Miracle-dz/UniFAR-FTUs huggingface dataset:
Diurnal regulation of brassinosteroid synthesis

Plant steroid hormones, brassinosteroids, are essential for normal photomorphogenesis. However, the mechanism by which light controls physiological functions via brassinosteroids is not well understood. Using transgenic plants carrying promoter-luciferase reporter gene fusions we show that in Arabidopsis thaliana the brassinosteroid-biosynthetic CPD and CYP85A2 genes are under diurnal regulation. The complex diurnal expression profile of CPD is determined by dual, light-dependent and circadian control. The severely decreased expression level of CPD in phytochrome-deficient background and the red light-specific induction in wild-type plants suggest that light regulation of CPD is primarily mediated by phytochrome signaling. The diurnal rhythmicity of CPD activity is maintained in bri1 transgenic seedlings, indicating that its transcriptional control is independent of hormonal feedback regulation. Diurnal changes in the expression of CPD and CYP85A2 are accompanied by changes of the endogenous brassinosteroid content during the day, leading to brassinolide accumulation at the middle of the light phase. We also show that CPD expression is repressed in extended darkness in a brassinosteroid feedback-dependent manner. In the dark the level of the bioactive hormone did not increase, therefore our data strongly suggest that light also influences the sensitivity of plants to brassinosteroids. we generated transgenic Arabidopsis lines expressing firefly luciferase ( LUC ) under the control of the CPD promoter in order to allow in vivo monitoring of temporal changes in promoter activity by luminescence imaging. Here we report that expression of the CPD:LUC fusion follows a complex diurnal pattern that is determined by both light and circadian regulation. Very similar diurnal cycles were observed with LUC driven by the promoter of CYP85A2 , the gene required for BL synthesis. We also show that light induction of CPD is mediated primarily by phytochrome signaling, and that both light
Autoantibodies make a U-turn: the toll hypothesis for autoantibody speciﬁcity

Like the immune response itself, our efforts to understand the “rules” for self– nonself discrimination are constantly evolving. The discovery of pattern recognition receptors—the Toll-like receptor (TLR) family in particular—shifted the emphasis of self–nonself recognition from lymphocytes functioning in the adaptive immune system to antigen-presenting cells (APCs) functioning in the innate immune system. Two new articles, one in a recent issue (1) and one in this issue (see Vollmer et al. [2] on p. 1575), demonstrate that antigen– antibody complexes containing RNAs activate B lymphocytes and dendritic cells (DCs) through interaction with TLR7 and/or TLR8. From these and other papers, one begins to see how specific types of autoantigens—by virtue of their capacity to act as TLR ligands—favor autoantibody production. This is known as the Toll hypothesis.
Stem Cell Repor ts Repor t Genes Associated with Pancreas Development and Function Maintain Open Chromatin in iPSCs Generated from Human Pancreatic Beta Cells

SUMMARY Current in vitro islet differentiation protocols suffer from heterogeneity and low efﬁciency. Induced pluripotent stem cells (iPSCs) derived from pancreatic beta cells (BiPSCs) preferentially differentiate toward endocrine pancreas-like cells versus those from ﬁbroblasts (FiPSCs). We interrogated genome-wide open chromatin in BiPSCs and FiPSCs via ATAC-seq and identiﬁed (cid:1) 8.3k signiﬁcant, differential open chromatin sites (DOCS) between the two iPSC subtypes (false discovery rate [FDR] < 0.05). DOCS where chromatin was more accessible in BiPSCs (Bi-DOCS) were signiﬁcantly enriched for known regulators of endodermal development, including bivalent and weak enhancers, and FOXA2 binding sites (FDR < 0.05). Bi-DOCS were associated with genes related to pancreas development and beta-cell function, includingtranscriptionfactorsmutated in monogenic diabetes( PDX1 , NKX2-2 , HNF1A ; FDR < 0.05). Moreover, Bi-DOCScorrelated withenhanced geneexpressioninBiPSC-deriveddeﬁnitiveendodermandpancreaticprogenitorcells. Bi-DOCSthereforehighlightgenes and pathways governing islet-lineage commitment, which can be exploited for differentiation protocol optimization, diabetes disease modeling, and therapeutic purposes.
Respiratory Syncytial Virus Responses Production and APC Function with Activation Is Essential for Innate Cytokine Autophagy-Mediated Dendritic Cell

