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NCYM is a cis-antisense gene of MYCN oncogene and encodes an oncogenic protein that stabilizes MYCN via inhibition of GSK3b. High NCYM expression levels are associated with poor clinical outcomes in human neuroblastomas, and NCYM overexpression promotes distant metastasis in animal models of neuroblastoma. Using vacuum-ultraviolet circular dichroism and small-angle X-ray scattering, we previously showed that NCYM has high flexibility with partially folded structures; however, further structural characterization is required for the design of anti-cancer agents targeting NCYM. Here we report the 1H, 15N and 13C nuclear magnetic resonance assignments of NCYM. Secondary structure prediction using Secondary Chemical Shifts and TALOS-N analysis demonstrates that the structure of NCYM is essentially disordered, even though residues in the central region of the peptide clearly present a propensity to adopt a dynamic helical structure. This preliminary study provides foundations for further analysis of interaction between NCYM and potential partners. [ABSTRACT FROM AUTHOR]

We begin a systematic study of the region of possible values of the volumes of Minkowski subset sums of a collection of M compact sets in R d , which we call the Lyusternik region, and make some first steps towards describing it. Our main result is that a fractional generalization of the Brunn–Minkowski–Lyusternik inequality conjectured by Bobkov et al. (in: Houdré et al. (eds) Concentration, functional inequalities and isoperimetry. Contemporary mathematics, American Mathematical Society, Providence, 2011) holds in dimension 1. Even though Fradelizi et al. (C R Acad Sci Paris Sér I Math 354(2):185–189, 2016) showed that it fails in general dimension, we show that a variant does hold in any dimension. [ABSTRACT FROM AUTHOR]

Recently, numerous physical attacks have been demonstrated against lattice-based schemes, often exploiting their unique properties such as the reliance on Gaussian distributions, rejection sampling and FFT-based polynomial multiplication. As the call for concrete implementations and deployment of postquantum cryptography becomes more pressing, protecting against those attacks is an important problem. However, few countermeasures have been proposed so far. In particular, masking has been applied to the decryption procedure of some lattice-based encryption schemes, but the much more difficult case of signatures (which are highly nonlinear and typically involve randomness) has not been considered until now. In this paper, we describe the first masked implementation of a lattice-based signature scheme. Since masking Gaussian sampling and other procedures involving contrived probability distributions would be prohibitively inefficient, we focus on the GLP scheme of Güneysu, Lyubashevsky and Pöppelmann (CHES 2012). We show how to provably mask it in the Ishai–Sahai–Wagner model (CRYPTO 2003) at any order in a relatively efficient manner, using extensions of the techniques of Coron et al. for converting between arithmetic and Boolean masking. Our proof relies on a mild generalization of probing security that supports the notion of public outputs. We also provide a proof-of-concept implementation to assess the efficiency of the proposed countermeasure. [ABSTRACT FROM AUTHOR]

Tropical rainforests host exceptional biodiversity and provide important ecosystem services, but they are facing anthropogenic and climatic threats. Preserving the genetic diversity of forest tree populations is essential for their capacity to adapt and exhibit resilience to environmental changes and anthropogenic pressures. Here, we collected conservation genetic baseline information for the heavily exploited timber tree Dicorynia guianensis Amshoff (Fabaceae) at the regional and local levels in French Guiana. Based on genotyping at five microsatellite loci in 1566 individuals collected in 23 forest locations, we documented the genetic differentiation of locations from the West of French Guiana and identified distinctive genetic diversity patterns with higher genetic diversity and some bottlenecked sites in the East and inland. The regional population genetic structure is likely the result of past population isolation in distinct Pleistocene refuges and different demographic histories potentially influenced by Holocene drought periods or palaeofires. Assessment of spatial genetic structure (Sp from 0 to 0.028) in five intensively sampled locations yielded estimates of Wright's neighborhood size of 35 to 313, indicative of restricted dispersal and local metapopulation dynamics, and useful as baseline information to assess the effects of selective logging for conservation management. These results support the current management strategies with low impact extraction of D. guianensis in three zones of the French Guiana permanent forest domain and allow us to make recommendations for further research and management to best preserve its genetic diversity and adaptive potential. [ABSTRACT FROM AUTHOR]

