Estimation of the variance in any point of an electron-density map for any space group

In a recent paper [Giacovazzo & Mazzone (2011). Acta Cryst. A67, 210-218] a mathematical expression of the variance at any point of the unit cell has been described. The formulas were derived in P1 for any type of Fourier synthesis (observed, difference and hybrid) under the following hypothesis: the current phases are distributed on the trigonometric circle about the correct values according to von Mises distributions. This general hypothesis allows the variance expressions to be valid at any stage of the phasing process. In this paper the method has been extended to any space group, no matter whether centric or acentric. The properties of the variance generated by space-group symmetry are described; in particular it is shown that the variance is strictly connected with the implication transformations, which are basic for Patterson deconvolution. General formulas simultaneously taking into account phase uncertainty and measurement errors have been obtained, valid no matter what the quality of the model

When is genetic testing useful in patients suspected to have inherited cardiac arrhythmias?

PURPOSE OF REVIEW: In this article, we will review the appropriate use of genetic testing in those patients suspected to have inherited arrhythmogenic diseases, with specific focus on the indications for testing and the expected probability of positive genotyping. RECENT FINDINGS: Important advances have been made in the identification of new genes, associated mutations, and polymorphisms that modulate susceptibility of acquired arrhythmias. We will examine the most recent advances relevant to the rational application of genetic analysis, guided by genotype-phenotype correlations derived from disease and patient-specific evaluation, as well as discussing novel technologies and recently published cost-effectiveness data. SUMMARY: Genetic analysis can be performed to identify the molecular substrate in those patients suspected to be affected by an inherited arrhythmogenic disease; however, the clinical usefulness of this information is often not straightforward. We hope to emphasize the concept that there is a significant difference in the impact of genetic testing within the various arrhythmogenic disorders, and the benefit of accessing genetic testing is not the same in all patients. The resultant integration between the expected yield of genetic screening and cost may allow the formation of criteria to prioritize access for those who could derive the most clinical benefit

Merging Natural Products: Muraymycin-Sansanmycin Hybrid Structures as Novel Scaffolds for Potential Antibacterial Agents

To overcome bacterial resistances, the need for novel antimicrobial agents is urgent. The class of so‐called nucleoside antibiotics furnishes promising candidates for the development of new antibiotics, as these compounds block a clinically unexploited bacterial target: the integral membrane protein MraY, a key enzyme in cell wall (peptidoglycan) biosynthesis. Nucleoside antibiotics exhibit remarkable structural diversity besides their uridine‐derived core motifs. Some sub‐classes also show specific selectivities towards different Gram‐positive and Gram‐negative bacteria, which are poorly understood so far. Herein, the synthesis of a novel hybrid structure is reported, derived from the 5′‐defunctionalized uridine core moiety of muraymycins and the peptide chain of sansanmycin B, as a new scaffold for the development of antimicrobial agents. The reported muraymycin–sansanmycin hybrid scaffold showed nanomolar activity against the bacterial target enzyme MraY, but displayed no significant antibacterial activity against S. aureus, E. coli, and P. aeruginosa

Letter regarding article by Coronel et al, ''right ventricular fibrosis and conduction delay in a patient with clinical signs of Brugada syndrome: a combined electrophysiological, genetic, histopathologic, and computational study''

Letter regarding article by Coronel et al, ''right ventricular fibrosis and conduction delay in a patient with clinical signs of Brugada syndrome: a combined electrophysiological, genetic, histopathologic, and computational study'

Deep learning techniques applied to skin lesion classification: a review

Skin cancer is one of the most common cancers in the world. The most dangerous type of skin cancer is melanoma, which can be lethal if not treated early. However, diagnosing skin lesions can be a difficult task. Therefore, deep learning techniques applied to the diagnosis of skin lesions have been explored by researchers, given their effectiveness in extracting features and classifying input data. In this work, we present a review of latest approaches that apply deep learning techniques to skin lesion classification task. In addition, some datasets used for training and validating the models are introduced, informing their characteristics and specificities, as well as popular pre-processing steps and skin lesion segmentation approaches. Finally, we comment the effectiveness of the proposed models.info:eu-repo/semantics/publishedVersio

Inherited calcium channelopathies in the pathophysiology of arrhythmias.

