Low-molecular-weight enzyme inhibitors suppress the development of experimental allergic encephalomyelitis

Summary We tested the activity of low-molecular-weight enzyme inhibitors with immunomodifying actions on the suppression of experimental allergic encephalomyelitis (EAE). Of the agents tested the inhibitors of alkaline phosphatase, aminopeptidase B and esterase gave significant protection againts the clinical expression of EAE in guinea pigs.Acknowledgments. This work was partly supported by a grant-in-aid for New Drug Development Research from the Ministry of Health and Welfare, Japan.     

Osteoprotection by semaphorin 3A

The bony skeleton is maintained by local factors that regulate bone-forming osteoblasts and bone-resorbing osteoclasts, in addition to hormonal activity. Osteoprotegerin protects bone by inhibiting osteoclastic bone resorption, but no factor has yet been identified as a local determinant of bone mass that regulates both osteoclasts and osteoblasts. Here we show that semaphorin 3A (Sema3A) exerts an osteoprotective effect by both suppressing osteoclastic bone resorption and increasing osteoblastic bone formation. The binding of Sema3A to neuropilin-1 (Nrp1) inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation by inhibiting the immunoreceptor tyrosine-based activation motif (ITAM) and RhoA signalling pathways. In addition, Sema3A and Nrp1 binding stimulated osteoblast and inhibited adipocyte differentiation through the canonical Wnt/β-catenin signalling pathway. The osteopenic phenotype in Sema3a?/? mice was recapitulated by mice in which the Sema3A-binding site of Nrp1 had been genetically disrupted. Intravenous Sema3A administration in mice increased bone volume and expedited bone regeneration. Thus, Sema3A is a promising new therapeutic agent in bone and joint diseases.     

Haploinsufficiency of NSD1 causes Sotos syndrome

We isolated NSD1 from the 5q35 breakpoint in an individual with Sotos syndrome harboring a chromosomal translocation. We identified 1 nonsense, 3 frameshift and 20 submicroscopic deletion mutations of NSD1 among 42 individuals with sporadic cases of Sotos syndrome. The results indicate that haploinsufficiency of NSD1 is the major cause of Sotos syndrome.     

产甲烷阶段季铵化合物的厌氧生物降解性研究(英文)

基于厌氧序批式测试系统,研究了一组季铵化合物的最终生物降解性和对生物气产生过程的毒性效果.四个测试物中每个化合物均带有四个相同的烷基,通式为R4N+Br-(TEAB,TPAB,TOAB和TODAB分别对应R=C2,C5,C8,C18,).测试物的矿化程度被用来评估其最终厌氧生物降解性;对碳源D-葡萄糖代谢过程的毒性可以利用测试物对生物气生成过程的抑制效果来指示.研究结果表明:带有偶碳数烷基链的季铵化合物,即TEAB、TOAB和TODAB在20 mg/L(以C计)能够被很容易地降解为CO2和CH4,它们对生物气生成过程的毒性随着所带烷基链长的增长而减小.测试物中带有最长碳链的TODAB,即使碳浓度提高到100 mg/L也可以顺利降解;并且在200 mg/L的高浓度条件下也没有发现其对代谢过程的毒性证据.相反,带有奇数碳链的TPAB很难被厌氧生物降解,而且在所有测试物中显示出最强的厌氧毒性,200 mg/L时的生物气抑制率高达69%.     

9-Methyl-7-bromoeudistomin D, a potent inducer of calcium release from sarcoplasmic reticulum of skeletal muscle

The Ca2+-releasing action of several derivatives of eudistomin D isolated from a marine tunicate was compared with that of caffeine. It was found that 9-methyl-7-bromoeudistomin D was approximately 1000 times more potent than caffeine in causing Ca2+ release from the sarcoplasmic reticulum.     

Antibody to tumor necrosis factor (TNF) reduces endotoxin fever

Antibody to tumor necrosis factor (TNF), injected intravenously, reduced endotoxin fever in the rabbit. The fever-reducing effect was apparent in the latter half of the febrile response.     

Crystallographic analysis of mutant human haemoglobins made in Escherichia coli

The expression of beta-globin in Escherichia coli has enabled us to study the functional role of individual amino-acid residues in haemoglobin (Hb) by site-directed mutagenesis. In contrast to mammalian Hbs, some teleost fish haemoglobins show a drastic lowering of oxygen affinity and cooperativity at low pH, a phenomenon known as the Root effect. We have produced the two mutant haemoglobins Hb Nymphéas [Cys(F9)93 beta----Ser] and Hb Daphne [His(H21)143 beta----Arg, Cys(F9)93 beta----Ser] to investigate this allosteric property. Although these substitutions were thought to be responsible for the Root effect, Hb Nymphéas and Hb Daphne show an increased oxygen affinity and a reduced effect of pH on oxygen affinity. Our X-ray crystallographic studies show that the hydroxyl group of Ser 93 beta forms a hydrogen bond with Asp 94 beta which is in equilibrium with the salt bridge between Asp 94 beta and His 146 beta. The oxygen-binding properties of Hbs Nymphéas and Daphne are accounted for by the partial disruption of the salt bridge.     

Pigment chemistry: the red sweat of the hippopotamus

Within a few minutes of perspiration, the colourless, viscous sweat of the hippopotamus gradually turns red, and then brown as the pigment polymerizes. Here we isolate and characterize the pigments responsible for this colour reaction. The unstable red and orange pigments turn out to be non-benzenoid aromatic compounds that are unexpectedly acidic and have antibiotic as well as sunscreen activity.