Human babesiosis is a vector-borne zoonotic infection caused mostly by the Apicomplexan parasite Babesia microti, distributed worldwide. The infection can result in severe symptoms such as hemolytic anemia, especially in immunodeficient patients. Also, asymptomatic patients continue transmission as unscreened blood donors, and represent a risk for Public Health. Early host-parasite interactions are mediated by BmSA1, the major surface antigen of Babesia microti, crucial for invasion and immune escape. Hence, a structural and functional characterization of the BmSA1 protein constitutes a first strategic milestone toward the development of innovative tools to control infection. Knowledge of the 3D structure of such an important antigen is crucial for the development of vaccines or new diagnostic tests. Here, we report the 1H, 15N and 13C NMR resonance assignment of ∆∆BmSA1, a truncated recombinant version of BmSA1 without the N-terminal signal peptide and the hydrophobic C-terminal GPI-anchor. Secondary structure prediction using CSI.3 and TALOS-N demonstrates a high content of alpha-helical structure. This preliminary study provides foundations for further structural characterization of BMSA1. [ABSTRACT FROM AUTHOR]

Mercury's magnetosphere is known to involve fundamental processes releasing particles and energy like at Earth due to the solar wind interaction. The resulting cycle is however much faster and involves acceleration, transport, loss, and recycling of plasma. Direct experimental evidence for the roles of electrons during this cycle is however missing. Here we show that in-situ plasma observations obtained during BepiColombo's first Mercury flyby reveal a compressed magnetosphere hosts of quasi-periodic fluctuations, including the original observation of dynamic phenomena in the post-midnight, southern magnetosphere. The energy-time dispersed electron enhancements support the occurrence of substorm-related, multiple, impulsive injections of electrons that ultimately precipitate onto its surface and induce X-ray fluorescence. These observations reveal that electron injections and subsequent energy-dependent drift now observed throughout Solar System is a universal mechanism that generates aurorae despite the differences in structure and dynamics of the planetary magnetospheres. BepiColombo mission had its first Mercury flyby on 1 October 2021. Here, the authors show plasma measurements taken during this flyby, which reveals that electron injections and subsequent energy-dependent drift is a universal mechanism generating aurorae in the planetary magnetospheres. [ABSTRACT FROM AUTHOR]

Remotely sensed interplanetary scintillation (IPS) data from the Institute for Space-Earth Environmental Research (ISEE), Japan, allows a determination of solar-wind parameters throughout the inner heliosphere. We show the 3D analysis technique developed for these data sets that forecast plasma velocity, density, and component magnetic fields at Earth, as well at the other inner heliospheric planets and spacecraft. One excellent coronal mass ejection (CME) example that occurred on the 10 March 2022 was viewed not only in the ISEE IPS analyses, but also by the spacecraft near Earth that measured the CME arrival at one AU. Solar Orbiter, that was nearly aligned along the Earth radial at 0.45 AU, also measured the CME in plasma density, velocity, and magnetic field. BepiColombo at 0.42 AU was also aligned with the STEREO A spacecraft, and viewed this CME. The instruments used here from BepiColombo include: 1) the European-Space-Agency Mercury-Planetary-Orbiter magnetic field measurements; 2) the Japan Aerospace Exploration Agency Mio spacecraft Solar Particle Monitor that viewed the CME Forbush decrease, and the Mercury Plasma Experiment/Mercury Electron Analyzer instruments that measured particles and solar-wind density from below the spacecraft protective sunshield covering. This article summarizes the analysis using ISEE, Japan real-time data for these forecasts: it provides a synopsis of the results and confirmation of the CME event morphology after its arrival, and discusses how future IPS analyses can augment these results. [ABSTRACT FROM AUTHOR]

