中国的炭疽杆菌DNA分型及其地理分布

炭疽广泛分布于中国各地,特别是西部地区,并经常造成人畜疾病,在一项合作研究中,用多位点VNTR分析（MLVA）对从1952-1998年自中国主要地理流行区域分离的病人,病畜和土壤等来源的炭疽杆菌进行了基因分型,MLVA分析结果揭示了21种新的基因型,其等位基因组合在以前世界范围分离物的研究中未曾发现,此外,分离物的分群显示,A3b组是地理上最广泛分布的基因组,说明该组可能是中国的“地方流行株”。而来自古丝绸之路重要贸易中心新疆的大量分离株其基因型特别分散。     

Metabolic profiling and systematic identification of flavonoids and isoflavonoids in roots and cell suspension cultures of Medicago truncatula using HPLC-UV-ESI-MS and GC-MS

An integrated approach utilizing HPLC-UV-ESI-MS and GC-MS was used for the large-scale and systematic identification of polyphenols in Medicago truncatula root and cell culture. Under optimized conditions, we were able to simultaneously quantify and identify 35 polyphenols including 26 isoflavones, 3 flavones, 2 flavanones, 2 aurones and a chalcone. All identifications were based upon UV spectra, mass spectral characteristics of protonated molecules, tandem mass spectral data, mass measurements obtained using a quadrupole time-of-flight mass spectrometer (QtofMS), and confirmed through the co-characterization of authentic compounds. In specific instances where the stereochemistry of sugar conjugates was uncertain, subsequent enzymatic hydrolysis of the conjugate followed by GC-MS was used to assign the sugar stereochemical configuration. Comparative metabolic profiling of Medicago truncatula root and cell cultures was then performed and revealed significant differences in the isoflavonoid composition of these two tissues.     

Social defeat and footshock increase body mass and adiposity in male Syrian hamsters

Obesity is a world-wide epidemic, and many factors, including stress, have been linked to this growing trend. After social stress (i.e., defeat), subordinate laboratory rats and most laboratory mice become hypophagic and, subsequently, lose body mass; the opposite is true of subordinate Syrian hamsters. After social defeat, Syrian hamsters become hyperphagic and gain body mass compared with nonstressed controls. It is unknown whether this increase in body mass and food intake is limited to subordinate hamsters. In experiment 1, we asked, do dominant hamsters increase food intake, body mass, and adiposity after an agonistic encounter? Subordinate hamsters increased food intake and body mass compared with nonstressed controls. Although there was no difference in food intake or absolute body mass between dominant and nonstressed control animals, cumulative body mass gain was significantly higher in dominant than in nonstressed control animals. Total carcass lipid and white adipose tissue (WAT) (i.e., retroperitoneal and epididymal WAT) masses were significantly increased in subordinate, but not dominant, hamsters compared with nonstressed controls. In experiment 2, we asked, does footshock stress increase food intake, body mass, and adiposity. Hamsters exposed to defeat, but not footshock stress, increased food intake relative to nonstressed controls. In animals exposed to defeat or footshock stress, body mass, as well as mesenteric WAT mass, increased compared with nonstressed controls. Collectively, these data demonstrate that social and nonsocial stressors increase body and lipid mass in male hamsters, suggesting that this species may prove useful for studying the physiology of stress-induced obesity in some humans.     

MATE2 mediates vacuolar sequestration of flavonoid glycosides and glycoside malonates in Medicago truncatula

The majority of flavonoids, such as anthocyanins, proanthocyanidins, and isoflavones, are stored in the central vacuole, but the molecular basis of flavonoid transport is still poorly understood. Here, we report the functional characterization of a multidrug and toxin extrusion transporter (MATE2), from Medicago truncatula. MATE 2 is expressed primarily in leaves and flowers. Despite its high similarity to the epicatechin 3'-O-glucoside transporter MATE1, MATE2 cannot efficiently transport proanthocyanidin precursors. In contrast, MATE2 shows higher transport capacity for anthocyanins and lower efficiency for other flavonoid glycosides. Three malonyltransferases that are coexpressed with MATE2 were identified. The malonylated flavonoid glucosides generated by these malonyltransferases are more efficiently taken up into MATE2-containing membrane vesicles than are the parent glycosides. Malonylation increases both the affinity and transport efficiency of flavonoid glucosides for uptake by MATE2. Genetic loss of MATE2 function leads to the disappearance of leaf anthocyanin pigmentation and pale flower color as a result of drastic decreases in the levels of various flavonoids. However, some flavonoid glycoside malonates accumulate to higher levels in MATE2 knockouts than in wild-type controls. Deletion of MATE2 increases seed proanthocyanidin biosynthesis, presumably via redirection of metabolic flux from anthocyanin storage.     

