LPS／D—GalN诱发ⅣF—KB转基因小鼠急性致死性肝损伤模型的建立

目的以NF—KB转基因BALB／c小鼠建立一个LPS／D—GaIN诱发的急性致死性肝损伤模型。方法采取腹腔注射高剂量的LPS／D-GalN建立急性致死性肝损伤小鼠模型,观察模型小鼠的促炎症细胞因子水平和NF—KB的活性改变,以及肝脏功能和病理改变情况。结果模型组小鼠生存时间为8—10h,模型建立后小鼠血清TNF—a、IL-6和MCP-1水平显著升高,在2—4h达到高峰;肝脏外观出现瘀血和出血,肝脏小叶被严重破坏,肝细胞严重坏死和出血;血清ALT／AST水平在模型诱发后持续迅速上升;整体成像显示胛-KB的活性在4～6h达到高峰。正常对照组小鼠以上指标无显著变化。结论成功建立LPS／D-GalN诱发的M-船转基因小鼠的急性致死性肝损伤模型。     

Mesenchymal stromal-cell transplants induce oligodendrocyte progenitor migration and remyelination in a chronic demyelination model

Demyelinating disorders such as leukodystrophies and multiple sclerosis are neurodegenerative diseases characterized by the progressive loss of myelin that may lead toward a chronic demyelination of the brain''s white matter, impairing normal axonal conduction velocity and ultimately causing neurodegeneration. Current treatments modifying the pathological mechanisms are capable of ameliorating the disease; however, frequently, these therapies are not sufficient to repress the progressive demyelination into a chronic condition and permanent loss of function. To this end, we analyzed the effect that bone marrow-derived mesenchymal stromal cell (BM-MSC) grafts exert in a chronically demyelinated mouse brain. As a result, oligodendrocyte progenitors were recruited surrounding the graft due to the expression of various trophic signals by the grafted MSCs. Although there was no significant reaction in the non-grafted side, in the grafted regions oligodendrocyte progenitors were detected. These progenitors were derived from the nearby tissue as well as from the neurogenic niches, including the subependymal zone and dentate gyrus. Once near the graft site, the cells matured to myelinating oligodendrocytes. Finally, electrophysiological studies demonstrated that axonal conduction velocity was significantly increased in the grafted side of the fimbria. In conclusion, we demonstrate here that in chronic demyelinated white matter, BM-MSC transplantation activates oligodendrocyte progenitors and induces remyelination in the tissue surrounding the stem cell graft.     

Connectivity in a pond system influences migration and genetic structure in threespine stickleback

Neutral genetic structure of natural populations is primarily influenced by migration (the movement of individuals and, subsequently, their genes) and drift (the statistical chance of losing genetic diversity over time). Migration between populations is influenced by several factors, including individual behavior, physical barriers, and environmental heterogeneity among populations. However, drift is expected to be stronger in populations with low immigration rate and small effective population size. With the technological advancement in geological information systems and spatial analysis tools, landscape genetics now allows the development of realistic migration models and increased insight to important processes influencing diversity of natural populations. In this study, we investigated the relationship between landscape connectivity and genetic distance of threespine stickleback (Gasterosteus aculeatus) inhabiting a pond complex in Belgjarskógur, Northeast Iceland. We used two landscape genetic approaches (i.e., least-cost-path and isolation-by-resistance) and asked whether gene flow, as measured by genetic distance, was more strongly associated with Euclidean distance (isolation-by-distance) or with landscape connectivity provided by areas prone to flooding (as indicated by Carex sp. cover)? We found substantial genetic structure across the study area, with pairwise genetic distances among populations (D_PS) ranging from 0.118 to 0.488. Genetic distances among populations were more strongly correlated with least-cost-path and isolation-by-resistance than with Euclidean distance, whereas the relative contribution of isolation-by-resistance and Euclidian distance could not be disentangled. These results indicate that migration among stickleback populations occurs via periodically flooded areas. Overall, this study highlights the importance of transient landscape elements influencing migration and genetic structure of populations at small spatial scales.     

p53 DNA Binding Cooperativity Is Essential for Apoptosis and Tumor Suppression In Vivo

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Calponin 2 Acts As an Effector of Noncanonical Wnt-Mediated Cell Polarization during Neural Crest Cell Migration

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Highlights? Cnn2 is expressed in NCCs and required for their migration in frogs and chicks ? Cnn2 is inactivated by noncanonical Wnt signaling ? Loss of Cnn2 causes a switch from cortical actin to central stress fibers ? Cnn2 polarizes the actin cytoskeleton downstream of PCP     

A Systematic Approach for the Genetic Dissection of Protein Complexes in Living Cells

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Effect of Dietary Mono- and Polyunsaturated Fatty Acids on the Fatty Acid Composition of Pigs' Adipose Tissues