Effectors are small and very diverse proteins secreted by fungi and translocated in plant cells during infection. Among them, MAX effectors (for Magnaporthe Avrs and ToxB) were identified as a family of effectors that share an identical fold topology despite having highly divergent sequences. They are mostly secreted by ascomycetes from the Magnaporthe genus, a fungus that causes the rice blast, a plant disease leading to huge crop losses. As rice is the first source of calories in many countries, especially in Asia and Africa, this constitutes a threat for world food security. Hence, a better understanding of these effectors, including structural and functional characterization, constitutes a strategic milestone in the fight against phytopathogen fungi and may give clues for the development of resistant varieties of rice. We report here the near complete 1H, 15 N and 13C NMR resonance assignment of three new putative MAX effectors (MAX47, MAX60 and MAX67). Secondary structure determination using TALOS-N and CSI.3 demonstrates a high content of β-strands in all the three proteins, in agreement with the canonic ß-sandwich structure of MAX effectors. This preliminary study provides foundations for further structural characterization, that will help in turn to improve sequence predictions of other MAX effectors through data mining. [ABSTRACT FROM AUTHOR]

Infrared cooled photodetectors must operate at higher temperatures to reduce their size, weight and power consumption (SWaP context). Their stability and image quality are then challenged by extra electrical activity of crystal defects. Knowledge of defect populations is mandatory to improve the material quality of the epitaxial Hg1−xCdxTe (MCT) active layer and the Cd1−xZnxTe (CZT) substrate. Positron annihilation spectroscopy with a slow positron beam was used to study near-surface open-volume defects profiles. Low- and high-momentum fractions (S , W ) were used to characterize the Doppler broadening of the 511 keV electron-positron pair annihilation-line as a function of the positron implantation energy E . The results show that three regions can be identified beneath the surface of the as-grown non-optimized MCT layer. The quasi-linear relationship between the annihilation characteristics in the regions suggests that the defect populations mainly correspond to the same open-volume defect in different concentrations. The probed defect is thought to be related to the mercury vacancy. This hypothesis is discussed in an original way with near-surface elemental profiles using scanning transmission electron spectroscopy combined to energy dispersive x-ray spectroscopy (STEM-EDX). Afterwards, this approach is extended to CZT substrates showing that surface and bulk properties of those fabricated by LYNRED tend to match those that are state-of-the-art. A common open-volume defect is probed, in concentration estimated by Hall effect around 1015 cm−3 and thought to be related to the cadmium vacancy. [ABSTRACT FROM AUTHOR]

Multidomain kinases use many ways to integrate and process diverse stimuli. Here, we investigated the mechanism by which the protein tyrosine kinase 2-beta (PYK2) functions as a sensor and effector of cellular calcium influx. We show that the linker between the PYK2 kinase and FAT domains (KFL) encompasses an unusual calmodulin (CaM) binding element. PYK2 KFL is disordered and engages CaM through an ensemble of transient binding events. Calcium increases the association by promoting structural changes in CaM that expose auxiliary interaction opportunities. KFL also forms fuzzy dimers, and dimerization is enhanced by CaM binding. As a monomer, however, KFL associates with the PYK2 FERM-kinase fragment. Thus, we identify a mechanism whereby calcium influx can promote PYK2 self-association, and hence kinase-activating trans-autophosphorylation. Collectively, our findings describe a flexible protein module that expands the paradigms for CaM binding and self-association, and their use for controlling kinase activity. Protein tyrosine kinase 2-beta is shown to function as a sensor and effector of cellular calcium influx through self-association. [ABSTRACT FROM AUTHOR]

The ongoing COVID-19 pandemic let to efforts to develop and deploy digital contact tracing systems to expedite contact tracing and risk notification. Unfortunately, the success of these systems has been limited, partly owing to poor interoperability with manual contact tracing, low adoption rates, and a societally sensitive trade-off between utility and privacy. In this work, we introduce a new privacy-preserving and inclusive system for epidemic risk assessment and notification that aims to address these limitations. Rather than capturing pairwise encounters between user devices as done by existing systems, our system captures encounters between user devices and beacons placed in strategic locations where infection clusters may originate. Epidemiological simulations using an agent-based model demonstrate that, by utilizing location and environmental information and interoperating with manual contact tracing, our system can increase the accuracy of contact tracing actions and may help reduce epidemic spread already at low adoption. [ABSTRACT FROM AUTHOR]