The regulation ofinnate immune responses during viral infection is a crucial step to promote antiviral reactions. Recent studies have drawn attention to a strong relationship of pathogen-associated molecular pattern recognition with autophagy for activation of APC function. Our initial observations indicated that autophagosomes formed in response to respiratory syncytial virus (RSV) infection of dendritic cells (DC). To further investigate whether RSV-induced DC activation and innate cytokine production were associated with autophagy, we used several methods to block autophagosome formation. Using 3-MA, small interfering RNA inhibition of LC3, or Beclin +/ 2 mouse-derived DC, studies established a relationship between RSV-induced autophagy and enhanced type I IFN, TNF, IL-6, and IL-12p40 expression. Moreover, autophagosome formation induced by starvation also promoted innate cytokine expression in DC. The induction of starvation-induced autophagy in combination with RSV infection synergistically enhanced DC cytokine expression that was blocked by an autophagy inhibitor. The latter synergistic responses were differentially altered in DC from MyD88 2 / 2 and TRIF 2 / 2 mice, supporting the concept of autophagy-mediated TLR signaling. In addition, blockade of autophagy in RSV-infected DC inhibited the maturation of DC as assessed by MHC class II and costimulatory molecule expression. Subsequently, we demonstrated that inhibition of autophagy in DC used to stimulate primary OVA-induced and secondary RSV-infected responses signiﬁcantly attenuated cytokine production by CD4 + T cells. Thus, these studies have outlined that autophagy in DC after RSV infection is a crucial mechanism for driving innate cytokine production, leading to altered acquired immune responses. The Journal of Immunology , 2011, 187: 000–000.
NBER WORKING PAPER SERIES UNDERSTANDING AND MISUNDERSTANDING RANDOMIZED CONTROLLED TRIALS

RCTs would be more useful if there were more realistic expectations of them and if their pitfalls were better recognized. For example, and contrary to many claims in the applied literature, randomization does not equalize everything but the treatment across treatments and controls, it does not automatically deliver a precise estimate of the average treatment effect (ATE), and it does not relieve us of the need to think about (observed or unobserved) confounders. Estimates apply to the trial sample only, sometimes a convenience sample, and usually selected; justification is required to extend them to other groups, including any population to which the trial sample belongs. Demanding “external validity” is unhelpful because it expects too much of an RCT while undervaluing its contribution. Statistical inference on ATEs involves hazards that are not always recognized. RCTs do indeed require minimal assumptions and can operate with little prior knowledge. This is an advantage when persuading distrustful audiences, but it is a disadvantage for cumulative scientific progress, where prior knowledge should be built upon and not discarded. RCTs can play a role in building scientific knowledge and useful predictions but they can only do so as part of a cumulative program, combining with other methods, including conceptual and theoretical development, to discover not “what works,” but “why things work”. Angus Deaton 361 Wallace Hall Woodrow Wilson School Princeton University Princeton, NJ 08544-1013 and NBER deaton@princeton.edu Nancy Cartwright Department of Philosophy Durham University 50 Old Elvet Durham, UK DH1 3HN and University of California, San Diego nancy.cartwright@durham.ac. uk
The Capitalization of Coupled and Decoupled CAP Payments into Land Rental Rates

: This paper explores the extent to which payments under the Common Agricultural Policy (CAP) are capitalized into land rents in Ireland with implications for the transfer efficiency of such payments, since subsidies may not benefit targeted recipients if they are capitalized into input prices. Capitalization in the years preceding and following the ‘decoupling’ of agricultural support payments from agricultural production is explored. In the period prior to decoupling, direct support (Pillar 1) payments were highly capitalized into Irish agricultural rents (67 to 90 cents per euro of subsidies), while in the post decoupling period capitalization appears to have declined somewhat.
Effects of Febuxostat in Early Gout: A Randomized, Double# Blind, Placebo#Controlled Study

