Evaluation of the efficacy of a pre-pandemic H5N1 vaccine (MG1109) in mouse and ferret models

The threat of a highly pathogenic avian influenza (HPAI) H5N1 virus causing the next pandemic remains a major concern. In this study, we evaluated the immunogenicity and efficacy of an inactivated whole-virus H5N1 pre-pandemic vaccine (MG1109) formulated by Green Cross Co., Ltd containing the hemagglutinin (HA) and neuraminidase (NA) genes of the clade 1 A/Vietnam/1194/04 virus in the backbone of A/Puerto Rico/8/34 (RgVietNam/04xPR8/34). Administration of the MG1109 vaccine (2-doses) in mice and ferrets elicited high HI and SN titers in a dose-dependent manner against the homologous (RgVietNam/04xPR8/34) and various heterologous H5N1 strains, (RgKor/W149/06xPR8/34, RgCambodia/04xPR8/34, RgGuangxi/05xPR8/34), including a heterosubtypic H5N2 (A/Aquatic bird/orea/W81/05) virus. However, efficient cross-reactivity was not observed against heterosubtypic H9N2 (A/Ck/Korea/H0802/08) and H1N1 (PR/8/34) viruses. Mice immunized with 1.9 μg HA/dose of MG1109 were completely protected from lethal challenge with heterologous wild-type HPAI H5N1 A/EM/Korea/W149/06 (clade 2.2) and mouse-adapted H5N2 viruses. Furthermore, ferrets administered at least 3.8 μg HA/dose efficiently suppressed virus growth in the upper respiratory tract and lungs. Vaccinated mice and ferrets also demonstrated attenuation of clinical disease signs and limited virus spread to other organs. Thus, this vaccine provided immunogenic responses in mouse and ferret models even against challenge with heterologous HPAI H5N1 and H5N2 viruses. Since the specific strain of HPAI H5N1 virus that would potentially cause the next outbreak is unknown, pre-pandemic vaccine preparation that could provide cross-protection against various H5 strains could be a useful approach in the selection of promising candidate vaccines in the future.     

Cytoskeletal dynamics underlying collateral membrane protrusions induced by neurotrophins in cultured Xenopus embryonic neurons

The establishment and refinement of neuronal connections depend on dynamic modification of the morphology and physiology of developing axons in response to extrinsic factors. In embryonic cultures of Xenopus spinal neurons, acute application of brain-derived neurotrophic factor (BDNF) induced rapid collateral protrusion of filopodium-like microspikes and lamellipodia along the neurite processes, leading to a morphologic alternation of the neuron. Both types of membrane protrusions contained high concentrations of actin filaments and depended on the polymerization of the actin cytoskeleton. Immunofluorescent staining, however, revealed the presence of microtubules (MTs) in lamellipodia induced by BDNF. These MTs appeared to have arisen from debundling of MTs in the neurite shaft at the protrusion sites, splaying and extending in the rapidly protruding lamellipodia. Inhibition of microtubule polymerization by nocodazole largely abolished the formation of lamellipodia but not of microspikes. Taken together, our results suggest that collateral sprouting of microspikes and lamellipodia involve distinctly different cytoskeletal mechanisms. Although the actin cytoskeleton is solely responsible for microspike formation, cooperative efforts by microtubules and actin filaments are essential for lamellipodial protrusion in response to extrinsic factors.     

