Effect of Oxycations in Clay Mineral on Adsorption—Vanadyl Exchange Bentonites and Their Ability for Amiloride Removal

The presence of drugs in aquatic bodies is a prevailing issue, and their removal by adsorption is an effective treatment. Among the adsorbents, those based clay minerals have been proposed. Bentonite is a clay mineral that is widely studied as an adsorbent due to its unique physicochemical properties, such as cation exchange capacity (CEC), intercalation, and adsorption. The properties of bentonites can be improved through chemical modifications, such as the incorporation of organic and/or inorganic compounds. These modifications allow for the efficient removal of different contaminants, including pharmaceutical compounds. In this work, raw sodium bentonite (Na+-Bent) and vanadyl bentonites were prepared using 100 (BentV1), 300 (BentV3), and 500% (BentV5) of the cationic exchange capacity of the Na+-Bent and further used for amiloride removal from aqueous solution. Analysis of X-ray fluorescence and Na+ in solution after interaction indicated that the principal mechanism of interaction between bentonite and ions was the ion exchange between sodium of the matrix and vanadyl in solution. Infrared spectroscopy suggested the contribution of coordination of the interlayer water with the vanadyl ions and hydrogen bonding between vanadyl and structural OH. X-ray diffraction analysis indicated that vanadyl ions were incorporated onto Na+-Bent. Amiloride adsorption was better at pH 5.8, using a solid dosage of 75 mg of Na+-Bent, 25 mg of BentV1 and BentV5, and 50 mg of BentV3. The adsorption occurred briefly until 20 min, and maximum removal values were 457.08, 374.64, 102.56, and 25.63 mg·g−1 for Na+-Bent, BentV1, BentV3, and BentV5, respectively. At lower drug concentrations (48.78 and 91.24 mg·g−1 for Na+-Bent and BentV3), the best performance was obtained for the BentV3 sample.

Ceragenin-Coated Non-Spherical Gold Nanoparticles as Novel Candidacidal Agents

Background: Infections caused by Candida spp. have become one of the major causes of morbidity and mortality in immunocompromised patients. Therefore, new effective fungicides are urgently needed, especially due to an escalating resistance crisis. Methods: A set of nanosystems with rod- (AuR), peanut- (AuP), and star-shaped (AuS) metal cores were synthesized. These gold nanoparticles were conjugated with ceragenins CSA-13, CSA-44, and CSA-131, and their activity was evaluated against Candida strains (n = 21) through the assessment of MICs (minimum inhibitory concentrations)/MFCs (minimum fungicidal concentrations). Moreover, in order to determine the potential for resistance development, serial passages of Candida cells with tested nanosystems were performed. The principal mechanism of action of Au NPs was evaluated via ROS (reactive oxygen species) generation assessment, plasma membrane permeabilization, and release of the protein content. Finally, to evaluate the potential toxicity of Au NPs, the measurement of hemoglobin release from red blood cells (RBCs) was carried out. Results: All of the tested nanosystems exerted a potent candidacidal activity, regardless of the species or susceptibility to other antifungal agents. Significantly, no resistance development after 25 passages of Candida cells with AuR@CSA-13, AuR@CSA-44, and AuR@CSA-131 nanosystems was observed. Moreover, the fungicidal mechanism of action of the investigated nanosystems involved the generation of ROS, damage of the fungal cell membrane, and leakage of intracellular contents. Notably, no significant RBCs hemolysis at candidacidal doses of tested nanosystems was detected. Conclusions: The results provide rationale for the development of gold nanoparticles of rod-, peanut-, and star-shaped conjugated with CSA-13, CSA-44, and CSA-131 as effective candidacidal agents.

