Molecular dynamics of structural effects of reactive carbonyl species derivate of lipid peroxidation on bovine serum albumin.

BACKGROUND: Serum albumin is the most abundant protein in the Mammalia blood plasma at where plays a decisive role in the transport wide variety of hydrophobic ligands. BSA undergoes oxidative modifications like the carbonylation by the reactive carbonyl species (RCSs) 4-hydroxy-2-nonenal (HNE), 4 hydroxy-2-hexenal (HHE), malondialdehyde (MDA) and 4-oxo-2-nonenal (ONE), among others. The structural and functional changes induced by protein carbonylation have been associated with the advancement of neurodegenerative, cardiovascular, metabolic and cancer diseases. METHODS: To elucidate structural effects of protein carbonylation with RCSs on BSA, parameters for six new non-standard amino acids were designated and molecular dynamics simulations of its mono­carbonylated-BSA systems were conducted in the AMBER force field. Trajectories were evaluated by RMSD, RMSF, PCA, RoG and SASA analysis. RESULTS: An increase in the conformational instability for all proteins modified with local changes were observed, without significant changes on the BSA global three-dimensional folding. A more relaxed compaction level and major solvent accessible surface area for modified systems was found. Four regions of high molecular fluctuation were identified in all modified systems, being the subdomains IA and IIIB those with the most remarkable local conformational changes. Regarding essential modes of domain movements, it was evidenced that the most representatives were those related to IA subdomain, while IIIB subdomain presented discrete changes. CONCLUSIONS: RCSs induces local structural changes on mono­carbonylated BSA. Also, this study extends our knowledge on how carbonylation by RCSs induce structural effects on proteins.

Corrigendum: Biogeography of southern ocean active prokaryotic communities over a large spatial scale.

[This corrects the article DOI: 10.3389/fmicb.2022.862812.].

Feeding Ecology of Odontaster validus under Different Environmental Conditions in the West Antarctic Peninsula.

To study how Odontaster validus can influence the spatial structure of Antarctic benthic communities and how they respond to disturbance, it is necessary to assess potential dietary shifts in different habitats. We investigated the diets of O. validus from Maxwell Bay and South Bay in the West Antarctic Peninsula. A multifaceted approach was applied including in situ observations of cardiac stomach everted contents, isotopic niche, and trophic diversity metrics. Results confirm the flexible foraging strategy of this species under markedly different environmental conditions, suggesting plasticity in resource use. The data also showed evidence of isotopic niche expansion, high δ15N values, and Nacella concinna as a common food item for individuals inhabiting a site with low seasonal sea ice (Ardley Cove), which could have significant ecological implications such as new trophic linkages within the Antarctic benthic community. These results highlight the importance of considering trophic changes of key species to their environment as multiple ecological factors can vary as a function of climatic conditions.

Biogeography of Southern Ocean Active Prokaryotic Communities Over a Large Spatial Scale.

The activity of marine microorganisms depends on community composition, yet, in some oceans, less is known about the environmental and ecological processes that structure their distribution. The objective of this study was to test the effect of geographical distance and environmental parameters on prokaryotic community structure in the Southern Ocean (SO). We described the total (16S rRNA gene) and the active fraction (16S rRNA-based) of surface microbial communities over a ~6,500 km longitudinal transect in the SO. We found that the community composition of the total fraction was different from the active fraction across the zones investigated. In addition, higher α-diversity and stronger species turnover were displayed in the active community compared to the total community. Oceanospirillales, Alteromonadales, Rhodobacterales, and Flavobacteriales dominated the composition of the bacterioplankton communities; however, there were marked differences at the order level. Temperature, salinity, silicic acid, particulate organic nitrogen, and particulate organic carbon correlated with the composition of bacterioplankton communities. A strong distance-decay pattern between closer and distant communities was observed. We hypothesize that it was related to the different oceanic fronts present in the Antarctic Circumpolar Current. Our findings contribute to a better understanding of the complex arrangement that shapes the structure of bacterioplankton communities in the SO.

