A new monoclonal antibody (3D3) generated with human respiratory mucins and directed against Lewis determinants

We have prepared a monoclonal antibody (MAb), 3D3, raised againstpurified human respiratory mucins. This antibody recognizedmucins and proteolytically derived glycopeptides. The epitoperecognized by the antibody was destroyed by -L-fucosidase, indicatingthat it was present on the carbohydrate moieties. Structuralspecificity was determined by adsorption on a variety of synthetic,insolubilized oligosaccharides. Several lines of evidence indicatethat the 3D3 MAb reacted strongly with the Lewis (Le^b) antigen,but also recognized Le^a and Le^y determinants. This antibodymight be useful to study mucin secretion. human bronchial mucins Lewis b     

Hydroxamic acid derivatives as histone deacetylase inhibitors: a DFT study of their tautomerism and metal affinities/selectivities

Hydroxamic acids are regarded as potent inhibitors of histone deacetylases (HDAC), and can therefore be used to reduce malignancy growth and size in affected organisms. Although there is a substantial body of information on the structures, syntheses, and biological activities of HDAC inhibitors, several important questions regarding their physicochemical properties and metal affinities/selectivities remain answered. First, how do the conformation and ionization of the hydroxamic group depend on its chemical composition and the dielectric properties of the medium? Second, how do these factors affect the affinities and selectivities of HDAC inhibitors for essential biogenic metal cations? Third, what is the preferred deprotonation site of the hydroxamic moiety and its mode of binding to the metal cation? The present work addressed these questions by performing density functional calculations combined with polarizable continuum model computations. The geometry, deprotonation pattern, metal-binding mode, and metal affinity/selectivity of SAHA, a typical HDAC inhibitor, were examined, and key factors affecting its ligation properties were elucidated. Sulfur- and selenium-containing analogs of SAHA were also modeled for the first time, and their potential as efficient metal-binding entities (to Mg²⁺, Fe²⁺, and Zn²⁺ cations) was assessed. The present calculations shed light on the thermodynamics of the binding of HDAC inhibitors to metal ions, and suggest techniques for enhancing their metal-ligating properties.     

Integrating correlation between traits improves spatial predictions of plant functional composition

Functional trait composition is increasingly recognized as key to better understand and predict community responses to environmental gradients. Predictive approaches traditionally model the weighted mean trait values of communities (CWMs) as a function of environmental gradients. However, most approaches treat traits as independent regardless of known tradeoffs between them, which could lead to spurious predictions. To address this issue, we suggest jointly modeling a suit of functional traits along environmental gradients while accounting for relationships between traits. We use generalized additive mixed effect models to predict the functional composition of alpine grasslands in the Guisane Valley (France). We demonstrate that, compared to traditional approaches, joint trait models explain considerable amounts of variation in CWMs, yield less uncertainty in trait CWM predictions and provide more realistic spatial projections when extrapolating to novel environmental conditions. Modeling traits and their co‐variation jointly is an alternative and superior approach to predicting traits independently. Additionally, compared to a ‘predict first, assemble later’ approach that estimates trait CWMs post hoc based on stacked species distribution models, our ‘assemble first, predict later’ approach directly models trait‐responses along environmental gradients, and does not require data and models on species’ distributions, but only mean functional trait values per community plot. This highlights the great potential of joint trait modeling approaches in large‐scale mapping applications, such as spatial projections of the functional composition of vegetation and associated ecosystem services as a response to contemporary global change.     

Complete genome sequencing of sixteen Francisella noatunensis subsp. orientalis isolates: A genomic approach for molecular characterization and spread dynamics of this clonal population

Francisella noatunensis subsp. orientalis (FNO) is an important emerging pathogen associated with disease outbreaks in farm-raised Nile tilapia. FNO genetic diversity using PCR-based typing, no intra-species discrimination was achieved among isolates/strains from different countries, thus demonstrating a clonal behaviour pattern. In this study, we aimed to evaluate the population structure of FNO isolates by comparing whole-genome sequencing data. The analysis of recombination showed that Brazilian isolates group formed a clonal population; whereas other lineages are also supported by this analysis for isolates from foreign countries. The whole-genome multilocus sequence typing (wgMLST) analysis showed varying numbers of dissimilar alleles, suggesting that the Brazilian clonal population are in expansion. Each Brazilian isolate could be identified as a single node by high-resolution gene-by-gene approach, presenting slight genetic differences associated to mutational events. The common ancestry node suggests a single entry into the country before 2012, and the rapid dissemination of this infectious agent may be linked to market sales of infected fingerlings.     

