Age-associated decreased activities of mitochondrial electron transport chain complexes in heart and skeletal muscle: role of L-carnitine

The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS), considered as the pathogenic agent of many diseases and aging. L-Carnitine (4-N-trimethylammonium-3-hydroxybutric acid) plays an important role in transport of fatty acid from cytoplasm to mitochondria for energy production. Previous studies in our laboratory reported L-carnitine as a free radical scavenger in aged rats. In the present study we focused the effect of L-carnitine on the activities of electron transport chain in young and aged rats. The activities of electron transport chain complexes were found to be significantly decreased in aged rats when compared to young control rats. Supplementation of carnitine to young and aged rats for 14 and 21 days improved the electron transport chain complexes levels in aged rats when compared with young rats in duration dependent manner. No significant changes were observed in young rats. Our result suggested that L-carnitine improved the activities of electron transport chain enzymes there by improving the energy status in aged rats.     

Strasburger’s legacy to mitosis and cytokinesis and its relevance for the Cell Theory

Eduard Strasburger was one of the most prominent biologists contributing to the development of the Cell Theory during the nineteenth century. His major contribution related to the characterization of mitosis and cytokinesis and especially to the discovery of the discrete stages of mitosis, which he termed prophase, metaphase and anaphase. Besides his observations on uninucleate plant and animal cells, he also investigated division processes in multinucleate cells. Here, he emphasised the independent nature of mitosis and cytokinesis. We discuss these issues from the perspective of new discoveries in the field of cell division and conclude that Strasburger's legacy will in the future lead to a reformulation of the Cell Theory and that this will accommodate the independent and primary nature of the nucleus, together with its complement of perinuclear microtubules, for the organisation of the eukaryotic cell.     

A new species of Anuretes Heller, 1865 (Copepoda: Caligidae) from the yellowbanded sweetlips Plectorhinchus lineatus (Haemulidae) off New Caledonia

A new species of caligid copepod, Anuretes justinei n. sp., is described from off New Caledonia. It is parasitic on the gill filaments of a haemulid fish, the yellowbanded sweetlips Plectorhinchus lineatus (Linnaeus). The new species is distinguished from its congeners by the combination of the following character states: (1) the fourth pedigerous somite is covered dorsally by the expanded free posterior margin of the cephalothorax; (2) a maxillary whip is present; (3) the relatively small genital complex is less than half the length of the cephalothorax; (4) leg 3 is armed with nine setae on the terminal exopodal segment and six setae on the terminal endopodal segment; and (5) leg 4 is long and slender with a setal armature of I, III twisted spines. The new species is an addition to the possibly monophyletic group of seven species that is characterised by the possession of a maxillary whip, all of which are found on haemulid hosts. The host-specificity of Anuretes is relatively high, its species being largely parasitic on reef-associated fishes, such as the families Haemulidae (eight species), Ephippidae (four species), Acanthuridae (four species) and Pomacanthidae (one species).     

A revision of the family Dissonidae Kurtz, 1924 (Copepoda: Siphonostomatoida)

Two new species of the parasitic copepod genus Dissonus Wilson, 1906 are described: D. excavatus n. sp. from the gills of a labrid, Bodianus perditio, and a lutjanid, Macolor niger, collected off New Caledonia and Taiwan, and D. inaequalis n. sp. from a hemiscylliid elasmobranch, Chiloscyllium punctatum, collected off Sarawak (Malaysia) and the Philippines. Material of D. heronensis Kabata, 1966 is described from a balistid host, Pseudobalistes fuscus, off New Caledonia, and this constitutes a new host record for this parasite. D. manteri Kabata, 1966 was collected from four serranid host species off New Caledonia and from one of the same hosts off Taiwan. Two of the hosts from New Caledonia, Plectropomus laevis and Epinephelus cyanopodus, represent new host records. D. pastinum Deets & Dojiri, 1990 was recognised as a new synonym of D. nudiventris Kabata, 1966, so the total number of valid species is now twelve. Material from museum collections of D. nudiventris, D. similis Kabata, 1966 and D. spinifer Wilson, 1906 was re-examined and provided new information which is utilised in a key to all valid species of Dissonus.     

