Explorations cardiologiques nucléaires dans la cardiomyopathie de Takotsubo

Transient left ventricular apical ballooning syndrome, also known as Takotsubo cardiomyopathy (TTC) was described for the first time in Japan in the earliest nineties. It represents 1 to 2 % of acute cardiac events and mimics closely acute myocardial infarction. The aim of this study was to investigate ^99mTc-tetrofosmine or ²⁰¹Thallium myocardial Single Photon Emission Computed Tomography (SPECT), ¹²³I-metaIodoBenzylGuanidine (¹²³I-mIBG) myocardial SPECT and myocardial Positron Emission Tomography using ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) in patients with TTC, assessing respectively left ventricular perfusion, innervation and metabolism. We studied four patients (three females) with TTC. We performed two weeks after acute phase (subacute phase) myocardial perfusion SPECT and ¹²³I-mIBG myocardial SPECT for each patient. Two of them underwent myocardial PET with FDG. Then, we assessed left ventricular innervation and metabolism three months (chronic phase I) and more than six months (chronic phase II) after the acute phase. We compared the discrepancies between radionuclides uptake in the left ventricular apical region during a follow-up period of more than six months. In subacute phase, perfusion SPECT was normal for each patient. Conversely, ¹²³I-mIBG SPECT and FDG-PET showed concordant apical uptake defect. This perfusion-metabolism pattern called “inverse flow-metabolism mismatch” is the metabolic state of stunned myocardium. After three months, we found improvement of apical tracer uptake in both FDG-PET and ¹²³I-mIBG SPECT. These findings suggest that TTC is characterized by myocardial apical stunning which is related to a disturbance of cardiac sympathetic innervation. ¹²³I-mIBG SPECT might be useful to diagnose earlier this pathology and to rule out acute myocardial infarction.     

Automated tetraploid genotype calling by hierarchical clustering

Key message

New software to make tetraploid genotype calls from SNP array data was developed, which uses hierarchical clustering and multiple F1 populations to calibrate the relationship between signal intensity and allele dosage.

Abstract

SNP arrays are transforming breeding and genetics research for autotetraploids. To fully utilize these arrays, the relationship between signal intensity and allele dosage must be calibrated for each marker. We developed an improved computational method to automate this process, which is provided as the R package ClusterCall. In the training phase of the algorithm, hierarchical clustering within an F1 population is used to group samples with similar intensity values, and allele dosages are assigned to clusters based on expected segregation ratios. In the prediction phase, multiple F1 populations and the prediction set are clustered together, and the genotype for each cluster is the mode of the training set samples. A concordance metric, defined as the proportion of training set samples equal to the mode, can be used to eliminate unreliable markers and compare different algorithms. Across three potato families genotyped with an 8K SNP array, ClusterCall scored 5729 markers with at least 0.95 concordance (94.6% of its total), compared to 5325 with the software fitTetra (82.5% of its total). The three families were used to predict genotypes for 5218 SNPs in the SolCAP diversity panel, compared with 3521 SNPs in a previous study in which genotypes were called manually. One of the additional markers produced a significant association for vine maturity near a well-known causal locus on chromosome 5. In conclusion, when multiple F1 populations are available, ClusterCall is an efficient method for accurate, autotetraploid genotype calling that enables the use of SNP data for research and plant breeding.

     

Natural cultch type influences habitat preference and predation,but not survival,in reef‐associated species

A shared origin with fresh and dredged cultch and availability via mining have made fossil cultch a commonly used reef restoration substrate. However, important differences in shape and size between whole‐shell cultch and fossil cultch may impact the complexity of reefs constructed from these materials. To determine if these differences may impact the development of restored reefs, we quantified the interstitial space each cultch type provides and constructed reef mesocosms to measure (1) the immediate effects of exposure to each cultch type on mortality of blue crab (Callinectes sapidus) and pink shrimp (Farfantepenaeus duorarum); (2) the tendency of crab, shrimp, and Florida crown conch (Melongena corona) to be found on habitats composed of each substrate type and their position within each in split‐substrate mesocosms; and (3) the influence of cultch type on predation of Eastern oysters (Crassostrea virginica) by crabs and conch. Aggregation of fossil cultch contains more shells and provides less interstitial space than an equivalent volume of whole‐shell cultch. Although immediate mortality following deployment was low and did not differ among cultch types, we found that all species were more likely to be found on fresh cultch over fossil cultch in choice experiments and used each habitat type differently. Cultch type also impacted the size of oysters consumed by crabs in short‐term feeding trials. The structure and traits of habitats created by various materials should be added to the growing list of issues considered when natural communities are to be restored in oyster reefs and other environments.     

