RANTES的多聚化及其意义

RANTES可以单体,双体和多聚体等形式存在,单体和双体形式的RANTES受体为CCR1,CCR3,CCR4和CCR5,而多聚体GAG。Glu26和Glu66在RANTES的多聚化过程中起着重要的作用。多聚体的RANTES与Jak2,Jak3和Src kinase p56(lck)等酪氨酸磷酸化有关,活化T细胞,单个核细胞及巨噬细胞,并可增强HIV的复制。     

Immunomodulatory cytokines in human seminal plasma correlate with immunomodulatory steroids

7alpha-Hydroxy-dehydroepiandrosterone and its 7beta-hydroxyepimer, which act as local immunomodulatory agents, dehydroepiandrosterone, cortisol, and major androgens, together with four cytokines-interleukins 2, 4, 10, and IFN-gamma, reflecting the activity of TH1 or TH2 cells present in semen, were measured in seminal plasma from 35 male donors. Cortisol, dehydroepiandrosterone, its sulfate, 7-hydroxy-dehydroepiandrosterone epimers, testosterone, and estradiol were also measured in their blood serum. Steroids and interleukins in semen as well as serum steroids and seminal interleukins were mutually correlated to find out whether a relationship between immunomodulatory steroids and cytokines influencing the immune environment does exist. A highly significant (P<0.001) positive correlation was found between seminal 7beta-hydroxy-dehydroepiandrosterone and IFN-gamma, while a negative correlation was found between cortisol and IL-10. Highly significant positive correlations were also found between serum 7alpha-hydroxy-dehydroepiandrosterone and seminal IFN-gamma and between serum 7beta-hydroxy-dehydroepiandrosterone and seminal IL-2, while a negative correlation was found between serum dehydroepiandrosterone and seminal IL-10. Different and in some instances, even contradictory findings concerning the influence of dehydroepiandrosterone and cortisol on TH1 and TH2 cytokines were observed in seminal plasma as compared to those found by others in serum. The differences can be ascribed to the different environments of mucosal and systemic immunity. Correlations between the levels of steroids and cytokines in seminal plasma did not always correspond to the correlations between given cytokines and hormones in sera. The results, however, are in agreement with our recent finding of an autonomous production of these steroids in the male reproductive tract.     

A divergent synthesis of [1-14C]-mono-E isomers of fatty acids

A convenient synthesis of [1-14C]-mono-trans fatty acid using olefin inversion as a key-step is described. This methodology allows for a facile synthesis of [1-14C]-labelled mono-trans analogues of oleic, linoleic and linolenic acids. As an example, only eleven steps were necessary to obtain the [1-14C]-mono-E isomers of linolenic acid from its commercial all-Z form. In the first step, Barton's decarboxylation procedure yielded a bromo intermediate. Epoxidation of this compound resulted in the formation of three monoepoxides, which could be separated by HPLC. After identification by 1H NMR and MS, the pure monoepoxides were then subjected to inversion consisting of a stereospecific deoxygenation followed by a beta-elimination step. Finally, the labelling was introduced by substitution of the bromine by a [14C]-cyano group followed by hydrolysis.     

Identification of the Orotidine-5′-Phosphate Decarboxylase Gene and Development of a Transformation System in the Yeast Saccharomyces exiguus Yp74L-3

To investigate the uracil biosynthetic pathway of the yeast Saccharomyces exiguus Yp74L-3, uracil auxotrophic mutants were isolated. Using conventional genetic techniques, four mutant genes concerned in uracil biosynthesis were identified and denoted as ura1, ura2, ura3, and ura4. Mutations in the URA3 and URA4 genes were specifically selected with 5-fluoroorotic acid (5-FOA). Vector plasmids containing the URA3 gene and an autonomously replicating sequence (ARS) of S. cerevisiae produced sufficient amounts of Ura⁺ transformants from the ura4 mutant of S. exiguus. This fact indicates that the S. exiguus URA4 gene encodes orotidine-5′-phosphate decarboxylase (OMP decarboxylase) and demonstrates that vector plasmids for S. cerevisiae are also usable in S. exiguus.     

