Leaf manganese concentrations as a tool to assess belowground plant functioning in phosphorus-impoverished environments

Plant and Soil - Root-released carboxylates enhance the availability of manganese (Mn), which enters roots through transporters with low substrate specificity. Leaf Mn concentration ([Mn]) has been...     

Reply to Manger’s Commentary on “A quantitative test of the thermogenesis hypothesis of cetacean brain evolution,using phylogenetic comparative methods”

In his Commentary (Manger PR. 2009. Subglacial cetaceans and other mathematical mysteries: a Commentary on “A quantitative test of the thermogenesis hypothesis of cetacean brain evolution, using phylogenetic comparative methods” by C. Maximino. Mar Fresh Behav Physiol. 42: 359–362) on my paper (Maximino C. 2009. A quantitative test of the thermogenesis hypothesis of cetacean brain evolution, using phylogenetic comparative methods. Mar Freshwater Behav Physiol. 42:1–17), Dr Paul Manger noted four errors in the quantitative analysis of the relationship between cetacean encephalization quotients (EQs) and water temperatures, which I suggested was a test of his thermogenesis hypothesis (Manger PR. 2006 Manger, PR. 2006. An examination of cetacean brain structure with a novel hypothesis correlating thermogenesis to the evolution of a big brain. Biol Rev Camb Philos Soc, 81: 293–338.  [Google Scholar]. An examination of cetacean brain structure with a novel hypothesis correlating thermogenesis to the evolution of a big brain. Biol Rev Camb Philos Soc. 81:293–338). These referred to incorrect raw data on water temperatures for two species, odd use of midpoint temperatures as independent variable, lack of inclusion of data on Mysticeti and the use of a differently derived EQ and midpoints instead of the EQs proposed by Manger and temperature ranges; Dr Manger proposed that these errors invalidate the analysis, with special emphasis in an observation that, since my paper did not address the relationship between EQs and temperature range, it did not actually test the thermogenesis hypothesis. In this Reply, I apologize for the mistakes which were made, and show that re-analysis using all the proposed alterations do not qualitatively or quantitatively alter the final result. I also argue that the relationship between phylogenetically correct EQs and midpoint temperatures is a better test of the thermogenesis hypothesis than the relationship between non-phylogenetic EQs and temperature ranges.     

Immobilization and stabilization of a bimolecular aggregate of the lipase from Pseudomonas fluorescens by multipoint covalent attachment

The soluble lipase from Pseudomonas fluorescens (PFL) forms bimolecular aggregates in which the hydrophobic active centers of the enzyme monomers are in close contact. This bimolecular aggregate could be immobilized by multipoint covalent linkages on glyoxyl supports at pH 8.5. The monomer of PFL obtained by incubation of the soluble enzyme in the presence of detergent (0.5% TRITON X-100) could not be immobilized under these conditions. The bimolecular aggregate has two amino terminal residues in the same plane. A further incubation of the immobilized derivative under more alkaline conditions (e.g., pH 10.5) allows a further multipoint attachment of lysine (Lys) residues located in the same plane as the amino terminal residues. Monomeric PFL was immobilized at pH 10.5 in the presence of 0.5% TRITON X-100. The properties of both PFL derivatives were compared. In general, the bimolecular derivatives were more active, more selective and more stable both in water and in organic solvents than the monomolecular ones. The bimolecular derivative showed twice the activity and a much higher selectivity (100 versus 20) for the hydrolysis of R,S-2-hydroxy-4-phenylbutyric acid ethyl ester (HPBEt) in aqueous media at pH 5.0 compared to the monomeric derivative. In experiments measuring thermal inactivation at 75 °C, the bimolecular derivative was 5-fold more stable than the monomeric derivative (and 50-fold more stable than a one-point covalently immobilized PFL derivative), and it had a half-life greater than 4 h. In organic solvents (cyclohexane and tert-amyl alcohol), the bimolecular derivative was much more stable and more active than the monomeric derivative in catalyzing the transesterification of olive oil with benzyl alcohol.     

