RNA and β-Hemolysin of Group B Streptococcus Induce Interleukin-1β (IL-1β) by Activating NLRP3 Inflammasomes in Mouse Macrophages

The inflammatory cytokine IL-1β is critical for host responses against many human pathogens. Here, we define Group B Streptococcus (GBS)-mediated activation of the Nod-like receptor-P3 (NLRP3) inflammasome in macrophages. NLRP3 activation requires GBS expression of the cytolytic toxin, β-hemolysin, lysosomal acidification, and leakage. These processes allow the interaction of GBS RNA with cytosolic NLRP3. The present study supports a model in which GBS RNA, along with lysosomal components including cathepsins, leaks out of lysosomes and interacts with NLRP3 to induce IL-1β production.     

Interaction of brassinosteroid functions and sucrose transporter SlSUT2 regulate the formation of arbuscular mycorrhiza

Transgenic tomato plants with reduced expression of the sucrose transporter SlSUT2 showed higher efficiency of mycorrhization suggesting a sucrose retrieval function of SlSUT2 from the peri-arbuscular space back into the cell cytoplasm plant cytoplasm thereby limiting mycorrhiza fungal development. Sucrose uptake in colonized root cells requires efficient plasma membrane-targeting of SlSUT2 which is often retained intracellularly in vacuolar vesicles. Protein-protein interaction studies suggested a link between SISUT2 function and components of brassinosteroid biosynthesis and signaling. Indeed, the tomato DWARF mutant d^x defective in BR synthesis¹ showed significantly reduced mycorrhization parameters.² The question has been raised whether the impact of brassinosteroids on mycorrhization is a general phenomenon. Here, we include a rice mutant defective in DIM1/DWARF1 involved in BR biosynthesis to investigate the effects on mycorrhization. A model is presented where brassinolides are able to impact mycorrhization by activating SUT2 internalization and inhibiting its role in sucrose retrieval.     

Modeling the Impact of Adjustable Gastric Banding on Survival in Patients with Morbid Obesity

Objective: Morbid obesity is associated with premature death. Adjustable gastric banding may lead to substantial weight loss in patients with morbid obesity. Little is known about the impact of weight loss on survival after adjustable gastric banding. We therefore developed a mathematical model to estimate life expectancy in patients with a body mass index (BMI) ≥40 kg/m² undergoing bariatric surgery. Research Methods and Procedures: We developed a nonhomogeneous Markov chain consisting of five states: the absorbing state (“dead”) and the four recurrent states BMI ≥40 kg/m², BMI 36 to 39 kg/m², BMI 32 to 35 kg/m², and BMI 25 to 31 kg/m². Scenarios of weight loss and age‐ and sex‐dependent risk of death, as well as BMI‐dependent excess mortality were extracted from life tables and published literature. All patients entered the model through the state of BMI ≥40 kg/m². Results: In men aged either 18 or 65 years at the time of surgery, who moved from the state BMI ≥40 kg/m² to the next lower state of BMI 36 to 39 kg/m², life expectancy increased by 3 and 0.7 years, respectively. In women aged either 18 or 65 years at the time of surgery, who moved from the state BMI ≥40 kg/m² to the next lower state BMI 36 to 39 kg/m², life expectancy increased by 4.5 and 2.6 years, respectively. Weight loss to lower BMI strata resulted in further gains of life expectancy in both men and women. Discussion: Within the limitations of the modeling study, adjustable gastric banding in patients with morbid obesity may substantially increase life expectancy.     

Linear Discrimination,Ordination, and the Visualization of Selection Gradients in Modern Morphometrics

Linear discriminant analysis (LDA) is a multivariate classification technique frequently applied to morphometric data in various biomedical disciplines. Canonical variate analysis (CVA), the generalization of LDA for multiple groups, is often used in the exploratory style of an ordination technique (a low-dimensional representation of the data). In the rare case when all groups have the same covariance matrix, maximum likelihood classification can be based on these linear functions. Both LDA and CVA require full-rank covariance matrices, which is usually not the case in modern morphometrics. When the number of variables is close to the number of individuals, groups appear separated in a CVA plot even if they are samples from the same population. Hence, reliable classification and assessment of group separation require many more organisms than variables. A simple alternative to CVA is the projection of the data onto the principal components of the group averages (between-group PCA). In contrast to CVA, these axes are orthogonal and can be computed even when the data are not of full rank, such as for Procrustes shape coordinates arising in samples of any size, and when covariance matrices are heterogeneous. In evolutionary quantitative genetics, the selection gradient is identical to the coefficient vector of a linear discriminant function between the populations before vs. after selection. When the measured variables are Procrustes shape coordinates, discriminant functions and selection gradients are vectors in shape space and can be visualized as shape deformations. Except for applications in quantitative genetics and in classification, however, discriminant functions typically offer no interpretation as biological factors.     