Regulation of calcium flux in the heart is a key process that affects cardiac excitability and contractility. Degenerative diseases, such as coronary artery disease, have long been recognized to alter the physiology of intracellular calcium regulation, leading to contractile dysfunction or arrhythmias. Since the discovery of the first gene mutation associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) in 2001, a new area of interest in this field has emerged-the genetic abnormalities of key components of the calcium regulatory system. Such anomalies cause a variety of genetic diseases characterized by the development of life-threatening arrhythmias in young individuals. In this Review, we provide an overview of the structural organization and the function of calcium-handling proteins and describe the mechanisms by which mutations determine the clinical phenotype. Firstly, we discuss mutations in the genes encoding the ryanodine receptor 2 (RYR2) and calsequestrin 2 (CASQ2). These proteins are pivotal to the regulation of calcium release from the sarcoplasmic reticulum, and mutations can cause CPVT. Secondly, we review defects in genes encoding proteins that form the voltage-dependent L-type calcium channel, which regulates calcium entry into myocytes. Mutations in these genes cause various phenotypes, including Timothy syndrome, Brugada syndrome, and early repolarization syndrome. The identification of mutations associated with 'calcium-handling diseases' has led to an improved understanding of the role of calcium in cardiac physiology

Muraymycin Nucleoside Antibiotics: Structure-Activity Relationship for Variations in the Nucleoside Unit

Muraymycins are a subclass of naturally occurring nucleoside antibiotics with promising antibacterial activity. They inhibit the bacterial enzyme translocase I (MraY), a clinically yet unexploited target mediating an essential intracellular step of bacterial peptidoglycan biosynthesis. Several structurally simplified muraymycin analogues have already been synthesized for structure–activity relationship (SAR) studies. We now report on novel derivatives with unprecedented variations in the nucleoside unit. For the synthesis of these new muraymycin analogues, we employed a bipartite approach facilitating the introduction of different nucleosyl amino acid motifs. This also included thymidine- and 5-fluorouridine-derived nucleoside core structures. Using an in vitro assay for MraY activity, it was found that the introduction of substituents in the 5-position of the pyrimidine nucleobase led to a significant loss of inhibitory activity towards MraY. The loss of nucleobase aromaticity (by reduction of the uracil C5-C6 double bond) resulted in a ca. tenfold decrease in inhibitory potency. In contrast, removal of the 20 -hydroxy group furnished retained activity, thus demonstrating that modifications of the ribose moiety might be well-tolerated. Overall, these new SAR insights will guide the future design of novel muraymycin analogues for their potential development towards antibacterial drug candidates

Simulated nature walks improve psychological well-being along a natural to urban continuum

Compared to urban environments, interactions with natural environments have been associated with several health benefits including psychological restoration and improved emotional well-being. However, dichotomizing environments as either natural or urban may emphasize between-category differences and minimize potentially important within-category variation (e.g., forests versus fields of crops; neighborhoods versus city centers). Therefore, the current experiment assessed how viewing brief videos of different environments, ranging along a continuum from stereotypically natural to stereotypically urban, influenced subjective ratings of mood, restoration, and well-being. Participants (n = 202) were randomly assigned to one of four video conditions, which depicted a simulated walk through a pine forest, a farmed field, a tree-lined urban neighborhood, or a bustling city center. Immediately before and after the videos, participants rated their current emotional states. Participants additionally rated the perceived restorativeness of the video. The results supported the idea that the virtual walks differentially influenced affect and perceived restoration, even when belonging to the same nominal category of natural or urban. The pine forest walk significantly improved happiness relative to both urban walks, whereas the farmed field walk did not. The bustling city center walk decreased feelings of calmness compared to all other walks, including the tree-lined neighborhood walk. The walks also differed on the perceived restorativeness measure of daydreaming in a graded fashion; however, the farmed field walk was found to be less fascinating than all other walks, including both urban walks. Taken together, these results suggest that categorizing environments as “natural versus urban” may gloss over meaningful within-category variability regarding the restorative potential of different physical environments