MicroRNAs in systemic rheumatic diseases

MicroRNAs (miRNAs) are endogenous, non-coding, single-stranded RNAs about 21 nucleotides in length. miRNAs have been shown to regulate gene expression and thus influence a wide range of physiological and pathological processes. Moreover, they are detected in a variety of sources, including tissues, serum, and other body fluids, such as saliva. The role of miRNAs is evident in various malignant and nonmalignant diseases, and there is accumulating evidence also for an important role of miRNAs in systemic rheumatic diseases. Abnormal expression of miRNAs has been reported in autoimmune diseases, mainly in systemic lupus erythematosus and rheumatoid arthritis. miRNAs can be aberrantly expressed even in the different stages of disease progression, allowing miRNAs to be important biomarkers, to help understand the pathogenesis of the disease, and to monitor disease activity and effects of treatment. Different groups have demonstrated a link between miRNA expression and disease activity, as in the case of renal flares in lupus patients. Moreover, miRNAs are emerging as potential targets for new therapeutic strategies of autoimmune disorders. Taken together, recent data demonstrate that miRNAs can influence mechanisms involved in the pathogenesis, relapse, and specific organ involvement of autoimmune diseases. The ultimate goal is the identification of a miRNA target or targets that could be manipulated through specific therapies, aiming at activation or inhibition of specific miRNAs responsible for the development of disease.     

Frequent coexistence of anti-topoisomerase I and anti-U1RNP autoantibodies in African American patients associated with mild skin involvement: a retrospective clinical study

Introduction  

The presence of anti-topoisomerase I (topo I) antibodies is a classic scleroderma (SSc) marker presumably associated with a unique clinical subset. Here the clinical association of anti-topo I was reevaluated in unselected patients seen in a rheumatology clinic setting.     

Repeated agonistic encounters in hamsters modulate AVP V1a receptor binding

Arginine vasopressin (AVP) regulates aggression in male Syrian hamsters. In this study, we used radioligand receptor autoradiography to examine whether changes in agonistic behavior following acute and repeated social defeat are accompanied by changes in AVP V1a receptor binding. Social defeat produced high levels of submissive behavior and a loss of territorial aggression when hamsters were subsequently tested with a novel intruder, and repeated agonistic encounters produced similar behavioral changes in subordinates. AVP V1a receptor binding was not reduced by acute social defeat but was affected by repeated agonistic encounters. Dominants had significantly more AVP V1a receptor binding in lateral portions of the ventromedial hypothalamus (VMHL) than did their subordinate opponents, but subordinates were no different from controls. In contrast, receptor binding did not differ in most other brain regions examined. The changes in receptor binding appear to be independent of testosterone levels, as testosterone levels did not differ among dominants, subordinates, and controls. Our results suggest that changes in AVP V1a receptors do not account for the changes in agonistic behavior produced by acute social defeat but AVP V1a binding in the VMHL correlates with, and may modulate, the behavioral changes that occur following repeated experiences of victory.     

Gonadal hormones modulate the display of submissive behavior in socially defeated female Syrian hamsters

There are striking differences in the behavioral response to social defeat between male and female Syrian hamsters. Whereas males exhibit a prolonged behavioral response to defeat (i.e., conditioned defeat), many females remain aggressive or show only a transient submissive response following defeat. The current study tested the hypothesis that sex steroids underlie this differential behavioral responsivity to social defeat. Female hamsters were ovariectomized and implanted with Silastic capsules containing estradiol (E(2)), testosterone (T), progesterone (P), dihydrotestosterone (DHT), or a blank capsule (no hormone replacement). After a 3-week recovery period, each subject was placed inside the home cage of a larger, more aggressive female for four 5-min defeat trials. The following day, each animal was tested for conditioned defeat by testing it in its own home cage in the presence of a smaller, non-aggressive intruder. Submissive, aggressive, social, and nonsocial behaviors were subsequently scored. Hamsters receiving E(2) or T displayed significantly lower levels of submissive behavior than did animals receiving P, DHT, or no hormone replacement. There were no significant differences in aggressive behavior among groups. These data suggest that gonadal hormones can influence submissive behavior in female hamsters. Collectively, these results suggest that the sex differences observed in conditioned defeat may, in part, be explained by sex differences in circulating gonadal hormones.     

Structural basis for dual functionality of isoflavonoid O-methyltransferases in the evolution of plant defense responses

In leguminous plants such as pea (Pisum sativum), alfalfa (Medicago sativa), barrel medic (Medicago truncatula), and chickpea (Cicer arietinum), 4'-O-methylation of isoflavonoid natural products occurs early in the biosynthesis of defense chemicals known as phytoalexins. However, among these four species, only pea catalyzes 3-O-methylation that converts the pterocarpanoid isoflavonoid 6a-hydroxymaackiain to pisatin. In pea, pisatin is important for chemical resistance to the pathogenic fungus Nectria hematococca. While barrel medic does not biosynthesize 6a-hydroxymaackiain, when cell suspension cultures are fed 6a-hydroxymaackiain, they accumulate pisatin. In vitro, hydroxyisoflavanone 4'-O-methyltransferase (HI4'OMT) from barrel medic exhibits nearly identical steady state kinetic parameters for the 4'-O-methylation of the isoflavonoid intermediate 2,7,4'-trihydroxyisoflavanone and for the 3-O-methylation of the 6a-hydroxymaackiain isoflavonoid-derived pterocarpanoid intermediate found in pea. Protein x-ray crystal structures of HI4'OMT substrate complexes revealed identically bound conformations for the 2S,3R-stereoisomer of 2,7,4'-trihydroxyisoflavanone and the 6aR,11aR-stereoisomer of 6a-hydroxymaackiain. These results suggest how similar conformations intrinsic to seemingly distinct chemical substrates allowed leguminous plants to use homologous enzymes for two different biosynthetic reactions. The three-dimensional similarity of natural small molecules represents one explanation for how plants may rapidly recruit enzymes for new biosynthetic reactions in response to changing physiological and ecological pressures.