Ursodeoxycholic acid prevents apoptosis of mouse sensory neurons induced by cisplatin by reducing P53 accumulation

Ursodeoxycholic acid (UDCA), a component of bile acid, which is abundant in the gall bladder of bears, has been used in clinical medicine for cholestatic liver diseases. Recently, it was demonstrated that UDCA and its derivative tauroursodeoxycholic acid block apoptotic cell death in both hepatic and non-hepatic cells. Cisplatin, an effective anti-cancer drug, is known to cause sensory neuropathy in patients receiving the drug. In the present study, whether UDCA is effective in blocking cisplatin-induced cell death in mouse hybrid sensory neurons was conducted. N18D3 mouse hybrid sensory neurons exposed to cisplatin were found to undergo apoptotic cell death. Preincubation with UDCA completely blocked cisplatin-induced apoptotic cell death in the sensory neurons, and cisplatin-induced p53 accumulation was suppressed by UDCA treatment. These results indicate that UDCA has a neuroprotective effect on the cisplatin-induced neuronal cell death of sensory neurons via the downregulation of the p53 signaling pathway.     

Mapping QTLs for defective female gametophyte development in an inter-subspecific cross in Oryza sativa L.

The embryo-sac is an essential structure for angiosperm reproduction. The cytological and genetic characterization of embryo-sac sterility was examined in a cross between Oryza sativa ssp. indica cv. ZYQ8 and ssp. japonica cultivar, JX17. The arrest of embryo-sac development was manifested following meiosis in the F₁ hybrid. When the megaspore carried the lethal genotype, the nucleus either failed to divide or divided only once, and the immature embryo-sac degenerated. Abortion of the embryo-sac in the indica-japonica hybrid background was not observed in their original parents, and an effect of cytoplasmic gene(s) on embryo-sac sterility in the reciprocal F₁ hybrids was not detected. Using a rice molecular linkage map based on a doubled haploid (DH) population from the cross of ZYQ8 /JX17, we mapped quantitative trait loci (QTLs) for the defective development of the female gametophyte in backcross progenies from the DH lines. The result demonstrated that a polygenic system is involved in both megagametogenesis and postzygotic isolation in inter-subspecific hybrid rice. Received: 4 May 2000 / Accepted: 20 September 2000     

Cytological and Reproductive Studies of Japanese Diplazium (Woodsiaceae; Pteridophyta). III. The Cytological Complexity of Species Groups with Simply Pinnate to Bipinnatifid Leaves

Diplazium with simply pinnate or bipinnatifid leaves. Diplazium wichurae var. wichurae, D. wichurae var. amabile, D. okudairae, and D. pin-faense are sexual diploids (2n=82; n=41II); D.× kidoi and D. × okudairaeoides are sterile diploids (2n= 82; meiosis irregular); D. donianum var. donianum is an apomictic triploid (2n=123; n=123II); D. donianum var. aphanoneuron is a sterile triploid (2n=123; meiosis irregular); D. crassiusculum, D. cavalerianum, D. incomptum, D. longicarpum, and D. pullingeri are sexual tetraploids (2n= 164; n=82II); and D. lobatum is an apomictic tetraploid (2n=164; n=164II). This is the first report of the chromosome numbers of D. lobatum, D. crassiusculum, D. incomptum, D. longicarpum, D. pullingeri, and D. × okudairaeoides, as well as the mitotic chromosome numbers of D. wichurae var. amabile, D. okudairae, D. pinfaense, and D. ×kidoi. The mitotic chromosome number, meiotic behavior, sterility, and allozyme analysis confirm that D. × kidoi and D. × okudairaeoides are hybrids between D. pin-faense and D. wichurae var. wichurae and D. okudairae and D. wichurae var. wichurae, respectively. Diplazium with simply pinnate to bipinnatifid leaves displayed an extraordinary cytological and reproductive complexity: a polyploidal series with diploids to hexaploids, sexual and apomictic reproduction, and natural hybridization. Received 14 August 2001/ Accepted in revised form 1 October 2001     

An Unexpected Major Groove Binding of Netropsin and Distamycin A to tRNAphe

Abstract

Crystalline complexes of yeast tRNA^phe and the oligopeptide antibiotics netropsin and distamycin A were prepared by diffusing drugs into crystals of tRNA. X-ray structure analyses of these complexes reveal a single common binding site for both drugs which is located in the major or deep groove of the tRNA T-stem. The netropsin-tRNA complex is stabilized by specific hydrogen bonds between the amide groups of the drug and the tRNA bases G51 0(6), U52 0(4) and G53 N(7) on one strand, and is further stabilized by electrostatic interactions between the positively charges guanidino side chain of the drug and the tRNA phosphate P53 on the same strand and the positively charged amidino propyl side chain and the phosphates P61, P62 and P63 on the opposite strand of the double helix. These results are in contrast to the implicated minor groove binding of these drugs to non-guanine sequences in DNA. The binding to the GUG sequence in tRNA implies that major groove binding to certain DNA sequences is possible.     

