Causal Link Research Articles

Differential sex-dependent role of lncRNAs in cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Education and Science Cardiovascular diseases are one of the most prevalent causes of mortality and morbidity worldwide. Structural diseases such as dilated and hypertrophic cardiomyopathy significantly contributed to it. In recent years, several studies have pinpointed the importance of non-coding genome in the pathogenesis of cardiomyopathy. We have previously reported the role of distinct lncRNAs in atrial fibrillation. We now explored the plausible role of these lncRNAs in cardiomyopathy by analyzing their expression in two different mouse mutant models of lamin (LMNA) - LMNAR249W and αMHCCreLMNAFF, a cardiac hypertrophic MyBPC3 mutant model as well as in experimental myocardial infarction mice. Importantly, both LMNA mutant models developed a dilated cardiomyopathy, a condition distinctly observed in males but not in females. Our data demonstrated that Walras, Gm26533, Wallrd, Walaa and Walrad are downregulated in females, but not males. Furthermore, differential deregulation is also observed in MyBPC3 mutant model but not in myocardial infarction. In vitro analyses demonstrated an estrogen-dependent regulation. In addition, expression analyses in distinct cardiovascular cell lines revealed enriched myocardial expression of Walras and Gm26533 while Wallrd and Walaa are preferentially expressed in endocardial cells. These data were further validated by in situ hybridization in embryonic cardiac tissues. Walras overexpression resulted in enhanced expression of two key factors of UPR signaling pathway, i.e. Atf6 and Ire1, while Walras inhibition downregulated them. Upregulation of both UPR factors in Walrasgain-of-function assays is accompanied by increased cardiomyocyte apoptosis. In contrast, Walras inhibition resulted in increased Bcl2 expression and therefore increased cell viability. Mechanistically, Walras directly interacts with calumenin protein, a known protective factor against UPR-associated apoptosis, as demonstrated by pulldown assays. In sum, we demonstrated sex-dependent regulation of distinct lncRNAs in different cardiomyopathic mouse models and at least one of them, i.e. Walras contributes to UPR-associated apoptosis regulation, providing a causative link to the development of distinct cardiomyopathies.

Does raising awareness about inequality decrease support for school closures? An information treatment survey experiment during the COVID-19 pandemic

The increase in inequalities during the ongoing COVID-19 pandemic has been the topic of intense scholarly and public debate. School closures are one of the containment measures that have been debated most critically in this regard. What drives support for closures of schools and pre-school services (daycare/kindergarten) during a public health crisis such as the current COVID-19 pandemic? More specifically, does inequality awareness affect this support? Theoretically, we assume that providing information on current levels of inequality can change policy preferences, as it increases awareness of their consequences for inequality. Moreover, we assume that the strength of the association between information provision and policy support varies across individuals—depending on their exposure to these policies, and the political attitudes that they hold. To identify causal linkages between awareness of inequalities and support for school and daycare/kindergarten closures, we use a survey experiment with information treatment, in which we randomly assign information designed to prime the respondents to think about either education inequality, gender inequality, or both. The experiment, involving more than 3,000 respondents, was conducted in the spring of 2021 at the end of a prolonged lockdown in Germany when a new piece of legislation was enacted, enabling or restricting school reopenings based on local infection rates. Using Probit Regression models for dichotomous dependent variables, we show that raising awareness of education inequality and gender inequality via an information treatment is associated with decreasing support for preschool and primary school closures. We also find that past exposure to school-closure policies strengthens the effects of information treatments, whereas previous political attitudes do not moderate the association between information treatments and support for preschool and school closures.

The Causal Linkages between Market Power and Cost Efficiency: Testing Quiet Life Hypothesis for the Banking Industry

This study aims to test the quiet life hypothesis considering the impact of market power on cost efficiency in Pakistani banks where managers of the banking industry slacken their efforts to enjoy a ‘quiet life’ due to market power and are not focused on the cost efficiency of their banks. Thus, banks with high market power are relatively less focused on the efficient allocation of resources, resulting in a loss of consumer surplus and efficiency. We take panel data for a sample of 25 commercial banks throughout 2006-2019. Our findings suggest Uni-directional causality running from cost efficiency towards market power in the case of Pakistan. In addition, to control for endogeneity, we adopt a dynamic two-step system GMM approach to model the relationship between market power and cost efficiency. Our findings suggest significantly negative effects of cost efficiency over market power, disproving the presence of quiet life in the case of Pakistan. This study provides substantial theoretical contributions in the form of the Quiet life hypothesis and welfare performance of banks. However, to the best of our knowledge, the causal linkages and the effects of market power on cost efficiency or vice versa are not documented for the banking industry of Pakistan.

