opposing effects
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2022 ◽  
Vol 9 ◽  
Ziv Sade ◽  
Shahar Hegyi ◽  
Itay Halevy

Equilibration times of dissolved inorganic carbon (DIC) depend on conversion reactions between CO2(aq) and the dissociation products of carbonic acid [S = (H2CO3) + (HCO3−) + (CO32−)]. Here, we develop analytical equations and a numerical model to calculate chemical equilibration times of DIC during pH transitions in buffered and unbuffered solutions. We approximate the equilibration degree of the DIC reservoir by the smaller of the CO2(aq) and S pools at the new pH, since the smaller pool is always farther from equilibrium during the chemical evolution. Both the amount of DIC converted and the rate of conversion differ between a pH increase and decrease, leading to distinct equilibration times for these general cases. Alkalinity perturbations in unbuffered solutions initially drive pH overshoots (increase or decrease) relative to the new equilibrium pH. The increased rates of DIC conversion associated with the pH overshoot yield shorter equilibration times compared to buffered solutions. Salinity has opposing effects on buffered and unbuffered solutions, decreasing and increasing equilibration times, respectively.

Azadeh Abbasi-Shavazi ◽  
Nicholas Biddle ◽  
Ben Edwards ◽  
Maria Jahromi

Using six waves of longitudinal data, we investigate wellbeing, psychological distress and loneliness differences between informal carers and non-carers in the context of COVID-19-related policy changes in Australia. Wellbeing levels fluctuated along with the virus case numbers. Free childcare temporarily alleviated the disparity between carers and non-carers, but by its cessation, carers, in particular, reported lower wellbeing and higher psychological distress. Wage subsidies and income supports had opposing effects for carers’ and non-carers’ mental health but decreased the loneliness of both groups. Victorians, living in the state where the second wave of infections in Australia was concentrated, experienced worse outcomes than other Australians.

2021 ◽  
Eric A Hanushek ◽  
Lavinia Kinne ◽  
Philipp Lergetporer ◽  
Ludger Woessmann

Abstract Patience and risk-taking – two preference components that steer intertemporal decision-making – are fundamental to human capital investment decisions. To understand how they contribute to international skill differences, we combine PISA tests with the Global Preference Survey. We find that opposing effects of patience (positive) and risk-taking (negative) together account for two-thirds of the cross-country variation in student skills. In an identification strategy addressing unobserved residence-country features, we find similar results when assigning migrant students their country-of-origin preferences in models with residence-country fixed effects. Associations of national preferences with family and school inputs suggest that both may act as channels.

Tinghui Lv ◽  
Shuting Zhang ◽  
Jingyue Guan ◽  
Meng Li ◽  
Qiaojuan Xing ◽  

Lycopene content is one of important factor for determining watermelon fruit quality. In this study, a small-type watermelon was grown in a greenhouse with supplementary red lighting 10 h per day after pollination 10 days. The results showed that supplementary red lighting promoted the lycopene accumulation earlier in watermelon flesh than the control. qRT-PCR analysis showed that among the lycopene metabolism pathway genes, ClPSY1 (phytoene synthase) expression increased significantly. Moreover, we identified PHYTOCHROME INTERACTING FACTORS 3 (ClPIF3) and bZIP transcription factor ELONGATED HYPOCOTYL 5 (ClHY5) in watermelon flesh, and red light has opposing effects on ClHY5 and ClPIF3 expression levels. The interaction experiments showed that ClHY5, a potent ClPIF3 antagonist, regulated ClPSY1 expression by directly targeting a common promoter cis-element (G-box). Collectively, our findings unraveled that ClHY5 and ClPIF3 form a dynamic activation-suppression transcriptional module responsive to red light cues to regulate watermelon lycopene accumulation.

2021 ◽  
Anne-Laure Hemonnot-Girard ◽  
Cédric Meersseman ◽  
Manuela Pastore ◽  
Nathalie Linck ◽  
Catherine Rey ◽  