Inhibiting AKT Phosphorylation Employing Non-Cytotoxic Anthraquinones Ameliorates TH2 Mediated Allergic Airways Disease and Rhinovirus Exacerbation

Background

Severe asthma is associated with T helper (T_H) 2 and 17 cell activation, airway neutrophilia and phosphoinositide-3-kinase (PI3K) activation. Asthma exacerbations are commonly caused by rhinovirus (RV) and also associated with PI3K-driven inflammation. Anthraquinone derivatives have been shown to reduce PI3K-mediated AKT phosphorylation in-vitro.

Objective

To determine the anti-inflammatory potential of anthraquinones in-vivo.

Methods

BALB/c mice were sensitized and challenged with crude house dust mite extract to induce allergic airways disease and treated with mitoxantrone and a novel non-cytotoxic anthraquinone derivative. Allergic mice were also infected with RV1B to induce an exacerbation.

Results

Anthraquinone treatment reduced AKT phosphorylation, hypoxia-inducible factor-1α and vascular endothelial growth factor expression, and ameliorated allergen- and RV-induced airways hyprereactivity, neutrophilic and eosinophilic inflammation, cytokine/chemokine expression, mucus hypersecretion, and expression of T_H2 proteins in the airways. Anthraquinones also boosted type 1 interferon responses and limited RV replication in the lung.

Conclusion

Non-cytotoxic anthraquinone derivatives may be of therapeutic benefit for the treatment of severe and RV-induced asthma by blocking pro-inflammatory pathways regulated by PI3K/AKT.     

Glocal Clinical Registries: Pacemaker Registry Design and Implementation for Global and Local Integration – Methodology and Case Study

Background

The ability to apply standard and interoperable solutions for implementing and managing medical registries as well as aggregate, reproduce, and access data sets from legacy formats and platforms to advanced standard formats and operating systems are crucial for both clinical healthcare and biomedical research settings.

Purpose

Our study describes a reproducible, highly scalable, standard framework for a device registry implementation addressing both local data quality components and global linking problems.

Methods and Results

We developed a device registry framework involving the following steps: (1) Data standards definition and representation of the research workflow, (2) Development of electronic case report forms using REDCap (Research Electronic Data Capture), (3) Data collection according to the clinical research workflow and, (4) Data augmentation by enriching the registry database with local electronic health records, governmental database and linked open data collections, (5) Data quality control and (6) Data dissemination through the registry Web site. Our registry adopted all applicable standardized data elements proposed by American College Cardiology / American Heart Association Clinical Data Standards, as well as variables derived from cardiac devices randomized trials and Clinical Data Interchange Standards Consortium. Local interoperability was performed between REDCap and data derived from Electronic Health Record system. The original data set was also augmented by incorporating the reimbursed values paid by the Brazilian government during a hospitalization for pacemaker implantation. By linking our registry to the open data collection repository Linked Clinical Trials (LinkedCT) we found 130 clinical trials which are potentially correlated with our pacemaker registry.

Conclusion

This study demonstrates how standard and reproducible solutions can be applied in the implementation of medical registries to constitute a re-usable framework. Such approach has the potential to facilitate data integration between healthcare and research settings, also being a useful framework to be used in other biomedical registries.     

Fish biodiversity of Saint Peter and Saint Paulʼs Archipelago,Mid-Atlantic Ridge,Brazil: new records and a species database

Saint Peter and Saint Paul's Archipelago (SPSPA), one of the smallest and most isolated island groups in the world, is situated on the Mid-Atlantic Ridge, between Brazil and the African continent. SPSPA has low species richness and high endemism; nonetheless, the diversity of fishes from deep habitats (>30 m depth) had not been previously studied in detail. Several expeditions conducted between 2009 and 2018 explored the shallow and deep reefs of SPSPA using scuba, closed-circuit rebreathers, manned submersibles, baited remote underwater stereo-videos (stereo-BRUV) and fishing between 0 and 1050 m depth. These expeditions yielded 41 new records of fishes for SPSPA: 9 in open waters, 9 in shallow waters (0–30 m), 8 in mesophotic ecosystems (30–150 m) and 15 in deeper reefs (>150 m). Combined with literature records of adult pelagic, shallow and deep-reef species, as well as larvae, the database of the fish biodiversity for SPSPA currently comprises 225 species (169 recorded as adult fishes and 79 as larvae, with 23 species found in both stages). Most of them (112) are pelagic, 86 are reef-associated species and 27 are deep-water specialists. Species accumulation curves show that the number of fish species has not yet reached an asymptote. Whereas the number of species recorded in SPSPA is similar to that in other oceanic islands in the Atlantic Ocean, the proportion of shorefishes is relatively lower, and the endemism level is the third highest in the Atlantic. Twenty-nine species are listed as threatened with extinction. Observations confirm the paucity of top predators on shallow rocky reefs of the island, despite the presence of several pelagic shark species around SPSPA. Because all of the endemic species are reef associated, it is argued that the new marine-protected areas created by the Brazilian government do not ensure the protection and recovery of SPSPA's biodiversity because they allow exploitation of the most vulnerable species around the archipelago itself. This study suggests a ban on reef fish exploitation inside an area delimited by the 1000 m isobath around the islands (where all known endemics are concentrated) as the main conservation strategy to be included in the SPSPA management plan being prepared by the Brazilian government.     