Soybean defense induction to <Emphasis Type="Italic">Spodoptera cosmioides</Emphasis> herbivory is dependent on plant genotype and leaf position

Plants have evolved a diverse array of defensive mechanisms against biotic and abiotic stresses, which can be either constitutive or inducible. Variation in plant-intrinsic factors such as the genotype and the leaf position coupled with insect herbivory can affect the expression of resistance to insects. We investigated if soybean defense induction triggered by Spodoptera cosmioides herbivory varies in function of the genotype and leaf position. This hypothesis was tested in two bioassays using leaf discs or entire leaflets collected from the upper and lower trifoliates of S. cosmioides-injured and uninjured V3-V4 soybean plants. We used one genotype that was constitutively resistant and one that was constitutively susceptible to S. cosmioides based on previous screening. Third-instar larvae were fed one of the treatments and assayed for leaf consumption, larval growth, and efficiency of conversion of ingested food. Genotype and leaf position significantly interacted with herbivory and affected soybean-induced resistance to S. cosmioides. Negative responses on S. cosmioides larvae consumption and growth rates were only observed when leaf material was originated from the upper soybean trifoliate. The susceptible soybean genotype did not exhibit induced resistance characteristics. Food offered as leaf disc was better at demonstrating induced resistance in previously injured soybean, whereas offering entire leaflet the induced effects were less pronounced. Here we provide new findings on soybean resistance by demonstrating that resistance induction to S. cosmioides herbivory is dependent on the plant genotype and leaf position where injury took place, with negative effects better evinced in bioassays using leaf discs than entire leaflets.     

Essential Elements as Biomarkers of Acute Kidney Injury and Spontaneous Reversion

Acute kidney injury (AKI) is an important health problem and can be caused by number of factors. The use of aminoglycosides, such as gentamicin, is one of these factors. Recently, an effort has been made to find biomarkers to guide treatment protocols. Inductively coupled plasma optical emission spectroscopy (ICP-OES) was used to estimate the contents of Ca, Cu, Fe, K, Mg, Mn, Na, P, and Zn in serum and urine of the healthy, AKI, and spontaneous recovery (SR) groups of animals. The animal model of AKI and SR was validated by measuring serum and urinary urea and creatinine. The quantitative determination of the elements showed a decrease in serum levels of Ca, and Fe in the AKI group (P<0.01 vs. healthy), with a return to normal levels in the SR group, without a significant difference between the healthy and SR groups. In the urine samples, there was a decrease in P and Na levels in the AKI group (P<0.001 and P<0.01 vs. healthy), but Ca levels were increased in this group compared with the healthy and SR groups (P<0.01). These findings indicate that mineral elements might be useful as biomarkers for AKI.     

Identification of a C-terminal poly(A)-binding protein (PABP)-PABP interaction domain: role in cooperative binding to poly (A) and efficient cap distal translational repression

The poly(A)-binding protein (PABP), bound to the 3' poly(A) tail of eukaryotic mRNAs, plays critical roles in mRNA translation and stability. PABP autoregulates its synthesis by binding to a conserved A-rich sequence present in the 5'-untranslated region of PABP mRNA and repressing its translation. PABP is composed of two parts: the highly conserved N terminus, containing 4 RNA recognition motifs (RRMs) responsible for poly(A) and eIF4G binding; and the more variable C terminus, which includes the recently described PABC domain, and promotes intermolecular interaction between PABP molecules as well as cooperative binding to poly(A). Here we show that, in vitro, GST-PABP represses the translation of reporter mRNAs containing 20 or more A residues in their 5'-untranslated regions and remains effective as a repressor when an A61 tract is placed at different distances from the cap, up to 126 nucleotides. Deletion of the PABP C terminus, but not the PABC domain alone, significantly reduces its ability to inhibit translation when bound to sequences distal to the cap, but not to proximal ones. Moreover, cooperative binding by multiple PABP molecules to poly(A) requires the C terminus, but not the PABC domain. Further analysis using pull-down assays shows that the interaction between PABP molecules, mediated by the C terminus, does not require the PABC domain and is enhanced by the presence of RRM 4. In vivo, fusion proteins containing parts of the PABP C terminus fused to the viral coat protein MS2 have an enhanced ability to prevent the expression of chloramphenicol acetyltransferase reporter mRNAs containing the MS2 binding site at distal distances from the cap. Altogether, our results identify a proline- and glutamine-rich linker located between the RRMs and the PABC domain as being strictly required for PABP/PABP interaction, cooperative binding to poly(A) and enhanced translational repression of reporter mRNAs in vitro and in vivo.