Identification of the redox partners of ERdj5/JPDI,a PDI family member,from an animal tissue

ERdj5 (also known as JPDI) is a member of PDI family conserved in higher eukaryotes. This protein possesses an N-terminal J domain and C-terminal four thioredoxin domains each having a redox active site motif. Despite the insights obtained at the cellular level on ERdj5, the role of this protein in vivo is still unclear. Here, we present a simple method to purify and identify the disulfide-linked complexes of this protein efficiently from a mouse tissue. By combining acid quenching and thiol-alkylation, we identified a number of potential redox partners of ERdj5 from the mouse epididymis. Further, we show that ERdj5 indeed interacted with two of the identified proteins via formation of intermolecular disulfide bond. Thus, this approach enabled us to detect and identify redox partners of a PDI family member from an animal tissue.     

Plasmacytoid dendritic cells in antiviral immunity and autoimmunity

Plasmacytoid dendritic cells (pDCs) represent a unique and crucial immune cell population capable of producing large amounts of type I interferons (IFNs) in response to viral infection. The function of pDCs as the professional type I IFN-producing cells is linked to their selective expression of Toll-like receptor 7 (TLR7) and TLR9, which sense viral nucleic acids within the endosomal compartments. Type I IFNs produced by pDCs not only directly inhibit viral replication but also play an essential role in linking the innate and adaptive immune system. The aberrant activation of pDCs by self nucleic acids through TLR signaling and the ongoing production of type I IFNs do occur in some autoimmune diseases. Therefore, pDC may serve as an attractive target for therapeutic manipulations of the immune system to treat viral infectious diseases and autoimmune diseases.     

Oriented solids as a colloid suspension in nematic liquid crystal – New tool for IR-spectroscopic and structural elucidation of inorganic compounds and glasses

Possibilities of the linear-polarized infrared (IR-LD) spectroscopy of oriented colloid suspensions in nematic liquid crystals, for structural and local structural elucidation for first time are demonstrated of inorganic compounds and glasses. The advantages of the method for tellurite and borate glasses are shown. The IR-band assignment of the typical local structural units in the glasses are proposed by a comparison with the IR-characteristics of appropriate crystalline analogues as α-TeO₂, V₂O₅, MoO₃ · H₂O and its high temperature form. The IR-spectroscopic characteristics of BO₃, BO₄ and boroxol ring are elucidated, using crystalline β-BaB₂O₄, SrB₄O₇, H₃BO₃ and B₂O₃ as model systems, where the structural moieties have been refined by single crystal X-ray diffraction.     

Fluidity,permeability and antioxidant behaviour of model membranes incorporated with α-tocopherol and vitamin E acetate

Magnetic resonance studies reveal a marked difference between the binding of α-tocopherol and that of the corresponding acetate (vitamin E acetate) with dipalmitoylphosphatidylcholine (DPPC) vesicles. This is reflected in differences in the phase-transition curves of the DPPC vesicles incorporated with the two compounds, as well as in the ¹³C relaxation times and line widths. A model for the incorporation of these molecules in lipid bilayers has been suggested. α-Tocopherol binds strongly with the lipids, possibly through a hydrogen bond formation between the hydroxyl group of the former and one of the oxygen atoms of the latter. The possibility of such a hydrogen bond formation is excluded in vitamin E acetate, which binds loosely through the normal hydrophobic interaction. The model for lipid-vitamin interaction explains the in vitro decomposition of H₂O₂ by α-tocopherol. α-Tocopherol in conjuction with H₂O₂ can also act as a free-radical scavenger in the lipid phase. The incorporation of α-tocopherol and vitamin E acetate in DPPC vesicles enhances the permeability of lipid bilayers for small molecules such as sodium ascorbate.     

Changes in the intracellular accumulation and distribution of metallothionein in rat liver and kidney during postnatal development

Metallothionein (MT) bound to zinc and copper was detected in high concentration in fetal and newborn rat livers by a cadmium saturation method. The levels of both hepatic zinc and MT remained high for the first 14 days after birth and decreased to adult levels by 24 days of age. There was a direct linear relationship between hepatic metallothionein and zinc concentrations during the first 31 days after birth. The ratio of MT to zinc levels also decreased with age suggesting a rapid degradation of MT during postnatal development. Immunohistochemical localization of MT by peroxidase-antiperoxidase technique, using a specific antibody to MT, showed intense intranuclear staining for MT in fetal and newborn rat liver which persisted until Day 9. The nuclear MT staining decreased with age; at 11 days it was equal both in nucleus and cytoplasm and at 14 days, MT was localized mainly in the cytoplasm, similar to adult rat liver pattern. The intranuclear localization of MT in neonates could be considered as a typical fetal-neonatal morphological pattern and its subsequent presence in the cytoplasm, an adult pattern.