A crucial role for CD44 in inflammation

Current therapies for chronic inflammatory diseases typically act through the nonspecific downregulation of immune cell activation. However, it is becoming increasingly evident that parenchymal cells are also active participants in the inflammatory process. Future prospects for the treatment of inflammation should therefore include the targeting of specific inflammatory pathways in both immune cells and parenchymal cells. CD44, a cell-adhesion molecule that is ubiquitously expressed on leukocytes and parenchymal cells, has been implicated, together with its ligand hyaluronan (HA), in several inflammatory diseases. The mechanisms of action of CD44-HA interactions in inflammation might provide potential targets for therapy.     

Amberlite IR-120 Modified with 8-Hydroxyquinoline as Efficient Adsorbent for Solid-Phase Extraction and Flame Atomic Absorption Determination of Trace Amounts of Some Metal Ions

In this study, a solid-phase extraction method combined with atomic absorption spectrometry for extraction, preconcentration, and determination of iron (Fe³⁺), copper (Cu²⁺), and lead (Pb²⁺) ions at trace levels in water samples has been reported. The influences of effective parameters such as flow rate, pH, eluent conditions (type, volume, and concentration), sample volumes, and interference of matrix ions on metal ions recoveries were studied. Under optimized conditions, the limits of detection were found in the range of 0.7–2.2 μg L⁻¹, while preconcentration factors for Fe³⁺, Cu²⁺, and Pb²⁺ ions were found to be 166, 200, and 250, respectively, and loading half time (t _1/2) values were less than 2 min for all analyte ions. The proposed procedure was applied for the determination of metal ions in different water samples with recovery of >94.4% and relative standard deviation less than 4.4% for N = 5.     

Relating tissue specialization to the differentiation of expression of singleton and duplicate mouse proteins

Background  

Gene duplications have been hypothesized to be a major factor in enabling the evolution of tissue differentiation. Analyses of the expression profiles of duplicate genes in mammalian tissues have indicated that, with time, the expression patterns of duplicate genes diverge and become more tissue specific. We explored the relationship between duplication events, the time at which they took place, and both the expression breadth of the duplicated genes and the cumulative expression breadth of the gene family to which they belong.     

Tomato MAPKKKε is a positive regulator of cell-death signaling networks associated with plant immunity

Mitogen-activated protein (MAP) kinase cascades are fundamental components of the signaling pathways associated with plant immunity. Despite the large number of MAP kinase kinase kinases (MAPKKK) encoded in the plant genome, only very few of them have an assigned function. Here, we identified MAPKKK gene of tomato (Solanum lycopersicum), SIMAPKKKε, which is required for hypersensitive response cell death and disease resistance against Gram-negative bacterial pathogens. Silencing of SIMAPKKKε compromised tomato resistance to Xanthomonas campestris and Pseudomonas syringae strains, resulting in the appearance of disease symptoms and enhanced bacterial growth. In addition, silencing of NbMAPKKKε in Nicotiana benthamiana plants significantly inhibited the cell death triggered by expression of different R gene/effector gene pairs. Conversely, overexpression of either the full-length SIMAPKKKε gene or its kinase domain in N. benthamiana leaves caused pathogen-independent activation of cell death that required an intact kinase catalytic domain. Moreover, by suppressing the expression of various MAPKK and MAPK genes and overexpressing the SIMAPKKKε kinase domain, we identified a signaling cascade acting downstream of SIMAPKKKε that includes MEK2, WIPK and SIPK. Additional epistasis experiments revealed that SIPKK functions as a negative regulator of SIMAPKKKε-mediated cell death. Our results provide evidence that SIMAPKKKε is a signaling molecule that positively regulates cell death networks associated with plant immunity.     