The role of competitive learning in the generation of DG fields from EC inputs

We follow up on a suggestion by Rolls and co-workers, that the effects of competitive learning should be assessed on the shape and number of spatial fields that dentate gyrus (DG) granule cells may form when receiving input from medial entorhinal cortex (mEC) grid units. We consider a simple non-dynamical model where DG units are described by a threshold-linear transfer function, and receive feedforward inputs from 1,000 mEC model grid units of various spacing, orientation and spatial phase. Feedforward weights are updated according to a Hebbian rule as the virtual rodent follows a long simulated trajectory through a single environment. Dentate activity is constrained to be very sparse. We find that indeed competitive Hebbian learning tends to result in a few active DG units with a single place field each, rounded in shape and made larger by iterative weight changes. These effects are more pronounced when produced with thousands of DG units and inputs per DG unit, which the realistic system has available, than with fewer units and inputs, in which case several DG units persists with multiple fields. The emergence of single-field units with learning is in contrast, however, to recent data indicating that most active DG units do have multiple fields. We show how multiple irregularly arranged fields can be produced by the addition of non-space selective lateral entorhinal cortex (lEC) units, which are modelled as simply providing an additional effective input specific to each DG unit. The mean number of such multiple DG fields is enhanced, in particular, when lEC and mEC inputs have overall similar variance across DG units. Finally, we show that in a restricted environment the mean size of the fields is unaltered, while their mean number is scaled down with the area of the environment.

Establishment of an Efficient Screening System in Gene Transformation of High Oleic Acid Peanut Using AhFAD2B as a Reporter Gene

Russian Journal of Plant Physiology - During gene transformation, selection makers are important for efficient screening of the transgenic lines. The commonly used selection marker genes in plants...     

纤维连接蛋白对支气管上皮细胞抗氧化损伤保护作用的研究

目的和方法：为验证整合素分子激活对支气管上皮细胞（BEC）的抗氧化性保护作用,本实验用臭氧（O3）攻击培养的兔BEC,测定细胞的^3H释放率、乳酸脱氢酶（LDH）释放活性及脂质过氧化产物丙二醛（MDA）含量,反映细胞损伤程度;观察纤维连接蛋白（Fn）及人工合成的精－甘－天冬氨酸片段（RGD肽）的保护效应。结果：①臭氧攻击使BEC的^3H释放率增高,Fn处理可减少臭氧所致的^3H释放,钙调素抑制剂W7能抑制Fn的这一作用,RGD可减轻臭氧所致的^3H释放;②臭氧攻击后细胞上清液中LDH释放增多,Fn或RGD处理均能降低LDH释放,W7阻断Fn的这一效奕;③臭氧作用后明显提高细胞内MDA含量,Fn或RGD可降低MDA含量;④臭氧攻击使细胞内GSH含量下降,Fn或RGD可增加BEC内GSH的含量;⑤Fn可增强BEC内过氧化氢酶（CAT）活性,但可被W7阻断,RGD则显示有剂量依赖性促进作用。结论：Fn及其特异识别片段与BEC的整合素分子结合后,可减轻臭氧对BEC细胞的损伤,其机理与经钙调素途径上调BEC抗氧化能力有关。     

Homology of ciliary bands in Spiralian Trochophores

A number of hypotheses have been presented regarding the originsof the metazoans and, more specifically, the Bilateria. Usingvarious phylogenetic analyses, characteristics have been mappedon phylogenetic trees to infer ancestral body plans and lifehistory strategies of those ancestors. Many arguments on theevolution of the Bilateria are based on the presumed homologyof certain characteristics of extant larva and adults, includingvarious ciliated bands involved in feeding and locomotion. Thisarticle considers a recent study indicating that the second,downstream-collecting, ciliated band in the veliger larva ofthe gastropod mollusc, Crepidula fornicata, is actually derivedfrom secondary trochoblasts (derived from second quartet micromeres),that normally form part of the prototrochal band found in otherspiralian phyla (Hejnol et al. 2007). Despite previous arguments,these new findings suggest that the second ciliated band inthe veliger larva is not homologous to the metatroch found inthe trochophore larva of some other spiralians, such as theannelid, Polygordius lacteus. In the latter case, the metatrochwas reported to be formed by a different set of lineage precursors(derived from third quartet micromeres) (Woltereck 1904). Thesefindings have important implications for the interpretationof various hypotheses related to the evolution of metazoan phyla.