Genomic instability and aging-like phenotype in the absence of mammalian SIRT6

The Sir2 histone deacetylase functions as a chromatin silencer to regulate recombination, genomic stability, and aging in budding yeast. Seven mammalian Sir2 homologs have been identified (SIRT1-SIRT7), and it has been speculated that some may have similar functions to Sir2. Here, we demonstrate that SIRT6 is a nuclear, chromatin-associated protein that promotes resistance to DNA damage and suppresses genomic instability in mouse cells, in association with a role in base excision repair (BER). SIRT6-deficient mice are small and at 2-3 weeks of age develop abnormalities that include profound lymphopenia, loss of subcutaneous fat, lordokyphosis, and severe metabolic defects, eventually dying at about 4 weeks. We conclude that one function of SIRT6 is to promote normal DNA repair, and that SIRT6 loss leads to abnormalities in mice that overlap with aging-associated degenerative processes.     

Insertional mutagenesis based on illegitimate recombination in Schizosaccharomyces pombe

An efficient insertional mutagenesis system has been developed for Schizosaccharomyces pombe based on linear PCR-generated cassettes containing selectable markers. It depends upon illegitimate recombination for integration into the genome. Various selectable markers of different sizes can be used to obtain sufficiently high transformation and integration frequencies. Based on Southern blotting, a single insertion is found in each strain and integration sites are broadly distributed in the genome. Sequence analysis of the insert junctions frequently reveals small regions of homology (4–10 bp) between the ends of the integrated cassette and the disrupted gene. The system has been used for simple genetic screens of various types and as a promoter trap for in-frame GFP fusions.     

Prophylactic Application of MA-[d-Leu-4]-OB3, a Small Molecule Synthetic Peptide Leptin Mimetic,Prevents or Slows the Progression of Obesity,Insulin Resistance,and Cognitive Impairment in a Mouse Model of Type 2 Diabetes Mellitus

International Journal of Peptide Research and Therapeutics - Oral delivery of MA-[d-Leu-4]-OB3 has been shown to significantly improve energy balance, glycemic control, dyslipidemia, and episodic...     

Genome-Wide Association Analysis with Gray Matter Volume as a Quantitative Phenotype in First-Episode Treatment-Na?ve Patients with Schizophrenia

Reduced Gray matter (GM) volume is a core feature of schizophrenia. Mapping genes that is associated with the heritable disease-related phenotypes may be conducive to elucidate the pathogenesis of schizophrenia. This study aims to identify the common genetic variants that underlie the deficits of GM volume in schizophrenia. High-resolution T1 images and whole genome genotyping data were obtained from 74 first-episode treatment-naïve patients with schizophrenia and 51 healthy controls in the Mental Health Centre of the West China Hospital, Sichuan University. All participants were scanned using a 3T MR imaging system and were genotyped using the HumanHap660 Bead Array. Reduced GM volumes in three brain areas including left hOC3v in the collateral sulcus of visual cortex (hOC3vL), left cerebellar vermis lobule 10 (vermisL10) and right cerebellar vermis lobule 10 (vermisR10) were found in patients with schizophrenia. There was a group by genotype interaction when genotypes from genome-wide scan were subsequently considered in the case-control analyses. SNPs from three genes or chromosomal regions (TBXAS1, PIK3C2G and HS3ST5) were identified to predict the changes of GM volume in hOC3vL, vermisL10 and vermisR10. These results also highlighted the usefulness of endophenotype in exploring the pathogenesis of neuropsychiatric diseases such as schizophrenia although further independent replication studies are needed in the future.     

A covalently bound photoisomerizable agonist. Comparison with reversibly bound agonists at electrophorus electroplaques

After disulphide bonds are reduced with dithiothreitol, trans-3- (α-bromomethyl)-3’-[α- (trimethylammonium)methyl]azobenzene (trans-QBr) alkylates a sulfhydryl group on receptors. The membrane conductance induced by this “tethered agonist” shares many properties with that induced by reversible agonists. Equilibrium conductance increases as the membrane potential is made more negative; the voltage sensitivity resembles that seen with 50 [mu]M carbachol. Voltage- jump relaxations follow an exponential time-course; the rate constants are about twice as large as those seen with 50 μM carbachol and have the same voltage and temperature sensitivity. With reversible agonists, the rate of channel opening increases with the frequency of agonist-receptor collisions: with tethered trans-Qbr, this rate depends only on intramolecular events. In comparison to the conductance induced by reversible agonists, the QBr-induced conductance is at least 10-fold less sensitive to competitive blockade by tubocurarine and roughly as sensitive to “open-channel blockade” bu QX-222. Light-flash experiments with tethered QBr resemble those with the reversible photoisomerizable agonist, 3,3’,bis-[α-(trimethylammonium)methyl]azobenzene (Bis-Q): the conductance is increased by cis {arrow} trans photoisomerizations and decreased by trans {arrow} cis photoisomerizations. As with Bis-Q, ligh-flash relaxations have the same rate constant as voltage-jump relaxations. Receptors with tethered trans isomer. By comparing the agonist-induced conductance with the cis/tans ratio, we conclude that each channel’s activation is determined by the configuration of a single tethered QBr molecule. The QBr-induced conductance shows slow decreases (time constant, several hundred milliseconds), which can be partially reversed by flashes. The similarities suggest that the same rate-limiting step governs the opening and closing of channels for both reversible and tethered agonists. Therefore, this step is probably not the initial encounter between agonist and receptor molecules.     

