JURNAL AGROTEKNOLOGI
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Prrx1b restricts fibrosis and promotes Nrg1-dependent cardiomyocyte proliferation during zebrafish heart regeneration
No full textFibroblasts are activated to repair the heart following injury. Fibroblast activation in the mammalian heart leads to a permanent fibrotic scar that impairs cardiac function. In other organisms, such as zebrafish, cardiac injury is followed by transient fibrosis and scar-free regeneration. The mechanisms that drive scarring versus scar-free regeneration are not well understood. Here, we show that the homeobox-containing transcription factor Prrx1b is required for scar-free regeneration of the zebrafish heart as the loss of Prrx1b results in excessive fibrosis and impaired cardiomyocyte proliferation. Through lineage tracing and single-cell RNA sequencing, we find that Prrx1b is activated in epicardial-derived cells where it restricts TGFβ ligand expression and collagen production. Furthermore, through combined in vitro experiments in human fetal epicardial-derived cells and in vivo rescue experiments in zebrafish, we conclude that Prrx1 stimulates Nrg1 expression and promotes cardiomyocyte proliferation. Collectively, these results indicate that Prrx1 is a key transcription factor that balances fibrosis and regeneration in the injured zebrafish heart
Beyond horizontal gene transfer: the role of plasmids in bacterial evolution
No full textPlasmids have a key role in bacterial ecology and evolution because they mobilize accessory genes by horizontal gene transfer. However, recent studies have revealed that the evolutionary impact of plasmids goes above and beyond being mere gene delivery platforms. Plasmids are usually kept at multiple copies per cell, producing islands of polyploidy in the bacterial genome. As a consequence, the evolution of plasmid-encoded genes is governed by a different set of rules than those affecting chromosomal genes, and these rules are shaped by unusual concepts in bacterial genetics such as genetic dominance, heteroplasmy or segregational drift. In this Review, we discuss recent advances that underscore the importance of plasmids in bacterial ecology and evolution beyond horizontal gene transfer. We focus on new evidence that suggests that plasmids might accelerate bacterial evolution, mainly by promoting the evolution of plasmid-encoded genes, but also by enhancing the adaptation of their host chromosome. Finally, we integrate the most relevant theoretical and empirical studies providing a global understanding of the forces that govern plasmid-mediated evolution in bacteria
Individual choices and universal rights for drinking water in rural Africa
No full textMore than 500 million rural Africans lack safe drinking water. The human right to water and United Nations Sustainable Development Goal SDG6.1 promote a policy shift from building water infrastructure to sustaining water services. However, the financial calculus is bleak with the costs of “safely managed”’ or “basic” water services in rural Africa beyond current government budgets and donor funds. The funding shortfall is compounded by the disappointing results of earlier policy initiatives in Africa. This is partly because of a failure to understand which attributes of water services rural people value. We model more than 11,000 choice observations in rural Kenya by attributes of drinking water quality, price, reliability, and proximity. Aggregate analysis disguises alternative user priorities in three choice classes. The two larger choice classes tolerate lower service levels with higher payments. A higher water service level reflects the smallest choice class favored by women and the lower wealth group. For the lower wealth group, slower repair times are accepted in preference to a lower payment. Some people discount potable water and proximity, and most people choose faster repair times and lower payments. We argue policy progress needs to chart common ground between individual choices and universal rights. Guaranteeing repair times may provide a policy lever to unlock individual payments to complement public investment in water quality and waterpoint proximity to support progressive realization of a universal right
Association of systolic blood pressure elevation with disproportionate left ventricular remodeling in very preterm-born young adults
No full textImportance: Preterm-born individuals have higher blood pressure with an increased risk of
hypertension by young adulthood, as well as potentially adverse cardiac remodeling, even when normotensive. To what extent blood pressure elevation impacts left ventricular (LV) structure and function in adults born preterm is currently unknown.
Objective: To investigate whether changes observed in LV structure and function in pretermborn adults make them more susceptible to cardiac remodeling in relation to blood pressure elevation.