Causal relationship between rheumatoid arthritis and bronchiectasis: a bidirectional mendelian randomization study

BackgroundEpidemiological observational studies have elucidated a correlation between rheumatoid arthritis (RA) and bronchiectasis. However, the causal nature of this association remains ambiguous. To clarify this potential causal linkage, we conducted a two-sample Mendelian randomization (MR) analysis to explore the bidirectional causality between RA and bronchiectasis.MethodsSummary statistics for RA and bronchiectasis were obtained from the IEU OpenGWAS database We employed various methods, including inverse variance weighting (IVW), MR-Egger, weighted median, weighted mode, and simple mode, to explore potential causal links between RA and bronchiectasis. Additionally, a series of sensitivity studies, such as Cochran’s Q test, MR Egger intercept test, and leave-one-out analysis, were conducted to assess the MR analysis’s accuracy further.ResultsIn the forward MR analysis, the primary analysis indicated that a genetic predisposition to RA correlated with an increased risk of bronchiectasis in European populations (IVW odds ratio (OR): 1.28, 95% confidence interval (CI): 1.20–1.37, p = 1.18E-13). Comparable results were noted in the East Asian subjects (IVW OR: 1.55, 95% CI: 1.30–1.34, p = 8.33E-07). The OR estimates from the other four methods were consistent with those obtained from the IVW method. Sensitivity analysis detected no evidence of horizontal pleiotropy or heterogeneity. Conversely, in the reverse MR analysis, we found no evidence to support a genetic causality between bronchiectasis and RA in either European or East Asian populations.ConclusionThis study indicates that genetic predisposition to RA correlates with a heightened risk of bronchiectasis in both European and East Asian populations. These results imply that routine screening for bronchiectasis in RA patients could be beneficial, and effective management of RA may contribute to a reduced risk of bronchiectasis. Future research should aim to clarify the underlying mechanisms linking these two conditions.

A review of natural resource extraction industries and their influence on the occurrence of poverty

PurposeThis research paper takes a narrow approach to examining the apparent link between poverty and the resource extraction industries. However, it acknowledges that much more is to be explored about this relationship. Many complexities influence the occurrence and degree of poverty in a particular country, region, or community.Design/methodology/approachThe literature review identified proposed and operational poverty reduction actions and processes categorized under the broad concept of community development projects. The surveyed cases describe how various corporate strategies, work processes, labor requirements and efficient management and governance solutions are purported to improve poverty-reduction efforts potentially.FindingsNo causal linkages between poverty and hypothetically valuable and successful community development projects were found. No poverty monitoring evaluations and learning data (MEL) for these projects were proposed and published in most of the literature. However, associations were observed between some business practices implemented in these resource extraction community development projects and observations of indicators of lower poverty levels.Practical implicationsThe research improves our understanding of the requirements and opportunities for successful community development projects by highlighting processes, company strategy, human resource programs and enlightened governance that can contribute to reducing poverty.Originality/valueThe paper identifies the characteristics of community development projects that appear to span natural resource extraction industries and countries. Effective management strategies and representative and formally designated organisational governance boards are essential for these projects.

Podocyte-targeted therapies - progress and future directions.

Podocytes are the key target cells for injury across the spectrum of primary and secondary proteinuric kidney disorders, which account for up to 90% of cases of kidney failure worldwide. Seminal experimental and clinical studies have established a causative link between podocyte depletion and the magnitude of proteinuria in progressive glomerular disease. However, no substantial advances have been made in glomerular disease therapies, and the standard of care for podocytopathies relies on repurposed immunosuppressive drugs. The past two decades have seen a remarkable expansion in understanding of the mechanistic basis of podocyte injury, with prospects increasing for precision-based treatment approaches. Dozens of disease-causing genes with roles in the pathogenesis of clinical podocytopathies have been identified, as well as a number of putative glomerular permeability factors. These achievements, together with the identification of novel targets of podocyte injury, the development of potential approaches to harness the endogenous podocyte regenerative potential of progenitor cell populations, ongoing clinical trials of podocyte-specific pharmacological agents and the development of podocyte-directed drug delivery systems, contribute to an optimistic outlook for the future of glomerular disease therapy.

