Influence of hydrodynamics and cell signaling on the structure and behavior of Pseudomonas aeruginosa biofilms

Biofilms were grown from wild-type (WT) Pseudomonas aeruginosa PAO1 and the cell signaling lasI mutant PAO1-JP1 under laminar and turbulent flows to investigate the relative contributions of hydrodynamics and cell signaling for biofilm formation. Various biofilm morphological parameters were quantified using Image Structure Analyzer software. Multivariate analysis demonstrated that both cell signaling and hydrodynamics significantly (P < 0.000) influenced biofilm structure. In turbulent flow, both biofilms formed streamlined patches, which in some cases developed ripple-like wave structures which flowed downstream along the surface of the flow cell. In laminar flow, both biofilms formed monolayers interspersed with small circular microcolonies. Ripple-like structures also formed in four out of six WT biofilms, although their velocity was approximately 10 times less than that of those that formed in the turbulent flow cells. The movement of biofilm cell clusters over solid surfaces may have important clinical implications for the dissemination of biofilm subject to fluid shear, such as that found in catheters. The ability of the cell signaling mutant to form biofilms in high shear flow demonstrates that signaling mechanisms are not required for the formation of strongly adhered biofilms. Similarity between biofilm morphologies in WT and mutant biofilms suggests that the dilution of signal molecules by mass transfer effects in faster flowing systems mollifies the dramatic influence of signal molecules on biofilm structure reported in previous studies.     

Lipopolysaccharide-induced injury is more pronounced in fetal transgenic ErbB4-deleted lungs

Pulmonary ErbB4 deletion leads to a delay in fetal lung development, alveolar simplification, and lung function disturbances in adult mice. We generated a model of intrauterine infection in ErbB4 transgenic mice to study the additive effects of antenatal LPS administration and ErbB4 deletion during fetal lung development. Pregnant mice were treated intra-amniotically with an LPS dose of 4 μg at E17 of gestation. Lungs were analyzed 24 h later. A significant influx of inflammatory cells was seen in all LPS-treated lungs. In heterozygote control lungs, LPS treatment resulted in a delay of lung morphogenesis characterized by a significant increase in the fraction of mesenchyme, a decrease in gas exchange area, and disorganization of elastic fibers. Surfactant protein (Sftp)b and Sftpc were upregulated, but mRNA of Sftpb and Sftpc was downregulated compared with non-LPS-treated controls. The mRNA of Sftpa1 and Sftpd was upregulated. In ErbB4-deleted lungs, the LPS effects were more pronounced, resulting in a further delay in morphological development, a more pronounced inflammation in the parenchyma, and a significant higher increase in all Sftp. The effect on Sftpb and Sftpc mRNA was somewhat different, resulting in a significant increase. These results imply a major role of ErbB4 in LPS-induced signaling in structural and functional lung development.     

Kinetics of Inactivation of Bacillus Spores Using Low Temperature Argon Plasma at Different Microwave Power Densities

The objective of this study was to determine the remarkable role of the microwave power density of argon plasma in the inactivation of Bacillus subtilis, Bacillus stearothermophilus and Bacillus pumilus spores deposited on polypropylene bio‐indicator carriers. In particular, spore survival by argon plasma was determined as a function of the initial spore density of the bio‐indicators. The microwave induced argon plasmas were generated at 1.47, 2.63 and 4.21 w/cm³ microwave power densities under a low gas pressure of 50 Pa at an ambient temperature of 15 °C to reach low temperature distribution of 31, 35 and 43 °C, respectively. Our results indicate that the different Bacillus spores showed distinct degrees of argon plasma sensitivity, and spore survival was significantly reduced when the microwave power density of the plasma treatments was increased. Among the three Bacillus strains, Bacillus subtilis was the most argon plasma resistant, whereas Bacillus stearothermophilus was the most sensitive. However, spore survival was not affected by the initial spore density of the bio‐indicators. Only a certain degree of the spore inactivation log (No/N) from 1.67 to 1.95 was observed despite the 4‐order differences in the initial spore density of the Bacillus pumilus bio‐indicators.     