Abstract Background: Research in recent years firmly established that microglial cells play an important role in the pathogenesis of Alzheimer's disease (AD). In parallel, a series of studies showed that, under both homeostatic and pathological conditions, microglia are a heterogeneous cell population. In AD, amyloid-b (Ab) plaque-associated microglia (PAM) display a clearly distinct phenotype compared to plaque-distant microglia (PCM), suggesting that these two microglia subtypes likely differently contribute to disease progression. So far, molecular characterization of PAM was performed indirectly using scRNA-seq approaches or based on markers that are supposedly up-regulated in this microglia subpopulation.Methods: In this study, we combined cell-specific laser capture and RNA-seq analysis to investigate, without preconceived notions of the molecular and/or functional changes that would affect these cells, the functional role of both plaque-associated and plaque-distant microglia. Results: First, we established that this approach allows selective isolation of microglia, while preserving spatial information and preventing transcriptome changes induced by classical purification approaches. Then, we identified, in PAM and PCM subpopulations, networks of co-deregulated genes and analyzed their potential functional roles in AD. Finally, we investigated the dynamics of microglia transcriptomic remodeling at early, intermediate and late stages of the disease. Conclusions: Our comprehensive study demonstrates that the proximity of microglia to Ab-plaques dramatically alters the microglial transcriptome and reveals that these changes can have both positive and negative impacts on the surrounding cells. These opposing effects may be driven by local microglia heterogeneity also demonstrated by this study. Our results also suggest that Ab plaque-associated microglia undergo exhaustion in the later stage of the disease. Our approach leads to molecularly define the overlooked plaque-distant microglia. We show that plaque-distant microglia are not bystanders of the disease, although the transcriptomic changes are far less striking compared to what is observed in plaque-associated microglia. In particular, our results suggest they are involved in Ab oligomer detection and in Ab-plaque initiation, with increased contribution as the disease progresses.

2021 ◽  
Hiroshi Ebata ◽  
Tomohiro Shima ◽  
Ryo Iizuka ◽  
Sotaro Uemura

Telomerase reverse transcriptase (TERT) is a protein that catalyzes the reverse transcription of telomere elongation. TERT is also expected to play a noncanonical role beyond telomere lengthening since it localizes not only in the nucleus but also in mitochondria, where telomeres do not exist. Several studies have reported that mitochondrial TERT regulates apoptosis induced by oxidative stress. However, there remains controversy about whether mitochondrial TERT promotes or inhibits apoptosis, mainly due to the lack of information on changes in the TERT distribution in individual cells over time. Here we simultaneously detected apoptosis and TERT localization after oxidative stress in individual HeLa cells by live-cell tracking. This tracking revealed that the stress-induced accumulation of TERT in mitochondria resulted in apoptosis but that the accumulation positively correlated with the time until cell death. The results suggest a new model in which mitochondrial TERT has two opposing effects at different stages of apoptosis: it predetermines apoptosis at the first stage of cell-fate determination but also delays apoptosis at the second stage. Because these distinct effects respectively support both sides of the controversy regarding the role of mitochondrial TERT in apoptosis, our model integrates two opposing hypotheses. Furthermore, detailed statistical analysis of TERT mutations, which have been predicted to inhibit TERT transport to mitochondria, revealed that these mutations suppress apoptosis independent of the mitochondrial localization of TERT. Together, these results indicate that the non-canonical functions of TERT affect a wide range of apoptotic pathways.

Deepa Kumari ◽  
Edward A. Fisher ◽  
Jeffrey L. Brodsky

Apolipoprotein B (ApoB) is the primary component of atherogenic lipoproteins, which transport serum fats and cholesterol. Therefore, elevated levels of circulating ApoB are a primary risk factor for cardiovascular disease. During ApoB biosynthesis in the liver and small intestine under nutrient-rich conditions, ApoB cotranslationally translocates into the endoplasmic reticulum (ER) and is lipidated and ultimately secreted. Under lipid-poor conditions, ApoB is targeted for ER Associated Degradation (ERAD). Although prior work identified select chaperones that regulate ApoB biogenesis, the contributions of cytoplasmic Hsp40s are undefined. To this end, we screened ApoB-expressing yeast and determined that a class A ER-associated Hsp40, Ydj1, associates with and facilitates the ERAD of ApoB. Consistent with these results, a homologous Hsp40, DNAJA1, functioned similarly in rat hepatoma cells. DNAJA1 deficient cells also secreted hyperlipidated lipoproteins, in accordance with attenuated ERAD. In contrast to the role of DNAJA1 during ERAD, DNAJB1—a class B Hsp40—helped stabilize ApoB. Depletion of DNAJA1 and DNAJB1 also led to opposing effects on ApoB ubiquitination. These data represent the first example in which different Hsp40s exhibit disparate effects during regulated protein biogenesis in the ER, and highlight distinct roles that chaperones can play on a single ERAD substrate.

