Modelling features of the biological pump and its impact on marine oxygen distribution

The marine biological pump not just impacts the uptake of atmospheric CO2 but also contributes to the regulation of ocean dissolved oxygen concentrations. The degree of ocean oxygenation has varied strongly throughout earth’s history. After several periods of oxygen depletion, the ocean currently exhibits relatively high oxygen concentrations. However, in the past 50 years, a decrease in oxygen concentrations of 2% in the global ocean has been observed and it is expected that the oxygen concentration will decrease even further with global change conditions, reducing the habitat volume of hypoxia-sensitive pelagic species. Although the interplay between supply of oxygen by ventilation and its consumption by biogeochemical processes is generally known, it is still unclear to which degree both processes influence the global marine oxygen distribution even under today’s climate conditions. Thus, this thesis focuses on features of the biological pump that might impact the marine oxygen distribution. Moreover, a comprehensive understanding of processes that influence the oxygen distribution is important to be able to estimate potential changes under future global change scenarios. Global models are an important tool to get a deeper insight into determinative processes for the marine oxygen distribution. In this thesis, three approaches regarding the biological pump are tested to advance the understanding of processes that determine the oxygen distribution under current climate conditions, which, in turn, potentially enable understanding of the expansion of oxygen minimum zones (OMZs) under future global change conditions: In the second chapter of this thesis, I test two competing feedbacks, which impact future oxygen concentrations, in the University of Victoria Earth System Climate Model (UVic ESCM) of intermediate complexity. This study shows, that the warming-induced phosphorus-oxygen feedback at the sediment-water interface and the resulting potential increase of released phosphorus does not constitute a major feedback in our model. It thus seems that other processes control the strength of future deoxygenation. In the third chapter of this thesis, a global biogeochemical ocean model is coupled to a particle aggregation model, which, using an appropriate parameterisation, improves the vertical and lateral representation of OMZs compared to the original model without aggregation. As there are still uncertainties in the parameterisation of the particle aggregation, a model calibration against an observed particle dataset seems necessary. In the fourth chapter two new processes influencing particle dynamics, namely particle breakup (disaggregation of large particles into smaller ones) and mesozooplankton migration are included in the biogeochemical model, which is optimised against observed particles, dissolved inorganic tracers and the overlap between modelled and observed OMZs. This study further improves the representation of OMZs. However, it also shows that the model is not able to represent shallow and deep particles realistically at the same time, which indicates that important processes that enhance particle export flux are still unknown and thus not considered in the model parameterisation

Nivel de motricidad de niños con síndrome de down de 6 a 10 años de edad medido a través del test de McClenaghan y Gallahue

Tesis (Profesor de Educación Física, Licenciado en Educación)El propósito de esta investigación, tiene como principal objetivo identificar el nivel y las diferencias del desarrollo motor que presentan los niños y niñas con Síndrome de Down de entre 6 y 10 años de edad. Es por esto que se ha investigado a fondo las características que presentan los sujetos con Síndrome de Down (Historia, características, genéticas, físicas y cognitivas), para luego hacer un estudio cuantitativo exploratorio, que consta de una evaluación motriz a sujetos con este síndrome mediante el test de Mc Clenaghan y Gallahue, la que considera los patrones motores de manipulación y locomoción los cuales son correr, saltar, lanzar, atrapar y patear. Una vez realizado el análisis de los datos, se puede concluir que comparando por pruebas no existen diferencias significativas en el nivel de adquisición de los patrones motores básicos de manipulación y locomoción en niños y niñas de 6 a 10 años en los centros Complementa, Rayún y Paul Harris, de las comunas Lo Barnechea, La Reina y Las Condes, Pero Comparando los centros y evaluando el test en general podemos ver que hay una diferencia significativa entre el centro complementa y Rayún

Synergistic effect between plant extracts and fluoride to protect against enamel erosion: An in vitro study.

Polyphenol-rich solutions, such as plant extracts and teas, can modify the salivary pellicle and improve the protection against dental erosion. In this study, we further explored how these polyphenol-rich plant extracts solutions behave in the presence of fluoride. We distributed enamel specimens into 9 groups (n = 15): Control_No_F- (Deionized water); Control_F- (500 ppm F-), Grape_Seed_No_F- (Grape seed extract), Grape_Seed_F- (Grape seed extract + 500 ppm F-), Grapefruit_Seed_No_F- (Grapefruit seed extract), Grapefruit_Seed_F- (Grapefruit seed extract + 500 ppm F-), Blueberry_No_F- (Blueberry extract), Blueberry_F- (Blueberry extract + 500 ppm F-), and Sn2+/F-_Rinse (commercial solution containing 800 ppm Sn2+ and 500 ppm F-). The specimens were submitted to 5 cycles (1 cycle per day), and each cycle consisted of: salivary pellicle formation (human saliva, 30 min, 37°C), modification of the pellicle (2 min, 25°C), pellicle formation (60 min, 37°C), and an erosive challenge (1 min, citric acid). Between cycles, the specimens were kept in a humid chamber. Relative surface hardness (rSH), relative surface reflection intensity (rSRI) and calcium released to the acid were analysed, using general linear models, and Kruskal-Wallis with post-hoc Dunn's tests. We observed that the presence of fluoride in synergy with the extract solutions provided better protection than the groups containing extract or fluoride only. For rSH, we observed a significant main effect of extracts (F(4,117) = 9.20; p<0.001) and fluoride (F(1,117) = 511.55; p<0.001), with a significant interaction (F(3,117) = 6.71; p<0.001). Grape_Seed_F- showed the best protection, better than fluoride, and Sn2+/F-_Rinse. Calcium results also showed greater protection for the groups containing fluoride, whereas for rSRI, despite a significant interaction between extract and fluoride (F(3,117) = 226.05; p<0.001), the differences between the groups were not as clearly observed. We conclude that polyphenols from plant extracts, when combined with fluoride, improve the protective effect of salivary pellicles against enamel erosion

