Design,synthesis, and evaluation of novel inhibitors for wild-type human serine racemase

Most of the endogenous free d-serine (about 90%) in the brain is produced by serine racemase (SR). d-Serine in the brain is involved in neurodegenerative disorders and epileptic states as an endogenous co-agonist of the NMDA-type glutamate receptor. Thus, SR inhibitors are expected to be novel therapeutic candidates for the treatment of these disorders. In this study, we solved the crystal structure of wild-type SR, and tried to identify a new inhibitor of SR by in silico screening using the structural information. As a result, we identified two hit compounds by their in vitro evaluations using wild-type SR.Based on the structure of the more potent hit compound 1, we synthesized 15 derivatives and evaluated their inhibitory activities against wild-type SR. Among them, the compound 9C showed relatively high inhibitory potency for wild-type SR. Compound 9C was a more potent inhibitor than compound 24, which was synthesized by our group based upon the structural information of the mutant-type SR.     

中国浙江合叶苔属(合叶苔科)一新种——毛茎合叶苔

描述了采自中国浙江九龙山的苔类植物一新种——毛茎合叶苔Scapania paraphyllia T.Cao,C．Gao,J．Sun＆B．R．Zuo。该新种与腋毛合叶苔S.bolanderiAust．相近,两种皆具带齿叶片和假鳞毛,但新种具如下特征可与腋毛合叶苔区别：（1）植物体小,通常红色;（2）假鳞毛多数,不分枝,不仅生于叶腋,茎上也有着生;（3）背脊为腹瓣长的1/4-1／3,背瓣为腹瓣大小1／2-1／3;（4）叶角质层表面粗糙,具粗瘤,直径达6-8μm。与另一个相似种sampliata Steph．相比,因新种具有粗糙的叶表面和假鳞毛等特征,也易于区别。     

Nature of T-cells resident in spleens of thymectomized,lethally irradiated,bone marrow-reconstituted mice

Adult thymectomized, lethally irradiated, bone marrow-reconstituted (ATxXB) mice that had been weakly primed with SRBC or HRBC between thymectomy and irradiation were shown to retain antigen-specific immunological memories for at least 1–5 months after bone marrow reconstitution. This could be shown by anamnestic antibody response in vivo as well as by proliferative response of the spleen cells to the test antigens in vitro. Spleen cells taken from ATxXB mice showed a reduced but significant proliferative response to nonspecific T-cell mitogens, in particular to Con A, in vitro. Treatment of the donor bone marrow cells used for reconstitution of ATxXB mice with anti-Thy 1.2 sera + C′ did not affect the generation of immunological memories nor the magnitude of the proliferative response of spleen cells to nonspecific T-cell mitogens in vitro, indicating that the cells responsible for such functions were host derived. Finally, the antibody-forming capacity of spleen cells derived from SRBC-primed ATxXB mice to the test antigen in vitro was completely abrogated by exposure to 450 R, whereas the helper function of the same cell suspension remained unaffected even after exposure to 1000 R. Implication of these findings on the nature of T cells resident in spleens of ATxXB mice was discussed.     

Diploidy, evolution and sex

A new gene for a new purpose may be created by mutation of a pre-existing gene. But if that original gene is still required for its original purpose, and is to be retained side by side with the new, a spare copy is needed initially as raw material for the innovation. Thus in haploids the original gene must be duplicated before it is modified. But in diploids a spare copy of every gene is always available, and a mutant allele serving a new purpose can be easily established and maintained by heterosis in parallel with the old allele. Subsequent gene duplication will lead, via crossing-over, to insertion of the new gene in tandem with the old, as a permanent addition to the genome. Calculations show that diploids can thus enlarge their genomes with new genes for new purposes much more readily than haploids; in particular, they can more easily evolve the complex gene control systems characteristic of differentiated multicellular organisms. Sexual reproduction preserves diploidy, and so can be seen as the basis of these richer possibilities for evolutionary innovation.     

贵州卷柏属(卷柏科)一新种——习水卷柏

描述了贵州卷柏属一新种,即习水卷柏Selaginella xishuiensis G. Q. Gou &; P. S. Wang。新种与蔓出卷柏S. davidii Franch.在体态和大小方面相近,但叶缘具睫状毛而不同;新种在体态上也与地卷柏S. prostrata H. S. Kung相似,但孢子叶一型而不同。     

四川无心菜属（石竹科）一新种

描述了四川无心菜属（石竹科）一新种——道孚无心菜Arenaria dawuensis A. J. Li&Q. Ban。该种具纺锤形根,聚伞花序,花柱2,线形而与纟遂瓣无心菜A. fimbriata（E. Pritz. ）Mattf. 相近,但叶匙形,萼片边缘具长缘毛,花瓣短于萼片,顶端细流苏状而不同。     

Interactions of La3+ with phosphatidylserine vesicles Binding,phase transition,leakage, 31P-NMR and fusion