2021 ◽  
Natalia Teruel ◽  
Matthew Crown ◽  
Matthew Bashton ◽  
Rafael Najmanovich

The recently reported Omicron (B.1.1.529) SARS-CoV-2 variant has a large number of mutations in the Spike (S) protein compared to previous variants. Here we evaluate the potential effect of Omicron S mutations on S protein dynamics and ACE2 binding as contributing factors to infectivity as well as propensity for immune escape. We define a consensus set of mutations from 77 sequences assigned as Omicron in GISAID as of November 25. We create structural models of the Omicron S protein in the open and closed states, as part of a complex with ACE2 and for each of 77 complexes of S bound to different antibodies with known structures. We have previously utilized Dynamical Signatures (DS) and the Vibrational Entropy Score (VDS) to evaluate the propensity of S variants to favour the open state. Here, we introduce the Binding Influence Score (BIS) to evaluate the influence of mutations on binding affinity based on the net gain or loss of interactions within the protein-protein interface. BIS shows excellent correlation with experimental data (Pearson correlation coefficient of 0.87) on individual mutations in the ACE2 interface for the Alpha, Beta, Gamma, Delta and Omicron variants combined. On the one hand, the DS of Omicron highly favours a more rigid open state and a more flexible closed state with the largest VDS of all variants to date, suggesting a large increase in the chances to interact with ACE2. On the other hand, the BIS shows that apart from N501Y, all other mutations in the interface reduce ACE2 binding affinity. VDS and BIS show opposing effects on the overall effectiveness of Omicron mutations to promote binding to ACE2 and therefore initiate infection. To evaluate the propensity for immune escape we calculated the net change of favourable and unfavourable interactions within each S-antibody interface. The net change of interactions shows a positive score (a net increase of favourable interactions and decrease of unfavourable ones) for 41 out of 77 antibodies, a nil score for 15 and a negative score for 21 antibodies. Therefore, in only 28% of S-antibody complexes (21/77) we predict some level of immune escape due to a weakening of the interactions with Omicron S. Considering that most antibody epitopes and the mutations are within the S-ACE2 interface our results suggest that mutations within the RBD of Omicron may give rise to only partial immune escape, which comes at the expense of reduced ACE2 binding affinity. However, this reduced ACE2 affinity appears to have been offset by increasing the occupancy of the open state of the Spike protein.

Computation ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 142
Tair Askar ◽  
Bekdaulet Shukirgaliyev ◽  
Martin Lukac ◽  
Ernazar Abdikamalov

Monte Carlo methods rely on sequences of random numbers to obtain solutions to many problems in science and engineering. In this work, we evaluate the performance of different pseudo-random number generators (PRNGs) of the Curand library on a number of modern Nvidia GPU cards. As a numerical test, we generate pseudo-random number (PRN) sequences and obtain non-uniform distributions using the acceptance-rejection method. We consider GPU, CPU, and hybrid CPU/GPU implementations. For the GPU, we additionally consider two different implementations using the host and device application programming interfaces (API). We study how the performance depends on implementation parameters, including the number of threads per block and the number of blocks per streaming multiprocessor. To achieve the fastest performance, one has to minimize the time consumed by PRNG seed setup and state update. The duration of seed setup time increases with the number of threads, while PRNG state update decreases. Hence, the fastest performance is achieved by the optimal balance of these opposing effects.

2021 ◽  
Natacha Motisi ◽  
Julien Papaïx ◽  
Sylvain Poggi

Coffee berry disease (CBD) can cause significant coffee yield losses along with major income losses for African smallholders. Although these farmers cannot afford to purchase pesticides to control the disease, agroecological solutions have rarely been investigated, and how epidemiological mechanisms are linked to the environment of the coffee tree and the plot remains unclear. Agroforestry systems are a promising agroecological option, but the effect of shade on CBD regulation is the subject of debate, and the use of plant species diversity remains uncertain. Here, we address how shade affects epidemiological mechanisms by modifying the microclimate. For this purpose, we developed a mechanistic susceptible-exposed-infectious-removed (SEIR) model, and used a Bayesian framework to infer the epidemiological parameters against microclimatic covariates. We show that shade has opposing effects on different epidemiological mechanisms. Specifically, shade can limit disease dynamics by reducing disease transmission while simultaneously promoting disease dynamics by reducing the latent period of the pathogen. However, in full sun, efficient disease transmission compensates for long latent periods. As a result, the balances between microclimatic variables can counterbalance the epidemiological rates, which can dramatically alter the fate of epidemics in shade versus full sun conditions. We propose research avenues to help design cost- and environmentally effective management strategies for CBD that are notably based on the functional traits of shade trees that could hamper CBD dispersal.

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