The role of auxin and sugar signaling in dominance inhibition of inflorescence growth by fruit load

Dominance inhibition of shoot growth by fruit load is a major factor that regulates shoot architecture and limits yield in agriculture and horticulture crops. In annual plants, the inhibition of inflorescence growth by fruit load occurs at a late stage of inflorescence development termed the end of flowering transition. Physiological studies show this transition is mediated by production and export of auxin from developing fruits in close proximity to the inflorescence apex. In the meristem, cessation of inflorescence growth is controlled in part by the age-dependent pathway, which regulates the timing of arrest. Here, we show the end of flowering transition is a two-step process in Arabidopsis (Arabidopsis thaliana). The first stage is characterized by a cessation of inflorescence growth, while immature fruit continues to develop. At this stage, dominance inhibition of inflorescence growth by fruit load is associated with a selective dampening of auxin transport in the apical region of the stem. Subsequently, an increase in auxin response in the vascular tissues of the apical stem where developing fruits are attached marks the second stage for the end of flowering transition. Similar to the vegetative and floral transition, the end of flowering transition is associated with a change in sugar signaling and metabolism in the inflorescence apex. Taken together, our results suggest that during the end of flowering transition, dominance inhibition of inflorescence shoot growth by fruit load is mediated by auxin and sugar signaling.

Dominance inhibition of inflorescence shoot growth by fruit load involves auxin and sugar signaling during the end of flowering transition.     

The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition

First identified as a neutrophil granule component, neutrophil gelatinase-associated lipocalin (NGAL; also called human neutrophil lipocalin, 24p3, uterocalin, or neu-related lipocalin) is a member of the lipocalin family of binding proteins. Putative NGAL ligands, including neutrophil chemotactic agents such as N-formylated tripeptides, have all been refuted by recent biochemical and structural results. NGAL has subsequently been implicated in diverse cellular processes, but without a characterized ligand, the molecular basis of these functions remained mysterious. Here we report that NGAL tightly binds bacterial catecholate-type ferric siderophores through a cyclically permuted, hybrid electrostatic/cation-pi interaction and is a potent bacteriostatic agent in iron-limiting conditions. We therefore propose that NGAL participates in the antibacterial iron depletion strategy of the innate immune system.     

Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis

Mechanotransduction is a key determinant of tissue homeostasis and tumor progression. It is driven by intercellular adhesions, cell contractility, and forces generated within the microenvironment and is dependent on extracellular matrix composition, organization, and compliance. We show that caveolin-1 (Cav1) favors cell elongation in three-dimensional cultures and promotes Rho- and force-dependent contraction, matrix alignment, and microenvironment stiffening through regulation of p190RhoGAP. In turn, microenvironment remodeling by Cav1 fibroblasts forces cell elongation. Cav1-deficient mice have disorganized stromal tissue architecture. Stroma associated with human carcinomas and melanoma metastases is enriched in Cav1-expressing carcinoma-associated fibroblasts (CAFs). Cav1 expression in breast CAFs correlates with low survival, and Cav1 depletion in CAFs decreases CAF contractility. Consistently, fibroblast expression of Cav1, through p190RhoGAP regulation, favors directional migration and invasiveness of carcinoma cells in vitro. In vivo, stromal Cav1 remodels peri- and intratumoral microenvironments to facilitate tumor invasion, correlating with increased metastatic potency. Thus, Cav1 modulates tissue responses through force-dependent architectural regulation of the microenvironment.     

Studies on the continuous production of (R)-(−)-phenylacetylcarbinol in an enzyme-membrane reactor

The optimization of a continuous enzymatic reaction yielding (R)-(−)-phenylacetylcarbinol ((R)-PAC), a key intermediate of the (1R,2S)-(−)-ephedrine synthesis, is presented. We compare the suitability of different mutants of the pyruvate decarboxylase (PDC) from Zymomonas mobilis with respect to their application in biotransformation using pyruvate or acetaldehyde and benzaldehyde as substrates, respectively. Starting from 90 mM pyruvate and 30 mM benzaldehyde, (R)-PAC was obtained with a space time yield of 27.4 g/(L·day) using purified PDCW392I in an enzyme-membrane reactor. Due to the high stability of the mutant enzymes PDCW392I and PDCW392M towards acetaldehyde, a continuous procedure using acetaldehyde instead of pyruvate was developed. The kinetic results of the enzymatic synthesis starting from acetaldehyde and benzaldehyde demonstrate that the carboligation to (R)-PAC is most efficiently performed using a continuous reaction system and feeding both aldehydes in equimolar concentration. Starting from an inlet concentration of 50 mM of both aldehydes, (R)-PAC was obtained with a space-time yield of 81 g/(L·day) using the mutant enzyme PDCW392M. The new reaction strategy allows the enzymatic synthesis of (R)-PAC from cheap substrates free of unwanted by-products with potent mutants of PDC from Z. mobilis in an aqueous reaction system.