The effect of marine aggregate parameterisations on nutrients and oxygen minimum zones in a global biogeochemical model

Particle aggregation determines the particle flux length scale and affects the marine oxygen concentration and thus the volume of oxygen minimum zones (OMZs) that are of special relevance for ocean nutrient cycles and marine ecosystems and that have been found to expand faster than can be explained by current state-of-the-art models. To investigate the impact of particle aggregation on global model performance, we carried out a sensitivity study with different parameterisations of marine aggregates and two different model resolutions. Model performance was investigated with respect to global nutrient and oxygen concentrations, as well as extent and location of OMZs. Results show that including an aggregation model improves the representation of OMZs. Moreover, we found that besides a fine spatial resolution of the model grid, the consideration of porous particles, an intermediate-to-high particle sinking speed and a moderate-to-high stickiness improve the model fit to both global distributions of dissolved inorganic tracers and regional patterns of OMZs, compared to a model without aggregation. Our model results therefore suggest that improvements not only in the model physics but also in the description of particle aggregation processes can play a substantial role in improving the representation of dissolved inorganic tracers and OMZs on a global scale. However, dissolved inorganic tracers are apparently not sufficient for a global model calibration, which could necessitate global model calibration against a global observational dataset of marine organic particles

A model study of warming-induced phosphorus-oxygen feedbacks in open-ocean oxygen minimum zones on millennial timescales

Observations indicate an expansion of oxygen minimum zones (OMZs) over the past 50 years, likely related to ongoing deoxygenation caused by reduced solubility, changes in stratification and circulation, and a potential acceleration of organic matter turnover in a warming climate. Higher temperatures also lead to enhanced weathering on land, which, in turn, increase the phosphorus and alkalinity flux into the ocean. The overall area of ocean sediments that are in direct contact with low oxygen bottom waters also increases with expanding OMZs. This leads to an additional release of phosphorus from ocean sediments and therefore raises the ocean's phosphorus inventory even further. Higher availability in phosphorus enhances biological production, remineralisation and oxygen consumption, and might therefore lead to further expansions of OMZs, representing a positive feedback. A negative feedback arises from the enhanced productivity-induced drawdown of carbon and also increased uptake of CO2 due to increased alkalinity, which, in turn, got there through weathering. This feedback leads to a decrease in atmospheric CO2 and weathering rates. Here we quantify these two competing feedbacks on millennial timescales for a high CO2 emission scenario. Using the UVic Earth System Climate Model of intermediate complexity, our model results suggest that the positive benthic phosphorus release feedback has only a minor impact on the size of OMZs in the next 1000 years, although previous studies assume that the phosphorus release feedback was the main factor for anoxic conditions during Cretaceous period. The increase in the marine phosphorus inventory under assumed business-as-usual global warming conditions originates, on millennial timescales, almost exclusively from the input via terrestrial weathering and causes a 4 to 5-fold expansion of the suboxic water volume in the model

Acute Downregulation but Not Genetic Ablation of Murine MCU Impairs Suppressive Capacity of Regulatory CD4 T Cells

By virtue of mitochondrial control of energy production, reactive oxygen species (ROS) generation, and maintenance of Ca2+ homeostasis, mitochondria play an essential role in modulating T cell function. The mitochondrial Ca2+ uniporter (MCU) is the pore-forming unit in the main protein complex mediating mitochondrial Ca2+ uptake. Recently, MCU has been shown to modulate Ca2+ signals at subcellular organellar interfaces, thus fine-tuning NFAT translocation and T cell activation. The mechanisms underlying this modulation and whether MCU has additional T cell subpopulationspecific effects remain elusive. However, mice with germline or tissue-specific ablation of Mcu did not show impaired T cell responses in vitro or in vivo, indicating that ‘chronic’ loss of MCU can be functionally compensated in lymphocytes. The current work aimed to specifically investigate whether and how MCU influences the suppressive potential of regulatory CD4 T cells (Treg). We show that, in contrast to genetic ablation, acute siRNA-mediated downregulation of Mcu in murine Tregs results in a significant reduction both in mitochondrial Ca2+ uptake and in the suppressive capacity of Tregs, while the ratios of Treg subpopulations and the expression of hallmark transcription factors were not affected. These findings suggest that permanent genetic inactivation of MCU may result in compensatory adaptive mechanisms, masking the effects on the suppressive capacity of Tregs

