Predicting the risk to develop preeclampsia in the first trimester combining promoter variant -98A/C of LGALS13 (placental protein 13), Black ethnicity, previous preeclampsia, obesity, and maternal age

BACKGROUND: We studied LGALS13 [Placental Protein 13 (PP13)] promoter DNA polymorphisms in preeclampsia (PE) prediction, given PP13’s effects on hypotension, angiogenesis and immunotolerance. METHODS: We retrieved 67 PE (49 term, 18 preterm) cases and 196 matched controls from first trimester plasma samples prospectively collected at King's College Hospital, London. Cell-free DNA was extracted and the four LGALS13 exons were sequenced after PCR amplification. Expression of LGALS13 promoter reporter constructs were determined in BeWo trophoblast-like cells with luciferase assays. RESULTS: A/C genotype in –98 position was the lowest in term PE compared to controls (p<0.032), similar to a South African cohort. Control but not all PE allele frequencies were in Hardy-Weinberg equilibrium (p=0.036). The Odds ratio for term PE calculated from prior risk, the A/A genotype and black ethnicity was 14 (p<0.001). In luciferase assays, the LGALS13 promoter “-98A" variant had 13% (p=0.04) and 26% (p<0.001) lower expression than the "-98C" variant in non-differentiated and differentiated BeWo cells, respectively. After 48-hour differentiation, there was 4.55- fold increase in expression of "-98C" variant versus 3.85-fold of "-98A" variant (p<0.001). CONCLUSION: Lower LGALS13 (PP13) expression by the "-98A/A" genotype appears to impose higher risk to develop PE and could aid in PE prediction

A Prediction Model to Prioritize Individuals for a SARS-CoV-2 Test Built from National Symptom Surveys

Background: The gold standard for COVID-19 diagnosis is detection of viral RNA through PCR. Due to global limitations in testing capacity, effective prioritization of individuals for testing is essential. Methods: We devised a model estimating the probability of an individual to test positive for COVID-19 based on answers to 9 simple questions that have been associated with SARS-CoV-2 infection. Our model was devised from a subsample of a national symptom survey that was answered over 2 million times in Israel in its first 2 months and a targeted survey distributed to all residents of several cities in Israel. Overall, 43,752 adults were included, from which 498 self-reported as being COVID-19 positive. Findings: Our model was validated on a held-out set of individuals from Israel where it achieved an auROC of 0.737 (CI: 0.712–0.759) and auPR of 0.144 (CI: 0.119–0.177) and demonstrated its applicability outside of Israel in an independently collected symptom survey dataset from the US, UK, and Sweden. Our analyses revealed interactions between several symptoms and age, suggesting variation in the clinical manifestation of the disease in different age groups. Conclusions: Our tool can be used online and without exposure to suspected patients, thus suggesting worldwide utility in combating COVID-19 by better directing the limited testing resources through prioritization of individuals for testing, thereby increasing the rate at which positive individuals can be identified. Moreover, individuals at high risk for a positive test result can be isolated prior to testing. Funding: E.S. is supported by the Crown Human Genome Center, Larson Charitable Foundation New Scientist Fund, Else Kroener Fresenius Foundation, White Rose International Foundation, Ben B. and Joyce E. Eisenberg Foundation, Nissenbaum Family, Marcos Pinheiro de Andrade and Vanessa Buchheim, Lady Michelle Michels, and Aliza Moussaieff and grants funded by the Minerva foundation with funding from the Federal German Ministry for Education and Research and by the European Research Council and the Israel Science Foundation. H.R. is supported by the Israeli Council for Higher Education (CHE) via the Weizmann Data Science Research Center and by a research grant from Madame Olga Klein – Astrachan

IPT9, a cis-zeatin cytokinin biosynthesis gene, promotes root growth

Cytokinin and auxin are plant hormones that coordinate many aspects of plant development. Their interactions in plant underground growth are well established, occurring at the levels of metabolism, signaling, and transport. Unlike many plant hormone classes, cytokinins are represented by more than one active molecule. Multiple mutant lines, blocking specific parts of cytokinin biosynthetic pathways, have enabled research in plants with deficiencies in specific cytokinin-types. While most of these mutants have confirmed the impeding effect of cytokinin on root growth, the ipt29 double mutant instead surprisingly exhibits reduced primary root length compared to the wild type. This mutant is impaired in cis-zeatin (cZ) production, a cytokinin-type that had been considered inactive in the past. Here we have further investigated the intriguing ipt29 root phenotype, opposite to known cytokinin functions, and the (bio)activity of cZ. Our data suggest that despite the ipt29 short-root phenotype, cZ application has a negative impact on primary root growth and can activate a cytokinin response in the stele. Grafting experiments revealed that the root phenotype of ipt29 depends mainly on local signaling which does not relate directly to cytokinin levels. Notably, ipt29 displayed increased auxin levels in the root tissue. Moreover, analyses of the differential contributions of ipt2 and ipt9 to the ipt29 short-root phenotype demonstrated that, despite its deficiency on cZ levels, ipt2 does not show any root phenotype or auxin homeostasis variation, while ipt9 mutants were indistinguishable from ipt29. We conclude that IPT9 functions may go beyond cZ biosynthesis, directly or indirectly, implicating effects on auxin homeostasis and therefore influencing plant growth

