Exploiting the DCAF16-SPIN4 interaction to identify DCAF16 ligands for PROTAC development.

Traditional small molecule drugs often target protein activity directly, but challenges arise when proteins lack suitable functional sites. An alternative approach is targeted protein degradation (TPD), which directs proteins to cellular machinery for proteolytic degradation. Recent studies have identified additional E3 ligases suitable for TPD, expanding the potential of this approach.

A CRISPR activation screen identifies FBXO22 supporting targeted protein degradation.

Targeted protein degradation (TPD) represents a potent chemical biology paradigm that leverages the cellular degradation machinery to pharmacologically eliminate specific proteins of interest. Although multiple E3 ligases have been discovered to facilitate TPD, there exists a compelling requirement to diversify the pool of E3 ligases available for such applications. Here we describe a clustered regularly interspaced short palindromic repeats (CRISPR)-based transcriptional activation screen focused on human E3 ligases, with the goal of identifying E3 ligases that can facilitate heterobifunctional compound-mediated target degradation.

Visual-functional impact of people affected by severe ocular trauma during social protests in Chile in 2019.

Purpose: To determine the impact on the functionality associated with visual loss (VFIP) in people with severe ocular trauma (SOT) caused by kinetic impact projectiles used in police crowd control through a prioritization tool in people admitted to a rehabilitation program in Santiago de Chile from December 02, 2019, to November 13, 2020.

Methods: A cross-sectional descriptive study of SOT victims (N = 85), average age 31.4 ± 11.

Does PLEX Elite 9000 OCT Identify and Characterize Most Posterior Pole Lesions in Highly Myopic Patients?

High myopia (HM) is defined as an axial length (AL) ≥ 26 mm that may result in various pathologies that constitute pathologic myopia (PM). The PLEX Elite 9000 (Carl Zeiss AC, Jena, Germany) is a new swept-source optical coherence tomography (SS-OCT) underdevelopment that allows wider, deeper and more detailed posterior-segment visualization; it can acquire ultra-wide OCT angiography (OCTA) or new ultra-wide high-density scans in one image. We assessed the technology's ability to identify/characterize/quantify staphylomas and posterior pole lesions or image biomarkers in highly myopic Spanish patients and estimate the technology's potential to detect macular pathology.

Analysis of the networks controlling the antimicrobial-peptide-dependent induction of Klebsiella pneumoniae virulence factors.

Antimicrobial peptides (APs) impose a threat to the survival of pathogens, and it is reasonable to postulate that bacteria have developed strategies to counteract them. Polymyxins are becoming the last resort to treat infections caused by multidrug-resistant Gram-negative bacteria and, similar to APs, they interact with the anionic lipopolysaccharide. Given that polymyxins and APs share the initial target, it is possible that bacterial defense mechanisms against polymyxins will be also effective against host APs.

Klebsiella pneumoniae increases the levels of Toll-like receptors 2 and 4 in human airway epithelial cells.

Airway epithelial cells act as the first barrier against pathogens. These cells recognize conserved structural motifs expressed by microbial pathogens via Toll-like receptors (TLRs) expressed on the surface. In contrast to the level of expression in lymphoid cells, the level of expression of TLR2 and TLR4 in airway epithelial cells is low under physiological conditions.

Quinolones sensitize gram-negative bacteria to antimicrobial peptides.

The treatment of infections caused by bacteria resistant to the vast majority of antibiotics is a challenge worldwide. Antimicrobial peptides (APs) make up the front line of defense in those areas exposed to microorganisms, and there is intensive research to explore their use as new antibacterial agents. On the other hand, it is known that subinhibitory concentrations of antibiotics affect the expression of numerous bacterial traits.

The uptake of a Klebsiella pneumoniae capsule polysaccharide mutant triggers an inflammatory response by human airway epithelial cells.

The means by which airway epithelial cells sense a bacterial infection and which intracellular signalling pathways are activated upon infection are poorly understood. A549 cells and human primary airway cells (NHBE) were used to investigate the response to infection with Klebsiella pneumoniae. Infection of A549 and NHBE with K.

Capsule polysaccharide mediates bacterial resistance to antimicrobial peptides.

The innate immune system plays a critical role in the defense of areas exposed to microorganisms. There is an increasing body of evidence indicating that antimicrobial peptides and proteins (APs) are one of the most important weapons of this system and that they make up the protective front for the respiratory tract. On the other hand, it is known that pathogenic organisms have developed countermeasures to resist these agents such as reducing the net negative charge of the bacterial membranes.