依据牙形刺确定的蒙古国塔琳波格德组（Taliin Bogd Formation）的时代

在蒙古南部波尔海尔汗乌尔(Bor hairhan uul)剖面的塔琳波格德组下部的6个样品中发现了牙形刺,通过研究清楚地表明含牙形刺动物群的塔琳波格德组下部的时代是中洛霍考夫阶(早泥盆世)到中艾菲尔阶(中泥盆世).塔琳波格德组的牙形刺动物群更接近于北美同时期的动物群,而与欧洲同期动物群相远.这一动物群可能属于冷水动物群.作者在文中描写了一个新种:Steptotaxis mongolianus sp.nov.Wang.     

Tumor-associated embryonic antigen-expressing vaccines that target CCR6 elicit potent CD8+ T cell-mediated protective and therapeutic antitumor immunity

Despite its potency, the wider use of immunotherapy for B cell malignancies is hampered by the lack of well-defined tumor-specific Ags. In this study, we demonstrate that an evolutionarily conserved 37-kDa immature laminin receptor protein (OFA-iLRP), a nonimmunogenic embryonic Ag expressed by a variety of tumors, is rendered immunogenic if targeted to the APCs using the CCR6 ligands MIP3alpha/CCL20 and mDF2beta. The CCR6 targeting facilitated efficient Ag cross-presentation and induction of tumor-neutralizing CTLs. Although the Ag targeting alone, without activation of dendritic cells (DCs), is proposed to induce tolerance, and MIP3alpha does not directly activate DCs, the MIP3alpha-based vaccine efficiently induced protective and therapeutic antitumor responses. The responses were as strong as those elicited by the OFA-iLRP fusions with moieties that activated DCs and Th1-type cytokine responses, mDF2beta, or mycobacterial Hsp70 Ag. Although the same cDNA encodes the dimerized high-affinity mature 67-kDa mLRP that is expressed in normal tissues to stabilize the binding of laminin to cell surface integrins, the vaccines expressing OFA-iLRP elicited long-term protective CD8(+) T cell-mediated memory responses against syngeneic B cell lymphoma, indicating the potential application of these simple vaccines as preventive and therapeutic formulations for human use.     

Effects of grazing and precipitation variability on vegetation dynamics in a Mongolian dry steppe

Aims Grazing and water availability are the primary drivers of vegetation dynamics in grazing-dominated regions of Mongolia with a semi-arid climate and frequent droughts. Nomadic animal husbandry still plays a large part in the economy of Mongolia, but more variable precipitation regime and increase in livestock number have severely affected grassland ecosystems through overgrazing, leading to pasture degradation. This study aimed to examine the effects of grazing exclusion, interannual variation of plant-available precipitation (PAP) and their interaction on the aboveground biomass (AGB) of each dominant species, the AGB of annual species and the total AGB in a Mongolian dry steppe, using long-term field data.Methods To detect the effect of grazing on vegetation dynamics, vegetation surveys were conducted in a non-grazed exclosure zone and a fully grazed area outside the exclosure. We assessed the effects of grazing, PAP and their interaction on AGB parameters using a generalized linear model. A detrended correspondence analysis (DCA) was used to visualize the effects of grazing and PAP on the AGB of each species.Important findings Grazing, PAP and their interaction had significant effects on AGB. The effect of grazing on AGB was larger with higher precipitation and higher amounts of AGB (i.e. forage) while AGB was strongly limited in drought years, which resulted in a smaller grazing effect. The current year PAP had the highest impact (r = 0.88, P < 0.01) on AGB. The dominance of annual species was characterized by the amount of PAP in the current and preceding years: annuals dominated in wet years that followed consecutive dry years. The DCA Axis 1 reflected the variation of AGB with interannual variation of PAP while the DCA Axis 2 differentiated the grazing effect. The DCA scatter diagram based on species score illustrated that Artemisia adamsii (an unpalatable herb) was clearly linked to grazing disturbance whereas palatable perennials such as Agropyron cristatum, Stipa krylovii and Cleistogenes squarrosa were related to grazing abandonment and wetter conditions. In brief, number of livestock, hence the grazing impacts on vegetation dynamic in this region could have driven by forage availability, which is mainly controlled by current-year PAP.     