Mendelian randomization analysis does not reveal a causal association between migraine and Meniere's disease.

According to observational research, migraine may increase the risk of Meniere's disease (MD). The two have not, however, been proven to be causally related. Using Mendelian random (MR) analysis, we aimed to evaluate any potential causal relationship between migraine and MD. We extracted single-nucleotide polymorphisms (SNPs) from large-scale genome-wide association studies (GWAS) involving European individuals, focusing on migraine and MD. The main technique used to evaluate effect estimates was inverse-variance weighting (IVW). To assess heterogeneity and pleiotropy, sensitivity analyses were carried out using weighted median, MR-Egger, simple mode, weighted mode, and MR-PRESSO. There was no discernible causative link between genetic vulnerability to MD and migraine. The migraine dose not increase the prevalence of MD in the random-effects IVW method (OR = 0.551, P = 0.825). The extra weighted median analysis (OR = 0.674, P = 0.909), MR-Egger (OR = 0.068, P = 0.806), Simple mode (OR = 0.170, P = 0.737), and Weighted mode (OR = 0.219, P= 0.760) all showed largely consistent results. The MD dose not increase the prevalence of migraine in the random-effects IVW method (OR = 0.999, P = 0.020). The extra weighted median analysis (OR = 0.999, P = 0.909), MR-Egger (OR = 0.999, P = 0.806), Simple mode (OR = 0.999, P = 0.737), and Weighted mode (OR = 1.000, P = 0.760). This Mendelian randomization study provides casual evidence that migraine is not a risk factor for MD and MD is also not a risk factor for migraine.

The impact of maternal smoking during pregnancy and the age of smoking initiation on incident dementia: A prospective cohort study.

The impact of early-life tobacco exposure on dementia has remained unknown. Using the UK Biobank, the associations of maternal smoking during pregnancy (MSDP) and age of smoking initiation (ASI) with the onset time of all-cause dementia were estimated with accelerated failure time models. The effects of MSDP and ASI on brain structure and their genetic correlation to Alzheimer's disease (AD) were analyzed. A Mendelian randomization (MR) analysis was conducted. The time ratios for smokers starting in childhood, adolescence, and adulthood (vs never smokers) were 0.87 (0.76 to 0.99), 0.92 (0.88 to 0.96), and 0.95 (0.89 to 1.01). MSDP and smoking in adolescence altered many brain regions, including the hippocampus. In genetic analysis, MSDP was genetically and causally linked to AD, and a younger ASI was genetically correlated to a higher AD risk. Early-life smoking accelerated dementia onset and was genetically correlated to AD. MSDP demonstrated genetic and causal linkage to AD risks. Unlike the commonly used Cox proportional hazards model, this article uses a parametric survival analysis method - the accelerated failure model - to explore the relationship between exposure to onset time. It can be used as an alternative method when the proportional hazards assumption is not met. Genetic analyses including genetic correlation study and MR analysis and brain structure analyses were conducted to support our findings and explore the potential mechanisms. The study reveals the relationship between different smoking initiation periods and the onset time of dementia and shows that earlier smoking exposure has a more significant impact on dementia. It emphasizes the importance of preventing early smoking. In the future, more research focusing on the relationship between early exposure and dementia is called for to provide more detailed prevention measures for dementia that cover all age groups.