The role of integrin glycosylation in galectin-8-mediated trabecular meshwork cell adhesion and spreading

Primary open angle glaucoma (POAG) is a major blindness-causingdisease, characterized by elevated intraocular pressure dueto an insufficient outflow of aqueous humor. The trabecularmeshwork (TM) lining the aqueous outflow pathway modulates theaqueous outflow facility. TM cell adhesion, cell–matrixinteractions, and factors that influence Rho signaling in TMcells are thought to play a pivotal role in the regulation ofaqueous outflow. In a recent study, we demonstrated that galectin-8(Gal8) modulates the adhesion and cytoskeletal arrangement ofTM cells and that it does so through binding to β₁ integrinsand inducing Rho signaling. The current study is aimed at thecharacterization of the mechanism by which Gal8 mediates TMcell adhesion and spreading. We demonstrate here that TM cellsadhere to and spread on Gal8-coated wells but not on galectin-1(Gal1)- or galectin-3 (Gal3)-coated wells. The adhesion of TMcells to Gal8-coated wells was abolished by a competing sugar,β-lactose, but not by a noncompeting sugar, sucrose. Also,a trisaccharide, NeuAc2-3Galβ1-4GlcNAc, which binds specificallyto the N-CRD of Gal8, inhibited the spreading of TM cells toGal8-coated wells. In contrast, NeuAc2-6Galβ1-4GlcNAc whichlacks affinity for Gal8 had no effect. Affinity chromatographyof cell extracts on a Gal8-affinity column and binding experimentswith plant lectins, Maakia Amurensis and Sambucus Nigra, revealedthat ₃β₁, ₅β₁, and _vβ₁ integrins are major counterreceptorsof Gal8 in TM cells and that TM cell β₁ integrins carrypredominantly 2-3-sialylated glycans, which are high-affinityligands for Gal8 but not for Gal1 or Gal3. These data lead usto propose that Gal8 modulates TM cell adhesion and spreading,at least in part, by interacting with 2-3-sialylated glycanson β₁ integrins.     

Reduction of isoprostanes and regression of advanced atherosclerosis by apolipoprotein E

Apolipoprotein E is a multifunctional protein synthesized by hepatocytes and macrophages. Plasma apoE is largely liver-derived and known to regulate lipoprotein metabolism. Macrophage-derived apoE has been shown to reduce the progression of atherosclerosis in mice. We tested the hypothesis that liver-derived apoE could directly induce regression of pre-existing advanced atherosclerotic lesions without reducing plasma cholesterol levels. Aged low density lipoprotein (LDL) receptor-deficient (LDLR(-/-)) mice were fed a western-type diet for 14 weeks to induce advanced atherosclerotic lesions. One group of mice was sacrificed for evaluation of atherosclerosis at base line, and two other groups were injected with a second generation adenoviruses encoding human apoE3 or a control empty virus. Hepatic apoE gene transfer increased plasma apoE levels by 4-fold at 1 week, and apoE levels remained at least 2-fold higher than controls at 6 weeks. There were no significant changes in plasma total cholesterol levels or lipoprotein composition induced by expression of apoE. The liver-derived human apoE gained access to and was retained in arterial wall. Compared with base-line mice, the control group demonstrated progression of atherosclerosis; in contrast, hepatic apoE expression induced highly significant regression of advanced atherosclerotic lesions. Regression of lesions was accompanied by the loss of macrophage-derived foam cells and a trend toward increase in extracellular matrix of lesions. As an index of in vivo oxidant stress, we quantitated the isoprostane iPF(2 alpha)-VI and found that expression of apoE markedly reduced urinary, LDL-associated, and arterial wall iPF(2 alpha)-VI levels. In summary, these results demonstrate that liver-derived apoE directly induced regression of advanced atherosclerosis and has anti-oxidant properties in vivo that may contribute to its anti-atherogenic effects.     

The Interplay between Scientific Overlap and Cooperation and the Resulting Gain in Co-Authorship Interactions

Considering the importance of scientific interactions, understanding the principles that govern fruitful scientific research is crucial to policy makers and scientists alike. The outcome of an interaction is to a large extent dependent on the balancing of contradicting motivations accompanying the establishment of collaborations. Here, we assembled a dataset of nearly 20,000 publications authored by researchers affiliated with ten top universities. Based on this data collection, we estimated the extent of different interaction types between pairwise combinations of researchers. We explored the interplay between the overlap in scientific interests and the tendency to collaborate, and associated these estimates with measures of scientific quality and social accessibility aiming at studying the typical resulting gain of different interaction patterns. Our results show that scientists tend to collaborate more often with colleagues with whom they share moderate to high levels of mutual interests and knowledge while cooperative tendency declines at higher levels of research-interest overlap, suggesting fierce competition, and at the lower levels, suggesting communication gaps. Whereas the relative number of alliances dramatically differs across a gradient of research overlap, the scientific impact of the resulting articles remains similar. When considering social accessibility, we find that though collaborations between remote researchers are relatively rare, their quality is significantly higher than studies produced by close-circle scientists. Since current collaboration patterns do not necessarily overlap with gaining optimal scientific quality, these findings should encourage scientists to reconsider current collaboration strategies.     