In two experiments with growing-finishing pigs six different dietary fats were added to a conventional diet (control - C) to study the effects of dietary monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA) on the fatty acid composition of backfat and kidney fat at similar amounts of double bonds in feed (Exp. 1:7% pork fat - PF, 4.95% olive oil - OO, 3.17% soybean oil - SO) or a constant amount of 5% of processed fats (Exp. 2: partially hydrogenated fat - SAT, fractionated pork fats: olein - OLE, stearin - STE). Compared with the control, PUFA were only slightly increased in backfat of pigs fed PF, OLE, STE or OO, although dietary PUFA intake was up to 70% higher. With SO PUFA were significantly increased in adipose tissues, predominantly at the expense of MUFA. Consequently, a non-linear relationship was found between PUFA intake and proportion in backfat. MUFA were incorporated at the expense of SFA, therefore, adipose tissues of OO fed animals were lowest in SFA. Despite comparable amounts of double bonds in feed (Exp. 1), the degree of unsaturation measured as fat score (sum of double bonds) was in the order SO > OO > PF > C. In contrast, the proportion of SFA was C > PF = SO > OO. Regarding the decisive role of SFA for fat consistency it may be concluded that MUFA should also be considered in feeding recommendations for pigs. Furthermore, in case of a high dietary supply of MUFA, a simple index of double bonds might not be sufficiently conclusive to judge pig fat quality.     

On the toxicokinetics and the metabolism of deoxynivalenol (don) in the pig

Eleven castrated male pigs weighing 88.1?±?3.9?kg on average were adapted to a diet containing DON (4.2?mg DON/kg) over a period of 7 days. Feed was given restrictively with 1.1?kg per meal (two meals per day). On the day of measurement, all pigs were slaughtered at different time intervals following the morning meal containing DON (1, 2, 3, 4, 5, 6, 8, 15, 18 and 24?h after feeding), with the exception of one pig which was slaughtered unfed. DON and de-epoxy-DON were analysed in serum and digesta from consecutive segments of the digestive tract (stomach, small intestine divided into three parts of a similar length, caecum, colon, rectum). DON was rapidly and nearly completely absorbed while passing through the stomach and the proximal small intestine. Maximum serum concentration appeared 4.1?h after the DON-containing meal and half of the systemically absorbed DON was eliminated after 5.8?h. De-epoxy-DON appeared in increasing proportions from the distal small intestine and reached approximately 80% of the sum of DON plus de-epoxy-DON in faeces collected from the rectum. It was concluded that de-epoxydation of DON, which primarily occurs in the hindgut, probably does not contribute much to a detoxification in the pig.     

Individualized closed-loop control of propofol anesthesia: A preliminary study

This paper proposes an individualized approach to closed-loop control of depth of hypnosis during propofol anesthesia. The novelty of the paper lies in the individualization of the controller at the end of the induction phase of anesthesia, based on a patient model identified from the dose–response relationship during induction of anesthesia. The proposed approach is shown to be superior to administration of propofol based on population-based infusion schemes tailored to individual patients. This approach has the potential to outperform fully adaptive approaches in regards to controller robustness against measurement variability due to surgical stimulation. To streamline controller synthesis, two output filters were introduced (inverting the Hill dose–response model and the linear time-invariant sensor model), which yield a close-to-linear representation of the system dynamics when used with a compartmental patient model. These filters are especially useful during the induction phase of anesthesia in which a nonlinear dose–response relationship complicates the design of an appropriate controller. The proposed approach was evaluated in simulation on pharmacokinetic and pharmacodynamic models of 44 patients identified from real clinical data. A model of the NeuroSense, a hypnotic depth monitor based on wavelet analysis of EEG, was also included. This monitor is similar to the well-known BIS, but has linear time-invariant dynamics and does not introduce a delay. The proposed scheme was compared with a population-based controller, i.e. a controller only utilizing models based on demographic covariates for its tuning. On average, the proposed approach offered 25% improvement in disturbance attenuation, measured as the integrated absolute error following a step disturbance. The corresponding standard deviation from the reference was also decreased by 25%. Results are discussed and possible directions of future work are proposed.     

Distribution patterns of Dikarya in arid and semiarid soils of Baja California,Mexico

Approximately four-fifths of the land area of Baja California (BC) in Mexico are occupied by arid and semiarid soils, the mycobiota of which is virtually uncharacterized. In the first culture-independent study of the mycobiota of BC, we collected soil from five different locations in the region and constructed a Dikarya-specific gene library for the ITS region of nuclear ribosomal DNA. Clones were analyzed by RFLP, were sequenced for phylogenetic analyses, and diversity and similarity indices were calculated. The ascomycete Penicillium dipodomyicola was the most frequent fungus found in soil at the most arid location studied, and the basidiomycete Coprinellus radians was the most frequent at the location receiving the highest rainfall. Other frequent members of the soil mycobiota were identified as Alternaria spp., Ceratobasidium sp., Coniozyma leucospermi, Nematoctonus robustus, Penicillium griseofulvum, Tulostoma kotlabae and uncultured members of the Dikarya. Several sequences were identified as those of uncultured fungi, one of which was previously reported from other hot deserts. Arid soils and the transitional zones between arid and semiarid soils had the most similar fungal diversity, with the former soils having a community from which basidiomycetes were absent, and the soil receiving the highest precipitation having a community dominated by basidiomycetes.