Climate Change, Identity Conflicts and the Politics of Cosmopolitanism in Nigeria

This article analyses how identity-based conflicts in Nigeria and national policy solutions to these conflicts affect the goals of cosmopolitanism. Cosmopolitanism refers to the idea of an individual defined as a citizen of a single global community. Marxist political economy theory guided the analysis. The article provides insights into the dynamics of indigene-settlers’ claims and contentions, and their causal linkages to climate change and herder-farmer conflicts, and argues that the politicisation of the conflict has implicated national policy solutions in such a way that they result in the devaluation of Nigerian citizenship and discriminatory tendencies that weaken solidarity between ethnic groups. Yet, building stronger ties amongst citizens and groups is a prerequisite for effective collective action against threats posed by climate change. The article concludes that climate solutions and policy responses to identity conflicts must be reconceptualised to re-enter the ideals of cosmopolitanism while recognising indigenous rights and identities.

Causal Links Between Systemic Disorders and Keratoconus in European Population

PurposeThe objective of this study was to establish the presence of a causal linkage between prevalent systemic diseases and keratoconus (KC). DesignMendelian randomization (MR) analysis. MethodsAfter an exhaustive screening process, genetic variants linked to various systemic diseases were identified as instrumental variables at the genome-wide significance level. Subsequently, MR analyses were conducted to elucidate their potential causal connection with KC (N = 26,742). The encompassed systemic ailments comprise diabetes, hay fever/allergic rhinitis/eczema, obstructive sleep apnea, thyroid dysfunction, aortic aneurysm, major depressive disorder, inflammatory bowel disease (including Crohn's disease and ulcerative colitis), and mitral valve prolapse. Our study adheres to the principles of Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization guidelines. ResultsUsing inverse variance weighting as the primary MR analysis method, our findings revealed that hay fever/allergic rhinitis/eczema (odds ratio, 10.144; 95% CI, 2.441 - 42.149; P = 0.001) and ulcerative colitis (odds ratio, 1.147; 95% CI, 1.054 - 1.248; P = 0.002) were associated with an increased risk of KC within the largest population under scrutiny. Conversely, the prolonged hyperglycemic state did not exhibit a potentially protective effect in delaying the pathogenesis of KC, and no correlation was observed between the two (odds ratio, 0.320; 95% CI, 0.029 - 3.549; P = 0.353). Also, obstructive sleep apnea, thyroid function, aortic aneurysm, major depressive disorder, Crohn's disease, and mitral valve prolapse did not exhibit a causal association with KC (P > 0.05 for all comparisons). ConclusionsThis study indicates an increased risk of KC related to hay fever/allergic rhinitis/eczema and ulcerative colitis, with diabetes not providing a protective effect. These findings may potentially contribute some insights to inform clinical interventions.

Abstract 2065: Activation Of Cgas-sting Axis By DNA Double-strand Breaks In Atherosclerosis: A Possible Link From DNA Damage To Inflammation And Cell Senescence

Aim: Premature atherosclerosis in some progeroid syndromes suggests the involvement of DNA damage in the progression of atherosclerosis. However, causative links between DNA double-strand breaks (DSBs) and atherosclerosis have yet to be determined. The aim of this study was to elucidate the role of DSBs in atherosclerosis using mice and vascular smooth muscle cells (VSMCs) deficient in Ku80, a DSB repair protein. Methods and Results: The plaque size and DSBs were increased in the aorta of Ku80-deficient apolipoprotein E knockout mice (Ku80 +/- ApoE -/- ) compared to those of ApoE -/- control after 4 weeks of a high-fat diet. At the early stages of atherosclerosis (two-week high-fat diet), although the plaque size of Ku80 +/- ApoE -/- was similar to that of ApoE -/- control, the number of DSBs and mRNA levels of inflammatory cytokines such as IL-6 and MCP-1 were significantly increased in the Ku80 +/- ApoE -/- aortas. We further investigated molecular links between DSBs and inflammatory responses using VSMCs isolated from Ku80 +/- mice. In VSMCs from Ku80 +/- mice, IL-6 mRNA level was elevated along with increased cellular senescence markers, such as p16 mRNA and senescence-associated (SA) β-gal activity. Additionally, Ku80 +/- VSMCs showed accumulated cytosolic free DNA, an increased level of cGAMP, and activation of TBK1, interferon regulatory factor 3 (IRF3) and NF-κB, suggesting the activation of cGAS-STING axis, a cytosolic DNA sensing machinery. Activation of cGAS-STING axis was also shown in the aortae from Ku80 +/- ApoE -/- in comparison with those from ApoE -/- control. Silencing IRF3, but not NF-κB attenuated the IL-6 mRNA level in Ku80 +/- VSMCs, so did cGAS-silencing. Of interest, cGAS-silencing also attenuated DNA damage-induced SA β-gal activity in wild-type VSMCs. Furthermore, depletion of either p16 or p53 suppressed IRF3 activation by DNA damage. Conclusions: These results suggest that accumulation of cytosolic DNA induced by DNA damage accelerates atherosclerosis via the activation of cGAS-STING-IRF3 axis. cGAS-STING-IRF3 axis may play a pivotal role as a common signaling pathway that serve as a link from DNA damage to inflammatory and cell senescence response in arterial wall.