Design, Setting, and Participants: This cross-sectional cohort study included 468 adults aged 18 to 40 years. Of these, 200 were born preterm (<37+0/7 weeks’ gestation) and 268 were born at term (37+0/7-42+0/7 weeks’ gestation). Cardiac magnetic resonance (CMR) imaging was used to characterise LV structure and function, with clinic blood pressure readings measured to assess hypertension status. Demographic and anthropometric data, as well as birth history and family medical history information, were collected.
Main Outcomes and Measures: CMR measures of LV structure and function in response to systolic blood pressure elevation.
Results: Normotensive and hypertensive preterm-born adults had higher LV mass index, reduced
LV function, and smaller LV volumes compared to both term-born normotensive and hypertensive individuals (P<0.01). In regression analyses of systolic blood pressure with LV
mass index and LV mass to end-diastolic volume ratio, there was a leftward shift in the slopes in preterm- compared to term-born adults. Compared to term-born adults, there was a 2.5-fold
greater LV mass index per 1mmHg elevation in systolic blood pressure in very and extremely preterm-born adults (<32+0/7 weeks’ gestation) (P<0.001) and a 1.6-fold greater elevation in LV mass index per 1mmHg elevation in systolic blood pressure increase in moderately preterm-born adults (32+0/7-36+6/7 weeks’ gestation) (P<0.001). LV mass to end-diastolic volume ratio per 1mmHg elevation in systolic blood pressure in the very and extremely preterm-born adults was 3.4-fold greater compared to those born moderately preterm (P<0.001) and 3.3-fold greater compared to those born at term (P<0.001).
Conclusions: Preterm-born adults have a unique LV structure and function that worsens with systolic blood pressure elevation. Additional primary prevention strategies specifically targeting cardiovascular risk reduction in this population may be warranted
The impact of the presence of autoantibodies against citrullinated, carbamylated and acetylated peptides on radiographic progression in patients with new onset rheumatoid arthritis: an observational study
No full textBackground: A range of anti-modified peptide autoantibodies (AMPA) are associated with rheumatoid arthritis (RA). We assessed the relationship between AMPA profiles and radiographic progression in new onset RA.
Methods: AMPAs (targeting citrullinated, carbamylated and acetylated peptides) were measured by ELISA in 362 patients with new onset RA from the Scottish Early Rheumatoid Arthritis Inception Cohort and Biobank (SERA). Radiographic progression in hands and feet was determined using the Sharp-van der Heijde (SvH) method. 233 patients with RA had AMPA status and radiographic progression scores after quality control. Differences in radiographic progression between groups were determined using least square means changes with baseline value of radiographic variable, rheumatoid factor, gender, age of onset of disease, symptom duration and baseline DAS28-CRP included as covariates.
Findings: Four main autoantibody groupings by class of modification were identified in RA patients (n=362) with reactivities against modified peptides as follows: citrullinated only (n=73, 20%), citrullinated and acetylated (n=45, 12%), citrullinated, carbamylated and acetylated (n=151, 42%) and AMPA negative (n=74, 20%). In RA patients with both antibody and radiographic data, those with antibodies against all three post-translational modifications (least square mean 1·7, n=97) had greater radiographic progression over 12 months compared to those with anti-citrullinated peptide antibodies (ACPA) only (least square mean 0·5, n=48) (least square mean difference of total SvH score of 1·2, 95% CI 0·05-2.40). There was no difference in progression comparing ACPA only with seronegative patients (least square mean 0.7, n=47) (least square mean difference -0.2, 95% CI -1·09-0·67).
Interpretation: RA patients with all three classes of AMPA have more rapid radiographic progression over 12 months than those with ACPA alone. Patients with ACPA alone had similar radiographic progression over 12 months to AMPA negative patients
Effects of hunger on model-based and model-free decision-making
No full textvan Swieten MMH, Manohar SG, Bogacz R
Description
In this study, healthy participants were tested on the effects of hunger on model-free and model-based decision-making. Each first-stage choice rocket was predominantly associated with one of the second-stage planets (common transition: 70% of the trials) and sometimes with the other second-stage planet (rare transition: 30% of the trials). Each second-stage alien probabilistically lead to a reward. The reward probabilities for each second-stage alien fluctuated across trials between 25% and 75% according to a Gaussian random walk.
