Structure-based targeting of the lipid A-modifying enzyme PmrC to contrast colistin resistance in .

Introduction: Antimicrobial-resistant pathogens are an ongoing threat to human and animal health. According to the World Health Organization (WHO), colistin is considered the last resort antibiotic against human infections due to multidrug-resistant Gram-negative organisms-including , a priority-1 pathogen. Despite colistin being considered a last resort antibiotic, transferable bacterial resistance to this drug has been reported in humans and animals.

Detecting images generated by diffusers.

In recent years, the field of artificial intelligence has witnessed a remarkable surge in the generation of synthetic images, driven by advancements in deep learning techniques. These synthetic images, often created through complex algorithms, closely mimic real photographs, blurring the lines between reality and artificiality. This proliferation of synthetic visuals presents a pressing challenge: how to accurately and reliably distinguish between genuine and generated images.

Correction to "Novel Antiproliferative Chimeric Compounds with Marked Histone Deacetylase Inhibitory Activity".

[This corrects the article DOI: 10.1021/ml5000959.].

Probing allosteric communication with combined molecular dynamics simulations and network analysis.

Understanding the allosteric mechanisms within biomolecules involved in diseases is of paramount importance for drug discovery. Indeed, characterizing communication pathways and critical hotspots in signal transduction can guide a rational approach to leverage allosteric modulation for therapeutic purposes. While the atomistic signatures of allosteric processes are difficult to determine experimentally, computational methods can be a remarkable resource.

Artificial light at night: a global disruptor of the night-time environment.

Light pollution is the alteration of the natural levels of darkness by an increased concentration of light particles in the night-time environment, resulting from human activity. Light pollution is profoundly changing the night-time environmental conditions across wide areas of the planet, and is a relevant stressor whose effects on life are being unveiled by a compelling body of research. In this paper, we briefly review the basic aspects of artificial light at night as a pollutant, describing its character, magnitude and extent, its worldwide distribution, its temporal and spectral change trends, as well as its dependence on current light production technologies and prevailing social uses of light.

Graph-based methods for Author Name Disambiguation: a survey.

Scholarly knowledge graphs (SKG) are knowledge graphs representing research-related information, powering discovery and statistics about research impact and trends. Author name disambiguation (AND) is required to produce high-quality SKGs, as a disambiguated set of authors is fundamental to ensure a coherent view of researchers' activity. Various issues, such as homonymy, scarcity of contextual information, and cardinality of the SKG, make simple name string matching insufficient or computationally complex.

The genetic variant SLC2A1 -rs1105297 is associated with the differential analgesic response to a glucose-based treatment in newborns.

Neonatal pain is a critical issue in clinical practice. The oral administration of glucose-based solutions is currently one of the most common and effective nonpharmacologic strategies for neonatal pain relief in daily minor procedures. However, a varying degree of analgesic efficacy has been reported for this treatment.

Human PNPase causes RNA stabilization and accumulation of R-loops in the Escherichia coli model system.

Polyribonucleotide phosphorylase (PNPase) is a phosphorolytic RNA exonuclease highly conserved throughout evolution. In Escherichia coli, PNPase controls complex phenotypic traits like biofilm formation and growth at low temperature. In human cells, PNPase is located in mitochondria, where it is implicated in the RNA import from the cytoplasm, the mitochondrial RNA degradation and the processing of R-loops, namely stable RNA-DNA hybrids displacing a DNA strand.

Innovative Strategy toward Mutant CFTR Rescue in Cystic Fibrosis: Design and Synthesis of Thiadiazole Inhibitors of the E3 Ligase RNF5.

In cystic fibrosis (CF), deletion of phenylalanine 508 (F508del) in the CF transmembrane conductance regulator (CFTR) is associated to misfolding and defective gating of the mutant channel. One of the most promising CF drug targets is the ubiquitin ligase RNF5, which promotes F508del-CFTR degradation. Recently, the first ever reported inhibitor of RNF5 was discovered, i.

