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1.
S B Scholnick P A Caruso J Klemencic G S Mastick C Mauro M Rotenberg 《Developmental biology》1991,146(2):423-437
2.
Further characterization of the binding of human recombinant interleukin 2 to heparin and identification of putative binding sites 总被引:1,自引:1,他引:1
We have previously provided compelling evidence that human recombinant
interleukin 2 (IL-2) binds to the sulfated polysaccharides heparin, highly
sulfated heparan sulfate and fucoidan. Here we show that IL-2 binding is
dependent on heparin chain length, but with fragments as small as 15-mers
retaining binding activity. The addition of exogenous heparin has no effect
on the in vitro biological activity of IL-2. In addition soluble IL-2
receptor alpha and beta polypeptides do not compete with heparin for the
binding of IL-2. IL-2 bound by heparin is still recognized by two IL-2
specific monoclonal antibodies, 3H9 and H2- 8, whose epitopes lie in the
amino terminal region. Murine IL-2 unlike its human counterpart fails to
bind to heparin. Human IL-2 analogs with single amino acid substitutions at
positions Lys43, Thr51, and Gln126 analogs no longer bind to heparin. By
contrast the Arg38Ala analog retains heparin full heparin binding activity.
These experimental findings together with molecular modeling studies
suggest two putative heparin binding sites on human IL-2, one involving
four basic residues, Lys48, Lys49, Lys54, and His55, and the other being a
discontinuous site comprising Lys43, Lys64, Arg81, and Arg83. Neither of
these two clusters is completely conserved in murine IL-2. Overall our data
suggest that the binding of human IL-2 to heparin and heparan sulfate does
not interfere with IL-2/IL-2 receptor interactions. Therefore, binding to
glycosaminoglycan may be a mechanism for retaining the cytokine in an
active form close to its site of secretion in the tissue, thus favoring a
paracrine role for IL-2.
相似文献
3.
Uxmal and Tulum are two important Mayan sites in the Yucatan peninsula. The buildings are mainly composed of limestone and grey/black discoloration is seen on exposed walls and copious greenish biofilms on inner walls. The principal microorganisms detected on interior walls at both Uxmal and Tulum were cyanobacteria; heterotrophic bacteria and filamentous fungi were also present. A dark‐pigmented mitosporic fungus and Bacillus cereus, both isolated from Uxmal, were shown to be acidogenic in laboratory cultures. Cyanobacteria belonging to rock‐degrading genera Synechocystis and Gloeocapsa were identified at both sites. Surface analysis previously showed that calcium ions were present in the biofilms on buildings at Uxmal and Tulum, suggesting the deposition of biosolubilized stone. Apart from their potential to degrade the substrate, the coccoid cyanobacteria supply organic nutrients for bacteria and fungi, which can produce organic acids, further increasing stone degradation. 相似文献
4.
Novak V Yang AC Lepicovsky L Goldberger AL Lipsitz LA Peng CK 《Biomedical engineering online》2004,3(1):39
Background
This study evaluated the effects of stroke on regulation of cerebral blood flow in response to fluctuations in systemic blood pressure (BP). The autoregulatory dynamics are difficult to assess because of the nonstationarity and nonlinearity of the component signals.Methods
We studied 15 normotensive, 20 hypertensive and 15 minor stroke subjects (48.0 ± 1.3 years). BP and blood flow velocities (BFV) from middle cerebral arteries (MCA) were measured during the Valsalva maneuver (VM) using transcranial Doppler ultrasound.Results
A new technique, multimodal pressure-flow analysis (MMPF), was implemented to analyze these short, nonstationary signals. MMPF analysis decomposes complex BP and BFV signals into multiple empirical modes, representing their instantaneous frequency-amplitude modulation. The empirical mode corresponding to the VM BP profile was used to construct the continuous phase diagram and to identify the minimum and maximum values from the residual BP (BPR) and BFV (BFVR) signals. The BP-BFV phase shift was calculated as the difference between the phase corresponding to the BPR and BFVR minimum (maximum) values. BP-BFV phase shifts were significantly different between groups. In the normotensive group, the BFVR minimum and maximum preceded the BPR minimum and maximum, respectively, leading to large positive values of BP-BFV shifts.Conclusion
In the stroke and hypertensive groups, the resulting BP-BFV phase shift was significantly smaller compared to the normotensive group. A standard autoregulation index did not differentiate the groups. The MMPF method enables evaluation of autoregulatory dynamics based on instantaneous BP-BFV phase analysis. Regulation of BP-BFV dynamics is altered with hypertension and after stroke, rendering blood flow dependent on blood pressure.5.