The interaction of La³⁺ with phosphatidylserine vesicles is studied by differential scanning calorimetry, ¹⁴⁰La binding, ³¹P-NMR chemical shifts and relaxation rates, carboxyfluorescein and [¹⁴C]sucrose release, X-ray diffraction and freeze-fracture electron microscopy. In the presence of La³⁺ concentrations above 1 mM and an incubation temperature of 38°C, i.e., at the phase transition temperature of the complex La/phosphatidylserine, the binding ratio of La/lipid exceeds a $\text{1}\text{3}$ ratio, reaching saturation at a $\text{1}\text{2}$ ratio. Analysis, employing a modified Gouy-Chapman equation, indicates a significant increase in the intrinsic binding constant of La/phosphatidylserine when the La³⁺ concentration exceeds the threshold concentration for leakage. The analysis illustrates that at the molecular level the binding of La³⁺ can be comparable to or even weaker than that of Ca²⁺, but that even when present at smaller concentrations La³⁺ competes with and partially displaces Ca²⁺ from membranes or other negatively charged surfaces. The results suggest that the sequence La³⁺>Ca²⁺>Mg²⁺ reflects both the binding strength of these cations to phosphatidylserine as well as their ability to induce leakage, enhancement of ³¹P spin-lattice relaxation rates, fusion and other structural changes. The leakage, fusion, and other structural changes are more pronounced at the phase transition temperature of the La/lipid complex.     

中国云南象牙参属(姜科)一新种——苍山象牙参

描述了中国云南姜科Zingiberaceae一新种——苍山象才参Roscoea cangshanensisM．H．LUO,X．F．Gao＆H．H．Lin。该种与大理象牙参R．forrestii Cowley在体态上相近,但唇瓣深裂成2裂片,每个裂片再2裂,基部收缩成具白色条纹的柄,叶片较狭窄,（2-）7-24×1．5-2．5cm,叶片基部狭缩成叶柄状而不同。该新种叶片基部狭缩成叶柄状,唇瓣倒卵状楔形,长2．5-3．5cm,宽2．5-3．0cm,基部收缩成具白色条纹的柄,与长柄象牙参R．debilis Gagnep．相似,但苞片非管状,较短,长5-15mm,隐藏于叶鞘内,花冠管较长,10-12.5cm,唇瓣深裂成2裂片,每个裂片再2裂,可与后者明显区别。     

湖北无心菜属(石竹科)一新种——神农架无心菜

描述了湖北省神农架地区发现的石竹科一新种——神农架无心菜Arenaria shennongjiaensis Z. E. Zhao &; Z. H. Shen,并绘出了线图。该种与秦岭无心菜A. giraldii (Diels) Mattf.相近,为柔弱草本,具纺锤形块根,花瓣顶端齿裂;不同之处在于其茎有1列腺毛,花瓣顶端具4齿裂,裂片又2浅裂。     

云南龙血树属(龙舌兰科)一新种——深脉龙血树

描述了龙血树属Dracaena一新种--深脉龙血树D. impressivenia Y. H. Yan &; H. J. Guo, 并绘了线图。该种产于中国云南盈江县, 与矮龙血树D. terniflora Roxb.叶形相似, 但侧脉深陷, 总状花序上具许多每6-9朵簇生的花, 苞片暗红色, 花被伸直, 长3-3.5 cm, 可与后者明显区别。     

Red cell ouabain binding sites, Na+K+-ATPase, and intracellular Na+ as individual characteristics

Healthy male volunteers were infused for three hours with either a dopamine hydrochloride solution at a rate of 4 ug/kg/min or with normal saline. Plasma amine oxidase and platelet MAO activity towards benzylamine both increased in response to intravenous dopamine. There was no increase in enzyme activity when dopamine was added to the platelet and plasma enzymes in vitro. This heretofore unreported increase in the oxidative deaminating capacity of the human organism may represent an adaptive physiologic response to the high circulating levels of dopamine and provides further evidence for a possible functional significance of these enzymes in man.     

Two new and rare mountain door-snails (Gastropoda, Pulmonata, Clausiliidae) from high mountain areas in Macedonia

Two species of Clausiliidaeare described as new to science. Euxinella alpinellasp. n. is the fourth species within genus Euxinella Nordsieck, 1973, and Vestia lazaroviisp. n. is the second species of genus Vestia recorded from the Republic of Macedonia. In both species, the clausilium apparatus shows a high degree of variation.     

Formation of hydroxyl radicals from the paraquat radical cation, demonstrated by a highly specific gas chromatographic technique. the role of superoxide radical anion, hydrogen peroxide, and glutathione reductase

Yeast glutathione reductase catalyzes an NADPH-dependent reduction of the herbicide paraquat in vitro. The single-electron reduced paraquat radical reacts with O2 to generate the superoxide radical, O2.-. Hydroxyl radicals (OH.) can also be detected in this assay system by their reaction with phenol to form diphenols, as assayed quantitatively by a highly specific and sensitive method employing gas-liquid chromatography. Formation of hydroxyl radicals can be virtually completely suppressed by catalase and partially suppressed by superoxide dismutase. The role of hydroxyl radicals and superoxide in paraquat toxicity in vivo is discussed.     

