Multispecies-compatible antitumor effects of a cross-species small-interfering RNA against mammalian target of rapamycin

Successful development of sequence-specific siRNA (small interfering RNA)-based drugs requires an siRNA design that functions consistently in different organisms. Utilizing the CAPSID program previously developed by our group, we here designed siRNAs against mammalian target of rapamycin (mTOR) that are entirely complementary among various species and investigated their multispecies-compatible gene-silencing properties. The mTOR siRNAs markedly reduced mTOR expression at both the mRNA and protein levels in human, mouse, and monkey cell lines. The reduction in mTOR expression resulted in inactivation of both mTOR complex I and II signaling pathways, as confirmed by reduced phosphorylation of p70S6K (70-kDa ribosomal protein S6 kinase), 4EBP1 (eIF4E-binding protein 1), and AKT, and nuclear accumulation of FOXO1 (forkhead box O1), with consequent cell-cycle arrest, proliferation inhibition, and autophagy activation. Moreover, interfering with mTOR activity in vivo using mTOR small-hairpin RNA-expressing recombinant adeno-associated virus led to significant antitumor effects in xenograft and allograft models. Thus, the present study demonstrates that cross-species siRNA successfully silences its target and readily produces multispecies-compatible phenotypic alterations-antitumor effects in the case of mTOR siRNA. Application of cross-species siRNA should greatly facilitate the development of siRNA-based therapeutic agents.     

利用杀菌剂防治松萎蔫病

松萎蔫病是一种非常复杂的病害。据报道,松材线虫(Bursaphelenchus xylophilus)及其携带的细菌诱导了该病,但是对于细菌的的作用尚存争议。笔者筛选出杀细菌剂进行了温室和林间防治松萎蔫病的实验。利用每株3年生赤松(Pinus densiflora)注射3 mg的恶喹酸,松萎蔫病防效达到71 %。利用恶喹酸或阿维菌素及两者混合物对大约20年生赤松的试验表明,3种处理均显示了很高的防效。以上结果证明伴生细菌是诱导松萎蔫病的必要因素,对松萎蔫病可利用杀细菌剂或杀细菌剂与杀线剂混合物进行防控。     

Two new Asian species of the genus Scottolana Huys, 2009 (Copepoda: Canuelloida: Canuellidae)

Two new species of the family Canuellidae Lang, 1944, Scottolana jasani sp. nov. collected from Gusipo Beach, Korea and S. huysi sp. nov. from Kata Beach, Phuket Island, Thailand, are described. So far 14 species are currently known in the genus, of which only two, S. bulbifera from Russia, China, and Korea, and S. geei from China, have been reported from Asia. The new species, Scottolana jasani sp. nov. and S. huysi sp. nov., belong to the longipes-group, defined by the presence of two postgenital segments in the female, and caudal ramus with a proximal hook-like inner projection. Scottolana jasani sp. nov. closely resembles S. geei. However, it is easily distinguished by the following characters: (1) number of segments of antennal exopod (8 in the new species, but 9 in S. geei); (2) setae I, and II of caudal ramus; (3) shape of genital field in both sexes; (4) segmentation of mandibular exopod; and (5) spinular ornamentation of endopod-2 in P1. Scottolana huysi sp. nov. is also closely related to S. geei. However, it is unique and different from S. geei by (1) indistinctly 4-segmented antennule in the female; (2) 5-segmented male antennule; (3) larger genital field in female; (4) inner long seta on P4 coxa; and (5) the morphology of caudal seta II, being long and plumose, with a bulbiform base in the female only.

www.zoobank.org/urn:lsid:zoobank.org:pub:33BFE1A2-8C95-4A9D-9E7A-B495CEEC3182     

Senescence suppressors: their practical importance in replicative lifespan extension in stem cells

Recent animal and clinical studies report promising results for the therapeutic utilization of stem cells in regenerative medicine. Mesenchymal stem cells (MSCs), with their pluripotent nature, have advantages over embryonic stem cells in terms of their availability and feasibility. However, their proliferative activity is destined to slow by replicative senescence, and the limited proliferative potential of MSCs not only hinders the preparation of sufficient cells for in vivo application, but also draws a limitation on their potential for differentiation. This calls for the development of safe and efficient means to increase the proliferative as well as differentiation potential of MSCs. Recent advances have led to a better understanding of the underlying mechanisms and significance of cellular senescence, facilitating ways to manipulate the replicative lifespan of a variety of primary cells, including MSCs. This paper introduces a class of proteins that function as senescence suppressors. Like tumor suppressors, these proteins are lost in senescence, while their forced expression delays the onset of senescence. Moreover, treatments that increase the expression or the activity of senescence suppressors, therefore, cause expansion of the replicative and differentiation potential of MSCs. The nature of the activities and putative underlying mechanisms of the senescence suppressors will be discussed to facilitate their evaluation.     

Can We Predict Exchange Rate Movements at Short Horizons?