Data format description in attached readme.txt. Data available to download from: https://data.mrc.ox.ac.uk/data-set/effects-hunger-model-based-and-model-free-decision-makin
Explaining cosmic ray antimatter with secondaries from old supernova remnants
No full textDespite significant efforts over the past decade, the origin of the cosmic ray positron excess has still not been unambiguously established. A popular class of candidate sources are pulsars or pulsar wind nebulae but these cannot also account for the observed hard spectrum of cosmic ray antiprotons. We revisit the alternative possibility that the observed high-energy positrons are secondaries created by spallation in supernova remnants during the diffusive shock acceleration of the primary cosmic rays, which are further accelerated by the same shocks. The resulting source spectrum of positrons at high energies is then naturally harder than that of the primaries, as is the spectrum of other secondaries such as antiprotons. We present the first comprehensive investigation of the full parameter space of this model—both the source parameters as well as those governing galactic transport. Various parametrizations of the cross sections for the production of positrons and antiprotons are considered, and the uncertainty in the model parameters discussed. We obtain an excellent fit to recent precision measurements by AMS-02 of cosmic ray protons, helium, positrons, and antiprotons, as well as of various primary and secondary nuclei. This model thus provides an economical explanation of the spectra of all secondary species—from a single well-motivated population of sources
A scoping review of considerations and practices for benefit sharing in biobanking
No full textBackground
Despite the rapid global growth of biobanking over the last few decades, and their potential for the advancement of health research, considerations specific to the sharing of benefits that accrue from biobanks have received little attention. Questions such as the types and range of benefits that can arise in biobanking, who should be entitled to those benefits, when they should be provided, by whom and in what form remain mostly unanswered. We conducted a scoping review to describe benefit sharing considerations and practices in biobanking in order to inform current and future policy and practice.
Methods
Drawing on the Arksey and O’Malley framework, we conducted a scoping review of the literature in three online databases (PubMed, Cochrane library, and Google Scholar). We extracted and charted data to capture general characteristics, definitions and examples of benefits and benefit sharing, justification for benefit sharing, challenges in benefit sharing, governance mechanisms as well as proposed benefit sharing mechanisms.
Results
29 articles published between 1999 and 2020 met the inclusion criteria for the study. The articles included 5 empirical and 24 non-empirical studies. Only 12 articles discussed benefit sharing as a stand-alone subject, while the remaining 17 integrated a discussion of benefits as one issue amongst others. Major benefit sharing challenges in biobanking were found to be those associated with uncertainties around the future use of samples and in resultant benefits.
Conclusion
Most of the benefit sharing definitions and approaches currently in use for biobanking are similar to those used in health research. These approaches may not recognise the distinct features of biobanking, specifically relating to uncertainties associated with the sharing and re-use of samples. We therefore support approaches that allow decisions about benefit sharing to be made progressively once it is apparent who samples are to be shared with, the intended purpose and expected benefits. We also highlight gaps in key areas informing benefit sharing in biobanking and draw attention to the need for further empirical research
Dietary carbohydrates and fats in nonalcoholic fatty liver disease
No full textThe global prevalence of nonalcoholic fatty liver disease (NAFLD) has dramatically increased in parallel with the epidemic of obesity. Controversy has emerged around dietary guidelines recommending low-fat–high-carbohydrate diets and the roles of dietary macronutrients in the pathogenesis of metabolic disease. In this Review, the topical questions of whether and how dietary fats and carbohydrates, including free sugars, differentially influence the accumulation of liver fat (specifically, intrahepatic triglyceride (IHTG) content) are addressed. Focusing on evidence from humans, we examine data from stable isotope studies elucidating how macronutrients regulate IHTG synthesis and disposal, alter pools of bioactive lipids and influence insulin sensitivity. In addition, we review cross-sectional studies on dietary habits of patients with NAFLD and randomized controlled trials on the effects of altering dietary macronutrients on IHTG. Perhaps surprisingly, evidence to date shows no differential effects between free sugars, with both glucose and fructose increasing IHTG in the context of excess energy. Moreover, saturated fat raises IHTG more than polyunsaturated or monounsaturated fats, with adverse effects on insulin sensitivity, which are probably mediated in part by increased ceramide synthesis. Taken together, the data support the use of diets that have a reduced content of free sugars, refined carbohydrates and saturated fat in the treatment of NAFLD