On the Generalization of Deep Learning Models in Video Deepfake Detection.

The increasing use of deep learning techniques to manipulate images and videos, commonly referred to as "deepfakes", is making it more challenging to differentiate between real and fake content, while various deepfake detection systems have been developed, they often struggle to detect deepfakes in real-world situations. In particular, these methods are often unable to effectively distinguish images or videos when these are modified using novel techniques which have not been used in the training set. In this study, we carry out an analysis of different deep learning architectures in an attempt to understand which is more capable of better generalizing the concept of deepfake.

Light pollution is skyrocketing.

Data from citizen scientists reveal a worrying growth in light pollution over the past decade.

Suppressor Mutations in LptF Bypass Essentiality of LptC by Forming a Six-Protein Transenvelope Bridge That Efficiently Transports Lipopolysaccharide.

Lipopolysaccharide (LPS) is an essential component of the outer membrane (OM) of many Gram-negative bacteria, providing a barrier against the entry of toxic molecules. In Escherichia coli, LPS is exported to the cell surface by seven essential proteins (LptA-G) that form a transenvelope complex. At the inner membrane, the ATP-binding cassette (ABC) transporter LptBFG associates with LptC to power LPS extraction from the membrane and transfer to the periplasmic LptA protein, which is in complex with the OM translocon LptDE.

Bus Violence: An Open Benchmark for Video Violence Detection on Public Transport.

The automatic detection of violent actions in public places through video analysis is difficult because the employed Artificial Intelligence-based techniques often suffer from generalization problems. Indeed, these algorithms hinge on large quantities of annotated data and usually experience a drastic drop in performance when used in scenarios never seen during the supervised learning phase. In this paper, we introduce and publicly release the benchmark, the first large-scale collection of video clips for violence detection on public transport, where some actors simulated violent actions inside a moving bus in changing conditions, such as the background or light.

The Face Deepfake Detection Challenge.

Multimedia data manipulation and forgery has never been easier than today, thanks to the power of Artificial Intelligence (AI). AI-generated fake content, commonly called Deepfakes, have been raising new issues and concerns, but also new challenges for the research community. The Deepfake detection task has become widely addressed, but unfortunately, approaches in the literature suffer from generalization issues.

Analyzing the Function of Essential Genes by Plasmid Shuffling.

Investigations on gene essentiality have important implications in several fields of basic and applied research. A variety of strategies have been developed over the years to identify essential genes. Here, we describe an implemented plasmid shuffling method useful to assess the essentiality of overlapped genes under very stringent conditions.

Deep networks for behavioral variant frontotemporal dementia identification from multiple acquisition sources.

Behavioral variant frontotemporal dementia (bvFTD) is a neurodegenerative syndrome whose clinical diagnosis remains a challenging task especially in the early stage of the disease. Currently, the presence of frontal and anterior temporal lobe atrophies on magnetic resonance imaging (MRI) is part of the diagnostic criteria for bvFTD. However, MRI data processing is usually dependent on the acquisition device and mostly require human-assisted crafting of feature extraction.

An embedded toolset for human activity monitoring in critical environments.

In many working and recreational activities, there are scenarios where both individual and collective safety have to be constantly checked and properly signaled, as occurring in dangerous workplaces or during pandemic events like the recent COVID-19 disease. From wearing personal protective equipment to filling physical spaces with an adequate number of people, it is clear that a possibly automatic solution would help to check compliance with the established rules. Based on an off-the-shelf compact and low-cost hardware, we present a deployed real use-case embedded system capable of perceiving people's behavior and aggregations and supervising the appliance of a set of rules relying on a configurable plug-in framework.

Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives.

In cystic fibrosis (CF), the deletion of phenylalanine 508 (F508del) in the CF transmembrane conductance regulator (CFTR) leads to misfolding and premature degradation of the mutant protein. These defects can be targeted with pharmacological agents named potentiators and correctors. During the past years, several efforts have been devoted to develop and approve new effective molecules.