This paper explains the unpredictability of exchange rate movements at short horizons and provides a plausible answer on the exchange rate disconnect puzzle. By generalizing Chaboud and Wright's (Journal of International Economics 2005; 66 : 349–362) work, it is shown that exchange rates follow a martingale process at short horizons but over long horizons may contain some predictable structure. The empirical results applied to several major currencies of the US dollar support our hypothesis. This evidence is not coincided with the explanation of the inefficient market hypothesis under which exchange rate movements can be predictable in both short and long horizons. Copyright © 2011 John Wiley & Sons, Ltd.     

A comparative analysis of the cell biology of senescence and aging

Various intracellular organelles, such as lysosomes, mitochondria, nuclei, and cytoskeletons, change during replicative senescence, but the utility of these changes as general markers of senescence and their significance with respect to functional alterations have not been comprehensively reviewed. Furthermore, the relevance of these alterations to cellular and functional changes in aging animals is poorly understood. In this paper, we review the studies that report these senescence-associated changes in various aging cells and their underlying mechanisms. Changes associated with lysosomes and mitochondria are found not only in cells undergoing replicative or induced senescence but also in postmitotic cells isolated from aged organisms. In contrast, other changes occur mainly in cells undergoing in vitro senescence. Comparison of age-related changes and their underlying mechanisms in in vitro senescent cells and aged postmitotic cells would reveal the relevance of replicative senescence to the physiological processes occurring in postmitotic cells as individuals age.     

Shallow water source localization using a mobile shor t horizontal array

This paper presents an approach to the challenging is- sue of passive source localization in shallow water using a mobile short horizontal linear array with length less than ten meters. The short array can be conveniently placed on autonomous underwa- ter vehicles and deployed for adaptive spatial sampling. However, the use of such small aperture passive sonar systems makes it difficult to acquire sufficient spatial gain for localizing long-range sources. To meet the requirement, a localization approach that employs matched-field based techniques that enable the short ho- rizontal linear array is used to passively localize acoustic sources in shallow water. Furthermore, the broadband processing and inter-position processing provide robustness against ocean en- vironmental mismatch and enhance the stability of the estimation process. The proposed approach＇s ability to localize acoustic sources in shallow water at different signal-to-noise ratios is examined through the synthetic test cases where the sources are located at the endfire and some other bearing of the mobile short horizontal linear array. The presented results demonstrate that the positional parameters of the estimated source build up over time as the array moves at a low speed along a straight line at a constant depth.     

Nicotinamide is an inhibitor of SIRT1 in vitro,but can be a stimulator in cells

Nicotinamide (NAM), a form of vitamin B₃, plays essential roles in cell physiology through facilitating NAD⁺ redox homeostasis and providing NAD⁺ as a substrate to a class of enzymes that catalyze non-redox reactions. These non-redox enzymes include the sirtuin family proteins which deacetylate target proteins while cleaving NAD⁺ to yield NAM. Since the finding that NAM exerts feedback inhibition to the sirtuin reactions, NAM has been widely used as an inhibitor in the studies where SIRT1, a key member of sirtuins, may have a role in certain cell physiology. However, once administered to cells, NAM is rapidly converted to NAD⁺ and, therefore, the cellular concentration of NAM decreases rapidly while that of NAD⁺ increases. The result would be an inhibition of SIRT1 for a limited duration, followed by an increase in the activity. This possibility raises a concern on the validity of the interpretation of the results in the studies that use NAM as a SIRT1 inhibitor. To understand better the effects of cellular administration of NAM, we reviewed published literature in which treatment with NAM was used to inhibit SIRT1 and found that the expected inhibitory effect of NAM was either unreliable or muted in many cases. In addition, studies demonstrated NAM administration stimulates SIRT1 activity and improves the functions of cells and organs. To determine if NAM administration can generate conditions in cells and tissues that are stimulatory to SIRT1, the changes in the cellular levels of NAM and NAD⁺ reported in the literature were examined and the factors that are involved in the availability of NAD⁺ to SIRT1 were evaluated. We conclude that NAM treatment can hypothetically be stimulatory to SIRT1.     

On Classification and Regression Trees for Multiple Responses and Its Application

In many application fields, multivariate approaches that simultaneously consider the correlation between responses are needed. The tree method can be extended to multivariate responses, such as repeated measure and longitudinal data, by modifying the split function so as to accommodate multiple responses. Recently, researchers have constructed some decision trees for multiple continuous longitudinal response and multiple binary responses using Mahalanobis distance and a generalized entropy index. However, these methods have limitations according to the type of response, that is, those that are only continuous or binary. In this paper, we will modify the tree for univariate response procedure and suggest a new tree-based method that can analyze any type of multiple responses by using GEE (generalized estimating equations) techniques. To compare the performance of trees, simulation studies on selection probability of true split variable will be shown. Finally, applications using epileptic seizure data and WWW data are introduced.