Development of a novel anti-biofilm peptide derived from profilin of Spodoptera frugiperda

Abstract

Candida yeast infections are the fourth leading cause of death worldwide. Peptides with antimicrobial activity are a promising alternative treatment for such infections. Here, the antifungal activity of a new antimicrobial peptide—PEP-IA18—was evaluated against Candida species. PEP-IA18 was designed from the primary sequence of profilin, a protein from Spodoptera frugiperda, and displayed potent activity against Candida albicans and Candida tropicalis, showing a minimum inhibitory concentration (MIC) of 2.5?µM. Furthermore, the mechanism of action of PEP-IA18 involved interaction with the cell membrane (ergosterol complexation). Treatment at MIC and/or 10?×?MIC significantly reduced biofilm formation and viability. PEP-IA18 showed low toxicity toward human fibroblasts and only revealed hemolytic activity at high concentrations. Thus, PEP-IA18 exhibited antifungal and anti-biofilm properties with potential applicability in the treatment of infections caused by Candida species.     

Activity of sodium trimetaphosphate,associated or not with fluoride,on dual-species biofilms

Abstract

A response surface methodology was used to build a model to predict reductions in uropathogenic Escherichia coli biofilms in response to three compounds: cranberry extract [CB] at 3.0–9.0%, and caprylic acid [CAR] and thymol [TM] at 0.01%–0.05%. The predictive model for microbial reduction had a high regression coefficient (R²?=?0.9988), and the accuracy of the model was verified (R²?=?0.9527). Values of CAR, TM, and the quadratic term CAR² were the most significant (P?10 reduction) determined by ridge analysis were 8.3% CB +0.04% CAR +0.04% TM at 37?°C for 1?min. The model could be used to predict the most cost-efficient amounts of antimicrobial agents for anti-urinary tract infection products such as catheter lock solution and antimicrobial coatings for catheters.     

Pam3CSK4 adjuvant given intranasally boosts anti-Leishmania immunogenicity but not protective immune responses conferred by LaAg vaccine against visceral leishmaniasis

The use of adjuvants in vaccine formulations is a well-established practice to improve immunogenicity and protective immunity against diseases. Previously, we have demonstrated the feasibility of intranasal vaccination with the antigen of killed Leishmania amazonensis promastigotes (LaAg) against experimental leishmaniasis. In this work, we sought to optimize the immunogenic effect and protective immunity against murine visceral leishmaniasis conferred by intranasal delivery of LaAg in combination with a synthetic TLR1/TLR2 agonist (Pam3CSK4). Intranasal vaccination with LaAg/PAM did not show toxicity or adverse effects, induced the increase of delayed-type hypersensitivity response and the production of inflammatory cytokines after parasite antigen recall. However, mice vaccinated with LaAg/PAM and challenged with Leishmania infantum presented significant reduction of parasite burden in both liver and spleen, similar to those vaccinated with LaAg. Although LaAg/PAM intranasal vaccination had induced higher frequencies of specific CD4⁺ and CD8⁺ T cells and increased levels of IgG2a antibody isotype in serum, both LaAg and LaAg/PAM groups presented similar levels of IL-4 and IFN-y and decreased production of IL-10 when compared to controls. Our results provide the first evidence of the feasibility of intranasal immunization with antigens of killed Leishmania in association with a TLR agonist, which may be explored for developing an effective and alternative strategy for vaccination against visceral leishmaniasis.