BANKING SECTOR DEVELOPMENT AND ECONOMIC GROWTH DEVELOPING COUNTRIES: A BOOTSTRAP PANEL GRANGER CAUSALITY ANALYSIS

The purpose of this paper is to revisit the Granger causal relationship between banking sector development and economic growth for forty developing countries in the period 1970-2012. We devised two indices to comprehensively assess the development of the banking sector and employed a panel bootstrapped approach for Granger causality testing. This method adequately addresses concerns related to cross-sectional dependence and heterogeneity. Our empirical findings offer modest backing for the supply-leading, demand-following, and complementarity hypotheses. Moreover, our analysis suggests a causal relationship between banking sector development and economic growth across twenty-five countries. This paper investigates the relationship between banking sector development and economic growth in developing countries using a Bootstrap Panel Granger Causality Analysis. The banking sector plays a crucial role in fostering economic development by mobilizing savings, allocating capital efficiently, and channeling investments into productive sectors. However, the precise nature of the causal linkages between banking sector development and economic growth remains subject to empirical scrutiny, particularly in the context of developing economies characterized by diverse institutional settings and economic structures. Employing a panel data approach, this study examines the causal dynamics between banking sector development and economic growth across a sample of developing countries. By leveraging the richness of cross-country variation and time-series dynamics, we aim to provide a nuanced understanding of the symbiotic relationship between banking sector development and economic growth. Our discoveries illuminate the causal connection between banking sector advancement and economic growth in developing nations, presenting significant insights for policymakers, economists, and scholars. Through informing policy discussions and promoting data-driven decision-making, this research contributes to the crucial goals of sustainable development and inclusive growth in developing economies.

Analyzing GDP Growth Drivers in Saudi Arabia: Investment or Consumption: An Evidence-Based ARDL-Bound Test Approach

This study delves into the intricate interplay of economic growth components, specifically focusing on consumption and investment in Saudi Arabia from 2000 to 2022. Employing vector error correction models and co-integration techniques, we analyze the short- and long-term dynamics within the relationship of consumption, investment, and economic growth. Granger causality analysis is also used to discern these pivotal variables’ causal connections. Our empirical analysis reveals a persistent long-term cointegration relationship among the variables, underscoring the enduring nature of their interdependency. Furthermore, our findings highlight consumption and investment’s statistically significant positive impact on economic growth. Notably, the short-term analysis unveils a stable model characterized by an annual adjustment to equilibrium of 100%. Moreover, the Granger causality study demonstrates unidirectional causal linkages among consumption, investment, and economic growth. These findings hold substantial implications for policy formulation in Saudi Arabia. Policymakers must grasp the ramifications of burgeoning prosperity and evolving private consumption patterns on future environmental outcomes. Achieving sustainable long-term results necessitates equal emphasis on bolstering private consumption and fostering other facets of economic growth.

Relation between the Pandemic COVID-19 and the outbreak of Crimean-Congo Hemorrhagic Fever in Iraq, 2023

Objective: This review examines the link between the COVID-19 pandemic and the outbreak of Crimean-Congo Hemorrhagic Fever (CCHF) in Iraq. Methods: We reviewed literature and data to explore potential associations between the two diseases. Results: No direct causative link between COVID-19 and increased CCHF cases in Iraq was found. However, changes in healthcare,agriculture, and human-animal interactions during the pandemic may have indirectly affected CCHF transmission. Conclusion: This review highlights the need for further research to confirm any connections between the COVID-19 pandemic and CCHFoutbreaks in Iraq. Understanding these links is crucial for effective public health responses to emerging infectious diseases.