Probability measures satisfying a Poincaré inequality are known to enjoy a dimension-free concentration inequality with exponential rate. A celebrated result of Bobkov and Ledoux shows that a Poincaré inequality automatically implies a modified logarithmic Sobolev inequality. As a consequence the Poincaré inequality ensures a stronger dimension-free concentration property, known as two-level concentration. We show that a similar phenomenon occurs for the Latała–Oleszkiewicz inequalities, which were devised to uncover dimension-free concentration with rate between exponential and Gaussian. Motivated by the search for counterexamples to related questions, we also develop analytic techniques to study functional inequalities for probability measures on the line with wild potentials. [ABSTRACT FROM AUTHOR]

Several homogeneous photo-based advanced oxidation processes-namely photolysis, photo-oxidation, and photo-Fenton oxidation—were investigated for the elimination of ibuprofen in water. The effects of several operating parameters, such as the lamp type (low or medium pressure mercury, xenon-arc), the concentration of hydrogen peroxide (0.5 to 7 times the stoichiometric amount required for mineralization), and the concentration of Fenton reagent, were quantified. Photo-Fenton oxidation was also combined with low-frequency sonication to investigate possible synergistic interactions. Ibuprofen degradation under ultraviolet photolysis and ultraviolet/hydrogen peroxide oxidation followed pseudo-first-order kinetics with respect to the pollutant concentration and the apparent rate constant increased with lamp power (6–10 W) and oxidant concentration. Photo-Fenton oxidation under ultraviolet light (L1 lamp, 254 nm, 6 W) and visible light (L2 lamp, 360–740 nm, 150 W) led to complete ibuprofen removal after 3 h, but the mineralization yield of the L1/Fenton process (82%) was higher than that of the L2/Fenton process (59%) because of the effects of ultraviolet/hydrogen peroxide oxidation in the former. Coupling L2/Fenton with sonication improved the degradation rate of the molecule at low Fenton reagent concentration, but the beneficial effect of ultrasound on ferrous iron regeneration vanished when the iron to ibuprofen molar ratio was close to 1. An overall reaction scheme for ibuprofen degradation is proposed based on the transformation products detected during these processes. [ABSTRACT FROM AUTHOR]

Arpp19 is a potent PP2A-B55 inhibitor that regulates this phosphatase to ensure the stable phosphorylation of mitotic/meiotic substrates. At G2-M, Arpp19 is phosphorylated by the Greatwall kinase on S67. This phosphorylated Arpp19 form displays a high affinity to PP2A-B55 and a slow dephosphorylation rate, acting as a competitor of PP2A-B55 substrates. The molecular determinants conferring slow dephosphorylation kinetics to S67 are unknown. PKA also phosphorylates Arpp19. This phosphorylation performed on S109 is essential to maintain prophase I-arrest in Xenopus oocytes although the underlying signalling mechanism is elusive. Here, we characterize the molecular determinants conferring high affinity and slow dephosphorylation to S67 and controlling PP2A-B55 inhibitory activity of Arpp19. Moreover, we show that phospho-S109 restricts S67 phosphorylation by increasing its catalysis by PP2A-B55. Finally, we discover a double feed-back loop between these two phospho-sites essential to coordinate the temporal pattern of Arpp19-dependent PP2A-B55 inhibition and Cyclin B/Cdk1 activation during cell division. Progression of the cell division cycle requires feedback loops including those of phosphorylation and dephosphorylation; however the precise regulation of phosphorylation kinetics of Arpp19, an inhibitor of protein phosphatase 2A, is unclear. Here, the authors report that feedback between phosphorylation states of Ser67 and Ser109 of Arpp19 coordinates Arpp19-dependent inhibition of PP2A-B55 and Cyclin B activation during cell cycle progression. [ABSTRACT FROM AUTHOR]