Conservation of the Native Orchids Through Seedling Culture and Reintroduction—A Singapore Experience

Singapore is located near the equator, off the southern tip of the Malay Peninsula. The whole country consists mostly of lowland. It has many interesting types of natural habitats such as primary rain forest, freshwater swamp forest, mangroves, secondary forests, shrub, grasslands, and urban parks and fields. The climate is equatorial with relatively uniform temperature and high humidity. Unfortunately, many of the natural habitats and the native orchids which thrive there have disappeared due to habitat destruction. Some 226 species of native orchids have been recorded in Singapore. However, of these 178 are considered to be extinct, and only five are common. The orchid conservation programme aims to monitor existing species, explore ways to conserve their germplasm, and increase their numbers in natural, semi-natural, and urban environments through ex-situ seedling culture and subsequent re-introduction into appropriate habitats, including roadside trees, parks and natural areas. In the first phase of the programme, we have successfully propagated and carried out experiments of re-introduction on five species of native orchids, namely, Grammatophyllum speciosum, Bulbophyllum vaginatum, Bulbophyllum membranaceum, Cymbidium finlaysonianum and Cymbidium bicolor. Survival percentages 8-yr after the reintroduction events ranged from 10 to 95 for G. speciosum, the target species of the earliest re-introduction experiments. Size of the seedlings at reintroduction, host trees, and relative humidity seemed to play significant roles in the success rate of the reintroductions.     

Dance education in Singapore: Policy,discourse, and practice

This article provides an overview of dance education in schools in Singapore with regard to physical education, co-curricular activity, initiatives by the National Arts Council's Arts Education unit, and pre-tertiary and tertiary dance programs. In an effort to gain a better understanding of how well the official discourse and the reality of schooling in dance interconnect, a meta-analysis of published articles, conference papers, committee reports, and curricula was conducted. Situated within the larger sociocultural, political, and historical contexts, Singapore presents a curious case for probing the merits and limitations of research, policy initiatives, and policy implementation. In the conclusion, the author argues that the development of a coherent dance education in Singapore requires “fixing” three dilemmas—meritocratic schooling in dance, the ill-defined and exhaustive use of the term “talent,” and the uneven research that has not kept pace with the policy initiatives.     

Limited dispersal and geographic barriers cause population differentiation and structuring in Begonia maxwelliana at both large and small scales

Background: Genetic divergence is one of the key processes in speciation. In the Begoniaceae, genetic divergence caused by limited gene flow may explain its high species diversity and endemicity. This hypothesis has been supported by past genetic work but there is a lack of empirical studies on the causes of limited gene flow.

Aim: To identify the causes of limited gene flow in Begonia.

Methods: We examined the genetic structure among the populations of Begonia maxwelliana at the macro- and micro-spatial scales using microsatellites, measured seed dispersal range and observed flowering phenology.

Results: Population differentiation and structuring were detected at both the macro- and micro-scales. Dispersal range was short, and all populations showed similar reproductive behaviour.

Conclusions: The strong population differentiation and structuring among the populations studied imply that they are evolutionarily significant units and possible candidates for speciation. Geographical barriers and limited seed dispersal restrict gene flow in the populations, and these factors may be responsible for the rapid speciation and large diversity in the family.     

Synthesis of poly-hydroxyalkanoates from activated sludge under various oxidation-reduction potentials

The production of poly-hydroxyalkanoates (PHA) from the activated sludge subjected to conditions with various oxidationreduction potentials (ORPs) was investigated. By controlling the dissolved oxygen concentration in the cultural media, the ORP were kept at preset levels of ?20, ?10, 0, and +10 mV. With glucose as the dedicated carbon source, we have demonstrated a correlating relationship with the ORP’s in the culture media to the PHA accumulation rate, the PHA production-yield, cell growth rate, glucose uptakes and 3-hydroxybutyrate to 3-hydroxyvalerate (HB/HV) mole ratios in the PHA copolymers. The highest PHA production yield of 0.26 g/g with HB/HV mole ratio of 8.03 was achieved at +10 mV ORP. We concluded that oxygen plays an important role in PHA accumulation and HB/HV mole ratio activated sludge-to-copolymer PHA conversion process.     

ADF proteins are involved in the control of flowering and regulate F-actin organization, cell expansion, and organ growth in Arabidopsis

Based mostly on the results of in vitro experiments, ADF (actin-depolymerizing factor) proteins are thought to be key modulators of the dynamic organization of the actin cytoskeleton. The few studies concerned with the in vivo function of ADF proteins that have been reported to date were performed almost exclusively using single-cell systems and have failed to produce consistent results. To investigate ADF functions in vivo and during the development of multicellular organs, we generated transgenic Arabidopsis plants that express a cDNA encoding an ADF protein (AtADF1) in the sense or the antisense orientation under the control of a strong constitutively active promoter. Selected lines with significantly altered levels of AtADF protein expression were characterized phenotypically. Overexpression of AtADF1 resulted in the disappearance of thick actin cables in different cell types, caused irregular cellular and tissue morphogenesis, and reduced the growth of cells and organs. In contrast, reduced AtADF expression promoted the formation of actin cables, resulted in a delay in flowering, and stimulated cell expansion as well as organ growth. These results are consistent with the molecular functions of ADF as predicted by in vitro studies, support the global roles of ADF proteins during the development of a multicellular organism, and demonstrate that these proteins are key regulators of F-actin organization, flowering, and cell and organ expansion in Arabidopsis.