PDGF receptors and Src family kinases are concentrated in caveolae, where signal transduction cascades involving these molecules are thought to be organized. The Src family tyrosine kinases are cotransducers of signals emanating from the activated PDGF receptor. However, the Src family kinase substrates that are involved in PDGF-induced signaling remain to be fully elucidated. We have identified a 29-kDa protein in caveolae that was phosphorylated in response to PDGF stimulation. This protein, pp29, was tightly bound to the caveolar coat protein caveolin-1. pp29 was among the most prominent phosphoproteins observed in cells overexpressing Fyn, suggesting that it may be a Fyn substrate. Consistent with this, pp29 was among a specific subset of proteins whose PDGF-stimulated phosphorylation was blocked by expression of kinase inactive Fyn. These data indicate that pp29 lies downstream of Fyn activation in a PDGF-stimulated signaling pathway, and that pp29 is an abundant site for nucleation of signal transduction cascades. 相似文献
6.
Danilo E Xavier Renata C Picão Raquel Girardello Lorena CC Fehlberg Ana C Gales 《BMC microbiology》2010,10(1):217
Background
Multi-drug efflux pumps have been increasingly recognized as a major component of resistance in P. aeruginosa. We have investigated the expression level of efflux systems among clinical isolates of P. aeruginosa, regardless of their antimicrobial susceptibility profile. 相似文献7.
Anna CC Aguiar Ananda C Cunha Isabela Penna Ceravolo Regina A Correia Gon?alves Arildo JB Oliveira Antoniana Ursine Krettli 《Memórias do Instituto Oswaldo Cruz》2015,110(7):906-913
Several species of Aspidosperma plants are used to treat diseases in
the tropics, including Aspidosperma ramiflorum, which acts against
leishmaniasis, an activity that is experimentally confirmed. The species, known as
guatambu-yellow, yellow peroba,
coffee-peroba andmatiambu, grows in the Atlantic
Forest of Brazil in the South to the Southeast regions. Through a guided
biofractionation of A. ramiflorum extracts, the plant activity
against Plasmodium falciparum was evaluated in vitro for toxicity
towards human hepatoma G2 cells, normal monkey kidney cells and nonimmortalised human
monocytes isolated from peripheral blood. Six of the seven extracts tested were
active at low doses (half-maximal drug inhibitory concentration < 3.8 µg/mL); the
aqueous extract was inactive. Overall, the plant extracts and the purified compounds
displayed low toxicity in vitro. A nonsoluble extract fraction and one purified
alkaloid isositsirikine (compound 5) displayed high selectivity indexes (SI) (= 56
and 113, respectively), whereas compounds 2 and 3 were toxic (SI < 10). The
structure, activity and low toxicity of isositsirikine in vitro are described here
for the first time in A. ramiflorum, but only the neutral and
precipitate plant fractions were tested for activity, which caused up to 53%
parasitaemia inhibition of Plasmodium berghei in mice with
blood-induced malaria. This plant species is likely to be useful in the further
development of an antimalarial drug, but its pharmacological evaluation is still
required. 相似文献
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9.
Andrews GL Tanglao S Farmer WT Morin S Brotman S Berberoglu MA Price H Fernandez GC Mastick GS Charron F Kidd T 《Development (Cambridge, England)》2008,135(23):3839-3848
Developing axons are attracted to the CNS midline by Netrin proteins and other as yet unidentified signals. Netrin signals are transduced in part by Frazzled (Fra)/DCC receptors. Genetic analysis in Drosophila indicates that additional unidentified receptors are needed to mediate the attractive response to Netrin. Analysis of Bolwig's nerve reveals that Netrin mutants have a similar phenotype to Down Syndrome Cell Adhesion Molecule (Dscam) mutants. Netrin and Dscam mutants display dose sensitive interactions, suggesting that Dscam could act as a Netrin receptor. We show using cell overlay assays that Netrin binds to fly and vertebrate Dscam, and that Dscam binds Netrin with the same affinity as DCC. At the CNS midline, we find that Dscam and its paralog Dscam3 act redundantly to promote midline crossing. Simultaneous genetic knockout of the two Dscam genes and the Netrin receptor fra produces a midline crossing defect that is stronger than the removal of Netrin proteins, suggesting that Dscam proteins also function in a pathway parallel to Netrins. Additionally, overexpression of Dscam in axons that do not normally cross the midline is able to induce ectopic midline crossing, consistent with an attractive receptor function. Our results support the model that Dscam proteins function as attractive receptors for Netrin and also act in parallel to Frazzled/DCC. Furthermore, the results suggest that Dscam proteins have the ability to respond to multiple ligands and act as receptors for an unidentified midline attractive cue. These functions in axon guidance have implications for the pathogenesis of Down Syndrome. 相似文献
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