Objective . To assess the effect of treatment with febuxostat versus placebo on joint damage in hyper-uricemic subjects with early gout (1 or 2 gout flares). Methods . In this double-blind, placebo-controlled study, 314 subjects with hyperuricemia (serum uric acid [UA] level of ≥ 7.0 mg/dl) and early gout were randomized 1:1 to receive once-daily febuxostat 40 mg (in-creased to 80 mg if the serum UA level was ≥ 6.0 mg/dl on day 14) or placebo. The primary efficacy end point was the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint. Additional efficacy end points included change from baseline to month 24 in the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) scores for synovitis, erosion, and edema in the single affected joint, the incidence of gout flares, and serum UA levels. Safety was assessed throughout the study. Results . Treatment with febuxostat did not lead to any notable changes in joint erosion over 2 years. In both treatment groups, the mean change from baseline to month 24 in the modified Sharp/van der Heijde erosion score for the single affected joint was minimal, with no between-group differences. However, treatment with febuxostat significantly improved the RAMRIS synovitis score at month 24 compared with placebo treatment ( change from baseline (cid:1) 0.43 versus (cid:1) 0.07; P < 0.001), decreased the overall incidence of gout flares (29.3% versus 41.4%; P < 0.05), and improved serum UA control (62.8% versus 5.7%; P < 0.001). No major safety concerns were reported. a difference in the change from baseline to month 24 in the modified SHS erosion score for the single affected joint at a 2-sided significance level of 0.05, assuming a mean change of 2.0 in the placebo group, 0.5 in the febuxostat group, and a common SD of 4.0 using the Wilcoxon-Mann-Whitney rank sum test. The calculation also assumed a dropout rate of 20%. These assumptions were based on the mean changes in the modified SHS erosion score observed in a study comparing adalimumab with placebo in patients with RA (15).
ReviewThe concept of folic acid in health and diseaseYulia Shulpekova1

Folates have a pterine core structure and high metabolic activity due to their ability to accept electrons and react with O-, S-, N-, C-bounds. Folates play a role as cofactors in essential onecarbon pathways donating methyl-groups to choline phospholipids, creatine, epinephrine, DNA. Compounds similar to folates are ubiquitous and have been found in different animals, plants, and microorganisms. Folates enter the body from the diet and are also synthesized by intestinal bacteria with consequent adsorption from the colon. Three types of folate and antifolate cellular transporters have been found, differing in tissue localization, substrate affinity, type of transferring, and optimal pH for function. Laboratory criteria of folate deficiency are accepted by WHO. Severe folate deficiencies, manifesting in early life, are seen in hereditary folate malabsorption and cerebral folate deficiency. Acquired folate deficiency is quite common and is associated with poor diet and malabsorption, alcohol consumption, obesity, and kidney failure. Given the observational data that folates have a protective effect against neural tube defects, ischemic events, and cancer, food folic acid fortification was introduced in many countries. However, high physiological folate concentrations and folate overload may increase the risk of impaired brain development in embryogenesis and possess a growth advantage for precancerous altered cells.
M-theory and E10: Billiards, Branes, and Imaginary Roots

Eleven dimensional supergravity compactified on $T^10$ admits classical solutions describing what is known as billiard cosmology - a dynamics expressible as an abstract (billiard) ball moving in the 10-dimensional root space of the infinite dimensional Lie algebra E10, occasionally bouncing off walls in that space. Unlike finite dimensional Lie algebras, E10 has negative and zero norm roots, in addition to the positive norm roots. The walls above are related to physical fluxes that, in turn, are related to positive norm roots (called real roots) of E10. We propose that zero and negative norm roots, called imaginary roots, are related to physical branes. Adding 'matter' to the billiard cosmology corresponds to adding potential terms associated to imaginary roots. The, as yet, mysterious relation between E10 and M-theory on $T^10$ can now be expanded as follows: real roots correspond to fluxes or instantons, and imaginary roots correspond to particles and branes (in the cases we checked). Interactions between fluxes and branes and between branes and branes are classified according to the inner product of the corresponding roots (again in the cases we checked). We conclude with a discussion of an effective Hamiltonian description that captures some features of M-theory on $T^10. $
Convective heat loss prediction from conical cavity receiver of solar parabolic dish collector using numerical method and artificial neural network