Seasonal and diel variations in the vertical distribution, composition, abundance and biomass of zooplankton in a deep Chilean Patagonian Fjord.

Comau Fjord is a stratified Chilean Patagonian Fjord characterized by a shallow brackish surface layer and a >400 m layer of aragonite-depleted subsurface waters. Despite the energetic burden of low aragonite saturation levels to calcification, Comau Fjord harbours dense populations of cold-water corals (CWC). While this paradox has been attributed to a rich supply of zooplankton, supporting abundance and biomass data are so far lacking. In this study, we investigated the seasonal and diel changes of the zooplankton community over the entire water column. We used a Nansen net (100 µm mesh) to take stratified vertical hauls between the surface and the bottom (0-50-100-200-300-400-450 m). Samples were scanned with a ZooScan, and abundance, biovolume and biomass were determined for 41 taxa identified on the web-based platform EcoTaxa 2.0. Zooplankton biomass was the highest in summer (209 g dry mass m-2) and the lowest in winter (61 g dry mass m-2). Abundance, however, peaked in spring, suggesting a close correspondence between reproduction and phytoplankton spring blooms (Chl a max. 50.86 mg m-3, 3 m depth). Overall, copepods were the most important group of the total zooplankton community, both in abundance (64-81%) and biovolume (20-70%) followed by mysids and chaetognaths (in terms of biovolume and biomass), and nauplii and Appendicularia (in terms of abundance). Throughout the year, diel changes in the vertical distribution of biomass were found with a daytime maximum in the 100-200 m depth layer and a nighttime maximum in surface waters (0-50 m), associated with the diel vertical migration of the calanoid copepod family Metridinidae. Diel differences in integrated zooplankton abundance, biovolume and biomass were probably due to a high zooplankton patchiness driven by biological processes (e.g., diel vertical migration or predation avoidance), and oceanographic processes (estuarine circulation, tidal mixing or water column stratification). Those factors are considered to be the main drivers of the zooplankton vertical distribution in Comau Fjord.

SARS-CoV-2 RBD-Tetanus Toxoid Conjugate Vaccine Induces a Strong Neutralizing Immunity in Preclinical Studies.

Controlling the global COVID-19 pandemic depends, among other measures, on developing preventive vaccines at an unprecedented pace. Vaccines approved for use and those in development intend to elicit neutralizing antibodies to block viral sites binding to the host's cellular receptors. Virus infection is mediated by the spike glycoprotein trimer on the virion surface via its receptor binding domain (RBD). Antibody response to this domain is an important outcome of immunization and correlates well with viral neutralization. Here, we show that macromolecular constructs with recombinant RBD conjugated to tetanus toxoid (TT) induce a potent immune response in laboratory animals. Some advantages of immunization with RBD-TT conjugates include a predominant IgG immune response due to affinity maturation and long-term specific B-memory cells. These result demonstrate the potential of the conjugate COVID-19 vaccine candidates and enable their advance to clinical evaluation under the name SOBERANA02, paving the way for other antiviral conjugate vaccines.

Post-liver transplant outcomes in patients with major psychiatric diagnosis in the United States.

INTRODUCTION AND OBJECTIVES: Higher rates of psychiatric disorders are reported among cirrhotic patients. This study examines the demographic and clinical outcomes post-liver transplant (LT) among cirrhotic patients with a major psychiatric diagnosis (cases) compared to those without psychiatric diagnosis (controls). MATERIALS AND METHODS: Retrospective case control design was used among 189 cirrhotic patients who had undergone LT at Methodist University Hospital Transplant Institute, Memphis, TN between January 2006 and December 2014. Multivariable regression and Cox proportional hazard regression were conducted to compare allograft loss and all-cause mortality. RESULTS: The study sample consisted of a matched cohort of 95 cases and 94 controls with LT. Females and those with Hepatic Encephalopathy (HE) were more likely to have psychiatric diagnosis. Patients with hepatocellular carcinoma (HCC) were twice as likely to have allograft loss. Psychiatric patients with HCC had two and a half times (HR 2.54; 95% CI: 1.20-5.37; p = 0.015) likelihood of all-cause mortality. Data censored at 1-year post-LT revealed that patients with psychiatric diagnosis have a three to four times higher hazard for allograft loss and all-cause mortality compared to controls after adjusting for covariates, whereas when the data is censored at 5 year, allograft loss and all-cause mortality have two times higher hazard ratio. CONCLUSIONS: The Cox proportional hazard regression analysis of censored data at 1 and 5 year indicate higher allograft loss and all-cause mortality among LT patients with psychiatric diagnosis. Patients with well-controlled psychiatric disorders who undergo LT need close monitoring and medication adherence.