Synthesis of sulfonamide,amide and amine hybrid pharmacophore,an entry of new class of carbonic anhydrase II inhibitors and evaluation of chemo-informatics and binding analysis

Selective inhibition of carbonic anhydrase (CA) enzyme is an active area of research for medicinal chemists. In the current account, a hybrid pharmacophore approach was employed to design sulfonamide, amide and amine containing new series of potent carbonic anhydrase II inhibitors. The aromatic fragment associated with pharmacophore was altered suitably in order to find effective inhibitors of CA-II. All the derivatives 4a-4m showed better inhibition compared to the standard acetazolamide. In particular, compound 4l exhibited significant inhibition with IC₅₀ value of 0.01796 ± 0.00036 µM. The chemo-informatics analysis justified that all the designed compounds possess <10 HBA and <5 HBD. The ligands-protein binding analyses showed that 4l confined in the active binding pocket with three hydrogen bonds observed with His63, Asn66 and Thr197 residues.     

mTOR upregulation of glycolytic enzymes promotes tumor development

Comment on: Zha X, et al. Cancer Res 2011; 71:13-8.     

Design,synthesis and biological evaluation of nitric oxide releasing derivatives of dapagliflozin as potential anti-diabetic and anti-thrombotic agents

The cardiovascular complications were highly prevalent in type 2 diabetes mellitus (T2DM), even at the early stage of T2DM or the state of intensive glycemic control. Therefore, there is an urgent need for the intervention of cardiovascular complications in T2DM. Herein, the new hybrids of NO donor and SGLT2 inhibitor were design to achieve dual effects of anti-hyperglycemic and anti-thrombosis. As expected, the preferred hybrid 2 exhibited moderate SGLT2 inhibitory effects and anti-platelet aggregation activities, and its anti-platelet effect mediated by NO was also confirmed in the presence of NO scavenger. Moreover, compound 2 revealed significantly hypoglycemic effects and excretion of urinary glucose during an oral glucose tolerance test in mice. Potent and multifunctional hybrid, such as compound 2, is expected as a potential candidate for the intervention of cardiovascular complications in T2DM.     

Comparison of NOCSAE head kinematics using the Hybrid III and EuroSID-2 necks

Anthropomorphic test devices (ATDs) are designed for specific loading scenarios and possess uniquely designed individual components including the neck. The purpose of this study was to determine the influence of the neck surrogate on head kinematics. Inertial loads were generated using a pendulum system with an anthropomorphic head attached to a Hybrid III (HIII) or EuroSID-2 (ES-2) neck. The ATD head-neck assemblies were tested under extension, flexion, lateral bending, oblique extension, and oblique flexion at 3.4 m/s. Peak head kinematics were found to be statistically different with the ES-2 versus HIII neck under certain cases. For extension, the resultant peak linear acceleration (PLA) and resultant peak angular acceleration (PAA) were statistically higher with the ES-2 versus HIII neck. For flexion and lateral bending, there were no statistical differences in the resultant PLA based on neck selection although the resultant PAA was statistically higher with the ES-2 versus HIII neck. For oblique extension, the resultant PLA and PAA statistically increased with the ES-2 versus HIII neck. Furthermore, the acceleration components a_x, α_x, and α_y were statistically higher with the ES-2 neck while a_y showed no statistical difference due to neck selection. For oblique flexion, the resultant PLA and PAA were statistically higher with the ES-2 versus HIII neck. Additionally, the acceleration components a_x, a_y, α_x, and α_y were statistically higher with the ES-2 versus HIII neck. These findings indicate that for certain loading directions and acceleration components, head kinematics were influenced by the neck surrogate used.     

Discrimination of macaques by macaques: the case of Sulawesi species

A series of work by the first author have demonstrated that many macaque species show a visual preference for the pictures of their own species when the monkeys actively press a lever to see the pictures. We expanded this study to Sulawesi macaques kept as a pet by local people with slight modification. All seven species of Sulawesi macaques were passively exposed to a variety of colored slides of Sulawesi macaques. The experimenter recorded the duration of visual fixation onto the pictures. Male monkeys of all the seven species clearly watched the pictures of their own species for longer duration than those of the other species. Such visual preference suggested that the seven Sulawesi macaques discriminate each other species and, thus, they may not be integrated into fewer number of species. This visual preference may work to prevent overall intergradation of the Sulawesi macaques who sometimes have hybrid zones only in limited areas. This preference was in general weaker in female monkeys. In one species,Macaca ochreata, females actively avoided to see the pictures of conspecifics. These results may be related to how female monkeys interact with other individuals.