Abstract In this work, detailed investigations of convection heat loss from conical cavity receiver of solar parabolic dish collector using a numerical method and artificial neural network have been performed. The convective heat loss from the cavity receiver is primarily influenced by geometrical parameters, receiver orientation, and wind characteristics. The heat loss estimation is carried out by considering wind speed (V = 0–10 m/s), wind direction ( = 90 and −90 ), receiver tilt ( = 0–90 ), diameter to height ratio (d/h = 0.5–1.5), and surface temperature (T s = 500–800 K). The utmost heat loss occurs at a tilt of 60 for d/h < 1 and 75 for d/h 1 in head-on high wind speed, while in back-on high wind speed, it occurs at a tilt of 30 for all d/h values. The heat loss is lowest at 90° for V > 4 m/s. The d/h value of 0.5 performs well compared to other values. Further, the correlation for the Nusselt number has been proposed for the conical cavity receiver.
Relationships between Volatile Organic Compounds Released by Wheat Plants Following Artificial Stress and Their Potential Influence on Natural Pest Management

There is an urgent need to establish new agro-technical practices that require the delivery of effective, natural, ecological, and verified solutions. The evaluation of possible applications in the field of cropping and farming in recent years has resulted in numerous products and approaches, which may potentially reduce our dependence on artificial pesticides. A major requirement to help establish these new agro-technical practices is to determine their efficiency. Here we present a study that investigates the relationship between volatile organic compounds (VOCs) released by Triticum sp. plants under two artificial stress conditions. We discuss their effectiveness in natural pest management and for use in monitoring crop health. Two varieties of spring wheat, “Kandela” and “Serenada”, were exposed to either mechanical (deliberate) wounding, to imitate the stress caused by insect attack, or exposure to methyl jasmonate, a defence volatile used by plants. Both stress factors caused an increased release of green leaf volatiles (C6 aldehydes and alcohols) and other volatile compounds, such as (E)-β-ocimene, linalool, β-caryophyllene, and (E)-β-farnesene. VOC emission rates are reported at three time points (24, 48, and 72 h) following a stress factor. Correlation coefficients between the emitted plant’s VOCs indicate the potential of monitoring just one single compound from the combination of volatiles emitted by plants to predict the overall condition of a crop. This has major implications for the development of a chemically specific and fieldable analytical sensor that could be used to provide an array of volatile monitoring stations delivering information continuously and in real-time. Finally, we demonstrate the effectiveness of the volatiles released by damaged spring wheat for pest management by exposing a shield bug (Bishop’s Mitre (Aelia acuminata L.), Hemiptera: Pentatomidae), to them.
Correlation between Objective Measures of Sun Exposure and Self‐Reported Sun Protective Behavior and Attitudes in Predominantly Hispanic Youth

Melanoma incidence is increasing, with poor prognosis cases growing faster in California Hispanics than in non‐Hispanic whites. Ultraviolet Radiation (UVR) exposure as a child has been found to disproportionately increase the risk of melanoma. To determine correlates of UVR exposure in this high‐risk population, we conducted a study in predominately Hispanic 4th and 5th grade classrooms in Los Angeles County, a high UVR environment, during the spring. To address potential reporting bias, electronic UV dosimeters were utilized to objectively measure the association between UVR exposure and constructs (acculturation, sun protective behavior and knowledge, family interventions) obtained on baseline questionnaires (n = 125). Tanning attitude (wanting to get a tan) was associated with lower median time spent outside (1.73 min versus 22.17, AUC 82.08, Sensitivity 0.78, Specificity 0.73) and standard erythemal dose (SED) on weekends, but positively associated with sun protective knowledge. Sun protective knowledge and family discussion of sunscreen were also inversely associated with objectively measured time outside. Students spent a median 30.61 (IQR 19.88) minutes outside per day (SED 0.30, IQR 0.20), with only 35.70% of it occurring in nonschool hours. We determined the majority of UVR exposure in this population occurs at school, providing valuable guidance for future interventions.
Spatio‐temporal changes in chimpanzee density and abundance in the Greater Mahale Ecosystem, Tanzania