Today, resilience in the face of cyclone risks has become a crucial issue for our societies. With climate change, the risk of strong cyclones occurring is expected to intensify significantly and to impact the way of life in many countries. To meet some of the associated challenges, the interdisciplinary ReNovRisk programme aims to study tropical cyclones and their impacts on the South-West Indian Ocean basin. This article is a presentation of the ReNovRisk programme, which is divided into four areas: study of cyclonic hazards, study of erosion and solid transport processes, study of water transfer and swell impacts on the coast, and studies of socio-economic impacts. The first transdisciplinary results of the programme are presented together with the database, which will be open access from mid-2021. [ABSTRACT FROM AUTHOR]

Background: Inflammatory vascular disease of the arteries, such as inflamed atheromatous plaques or arteritis, may cause aneurysms or ischemic strokes. In this context, using positron emission tomography (PET) to image inflammation may help select patients who would benefit from appropriate therapeutic interventions. This study sought to assess the usefulness of the 18 kDa translocator protein (TSPO) tracers [11C]-PBR28 and [18F]-PBR06 for imaging inflammatory vascular disease in vitro and in vivo. Immunohistochemistry for macrophage infiltration as well as autoradiography with [18F]-PBR06 were performed on eight paraffin-embedded, formalin-fixed atherosclerosis plaques prospectively collected after carotid endarterectomy of eight patients affected by ischemic stroke. Six different patients, one of whom was also included in the in vitro study, underwent PET imaging. Two patients with carotid stenosis associated with ischemic stroke were imaged with [18F]-PBR06 PET/CT, and four other patients (three with large vessel vasculitis and one with bilateral carotid stenosis but without stroke) were imaged with [11C]-PBR28. Results: All in vitro sections showed specific binding of [18F]-PBR06, which co-localized with immunohistochemistry markers for inflammation. However, in vivo TSPO imaging with either [11C]-PBR28 or [18F]-PBR06 was negative in all participants. Conclusion: Despite good uptake on surgical samples in vitro, [11C]-PBR28 and [18F]-PBR06 are not viable clinical tools for imaging inflammatory vascular disease. Trial registration: NCT02513589, registered 31 July 2015 and NCT00547976, registered 23 October 2007. https://clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

This paper constitutes the second part of a paper published in Barthe et al. (J Autom Reason, 2017. 10.1007/s10817-017-9441-5). Cache-based attacks are a class of side-channel attacks that are particularly effective in virtualized or cloud-based environments, where they have been used to recover secret keys from cryptographic implementations. One common approach to thwart cache-based attacks is to use constant-time implementations, i.e. those which do not branch on secrets and do not perform memory accesses that depend on secrets. However, there is no rigorous proof that constant-time implementations are protected against concurrent cache-attacks in virtualization platforms with shared cache. We propose a new information-flow analysis that checks if an x86 application executes in constant-time, and show that constant-time programs do not leak confidential information through the cache to other operating systems executing concurrently on virtualization platforms. Our static analysis targets the pre-assembly language of the CompCert verified compiler. Its soundness proof is based on a connection between CompCert semantics and our idealized model of virtualization, and uses isolation theorems presented in Part I. We then extend our model of virtualization platform and our static analysis to accommodate stealth memory, a countermeasure which provisions a small amount of private cache for programs to carry potentially leaking computations securely. Stealth memory induces a weak form of constant-time, called S-constant-time, which encompasses some widely used cryptographic implementations. Our results provide the first rigorous analysis of stealth memory and S-constant-time, and the first tool support for checking if applications are S-constant-time. We formalize our results using the Coq proof assistant and we demonstrate the effectiveness of our analyses on cryptographic implementations, including PolarSSL AES, DES and RC4, SHA256 and Salsa20. [ABSTRACT FROM AUTHOR]