Photochemical processes, carbon assimilation and RNA accumulation of sucrose transporter genes in tomato arbuscular mycorrhiza

Arbuscular mycorrhizal fungi enhance CO₂ assimilation of their hosts which ensure the demand for carbohydrates of these obligate biotrophic microorganisms. Photosynthetic parameters were measured in tomato colonised or not by the arbuscular mycorrhizal fungus Glomus mosseae. In addition, carbohydrate contents and mRNA accumulation of three sucrose transporter genes were analysed. Mycorrhizal plants showed increased opening of stomata and assimilated significant more CO₂. A higher proportion of the absorbed light was used for photochemical processes, while non-photochemical quenching and the content of photoprotective pigments were lower. Analysis of sugar contents showed no significant differences in leaves but enhanced levels of sucrose and fructose in roots, while glucose amounts stayed constant. The three sucrose transporter encoding genes of tomato SlSUT1, SlSUT2 and SlSUT4 were up-regulated providing transport capacities to transfer sucrose into the roots. It is proposed that a significant proportion of sugars is used by the mycorrhizal fungus, because only amounts of fructose were increased, while levels of glucose, which is mainly transferred towards the fungus, were nearly constant.     

Gut microbiota composition is associated with environmental landscape in honey bees

There is growing recognition that the gut microbial community regulates a wide variety of important functions in its animal hosts, including host health. However, the complex interactions between gut microbes and environment are still unclear. Honey bees are ecologically and economically important pollinators that host a core gut microbial community that is thought to be constant across populations. Here, we examined whether the composition of the gut microbial community of honey bees is affected by the environmental landscape the bees are exposed to. We placed honey bee colonies reared under identical conditions in two main landscape types for 6 weeks: either oilseed rape farmland or agricultural farmland distant to fields of flowering oilseed rape. The gut bacterial communities of adult bees from the colonies were then characterized and compared based on amplicon sequencing of the 16S rRNA gene. While previous studies have delineated a characteristic core set of bacteria inhabiting the honey bee gut, our results suggest that the broad environment that bees are exposed to has some influence on the relative abundance of some members of that microbial community. This includes known dominant taxa thought to have functions in nutrition and health. Our results provide evidence for an influence of landscape exposure on honey bee microbial community and highlight the potential effect of exposure to different environmental parameters, such as forage type and neonicotinoid pesticides, on key honey bee gut bacteria. This work emphasizes the complexity of the relationship between the host, its gut bacteria, and the environment and identifies target microbial taxa for functional analyses.     

Targeting the Acute Promyelocytic Leukemia-Associated Fusion Proteins PML/RARα and PLZF/RARα with Interfering Peptides

In acute promyelocytic leukemia (APL), hematopoietic differentiation is blocked and immature blasts accumulate in the bone marrow and blood. APL is associated with chromosomal aberrations, including t(15;17) and t(11;17). For these two translocations, the retinoic acid receptor alpha (RARα) is fused to the promyelocytic leukemia (PML) gene or the promyelocytic zinc finger (PLZF) gene, respectively. Both fusion proteins lead to the formation of a high-molecular-weight complex. High-molecular-weight complexes are caused by the “coiled-coil” domain of PML or the BTB/POZ domain of PLZF. PML/RARα without the “coiled-coil” fails to block differentiation and mediates an all-trans retinoic acid-response. Similarly, mutations in the BTB/POZ domain disrupt the high-molecular-weight complex, abolishing the leukemic potential of PLZF/RARα. Specific interfering polypeptides were used to target the oligomerization domain of PML/RARα or PLZF/RARα. PML/RARα and PLZF/RARα were analyzed for the ability to form high-molecular-weight complexes, the protein stability and the potential to induce a leukemic phenotype in the presence of the interfering peptides. Expression of these interfering peptides resulted in a reduced replating efficiency and overcame the differentiation block induced by PML/RARα and PLZF/RARα in murine hematopoietic stem cells. This expression also destabilized the PLZF/RARα-induced high-molecular-weight complex formation and caused the degradation of the fusion protein. Targeting fusion proteins through interfering peptides is a promising approach to further elucidate the biology of leukemia.     

Genomic changes underlying host specialization in the bee gut symbiont Lactobacillus Firm5

Bacteria that engage in long‐standing associations with particular hosts are expected to evolve host‐specific adaptations that limit their capacity to thrive in other environments. Consistent with this, many gut symbionts seem to have a limited host range, based on community profiling and phylogenomics. However, few studies have experimentally investigated host specialization of gut symbionts and the underlying mechanisms have largely remained elusive. Here, we studied host specialization of a dominant gut symbiont of social bees, Lactobacillus Firm5. We show that Firm5 strains isolated from honey bees and bumble bees separate into deep‐branching host‐specific phylogenetic lineages. Despite their divergent evolution, colonization experiments show that bumble bee strains are capable of colonizing the honey bee gut. However, they were less successful than honey bee strains, and competition with honey bee strains completely abolished their colonization. In contrast, honey bee strains of divergent phylogenetic lineages were able to coexist within individual bees. This suggests that both host selection and interbacterial competition play important roles in host specialization. Using comparative genomics of 27 Firm5 isolates, we found that the genomes of honey bee strains harbour more carbohydrate‐related functions than bumble bee strains, possibly providing a competitive advantage in the honey bee gut. Remarkably, most of the genes encoding carbohydrate‐related functions were not conserved among the honey bee strains, which suggests that honey bees can support a metabolically more diverse community of Firm5 strains than bumble bees. These findings advance our understanding of the genomic changes underlying host specialization.     

Host-Polarized Cell Growth in Animal Symbionts

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