Molecular and Clinical Characteristics of MSH6 Variants: An Analysis of 25 Index Carriers of a Germline Variant

The MSH6 gene is one of the mismatch-repair genes involved in hereditary nonpolyposis colorectal cancer (HNPCC). Three hundred sixteen individuals who were known or suspected to have HNPCC were analyzed for MSH6 germline mutations. For 25 index patients and 8 relatives with MSH6 variants, molecular and clinical features are described. For analysis of microsatellite instability (MSI), the five consensus markers were used. Immunohistochemical analysis of the MLH1, MSH2, and MSH6 proteins was performed. Five truncating MSH6 mutations, of which one was detected seven times, were found in 12 index patients, and 10 MSH6 variants with unknown pathogenicity were found in 13 index patients. Fourteen (54%) of 26 colorectal cancers (CRCs) and endometrial cancers showed no, or only weak, MSI. Twelve of 18 tumors of truncating-mutation carriers and 3 of 17 tumors of missense-mutation carriers showed loss of MSH6 staining. Six of the families that we studied fulfilled the original Amsterdam criteria; most families with MSH6, however, were only suspected to have HNPCC. In families that did not fulfill the revised Amsterdam criteria, the prevalence of MSH6 variants is about the same as the prevalence of those in MLH1/MSH2. Endometrial cancer and/or atypical hyperplasia were diagnosed in 8 of 12 female carriers of MSH6 truncating mutations. Most CRCs were localized distally in the colon. Although, molecularly, missense variants are labeled as doubtfully pathogenic, clinical data disclose a great resemblance between missense-variant carriers and truncating-mutation carriers. We conclude that, in all patients suspected to have HNPCC, MSH6-mutation analysis should be considered. Neither MSI nor immunohistochemistry should be a definitive selection criterion for MSH6-mutation analysis.     

Diosgenin from Dioscorea bulbifera: Novel Hit for Treatment of Type II Diabetes Mellitus with Inhibitory Activity against α-Amylase and α-Glucosidase

Diabetes mellitus is a multifactorial metabolic disease characterized by post-prandial hyperglycemia (PPHG). α-amylase and α-glucosidase inhibitors aim to explore novel therapeutic agents. Herein we report the promises of Dioscorea bulbifera and its bioactive principle, diosgenin as novel α-amylase and α-glucosidase inhibitor. Among petroleum ether, ethyl acetate, methanol and 70% ethanol (v/v) extracts of bulbs of D. bulbifera, ethyl acetate extract showed highest inhibition upto 72.06 ± 0.51% and 82.64 ± 2.32% against α-amylase and α-glucosidase respectively. GC-TOF-MS analysis of ethyl acetate extract indicated presence of high diosgenin content. Diosgenin was isolated and identified by FTIR, ¹H NMR and ¹³C NMR and confirmed by HPLC which showed an α-amylase and α-glucosidase inhibition upto 70.94 ± 1.24% and 81.71 ± 3.39%, respectively. Kinetic studies confirmed the uncompetitive mode of binding of diosgenin to α-amylase indicated by lowering of both Km and Vm. Interaction studies revealed the quenching of intrinsic fluorescence of α-amylase in presence of diosgenin. Similarly, circular dichroism spectrometry showed diminished negative humped peaks at 208 nm and 222 nm. Molecular docking indicated hydrogen bonding between carboxyl group of Asp300, while hydrophobic interactions between Tyr62, Trp58, Trp59, Val163, His305 and Gln63 residues of α-amylase. Diosgenin interacted with two catalytic residues (Asp352 and Glu411) from α-glucosidase. This is the first report of its kind that provides an intense scientific rationale for use of diosgenin as novel drug candidate for type II diabetes mellitus.     

Targeting RNA for Degradation with a (2′, 5′)-Oligoadenylate Antisense Chimera

Abstract

A novel method is described to selectively cleave RNA by harnessing the 2-5A-dependent ribonuclease.