Thermal adaptation of mRNA secondary structure: stability versus lability

Macromolecular function commonly involves rapidly reversible alterations in three-dimensional structure (conformation). To allow these essential conformational changes, macromolecules must possess higher order structures that are appropriately balanced between rigidity and flexibility. Because of the low stabilization free energies (marginal stabilities) of macromolecule conformations, temperature changes have strong effects on conformation and, thereby, on function. As is well known for proteins, during evolution, temperature-adaptive changes in sequence foster retention of optimal marginal stability at a species’ normal physiological temperatures. Here, we extend this type of analysis to messenger RNAs (mRNAs), a class of macromolecules for which the stability–lability balance has not been elucidated. We employ in silico methods to determine secondary structures and estimate changes in free energy of folding (ΔGfold) for 25 orthologous mRNAs that encode the enzyme cytosolic malate dehydrogenase in marine mollusks with adaptation temperatures spanning an almost 60 °C range. The change in free energy that occurs during formation of the ensemble of mRNA secondary structures is significantly correlated with adaptation temperature: ΔGfold values are all negative and their absolute values increase with adaptation temperature. A principal mechanism underlying these adaptations is a significant increase in synonymous guanine + cytosine substitutions with increasing temperature. These findings open up an avenue of exploration in molecular evolution and raise interesting questions about the interaction between temperature-adaptive changes in mRNA sequence and in the proteins they encode.

East or Easter? Keys to the orientation of Romanesque churches along the Way of Saint James

The pilgrimage along the Way of Saint James constituted the principal mechanism for the introduction of new currents of thought into the Iberian Peninsula, such as Romanesque architecture. Taking this into account, we examined whether the standard tradition on the orientation of Christian churches was followed. We measured the orientation of 108 churches built between the end of the 10th and 13th centuries near the French Way, in the ancient kingdoms of Leon and Castile. The statistical analysis shows a clear tendency to orientate the apse of the church eastwards, specifically slightly to the north of due east. Furthermore, we found that the orientation patterns differ from one kingdom to the other. In Leon, there seems to be a predilection for the local tradition of aligning the apse toward the ecclesiastical equinox. Castile, in contrast, built their churches orientated to Easter, one of the most important feast days of Christianity.

Net Geochemical Release of Base Cations From 25 Forested Watersheds in the Catskill Region of New York

Chemical weathering of minerals is the principal mechanism by which base cations (Ca2+, Mg2+, K+, and Na+) are released and acidity is neutralized in soils, bedrock, and drainage waters. Quantifying the release of base cations from watershed soils is therefore crucial for the calculation of “critical loads” of atmospheric acidity to forest ecosystems. We used a mass-balance approach to estimate the rate of release of base cations in 25 headwater catchments in the Catskill region of New York, an area historically subject to high inputs of acid deposition. In 2010–2013, total net base cation release via geochemical processes averaged 1,704 eq ha–1 yr–1 (range: 928–2,622). Calcium accounted for 58% of this total, averaging 498 mol ha–1 yr–1 (range: 209–815). Mass balance estimates of net geochemical release of base cations were most strongly driven by stream export and biomass uptake fluxes, with only minor contributions from precipitation. Documented rates of base cation depletion from soil exchange sites in the region were also small relative to the net geochemical release rates. We observed a significant influence of bedrock type on net base cation release rates (P = 0.002), and a weak but significant negative correlation with watershed elevation (r = −0.51). Relationships with other geographic factors such as aspect and watershed size were not significant. Net base cation release was 4.5 times higher than precipitation inputs of SO42– and NO3–, suggesting that sources of acidity internal to the watershed are now more important drivers of weathering than acid deposition. Our data suggest that release of base cations from most Catskill forest soils is sufficient to neutralize existing inputs of acidity.

Sodium channel activation underlies transfluthrin repellency in Aedes aegypti

Background Volatile pyrethroid insecticides, such as transfluthrin, have received increasing attention for their potent repellent activities in recent years for controlling human disease vectors. It has been long understood that pyrethroids kill insects by promoting activation and inhibiting inactivation of voltage-gated sodium channels. However, the mechanism of pyrethroid repellency remains poorly understood and controversial. Methodology/Principal findings Here, we show that transfluthrin repels Aedes aegypti in a hand-in-cage assay at nonlethal concentrations as low as 1 ppm. Contrary to a previous report, transfluthrin does not elicit any electroantennogram (EAG) responses, indicating that it does not activate olfactory receptor neurons (ORNs). The 1S-cis isomer of transfluthrin, which does not activate sodium channels, does not elicit repellency. Mutations in the sodium channel gene that reduce the potency of transfluthrin on sodium channels decrease transfluthrin repellency but do not affect repellency by DEET. Furthermore, transfluthrin enhances DEET repellency. Conclusions/Significance These results provide a surprising example that sodium channel activation alone is sufficient to potently repel mosquitoes. Our findings of sodium channel activation as the principal mechanism of transfluthrin repellency and potentiation of DEET repellency have broad implications in future development of a new generation of dual-target repellent formulations to more effectively repel a variety of human disease vectors.

