CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locus

An expansion of a CTG repeat at the DM1 locus causes myotonic dystrophy (DM) by altering the expression of the two adjacent genes, DMPK and SIX5, and through a toxic effect of the repeat-containing RNA. Here we identify two CTCF-binding sites that flank the CTG repeat and form an insulator element between DMPK and SIX5. Methylation of these sites prevents binding of CTCF, indicating that the DM1 locus methylation in congenital DM would disrupt insulator function. Furthermore, CTCF-binding sites are associated with CTG/CAG repeats at several other loci. We suggest a general role for CTG/CAG repeats as components of insulator elements at multiple sites in the human genome.     

Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death

Programmed cell death is a fundamental requirement for embryogenesis, organ metamorphosis and tissue homeostasis. In mammals, release of mitochondrial cytochrome c leads to the cytosolic assembly of the apoptosome-a caspase activation complex involving Apaf1 and caspase-9 that induces hallmarks of apoptosis. There are, however, mitochondrially regulated cell death pathways that are independent of Apaf1/caspase-9. We have previously cloned a molecule associated with programmed cell death called apoptosis-inducing factor (AIF). Like cytochrome c, AIF is localized to mitochondria and released in response to death stimuli. Here we show that genetic inactivation of AIF renders embryonic stem cells resistant to cell death after serum deprivation. Moreover, AIF is essential for programmed cell death during cavitation of embryoid bodies-the very first wave of cell death indispensable for mouse morphogenesis. AIF-dependent cell death displays structural features of apoptosis, and can be genetically uncoupled from Apaf1 and caspase-9 expression. Our data provide genetic evidence for a caspase-independent pathway of programmed cell death that controls early morphogenesis.     

N-ethylmaleimide antagonizes stress-induced gastric ulcers in rats

Summary N-ethylmaleimide (NEM) 10 or 25 mg/kg b.wt, given s.c. 20 min beforehand, dose-dependently and significantly antagonizes the severity of gastric glandular ulcers produced by restraint at 4°C (stress) for 2 h. These findings suggest that reduced activity of endogenous nonprotein sulfhydryl substances in gastric tissue does not worsen stress-induced ulceration in rat stomachs, unlike the deleterious effect its depletion is claimed to have on ethanol-evoked gastric mucosal damage. Thus, decreased SH activity appears not to play a role in the aetiology of mucosal ulcers due to stress.     

Variance intervention

Variance intervention is a simple state-space approach to handling sharp discontinuities of level or slope in the states or parameters of models for non-stationary time-series. It derives from earlier procedures used in the 1960s for the design of self-adaptive, state variable feedback control systems. In the alternative state-space forecasting context considered in the present paper, it is particularly useful when applied to structural time series models. The paper compares the variance intervention procedure with the related ‘subjective intervention’ approach proposed by West and Harrison in a recent issue of the Journal of Forecasting, and demonstrates it efficacy by application to various time-series data, including those used by West and Harrison.     

Elevational patterns and determinants of plant diversity in the Baekdudaegan Mountains, South Korea: Species vs. functional diversity

The elevational gradient present in mountainous areas provides the most powerful natural experimental system available to clarify the ecological and evolutionary responses of living organisms to geophysical influences. In this study, we explored the elevational patterns of plant species and functional diversity and the effects of area, mid-domain effect, climatic variables and net primary productivity on the observed diversity patterns along the ridge of the Baekdudaegan Mountains, South Korea. Rapoport’s elevational rule was also evaluated by examining the relationship between elevational range size of plant species and elevation. A total of 802 plant species from 97 families and 342 genera were found in 1100 plots along a 200–-1900-m elevational gradient along the ridge. The elevational patterns of plant species diversity along the ridge of the Baekdudaegan depicted distinctly hump-shaped patterns, whereas the functional diversity decreased monotonically with elevation. The mid-domain effect was the most powerful explanatory variable for species diversity patterns. However, climatic variables were better predictors for functional diversity. Moreover, Rapoport’s elevational rule was not supported. Our study suggests that different elevational patterns may be observed among different diversity measurements even in the same taxon and that there may be fundamental differences in the mechanisms underlying these diversity patterns.     

TMEM16A confers receptor-activated calcium-dependent chloride conductance

Calcium (Ca(2+))-activated chloride channels are fundamental mediators in numerous physiological processes including transepithelial secretion, cardiac and neuronal excitation, sensory transduction, smooth muscle contraction and fertilization. Despite their physiological importance, their molecular identity has remained largely unknown. Here we show that transmembrane protein 16A (TMEM16A, which we also call anoctamin 1 (ANO1)) is a bona fide Ca(2+)-activated chloride channel that is activated by intracellular Ca(2+) and Ca(2+)-mobilizing stimuli. With eight putative transmembrane domains and no apparent similarity to previously characterized channels, ANO1 defines a new family of ionic channels. The biophysical properties as well as the pharmacological profile of ANO1 are in full agreement with native Ca(2+)-activated chloride currents. ANO1 is expressed in various secretory epithelia, the retina and sensory neurons. Furthermore, knockdown of mouse Ano1 markedly reduced native Ca(2+)-activated chloride currents as well as saliva production in mice. We conclude that ANO1 is a candidate Ca(2+)-activated chloride channel that mediates receptor-activated chloride currents in diverse physiological processes.     

A study of the suppression of the high-temperature helium embrittlement in an oxide-particle dispersion strengthened alloy

In this paper, an investigation on the micro-structure of an Fe-base oxide-dispersion-strengthened （ODS） alloy irradiated with high-energy ^20Ne ions to different doses at a temperature around 0.5Tin （Tin is the melting point of the alloy） is presented. Investigation with the transmission electron microscopy found that the accelerated growth of voids at grain-boundaries, which is usually a concern in conven- tional Fe-base alloys under conditions of inert-gas implantation, was not observed in the ODS alloy irradiated even to the highest dose （12000 at.ppm Ne）. The reason is ascribed to the enhanced recombination of point defects and strong trapping of Ne atoms at the interfaces of the nano-scale oxide particles in grains. The study showed that ODS alloys have good resistance to the high-temperature inter-granular embrittlement due to inert-gas accumulation, exhibiting prominence of application in harsh situations of considerable helium production at elevated temperatures like in a fusion reactor.     

Optimization of Casting Process for Heat and Abrasion Resistant Large Gray Iron Castings

Numerical simulations were used to optimize the casting design and conditions for large cast iron castings for marine engines, Simulations of the mold filling and solidification sequences were used to analyze the problems of previous casting conditions with marked improvements for large cylinder liner parts, The amount and positions of chills were optimized to improve the mechanical properties and to minimize the shrinkage and micro porosity in the castings. Ultra sonic testing, penetration testing, and mechanical property testing show no defects in the castings with the productivity significantly increased.