta-CREB (0.17 microM) was stoichiometric within 30 s when using a concentration of cAK which approximated the intracellular level (0.2 microM). The rate of phosphorylation of delta-CREB was comparable to the rates of the best physiological substrates of cAK tested. The rate of CREBtide phosphorylation was at least as great as that of delta-CREB, indicating that the peptide retained the determinants of delta-CREB which were responsible for substrate efficacy. The apparent Km of CREBtide phosphorylation by cAK was 3.9 microM, which is 10-fold lower than that of kemptide (Km = 39 microM), the synthetic peptide substrate most often employed for cAK measurement. The Vmax values were 12.4 mumol/(min.mg) for CREBtide and 9.8 mumol/(min.mg) for kemptide. The apparent Km of CREBtide phosphorylation by cGMP-dependent protein kinase (cGK) was 2.9 microM and the Vmax value was 3.2 mumol/(min.mg). Both delta-CREB and CREBtide were phosphorylated at a much slower rate by cGK as compared with cAK, implying that the high cAK/cGK specificity exhibited by delta-CREB was retained by the peptide. Taken together, the results indicated that delta-CREB and CREBtide are among the best substrates tested for cAK and suggested that phosphorylation of CREB by this enzyme could occur in intact cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