Pilot study of the multicentre DISCHARGE trial: image quality and protocol adherence results of computed tomography and invasive coronary angiography (vol 30, pg 1997, 2020)

The original version of this article, published on 16 December 2019, unfortunately contained two mistakes.Cardiovascular Aspects of Radiolog

Constructing narratives and reading texts: Approaches to history and power struggles between philosophy and emergent disciplines in inter-war France

In inter-war France, history of philosophy was a very important academic discipline, but nevertheless its practitioners thought it necessary to defend its identity, which was threatened by its vicinity to many other disciplines, and especially by the emergent social sciences and history of science. I shall focus on two particular issues that divided traditional historians of philosophy from historians of science, ethnologists and sociologists, and that became crucial in the definition of the identity of their disciplines: the conception of history and the interpretation of texts. By analysing representative discussions and positions, I shall show that traditional historians of philosophy needed to reassert their own approach to history, which, borrowing the term from Bergson, I define as ‘snapshot’. This approach is focused on a particular idea or text rather than a narrative. I shall also show that history of philosophy, in its traditional form, would have been undermined both intellectually and institutionally by the opposite ‘narrative’ approach of history of science and of the social sciences. Social scientists openly attacked history of philosophy’s methods and, in the eyes of traditional philosophers, its existence as an academic discipline. The same opposition is to be found in evaluation of past texts, which for traditional historians of philosophy were to be read as timeless documents, while for historians of science, ethnologists and sociologists were to be considered as documents exhibiting a particular mentality. However, between these alternatives there were intermediate positions. I shall in particular consider that of Léon Brunschvicg: he embraced a narrative approach and considered texts as documents of different ways of thinking, but at the same time carried on employing philosophical methods and defending the institutional position of philosophy. I shall argue that this was possible partly because of the considerable amount of power he enjoyed at the Sorbonne

Tissue-specific hormone profiles from woody poplar roots under bending stress

Mechanical forces induced by bending are able to trigger an asymmetrical response in Populus nigra L. woody taproots. This response includes the recruitment of new lateral roots on the convex side and the deposition of reaction wood (RW) on the opposite concave side. Since these responses seem to be induced by asymmetric activity and differentiation of cambium cells, we investigated, in the present work, how mechanical forces could influence the activation of specific phytohormone signaling pathways on the two sides of the vascular cambium. Thus, distinctive tissues were isolated from convex and concave sides of bent poplar root using cryosectioning. Successively, the isolated tissues, represented by the cambial zone, and the developing phloem and xylem, were analyzed using liquid chromatography coupled to tandem mass spectrometry to profile auxins, abscisic acid (ABA), cytokinins (CKs) and their metabolites. The auxin gradient on the concave side, with the IAA maximum localized in the cambium and decreasing level toward the developing phloem and xylem, suggests a pivotal role of IAA in the control of cambial growth rate, xylem differentiation and RW production. The IAA differences between the two bent root sides could be at the basis of the strictly unidirectional RW production. The higher levels of ABA and all CKs metabolites on the concave side support their involvement in RW production, whereby ABA could mediate the adaptation to the deforming conditions generated by bending, while CKs could act in synergy with IAA in controlling cell differentiation and meristem size

Tissue-specific hormone profiles from woody poplar roots under bending stress

Mechanical forces induced by bending are able to trigger an asymmetrical response in Populus nigra L. woody taproots. This response includes the recruitment of new lateral roots on the convex side and the deposition of reaction wood (RW) on the opposite concave side. Since these responses seem to be induced by asymmetric activity and differentiation of cambium cells, we investigated, in the present work, how mechanical forces could influence the activation of specific phytohormone signaling pathways on the two sides of the vascular cambium. Thus, distinctive tissues were isolated from convex and concave sides of bent poplar root using cryosectioning. Successively, the isolated tissues, represented by the cambial zone, and the developing phloem and xylem, were analyzed using liquid chromatography coupled to tandem mass spectrometry to profile auxins, abscisic acid (ABA), cytokinins (CKs) and their metabolites. The auxin gradient on the concave side, with the IAA maximum localized in the cambium and decreasing level toward the developing phloem and xylem, suggests a pivotal role of IAA in the control of cambial growth rate, xylem differentiation and RW production. The IAA differences between the two bent root sides could be at the basis of the strictly unidirectional RW production. The higher levels of ABA and all CKs metabolites on the concave side support their involvement in RW production, whereby ABA could mediate the adaptation to the deforming conditions generated by bending, while CKs could act in synergy with IAA in controlling cell differentiation and meristem size