The Geodynamic Significance of Continental UHP Exhumation: New Constraints From the Tso Morari Complex, NW Himalaya

AbstractThe burial and exhumation of continental crust to and from ultrahigh‐pressure (UHP) is an important orogenic process, often interpreted with respect to the onset and/or subduction dynamics of continent‐continent collision. Here, we investigate the timing and significance of UHP metamorphism and exhumation of the Tso Morari complex, North‐West Himalaya. We present new petrochronological analyses of mafic eclogites and their host‐rock gneisses, combining U‐Pb zircon, rutile and xenotime geochronology (high‐precision CA‐ID‐TIMS and high‐spatial resolution LA‐ICP‐MS), garnet element maps, and petrographic observations. Zircon from mafic eclogite have a CA‐ID‐TIMS age of 46.91 ± 0.07 Ma, with REE profiles indicative of growth at eclogite facies conditions. Those ages overlap with zircon rim ages (48.9 ± 1.2 Ma, LA‐ICP‐MS) and xenotime ages (47.4 ± 1.4 Ma; LA‐ICP‐MS) from the hosting Puga gneiss, which grew during breakdown of UHP garnet rims. We argue that peak zircon growth at 47–46 Ma corresponds to the onset of exhumation from UHP conditions. Subsequent exhumation through the rutile closure temperature, is constrained by new dates of 40.4 ± 1.7 and 36.3 ± 3.8 Ma (LA‐ICP‐MS). Overlapping ages from Kaghan imply a coeval time‐frame for the onset of UHP exhumation across the NW Himalaya. Furthermore, our regional synthesis demonstrates a causative link between changes in the subduction dynamics of the India‐Asia collision zone at 47–46 Ma and the resulting mid‐Eocene plate network reorganization. The onset of UHP exhumation therefore provides a tightly constrained time‐stamp significant geodynamic shifts within the orogen and wider plate network.

SGLT2 inhibition, plasma proteins, and heart failure: a proteome-wide Mendelian Randomization and colocalization study.

To investigate the causal contributions of Sodium-glucose cotransporter 2 (SGLT2) inhibition on Heart Failure (HF) and identify the circulating proteins that mediate SGLT2 inhibition's effects on HF. Applying a two-sample, two-step Mendelian Randomization (MR) analysis, we aimed to estimate: (1) the causal impact of SGLT2 inhibition on HF; (2) the causal correlation of SGLT2 inhibition on 4,907 circulating proteins; (3) the causal association of SGLT2 inhibition-driven plasma proteins on HF. Genetic variants linked to SGLT2 inhibition derived from the previous studies. The 4,907 circulating proteins were derived from the deCODE study. Genetic links to HF were obtained through the Heart Failure Molecular Epidemiology for Therapeutic Targets (HERMES) consortium. SGLT2 inhibition demonstrated a lower risk of HF (odds ratio [OR] = 0.44, 95% CI [0.26, 0.76], P = 0.003). Among 4,907 circulating proteins, we identified leucine rich repeat transmembrane protein 2 (LRRTM2), which was related to both SGLT2 inhibition and HF. Mediation analysis revealed that the impact of SGLT2 inhibition on HF operates indirectly through LRRTM2 [β = -0.20, 95% CI (-0.39, -0.06), P = 0.02] with a mediation proportion of 24.6%. Colocalization analysis provided support for the connections between LRRTM2 and HF. The study indicated a causative link between SGLT2 inhibition and HF, with plasma LRRTM2 potentially serving as a mediator.

A tale of two pumps: Blue light and abscisic acid alter Arabidopsis leaf hydraulics via bundle sheath cell H+-ATPases.