We present an efficient and stable method for simulating the two-way coupling of incompressible fluids and deformable bodies. In our method, the fluid is represented by particles, and simulated using divergence-free incompressible smoothed-particle hydrodynamics (ISPH). The deformable bodies are represented by polygonal meshes, where the elastic deformations are simulated using a position-based dynamics scheme. Our technique enforces incompressibility on the fluid using divergence-free constraints on the velocity field, while it effectively simulates the physical features of deformable bodies. Most current ISPH methods are struggling with the issue of free-surface boundary conditions. We handle this problem by introducing a novel free-surface formulation, where our free-surface model obviates the need to identify the surface particles. For the interaction between the fluid and the deformable solids, we model the forces that both phases, fluid and solid, exert upon each other. We demonstrate that our approach effectively handles complex coupling scenarios between fluids and thin deformable shells or highly deformable solids, and produces plausible results. [ABSTRACT FROM AUTHOR]

Refreshing algorithms are a critical ingredient for secure masking. They are instrumental in enabling sound composability properties for complex circuits, and their randomness requirements dominate the performance overheads in (very) high-order masking. In this paper, we improve a proposal of mask refreshing algorithms from EUROCRYPT 2017 that has excellent implementation properties in software and hardware, in two main directions. First, we provide a generic proof that this algorithm is secure at arbitrary orders—a problem that was left open so far. We introduce parametrized non-interference as a new technical ingredient for this purpose that may be of independent interest. Second, we use automated tools to further explore the design space of such algorithms and provide the best known parallel mask refreshing gadgets for concretely relevant security orders. Incidentally, we also prove the security of a recent proposal of mask refreshing with improved resistance against horizontal attacks from CHES 2017. [ABSTRACT FROM AUTHOR]

We define a call-by-value variant of Gödel's system T with references, and equip it with a linear dependent type and effect system, called d ℓ T , that can estimate the time complexity of programs, as a function of the size of their inputs. We prove that the type system is intentionally sound, in the sense that it over-approximates the complexity of executing the programs on a variant of the CEK abstract machine. Moreover, we define a sound and complete type inference algorithm which critically exploits the subrecursive nature of d ℓ T . Finally, we demonstrate the usefulness of d ℓ T for analyzing the complexity of cryptographic reductions by providing an upper bound for the constructed adversary of the Goldreich–Levin theorem. [ABSTRACT FROM AUTHOR]

This work focuses on the study of constant-time implementations; giving formal guarantees that such implementations are protected against cache-based timing attacks in virtualized platforms where their supporting operating system executes concurrently with other, potentially malicious, operating systems. We develop a model of virtualization that accounts for virtual addresses, physical and machine addresses, memory mappings, page tables, translation lookaside buffer, and cache; and provides an operational semantics for a representative set of actions, including reads and writes, allocation and deallocation, context switching, and hypercalls. We prove a non-interference result on the model that shows that an adversary cannot discover secret information using cache side-channels, from a constant-time victim. [ABSTRACT FROM AUTHOR]

We initiate the study of principled, automated methods for analyzing hardness assumptions in generic group models, following the approach of symbolic cryptography. We start by defining a broad class of generic and symbolic group models for different settings—symmetric or asymmetric (leveled) k-linear groups—and by proving "computational soundness" theorems for the symbolic models. Based on this result, we formulate a very general master theorem that formally relates the hardness of a (possibly interactive) assumption in these models to solving problems in polynomial algebra. Then, we systematically analyze these problems. We identify different classes of assumptions and obtain decidability and undecidability results. Next, we develop and implement automated procedures for verifying the conditions of master theorems, and thus the validity of hardness assumptions in generic group models. The concrete outcome of this work is an automated tool which takes as input the statement of an assumption and outputs either a proof of its generic hardness or shows an algebraic attack against the assumption. [ABSTRACT FROM AUTHOR]