Black carbon pollution in snow and its impact on albedo near the Chilean stations on the Antarctic peninsula: First results.

BC can be transported through the atmosphere from low and mid-latitudes to Antarctica, or it can be emitted in the Antarctica in situ. To establish a possible relationship between BC and the human activities in Antarctica, shallow snow samples were taken in four sites from Antarctic peninsula during summer periods (2014-2019): Chilean Base O'Higgins (BO), La Paloma Glacier (LP) (6 km away from BO); Chilean Base Yelcho (BY) and P4 (5 km away from BY). BC concentration in snow samples was determined by using a novel methodology recently developed, published and patented by the authors. The methodology consisted in a filter-based optical transmission method at a wavelength of 880 nm. Results showed that snow from BO presented the highest BC concentration (3395.7 µg kg-1), followed by BY (1309.2 µg kg-1), LP 2016 (745.9 µg kg-1), LP 2015 (233.6 µg kg-1) and finally P4 (179.4 µg kg-1). BC values observed in Antarctic snow were higher than others previously reported in the literature and showed the influence of anthropic activities in the study area, considering that the two highest values of BC concentration in snow were found at sites near the bases. To evaluate the impact of the BC concentrations found in the snow of the study area, snow albedo modeling was performed, using the on-line version of the "Snow, Ice, and Aerosol Radiative" (SNICAR) Model. Modeling outputs exposed that the measured variations in BC content caused large differences in the modeled albedo in the visible range of the spectra, which showed to be more sensitive at lower BC concentrations. These data could help to understand the role of BC in the actual scenario of climate change, in which Antarctica is presented as a very fragile environment that needs to be protected, starting with the management of the activities developed in-situ.

AMBER parameters and topology data of 2-pentylpyrrole adduct of arginine with 4-hydroxy-2-nonenal.

The data described here supports a part of the research article "Effect of 4­HNE Modification on ZU5-ANK Domain and the Formation of Their Complex with ß­Spectrin: A Molecular Dynamics Simulation Study" [1]. Dataset on Gaff force field parameters of AMBER is provided for the non-standard arginine resulting of reaction with 4-hydroxy-2-nonenal (4-HNE), the major secondary product of lipids peroxidation. Arg-HNE 2-pentilpyrrole adduct is part of the 4-hydroxyalkenals described in various physiopathological disorders related to increased oxidative stress. Data include a framework for derivation of missing bonds, angles and dihedral parameters for modified arginine, alongside optimized partial charges derived with Restrained Electrostatic Potential (RESP) method and the new force field parameters obtained by quantum mechanicals methods (QM) using Hartree-Fock (HF)/6 - 31G** level of theory. Benchmark as a graphics tutorial summary steps to obtained new parameters and the validation of non-standard amino acids is presented. The new residue constructed is put available to the scientific community to perform molecular dynamics simulations of modified 4-HNE proteins on arginine residue and complete the set of data parameters for nucleophilic residues with this reactive aldehyde ADDIN EN.CITE ADDIN EN.CITE.DATA [2]. Data that could be used for the researchers interested in the role of protein oxidation as mediator in cellular pathophysiological.

Effect of 4-HNE Modification on ZU5-ANK Domain and the Formation of Their Complex with ß-Spectrin: A Molecular Dynamics Simulation Study.