Inhibition of SARS-CoV-2 Replication by a Small Interfering RNA Targeting the Leader Sequence

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected almost 200 million people worldwide and led to approximately 4 million deaths as of August 2021. Despite successful vaccine development, treatment options are limited. A promising strategy to specifically target viral infections is to suppress viral replication through RNA interference (RNAi). Hence, we designed eight small interfering RNAs (siRNAs) targeting the highly conserved 5′-untranslated region (5′-UTR) of SARS-CoV-2. The most promising candidate identified in initial reporter assays, termed siCoV6, targets the leader sequence of the virus, which is present in the genomic as well as in all subgenomic RNAs. In assays with infectious SARS-CoV-2, it reduced replication by two orders of magnitude and prevented the development of a cytopathic effect. Moreover, it retained its activity against the SARS-CoV-2 alpha variant and has perfect homology against all sequences of the delta variant that were analyzed by bioinformatic means. Interestingly, the siRNA was even highly active in virus replication assays with the SARS-CoV-1 family member. This work thus identified a very potent siRNA with a broad activity against various SARS-CoV viruses that represents a promising candidate for the development of new treatment options

Importance of external quality assessment for SARS-CoV-2 antigen detection during the COVID-19 pandemic

Background: Antigen testing has become an essential part of fighting the ongoing COVID-19 pandemic. With the continual increase in available tests, independent and extensive comparative evaluations using data from external quality assessment (EQA) studies to evaluate test performance between different users are required.Objectives: An EQA scheme was established to assess the sensitivity of antigen tests and the potential impact of circulating SARS-CoV-2 strains on their performance.Study design: Panels were prepared for three challenges in 2021 containing inactivated SARS-CoV-2-positive samples of various genetic strains (including variants of concern, VOCs) at different concentrations, and negative samples. Data was analysed based on qualitative testing results in relation to the antigen test used. Results: Participants registered for each individual challenge in any combination. In total, 258 respondents from 27 countries worldwide were counted submitting 472 datasets. All core samples were correctly reported by 76.7 to 83.1% at participant level and by 73.5 to 83.8% at dataset level. Sensitivity differences could be shown in viral loads and SARS-CoV-2 strains/variants including the impact on performance by a B.1.1.7-like mutant strain with a deletion in the nucleoprotein gene. Lateral flow rapid antigen tests showed a higher rate of false negatives in general compared with automated point-of-care tests and laboratory ELISA/immunoassays.Conclusions: EQA schemes can provide valuable data to inform participants about weaknesses in their testing process or methods and support ongoing assay evaluations for regulatory approval or post-market surveillance

The SARS-coronavirus-host interactome

Coronaviruses (CoVs) are important human and animal pathogens that induce fatal respiratory, gastrointestinal and neurological disease. The outbreak of the severe acute respiratory syndrome (SARS) in 2002/2003 has demonstrated human vulnerability to (Coronavirus) CoV epidemics. Neither vaccines nor therapeutics are available against human and animal CoVs. Knowledge of host cell proteins that take part in pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach employing a genome-wide yeast-two hybrid interaction screen to identify immunopilins (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B) as interaction partners of the CoV non-structural protein 1 (Nsp1). These molecules modulate the Calcineurin/NFAT pathway that plays an important role in immune cell activation. Overexpression of NSP1 and infection with live SARS-CoV strongly increased signalling through the Calcineurin/NFAT pathway and enhanced the induction of interleukin 2, compatible with late-stage immunopathogenicity and long-term cytokine dysregulation as observed in severe SARS cases. Conversely, inhibition of cyclophilins by cyclosporine A (CspA) blocked the replication of CoVs of all genera, including SARS-CoV, human CoV-229E and -NL-63, feline CoV, as well as avian infectious bronchitis virus. Non-immunosuppressive derivatives of CspA might serve as broad-range CoV inhibitors applicable against emerging CoVs as well as ubiquitous pathogens of humans and livestock

SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection

Autophagy is an essential cellular process affecting virus infections and other diseases and Beclin1 (BECN1) is one of its key regulators. Here, we identified S-phase kinase-associated protein 2 (SKP2) as E3 ligase that executes lysine-48-linked poly-ubiquitination of BECN1, thus promoting its proteasomal degradation. SKP2 activity is regulated by phosphorylation in a hetero-complex involving FKBP51, PHLPP, AKT1, and BECN1. Genetic or pharmacological inhibition of SKP2 decreases BECN1 ubiquitination, decreases BECN1 degradation and enhances autophagic flux. Middle East respiratory syndrome coronavirus (MERS-CoV) multiplication results in reduced BECN1 levels and blocks the fusion of autophagosomes and lysosomes. Inhibitors of SKP2 not only enhance autophagy but also reduce the replication of MERS-CoV up to 28,000-fold. The SKP2-BECN1 link constitutes a promising target for host-directed antiviral drugs and possibly other autophagy-sensitive conditions