陕西鸟巢兰属一新种--太白山鸟巢兰

对中国陕西产的兰科新种太白山鸟巢兰Neottia taibaishanensis P H．Yang ＆ K．Y．Lang作了描述和绘图。本新种与尖唇鸟巢兰N acuminata相似,但整个植株为灰黑色,花序轴被贴伏银灰色长柔毛,萼片、花瓣和唇瓣灰黑色而边缘为灰白色,唇瓣宽倒卵形或近圆形,先端具短尖而不同。     

中国云南秋海棠属(秋海棠科)一新种——假侧膜秋海棠

描述了中国云南秋海棠科Begoniaceae秋海棠属Begonia扁果组sect．Platycentrum的一新种——假侧膜秋海棠Begonia coelocentroides Y.M．Shui＆Z．D．Wei。该种与山地秋海棠B．oreodoxa Chun＆F．Chun相似,子房上部为侧膜胎座,但雌花被片5,蒴果最大翅舌形,长20-22mm,而易于区别。     

云南节肢蕨属(水龙骨科)一新种——贯众叶节肢蕨

报道了产于中国云南高黎贡山的水龙骨科Polypodiaceae节肢蕨属Arthromeris一新种——贯众叶节肢蕨A.cyrtomioides S.G Lu＆C.D.Xu。该新种的植标大小与节肢蕨A .lehmanni（Mett.）Ching相似。但叶片的背面密被绒毛,表面被短柔毛,侧生羽片9-16对。该新种在毛被方面与厚毛羽毛节肢蕨A.tomentosa W.M.Chu相似,但羽片边缘无软骨质的膜质边,侧生羽片多达9-16对。     

中国重庆毛茛科银莲花属一新种——涪陵银莲花

描述了中国重庆市涪陵区的毛莨科Ranunculaceae银莲花属Anemone一新种——涪陵银莲花A．fulingensisW.T．Wang＆Z．Y.Liu,并绘出墨线图。根据此新种的总苞苞片无柄,花具4-5枚萼片,花丝丝形,花粉具散沟等特征,可以确定此种应是属于银莲花属鹅掌草组Anemone sect．Stolonifera的一个成员;在该组中,此种以其独特的由2-10个块茎组成的念珠状根状茎而与该组的其他种相区别。鉴于在银莲花属中块茎出现于不同的演化路线中,以及这些块茎的出现系次生现象,可见此新种应是鹅掌草组的进化种。     

云南百合科球子草属一新种———粗穗球子草

对中国云南百合科一新种———粗穗球子草Peliosanthes pachystachya W.H.Chen&Y.M.Shui进行了描述和绘图。该新种的匍匐茎具长约18cm的节间,与匍匐球子草P.sinica Wang&Tang接近,但因叶具9-13条叶脉,花梗长9-10mm,无小苞片,花被片卵状三角形而明显不同。该新种因花被片卵状三角形,苞片披针形,也近似于长苞球子草P.ophiopogonoides Wang&Tang,但匍匐茎长,叶具9-13条叶脉,花梗长9-10mm,花葶和花序均较短而不同。     

中国湖南杜鹃花科杜鹃花属一新种——天门山杜鹃

报道了中国湖南天门山国家森林公园内发现的杜鹃花科Ericaceae杜鹃花属Rhododendron一新种——天门山杜鹃R．tianmenshanense C．L．Peng＆L．H．Yan。该种与雪山杜鹃R．aganniphum Balf.f.＆K．Ward近似,但以叶为长圆状椭圆形,叶背具两层毛被,上层为银白色短绒毛,下层为紧贴的鳞片状细毛,总花梗和花梗具密而短的腺毛,花常5朵组成总状花序而不同。该种隶属常绿杜鹃组大理杜鹃亚组sect．Ponticum subsect.Talienisa。     

ClTI,a Kunitz trypsin inhibitor purified from Cassia leiandra Benth. seeds,exerts a candidicidal effect on Candida albicans by inducing oxidative stress and necrosis

Cassia leiandra is an Amazonian plant species that is used popularly for the treatment of mycoses. Recently, a protease inhibitor, named ClTI, with insecticidal activity against Aedes aegypti, was purified from the mature seeds of C. leiandra. In this work, we show that ClTI has antifungal activity against Candida species and describe its mode of action towards Candida albicans. This study is relevant because the nosocomial infections caused by Candida species are a global public health problem that, together with the growing resistance to current drugs, has increased the urgency of the search for new antifungal compounds. ClTI inhibited the growth of Candida albicans, Candida tropicalis, Candida parapsilosis, and Candida krusei. However, ClTI was more potent against C. albicans. The candidicidal mode of action of ClTI on C. albicans involves enhanced cell permeabilization, alteration of the plasma membrane proton-pumping ATPase function (H+ -ATPase), induction of oxidative stress, and DNA damage. ClTI also exhibited antibiofilm activity and non-cytotoxicity to mammalian cells. These results indicate that ClTI is a promising candidate for the future development of a new, natural, and safe agent for the treatment of infections caused by C. albicans.