4-HNE-modified ankyrins have been described in diseases such as diabetes, renal failure, G6PD deficient, sickle cell trait, and P. falciparum infected erythrocytes with different AB0 blood groups. However, effects at the atomic level of this carbonylation on structure and function of modified protein are not yet fully understood. We present a study based on molecular dynamics simulations of nine 4-HNE modified residues of the ZU5-ANK ankyrin domain with ß-spectrin and their binding energy profiles. Results show that 4-HNE induced local conformational changes over all protein systems evaluated, increased mobility in the modification sites, and localized structural changes between the positively charged patch of the ZU5-ANK domain. Carbonylation with 4-HNE on lysine residues decreased the affinity between ZU5-ANK and the 14-ß-spectrin repeat by reducing electrostatic and van der Waals interactions. The presented work provides further insight into understanding the loss of human erythrocyte deformation capacity under conditions of oxidative stress in different diseases.

Highly variable iron content modulates iceberg-ocean fertilisation and potential carbon export.

Marine phytoplankton growth at high latitudes is extensively limited by iron availability. Icebergs are a vector transporting the bioessential micronutrient iron into polar oceans. Therefore, increasing iceberg fluxes due to global warming have the potential to increase marine productivity and carbon export, creating a negative climate feedback. However, the magnitude of the iceberg iron flux, the subsequent fertilization effect and the resultant carbon export have not been quantified. Using a global analysis of iceberg samples, we reveal that iceberg iron concentrations vary over 6 orders of magnitude. Our results demonstrate that, whilst icebergs are the largest source of iron to the polar oceans, the heterogeneous iron distribution within ice moderates iron delivery to offshore waters and likely also affects the subsequent ocean iron enrichment. Future marine productivity may therefore be not only sensitive to increasing total iceberg fluxes, but also to changing iceberg properties, internal sediment distribution and melt dynamics.

Carbon and Calcium Carbonate Export Driven by Appendicularian Faecal Pellets in the Humboldt Current System off Chile.

The role of appendicularian faecal pellet (FPa) size fractions on coccolithophore-derived particulate organic carbon (POC) and calcium carbonate (CaCO3) export to the deep sea was assessed from sediment traps within a period of ten years (1995-2004) off Coquimbo (CQ, 30°S) and five years (2005-2009) off Concepción (CC, 36°S) in the Humboldt Current System (HCS) off Chile. The composition and size distribution of 1,135 FPa samples from sediment traps deployed at 2,300 and 1,000 m depths showed non-linear, inverse relationships between the FPa size-fractions and their volume-specific POC and CaCO3 contents, which were up to ten times higher for small (<100 µm in diameter) than large (>100 µm) FPa. On average, 13 and 2% of the total POC and CaCO3 fluxes, respectively, were contributed mainly by small FPa (90%), with maxima during the autumn and summer. Thus, a non-linear, exponential model of volume-specific POC and CaCO3 contents of FPa substantially improved vertical flux rate estimates. In the HCS, annual carbon flux based on a non-linear FPa carbon load was double the estimate assuming a linear-volume to carbon load for FPa (345 and 172 kton C y-1). We recommend a widespread consideration of this non-linear model in global carbon estimates.

Organic matter distribution, composition and its possible fate in the Chilean North-Patagonian estuarine system.

The distribution, composition, and transport of both dissolved and particulate organic carbon (DOC and POC) were studied across a terrestrial - marine transition system in the Chilean North-Patagonia (41°S). At the land-fjord boundary we reported: (i) high concentrations of both silicic acid (up to 100 µM) and integrated chlorophyll a (62 mg m-2), (ii) dominance of nanophytoplankton (63%), humic-, terrigenous-derived, and protein-like DOC (19 and 36%, respectively), and (iii) a shallow photic zone (12 m depth). In contrast, the estuarine-ocean boundary was characterized by (i) high concentrations of nitrate and phosphate (20 and 2 µM respectively) and low chlorophyll a concentration (11 mg m-2), (ii) dominance of microphytoplankton (59%) and tyrosine-like C3 autochthonous DOC (34%), and (iii) a deep photic zone (29 m depth). Allochthonous DOC input at the fjord head and the ocean accounted for 60% and 10% of total DOC, respectively. The input of humic-like substances was enhanced by intense forestry and agriculture activity around the Puelo River watershed, contributing from 50% to 14% of total DOC along the fjord - ocean transect. In contrast, autochthonous tyrosine-like substances increased from 25% to 41% of total DOC, highlighting the role of bacterial metabolism in regulating DOM composition. The high correlation (R2 = 0.7) between the UVC-humic:UVA-humic ratio and salinity suggest that processes associated to freshwater input impinged on the DOC chemical characteristics and origins. Overall, our observations support the view that climate warming (freshwater input) and anthropogenic practices (aquaculture) boost the mobilization of terrestrial carbon pools and their intrusion into coastal ocean areas, a process that should be given more attention in climate prediction models.