SAMHD1 was previously characterized as a dNTPase that protects cells from viral infections. Mutations in SAMHD1 are implicated in cancer development and in a severe congenital inflammatory disease known as Aicardi-Goutières syndrome. The mechanism by which SAMHD1 protects against cancer and chronic inflammation is unknown. Here we show that SAMHD1 promotes degradation of nascent DNA at stalled replication forks in human cell lines by stimulating the exonuclease activity of MRE11. This function activates the ATR-CHK1 checkpoint and allows the forks to restart replication. In SAMHD1-depleted cells, single-stranded DNA fragments are released from stalled forks and accumulate in the cytosol, where they activate the cGAS-STING pathway to induce expression of pro-inflammatory type I interferons. SAMHD1 is thus an important player in the replication stress response, which prevents chronic inflammation by limiting the release of single-stranded DNA from stalled replication forks. SAMHD1 has an essential role in the replication stress response and prevents inflammation by activating the MRE11 nuclease to degrade nascent DNA strands at stalled replication forks, thus enabling replication. [ABSTRACT FROM AUTHOR]

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetically-determined cardiac heart muscle disorder characterized by fibro-fatty replacement of the myocardium that results in heart failure and sudden cardiac death (SCD), predominantly in young males. The disease is often caused by mutations in genes encoding proteins of the desmosomal complex, with a significant minority caused by mutations in non-desmosomal proteins. Existing treatment options are based on SCD prevention with the implantable cardioverter defibrillator, antiarrhythmic drugs, and anti-heart failure medication. Heart transplantation may also be required and there is currently no cure. Several genetically modified animal models have been developed to characterize the disease, assess its progression, and determine the influence of potential environmental factors. These models have also been very valuable for translational therapeutic approaches, to screen new treatment options that prevent and/or reverse the disease. Here, we review the available ARVC animal models reported to date, highlighting the most important pathophysiological findings and discussing the effect of treatments tested so far in this setting. We also describe gaps in our knowledge of the disease, with the goal of stimulating research and improving patient outcomes. [ABSTRACT FROM AUTHOR]

This study sought to determine the usefulness of genetic testing to predict evolution in hypertrophic cardiomyopathy (HCM) and to assess the role of genetic testing in clinical practice. Genetic results of 100 HCM patients tested for mutations in ≥10 HCM-causing genes were evaluated. Patients were classified as with poor (group A) or favourable (group B) clinical course. Forty-five pathogenic mutations (PM) were identified in 28 patients (56 %) from group A and in 23 (46 %) from group B ( p = 0.317). Only 40 patients (40 %) exhibited PM that had been previously reported and only 15 (15 %) had PM reported in ≥10 individuals. PM associated with poor prognosis were identified in just five patients from group A (10 %). Genetic findings are not useful to predict prognosis in most HCM patients. By contrast, real-world data reinforce the usefulness of genetic testing to provide genetic counselling and to enable cascade genetic screening. [ABSTRACT FROM AUTHOR]

Four caulimovirus-derived constitutive promoters were evaluated for gene expression in citrus and their expression levels were compared with a 35S promoter. Chimeric promoters made with duplicated enhancer sequences from the cauliflower mosaic virus (D35S), the cassava vein mosaic virus (DCsVMV), the figwort mosaic virus (DFMV), the mirabilis mosaic virus (DMMV) and the peanut chlorotic streak virus (DPCLSV) were inserted into a transformation vector fused to the gus reporter gene. Gene expression patterns driven by these promoters were analyzed in the transgenic citrus cultivar Carrizo citrange ( Citrus sinensis Osb. × Poncirus trifoliata L. Raf.). The histochemical and fluorometric measurement of GUS activity and the gene expression quantification by RT-qPCR analysis demonstrate that the DMMV promoter is able to direct gene expression in citrus as strongly as the D35S promoter and represents great application potential in citrus biotechnology. The DFMV, DCsVMV and DPCLSV constitutive promoters were weaker compared to the D35S promoter but can be considered for use in gene stacking strategies for the development of transgenic citrus. Our results also reveal the importance of the evaluation of specific promoter fragments for a particular crop cultivar due to the availability of species-specific transcription factors that can define the strength and tissue specificity of a determinate promoter. [ABSTRACT FROM AUTHOR]