The bundle sheath cell (BSC) layer tightly enveloping the xylem throughout the leaf is recognized as a major signal-perceiving "valve" in series with stomata, regulating leaf hydraulic conductance (Kleaf) and thereby radial water flow via the transpiring leaf. The BSC blue light (BL) signaling pathway increases Kleaf and the underlying BSC water permeability. Here, we explored the hypothesis that BSCs also harbor a Kleaf-downregulating signaling pathway related to the stress phytohormone abscisic acid (ABA). We employed fluorescence imaging of xylem sap in detached leaves and BSC protoplasts from different genotypes of Arabidopsis (Arabidopsis thaliana) plants, using pH and membrane potential probes to monitor physiological responses to ABA and BL in combination with pharmacological agents. We found that BL-enhanced Kleaf required elevated BSC cytosolic Ca2+. ABA inhibited BL-activated xylem-sap-acidifying BSC H+-ATPase AHA2 (Arabidopsis H+-ATPase 2), resulting in depolarized BSCs and alkalinized xylem sap. ABA also stimulated BSC vacuolar H+-ATPase (VHA), which alkalinized the BSC cytosol. Each pump stimulation, AHA2 by BL and VHA by ABA (under BL), also required Ca2+. ABA stimulated VHA in the dark depending on Ca2+, but only in an alkaline external medium. Taken together with earlier findings on the pH sensitivity of BSC osmotic water permeability (i.e. aquaporin activity), our results suggest a Ca2+-dependent and pH-mediated causative link between the BL- and ABA-regulated activities of two BSC H+-ATPases and Kleaf.

Machine learning applications on IoT data in manufacturing operations and their interpretability implications: A systematic literature review

Industry 4.0 has transformed manufacturing with real-time plant data collection across operations and effective analysis is crucial to unlock the full potential of Internet-of-Things (IoT) sensor data, integrating IoT with Artificial Intelligence (AI) techniques, such as Machine Learning (ML) and Deep Learning (DL). They can provide powerful predictions but anticipating issues is not enough. Manufacturing companies must prioritize avoiding inefficiencies, thereby developing improvement strategies from an Operational Excellence perspective. Here, the interpretability dimension of AI-based models could support a complete understanding of the reasons behind the outcomes, making ML and DL models transparent, and allowing the identification of the causal linkages between the inputs and outputs of the system. Within this context, this study aims first to deliver a comprehensive overview of the existing applications of Advanced Analytics techniques leveraging IoT data in manufacturing environments to then analyze their interpretability implications, referring to the interpretability as the description of the link between the independent and dependent variables in a way that is understandable to humans. Different gaps in terms of lack of full data enhancement are highlighted, providing directions for future research.

An integrated metagenomic, metabolomic and transcriptomic survey of Populus across genotypes and environments

Bridging molecular information to ecosystem-level processes would provide the capacity to understand system vulnerability and, potentially, a means for assessing ecosystem health. Here, we present an integrated dataset containing environmental and metagenomic information from plant-associated microbial communities, plant transcriptomics, plant and soil metabolomics, and soil chemistry and activity characterization measurements derived from the model tree species Populus trichocarpa. Soil, rhizosphere, root endosphere, and leaf samples were collected from 27 different P. trichocarpa genotypes grown in two different environments leading to an integrated dataset of 318 metagenomes, 98 plant transcriptomes, and 314 metabolomic profiles that are supported by diverse soil measurements. This expansive dataset will provide insights into causal linkages that relate genomic features and molecular level events to system-level properties and their environmental influences.

Data-driven dimensionality reduction and causal inference for spatiotemporal climate fields.

We propose a data-driven framework to describe spatiotemporal climate variability in terms of a few entities and their causal linkages. Given a high-dimensional climate field, the methodology first reduces its dimensionality into a set of regionally constrained patterns. Causal relations among such patterns are then inferred in the interventional sense through the fluctuation-response formalism. To distinguish between true and spurious responses, we propose an analytical null model for the fluctuation-dissipation relation, therefore allowing us for uncertainty estimation at a given confidence level. We showcase the methodology on the sea surface temperature field from a state-of-the-art climate model. The usefulness of the proposed framework for spatiotemporal climate data is demonstrated in several ways. First, we focus on the correct identification of known causal relations across tropical basins. Second, we show how the methodology allows us to visualize the cumulative response of the whole system to climate variability in a few selected regions. Finally, each pattern is ranked in terms of its causal strength, quantifying its relative ability to influence the system's dynamics. We argue that the methodology allows us to explore and characterize causal relations in spatiotemporal fields in a rigorous and interpretable way.