4-HNE carbonylation induces local conformational changes on bovine serum albumin and thioredoxin. A molecular dynamics study.

4-hydroxy-2-nonenal (4-HNE) is the main end product of peroxidation in lipids, capable of introduce carbonyl groups to nucleophilic amino acids via Michael additions and alter protein function. It has been reported that 4-HNE protein carbonylation is associated with intracellular protein aggregation, the pathogenesis of neurodegenerative and metabolic diseases and yet it is unclear how the carbonylation affects the protein structure and dynamics at the atomic level. Here, we analysis the structural effects of 4-HNE modification through formation of Michael adducts of Cys-4HNE, His-4HNE and Lys-4HNE on Serum Albumin (BSA) and Thioredoxin (TRX). Since both proteins have experimental evidence to possess 4-HNE-modifications on cysteine, histidine and lysine residues, extended molecular dynamics simulations were performed with AMBER to study the carbonylation effects in the structure of these proteins. BSA is the main protein of plasma while TRX is an important antioxidant enzyme. Results showed local changes and alteration in the conformational stability, folding and flexibility after including the 4-HNE modification. DSSP analysis showed important structural modifications as a consequence of the inclusion of the modified residues. Analysis of the computed trajectories suggests that 4-HNE decreases stability, increases local flexibility and produced modest unfolding on both tested proteins. Finally, all the systems evaluated shown an increase in the lipophilic potential and a modest decrease in the electrostatic potential in BSA but an increase in TRX.

All you can eat: the functional response of the cold-water coral Desmophyllum dianthus feeding on krill and copepods.

The feeding behavior of the cosmopolitan cold-water coral (CWC) Desmophyllum dianthus (Cnidaria: Scleractinia) is still poorly known. Its usual deep distribution restricts direct observations, and manipulative experiments are so far limited to prey that do not occur in CWC natural habitat. During a series of replicated incubations, we assessed the functional response of this coral feeding on a medium-sized copepod (Calanoides patagoniensis) and a large euphausiid (Euphausia vallentini). Corals showed a Type I functional response, where feeding rate increased linearly with prey abundance, as predicted for a tentaculate passive suspension feeder. No significant differences in feeding were found between prey items, and corals were able to attain a maximum feeding rate of 10.99 mg C h-1, which represents an ingestion of the 11.4% of the coral carbon biomass per hour. These findings suggest that D. dianthus is a generalist zooplankton predator capable of exploiting dense aggregations of zooplankton over a wide prey size-range.

Multiscale modelization in a small virus: Mechanism of proton channeling and its role in triggering capsid disassembly.

In this work, we assess a previously advanced hypothesis that predicts the existence of ion channels in the capsid of small and non-enveloped icosahedral viruses. With this purpose we examine Triatoma Virus (TrV) as a case study. This virus has a stable capsid under highly acidic conditions but disassembles and releases the genome in alkaline environments. Our calculations range from a subtle sub-atomic proton interchange to the dismantling of a large-scale system representing several million of atoms. Our results provide structure-based explanations for the three roles played by the capsid to enable genome release. First, we observe, for the first time, the formation of a hydrophobic gate in the cavity along the five-fold axis of the wild-type virus capsid, which can be disrupted by an ion located in the pore. Second, the channel enables protons to permeate the capsid through a unidirectional Grotthuss-like mechanism, which is the most likely process through which the capsid senses pH. Finally, assuming that the proton leak promotes a charge imbalance in the interior of the capsid, we model an internal pressure that forces shell cracking using coarse-grained simulations. Although qualitatively, this last step could represent the mechanism of capsid opening that allows RNA release. All of our calculations are in agreement with current experimental data obtained using TrV and describe a cascade of events that could explain the destabilization and disassembly of similar icosahedral viruses.