Increasing global agricultural production by reducing ozone damages via methane emission controls and ozone‐resistant cultivar selection

Meeting the projected 50% increase in global grain demand by 2030 without further environmental degradation poses a major challenge for agricultural production. Because surface ozone (O₃) has a significant negative impact on crop yields, one way to increase future production is to reduce O₃‐induced agricultural losses. We present two strategies whereby O₃ damage to crops may be reduced. We first examine the potential benefits of an O₃ mitigation strategy motivated by climate change goals: gradual emission reductions of methane (CH₄), an important greenhouse gas and tropospheric O₃ precursor that has not yet been targeted for O₃ pollution abatement. Our second strategy focuses on adapting crops to O₃ exposure by selecting cultivars with demonstrated O₃ resistance. We find that the CH₄ reductions considered would increase global production of soybean, maize, and wheat by 23–102 Mt in 2030 – the equivalent of a ~2–8% increase in year 2000 production worth $3.5–15 billion worldwide (USD₂₀₀₀), increasing the cost effectiveness of this CH₄ mitigation policy. Choosing crop varieties with O₃ resistance (relative to median‐sensitivity cultivars) could improve global agricultural production in 2030 by over 140 Mt, the equivalent of a 12% increase in 2000 production worth ~$22 billion. Benefits are dominated by improvements for wheat in South Asia, where O₃‐induced crop losses would otherwise be severe. Combining the two strategies generates benefits that are less than fully additive, given the nature of O₃ effects on crops. Our results demonstrate the significant potential to sustainably improve global agricultural production by decreasing O₃‐induced reductions in crop yields.     

Association between translation efficiency and horizontal gene transfer within microbial communities

Horizontal gene transfer (HGT) is a major force in microbial evolution. Previous studies have suggested that a variety of factors, including restricted recombination and toxicity of foreign gene products, may act as barriers to the successful integration of horizontally transferred genes. This study identifies an additional central barrier to HGT-the lack of co-adaptation between the codon usage of the transferred gene and the tRNA pool of the recipient organism. Analyzing the genomic sequences of more than 190 microorganisms and the HGT events that have occurred between them, we show that the number of genes that were horizontally transferred between organisms is positively correlated with the similarity between their tRNA pools. Those genes that are better adapted to the tRNA pools of the target genomes tend to undergo more frequent HGT. At the community (or environment) level, organisms that share a common ecological niche tend to have similar tRNA pools. These results remain significant after controlling for diverse ecological and evolutionary parameters. Our analysis demonstrates that there are bi-directional associations between the similarity in the tRNA pools of organisms and the number of HGT events occurring between them. Similar tRNA pools between a donor and a host tend to increase the probability that a horizontally acquired gene will become fixed in its new genome. Our results also suggest that frequent HGT may be a homogenizing force that increases the similarity in the tRNA pools of organisms within the same community.     

PfSR1 controls alternative splicing and steady‐state RNA levels in Plasmodium falciparum through preferential recognition of specific RNA motifs

Plasmodium species have evolved complex biology to adapt to different hosts and changing environments throughout their life cycle. Remarkably, these adaptations are achieved by a relatively small genome. One way by which the parasite expands its proteome is through alternative splicing (AS). We recently identified PfSR1 as a bona fide Ser/Arg‐rich (SR) protein that shuttles between the nucleus and cytoplasm and regulates AS in Plasmodium falciparum. Here we show that PfSR1 is localized adjacent to the Nuclear Pore Complex (NPC) clusters in the nucleus of early stage parasites. To identify the endogenous RNA targets of PfSR1, we adapted an inducible overexpression system for tagged PfSR1 and performed RNA immunoprecipitation followed by microarray analysis (RIP‐chip) to recover and identify the endogenous RNA targets that bind PfSR1. Bioinformatic analysis of these RNAs revealed common sequence motifs potentially recognized by PfSR1. RNA‐EMSAs show that PfSR1 preferentially binds RNA molecules containing these motifs. Interestingly, we find that PfSR1 not only regulates AS but also the steady‐state levels of mRNAs containing these motifs in vivo.