MicroRNA-497/195 is tumor-suppressive and cooperates with CDKN2A/B in pediatric acute lymphoblastic leukemia

We previously identified an association of rapid engraftment of patient-derived leukemia cells transplanted into NOD/SCID mice with early relapse in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In search for the cellular and molecular profiles associated with this phenotype, we investigated the expression of microRNAs (miRNAs) in different engraftment phenotypes and patient outcomes and found high miR-497/195 expression in patient-derived xenograft samples with slow engraftment, derived from patients with favorable outcome. In contrast, epigenetic repression and low expression of these miRNAs was observed in rapidly engrafting samples associated with early relapse. Overexpression of miR-497/195 in patient-derived leukemia cells suppressed in vivo growth of leukemia and prolonged recipient survival. Conversely, inhibition of miR-497/195 led to increased leukemia cell growth. Key cell cycle regulators were downregulated upon miR-497/195 overexpression and we identified CDK4/CCND3-mediated control of G1/S transition as a principal mechanism for the suppression of BCP-ALL progression by miR-497/195. The critical role for miR-497/195-mediated cell cycle regulation was underscored by the finding in an additional independent series of patient samples, showing that high miR-497/195 expression together with a full sequence of CDKN2A/B was associated with excellent outcome, while deletion of CDKN2A/B together with low expression of miR-497/195 was associated with clearly inferior relapse-free survival. These findings point to the cooperative loss of cell cycle regulators as new prognostic factor indicating possible therapeutic targets for pediatric BCP-ALL.

Attention Trade-Off for Localization and Saccadic Remapping

Predictive remapping may be the principal mechanism of maintaining visual stability, and attention is crucial for this process. We aimed to investigate the role of attention in predictive remapping in a dual task paradigm with two conditions, with and without saccadic remapping. The first task was to remember the clock hand position either after a saccade to the clock face (saccade condition requiring remapping) or after the clock being displaced to the fixation point (fixation condition with no saccade). The second task was to report the remembered location of a dot shown peripherally in the upper screen for 1 s. We predicted that performance in the two tasks would interfere in the saccade condition, but not in the fixation condition, because of the attentional demands needed for remapping with the saccade. For the clock estimation task, answers in the saccadic trials tended to underestimate the actual position by approximately 37 ms while responses in the fixation trials were closer to veridical. As predicted, the findings also revealed significant interaction between the two tasks showing decreased predicted accuracy in the clock task for increased error in the localization task, but only for the saccadic condition. Taken together, these results point at the key role of attention in predictive remapping.

Spontaneous modulations of high frequency cortical activity

Objective: We clarified the clinical and mechanistic significance of physiological modulations of high-frequency broadband cortical activity associated with spontaneous saccadic eye movements during a resting state. Methods: We studied 30 patients who underwent epilepsy surgery following extraoperative electrocorticography and electrooculography recordings. We determined whether high-gamma activity at 70-110 Hz preceding saccade onset would predict upcoming ocular behaviors. We assessed how accurately the model incorporating saccade-related high-gamma modulations would localize the primary visual cortex defined by electrical stimulation. Results: The whole-brain level dynamic atlas demonstrated transient high-gamma suppression in the striatal region before saccade onset and high-gamma augmentation subsequently involving the widespread posterior brain regions. More intense striatal high-gamma suppression predicted the upcoming saccade directed to the ipsilateral side and lasting longer in duration. The bagged-tree-ensemble model demonstrated that intense saccade-related high-gamma modulations localized the visual cortex with an accuracy of 95%. Conclusions: We successfully animated the neural dynamics supporting saccadic suppression, a principal mechanism minimizing the perception of blurred vision during rapid eye movements. The primary visual cortex per se may prepare actively in advance for massive image motion expected during upcoming prolonged saccades. Significance: Measuring saccade-related electrocorticographic signals may help localize the visual cortex and avoid misperceiving physiological high-frequency activity as epileptogenic.