Development and benchmark to obtain AMBER parameters dataset for non-standard amino acids modified with 4-hydroxy-2-nonenal.

The data described here support the research article "4-HNE carbonylation induces local conformational changes on bovine serum albumin and thioredoxin. A molecular dynamics study" (Alviz-Amador et al., 2018) . Dataset on Gaff force field parameters of AMBER is provided for assembled three non-standard amino acids resulting of the 4-HNE Michael addition, the main end product of lipids peroxidation. Data include a framework for derivation of missing bonds, angles and dihedral parameters for Cys, His, and Lys modified amino acids, alongside optimized partial charges derived with Restrained Electrostatic Potential (RESP) method and the new force field parameters obtained by quantic mechanical (QM) using HF/6-31G** level of theory. Benchmark as a graphics tutorial summary steps to obtained new parameters and the validation of non-standard amino acids is presented. The new residues constructed are put available to the scientific community to perform molecular dynamics simulations of modified 4-HNE proteins.

Cardiac senile amyloidosis: a review / Amiloidosis cardíaca senil: una revisión

Abstract: Cardiac senile amyloidosis related to wild-type transthyretin is not so infrequent as previously thought, several cases of heart failure with preserved ejection fraction might be related to this infiltrative disorder. Usually it is underdiagnosed because of the requirement of histological diagnosis and reluctance to do biopsy in this frail elderly population. Noninvasive diagnostic methods available will increase diagnosis of cardiac transthyretin amyloidosis (ATTR), and the direct consequence will be more investigations and clinical trials on diagnosis and therapeutics of ATTR.

Resumen: La amiloidosis cardiaca senil relacionada con transtiretina tipo salvaje no es tan infrecuente como se ha pensado previamente, varios casos de insuficiencia cardiaca con fracción de expulsión preservada pueden estar relacionadas con esta enfermedad infiltrativa. Habitualmente es sub-diagnosticada debido a que se requiere estudio histológico y existe reticencia a realizar biopsias en esta población de pacientes seniles por su fragilidad. Nuevos métodos diagnósticos no invasivos incrementarán el diagnóstico de amiloidosis cardiaca por transtiretina, y la consecuencia directa será una mayor investigación y ensayos clínicos para su diagnóstico y tratamiento.

MD Simulations of Viruslike Particles with Supra CG Solvation Affordable to Desktop Computers.

Viruses are tremendously efficient molecular devices that optimize the packing of genetic material using a minimalistic number of proteins to form a capsid or envelope that protects them from external threats, being also part of cell recognition, fusion, and budding machineries. Progress in experimental techniques has provided a large number of high-resolution structures of viruses and viruslike particles (VLP), while molecular dynamics simulations may furnish lively and complementary insights on the fundamental forces ruling viral assembly, stability, and dynamics. However, the large size and complexity of these macromolecular assemblies pose significant computational challenges. Alternatively, Coarse-Grained (CG) methods, which resign atomistic resolution privileging computational efficiency, can be used to characterize the dynamics of VLPs. Still, the massive amount of solvent present in empty capsids or envelopes suggests that hybrid schemes keeping a higher resolution on regions of interest (i.e., the viral proteins and their surroundings) and a progressively coarser description on the bulk may further improve efficiency. Here we introduce a mesoscale explicit water model to be used in double- or triple-scale simulations in combination with popular atomistic parameters and the CG water used by the SIRAH force field. Simulations performed on VLPs of different sizes, along with a comprehensive analysis of the PDB, indicate that most of the VLPs so far reported are amenable to be handled on a GPU-accelerated desktop computer using this simulation scheme.