Activity and Function in Human Cells of the Evolutionary Conserved Exonuclease Polynucleotide Phosphorylase.

Polynucleotide phosphorylase (PNPase) is a phosphorolytic RNA exonuclease highly conserved throughout evolution. Human PNPase (hPNPase) is located in mitochondria and is essential for mitochondrial function and homeostasis. Not surprisingly, mutations in the gene, encoding hPNPase, cause serious diseases.

MOCCA: Multilayer One-Class Classification for Anomaly Detection.

Anomalies are ubiquitous in all scientific fields and can express an unexpected event due to incomplete knowledge about the data distribution or an unknown process that suddenly comes into play and distorts the observations. Usually, due to such events' rarity, to train deep learning (DL) models on the anomaly detection (AD) task, scientists only rely on "normal" data, i.e.

Searching for New Microbiome-Targeted Therapeutics through a Drug Repurposing Approach.

Commonly used non-antibiotic drugs have been associated with changes in gut microbiome composition, paving the way for the possibility of repurposing FDA-approved molecules as next-generation microbiome therapeutics. Herein, we developed and validated an high-throughput screening platform─the mini gut model─to underpin human gut microbiome response to molecular modulators. Ten FDA-approved compounds, selected based on maximum structural diversity of molecular fingerprints, were screened against the gut microbiome of five healthy subjects to characterize the ability of human-targeted drugs to modulate the human gut microbiome network.

Sanguinarine Inhibits the 2-Ketogluconate Pathway of Glucose Utilization in .

Interfering with the ability of pathogenic bacteria to import glucose may represent a new promising antibacterial strategy, especially for the treatment of infections occurring in diabetic and other hyperglycemic patients. Such patients are particularly susceptible to infections caused by a variety of bacteria, among which opportunistic pathogens like . In , glucose can be directly imported into the cytoplasm or after its periplasmic oxidation into gluconate and 2-ketogluconate (2-KG).

The VISIONE Video Search System: Exploiting Off-the-Shelf Text Search Engines for Large-Scale Video Retrieval.

This paper describes in detail VISIONE, a video search system that allows users to search for videos using textual keywords, the occurrence of objects and their spatial relationships, the occurrence of colors and their spatial relationships, and image similarity. These modalities can be combined together to express complex queries and meet users' needs. The peculiarity of our approach is that we encode all information extracted from the keyframes, such as visual deep features, tags, color and object locations, using a convenient textual encoding that is indexed in a single text retrieval engine.

Hebbian semi-supervised learning in a sample efficiency setting.

We propose to address the issue of sample efficiency, in Deep Convolutional Neural Networks (DCNN), with a semi-supervised training strategy that combines Hebbian learning with gradient descent: all internal layers (both convolutional and fully connected) are pre-trained using an unsupervised approach based on Hebbian learning, and the last fully connected layer (the classification layer) is trained using Stochastic Gradient Descent (SGD). In fact, as Hebbian learning is an unsupervised learning method, its potential lies in the possibility of training the internal layers of a DCNN without labels. Only the final fully connected layer has to be trained with labeled examples.

Different Expression Levels in C versus K-12 . Strains Affect Biofilm Formation and Impact the Regulatory Mechanism Presided by the CsrB and CsrC Small RNAs.

C is a strong biofilm producer in comparison to K-12 laboratory strains due to higher expression of the operon encoding the enzymes for the biosynthesis of the extracellular polysaccharide poly-β-1,6--acetylglucosamine (PNAG). The operon is negatively regulated at the post-transcriptional level by two factors, namely CsrA, a conserved RNA-binding protein controlling multiple pathways, and the RNA exonuclease polynucleotide phosphorylase (PNPase). In this work, we investigated the molecular bases of different PNAG production in C-1a and MG1655 strains taken as representative of C and K-12 strains, respectively.