CCR4-expressing T cell tumors can be specifically controlled via delivery of toxins to chemokine receptors

Expression of chemokine receptors by tumors, specifically CCR4 on cutaneous T cell lymphomas, is often associated with a poor disease outcome. To test the hypothesis that chemokine receptor-expressing tumors can be successfully controlled by delivering toxins through their chemokine receptors, we have generated fusion proteins designated chemotoxins: chemokines fused with toxic moieties that are nontoxic unless delivered into the cell cytosol. We demonstrate that chemokines fused with human RNase eosinophil-derived neurotoxin or with a truncated fragment of Pseudomonas exotoxin 38 are able to specifically kill tumors in vitro upon internalization through their respective chemokine receptors. Moreover, treatment with the thymus and activation-regulated chemokine (CCL17)-expressing chemotoxin efficiently eradicated CCR4-expressing cutaneous T cell lymphoma/leukemia established in NOD-SCID mice. Taken together, this work represents a novel concept that may allow control of growth and dissemination of tumors that use chemokine receptors to metastasize and circumvent immunosurveillance.     

Human peripheral blood T regulatory cells (Tregs), functionally primed CCR4+ Tregs and unprimed CCR4- Tregs, regulate effector T cells using FasL

Regulatory CD25(+)CD4(+) T cells (Tregs) play an important role in the control of peripheral tolerance. In this study we demonstrate that human peripheral blood Tregs can be divided into two distinct populations based on the expression of CCR4. The majority ( approximately 75%) of freshly isolated Tregs express CCR4 and presumably represent memory-type Tregs. Interestingly, CCR4(-) Tregs require anti-CD3 Ab-mediated activation to acquire a regulatory activity, while CCR4(+) Tregs appear to be already primed to suppress the proliferation of CD8(+) T cells. CCR4 is also expressed on CD25(low)CD4(+) T cells (CCR4(+) non-Tregs) that mostly suppress Th1-type polarization without affecting T cell proliferation, presumably via the production of immunomodulatory cytokines like IL-10. In contrast, CCR4(+) Tregs express FasL to primarily regulate T cell proliferation via a contact-mediated process involving FasL/Fas signaling, a major regulatory pathway of T cell homeostasis. Finally, we also demonstrate that the depletion of CCR4(+) T cells leads to Th1-type polarization of CD4(+) T cells and augmentation of CD8(+) T cell responses to tumor Ags.     

A comprehensive phylogeography of the widespread pond snail genus Radix revealed restricted colonization due to niche conservatism

To clarify the effect of niche conservatism on evolutionary history, we focused on freshwater snails, which have different ecological and phylogenetic properties from previously tested taxa. We conducted a phylogenetic analysis using 750 lymnaeid individuals from 357 sites of eleven Radix species. Then, we estimated the ancestral distribution using the geographic coordinates and colonization routes. In addition, a statistical test of the colonization distances in the latitudinal and longitudinal directions was performed. We also conducted ecological niche modeling for two widely distributed species using climatic data. Ancestral geographic reconstruction estimated the origin of the genus to be around the Indian subcontinental region and showed that latitudinal immigration distances were shorter than longitudinal immigration distances in the diversification process. Ecological niche models suggested that the current distribution was restricted by climate, with annual mean temperature and precipitation of the driest month as particularly strong factors. Niche conservatism to the climate can affect the diversification of freshwater snails.