Abstract Species conservation and management require reliable information about animal distribution and population size. Better management actions within a species' range can be achieved by identifying the location and timing of population changes. In the Greater Mahale Ecosystem (GME), western Tanzania, deforestation due to the expansion of human settlements and agriculture, annual burning, and logging are known threats to wildlife. For one of the most charismatic species, the endangered eastern chimpanzee (Pan troglodytes schweinfurthii), approximately 75% of the individuals are distributed outside national park boundaries, requiring monitoring and protection efforts over a vast landscape of various protection statuses. These efforts are especially challenging when we lack data on trends in density and population size. To predict spatio‐temporal chimpanzee density and abundance across the GME, we used density surface modeling, fitting a generalized additive model to a 10‐year time‐series data set of nest counts based on line‐transect surveys. The chimpanzee population declined at an annual rate of 2.41%, including declines of 1.72% in riparian forests (from this point forward, forests), 2.05% in miombo woodlands (from this point forward, woodlands) and 3.45% in nonforests. These population declines were accompanied by ecosystem‐wide declines in vegetation types of 1.36% and 0.32% per year for forests and woodlands, respectively; we estimated an annual increase of 1.35% for nonforests. Our model predicted the highest chimpanzee density in forests (0.86 chimpanzees/km2, 95% confidence intervals (CIs) 0.60–1.23; as of 2020), followed by woodlands (0.19, 95% CI 0.12–0.30) and nonforests (0.18, 95% CI 0.10–1.33). Although forests represent only 6% of the landscape, they support nearly one‐quarter of the chimpanzee population (769 chimpanzees, 95% CI 536–1103). Woodlands dominate the landscape (71%) and therefore support more than a half of the chimpanzee population (2294; 95% CI 1420–3707). The remaining quarter of the landscape is represented by nonforests and supports another quarter of the chimpanzee population (750; 95% CI 408–1381). Given the pressures on the remaining suitable habitat in Tanzania, and the need of chimpanzees to access both forest and woodland vegetation to survive, we urge future management actions to increase resources and expand the efforts to protect critical forest and woodland habitat and promote strategies and policies that more effectively prevent irreversible losses. We suggest that regular monitoring programs implement a systematic random design to effectively inform and allocate conservation actions and facilitate interannual comparisons for trend monitoring, measuring conservation success, and guiding adaptive management.
Can vaccines control bacterial virulence and pathogenicity? Bordetella pertussis: the advantage of fitness over virulence

Abstract Some vaccines, such as diphtheria toxoid and acellular pertussis vaccines (aPVs), may favor the emergence of less pathogenic strains of the respective bacteria they target. This review discusses the impact of the wide use of aPV on Bordetella pertussis phenotype evolutions and their beneficial consequences in the light of the diphtheria toxoid immunization program experience and structuring evidence review in a causal analysis following Bradford Hill’s causality criteria. All aPVs contain the pertussis toxin (PT), the main virulence factor of B.pertussis, alone or with one adhesin (filamentous hemagglutinin (FHA)), two adhesins (FHA and pertactin (PRN)) or four adhesins (FHA, PRN and two fimbriae (Fim 2/3)). In countries where the coverage of aPVs containing PRN is high, PRN negative B.pertussis isolates are increasing in prevalence, but isolates nonproducing the other antigens are rarely reported. We hypothesize that the selective pressure at play with PRN should exist against all aVP antigens, although detection biases may hinder its detection for other antigens, especially PT. PT being responsible for clinically frank cases of the disease, the opportunity to collect PT negative isolates is far lower than to collect PRN negative isolates which have a limited clinical impact. The replacement of the current B.pertussis by far less pathogenic isolates no longer producing the factors contained in aPVs should be expected as a consequence of the wide aPV use.
Aggregate fluctuations and the cross‐sectional dynamics of firm growth

Summary. The paper explores time variation in the distribution of firm level growth of total sales. Three novel results are reported. First, firms on the left‐hand side of the distribution, i.e. firms that are growing more slowly or declining, are typically more responsive to aggregate shocks than those on the right‐hand side of the distribution. Second, trending behaviour in the volatility of firm growth is predominantly driven by increasing dispersion in the growth of highly performing firms. Third, shifts in the probability mass on either side of the mode may act as important propagators of business fluctuations. Financial frictions emerge as a mechanism that is capable of accounting for these facts.