Catalytic asymmetric synthesis of meta benzene isosteres.

Although aromatic rings are common elements in pharmaceutically active compounds, the presence of these motifs brings several liabilities with respect to the developability of a drug. Nonoptimal potency, metabolic stability, solubility and lipophilicity in pharmaceutical compounds can be improved by replacing aromatic rings with non-aromatic isosteric motifs. Moreover, whereas aromatic rings are planar and lack three-dimensionality, the binding pockets of most pharmaceutical targets are chiral.

Opioid-Free Analgesia is Safe and Effective in Anterior Cervical Spine Surgery: A Randomized Controlled Trial.

Study Design: Randomized controlled trial (RCT).

Objective: Compare the efficacy of a multimodal, opioid-free (OF) pain management pathway with a traditional opioid-containing (OC) pathway in patients undergoing anterior cervical procedures.

Summary Of Background Data: Previous studies have compared opioid-based pain regimens to opioid-sparing regimens following cervical spine surgery, but have been limited by high rates of crossover, retrospective designs, reliance on indwelling pain catheters, opioid utilization for early postoperative analgesia, and/or a lack of patient-reported outcome measures.

Microbial warfare: B. subtilis antagonizes E. coli biofilm formation.

Biofilm formation helps bacteria to survive environmental challenges. Biofilm development often involves multiple genetic pathways that can be regulated by external signals. Diego Serra and his team (Cordisco et al.

Digestive exophagy of biofilms by intestinal amoeba and its impact on stress tolerance and cytotoxicity.

The human protozoan parasite Entamoeba histolytica is responsible for amebiasis, a disease endemic to developing countries. E. histolytica trophozoites colonize the large intestine, primarily feeding on bacteria.

Cell surface-localized CsgF condensate is a gatekeeper in bacterial curli subunit secretion.

Curli are functional amyloids present on the outer membrane of E. coli. CsgF is required for the proper assembly of curli.

Electrostatic interactions mediate the nucleation and growth of a bacterial functional amyloid.

Bacterial biofilm formation can have severe impacts on human and environmental health. Enteric bacteria produce functional amyloid fibers called curli that aid in biofilm formation and host colonization. CsgA is the major proteinaceous component of curli amyloid fibers and is conserved in many gram-negative enteric bacteria.

Mechanistic insights into accelerated α-synuclein aggregation mediated by human microbiome-associated functional amyloids.

The gut microbiome has been shown to have key implications in the pathogenesis of Parkinson's disease (PD). The Escherichia coli functional amyloid CsgA is known to accelerate α-synuclein aggregation in vitro and induce PD symptoms in mice. However, the mechanism governing CsgA-mediated acceleration of α-synuclein aggregation is unclear.

Bacterial Amyloid Curli Associated Gut Epithelial Neuroendocrine Activation Predominantly Observed in Alzheimer's Disease Mice with Central Amyloid-β Pathology.

Background: Substantial evidence from recent research suggests an influential and underappreciated force in Alzheimer's disease (AD) pathogenesis: the pathological signals originate from outside the brain. Pathogenic bacteria produce amyloid-like proteins "curli" that form biofilms and show functional similarities to human amyloid-β (Aβ). These proteins may contribute to neurological disease progression via signaling cascade from the gut to the brain.

Functional Amyloids Are the Rule Rather Than the Exception in Cellular Biology.

Amyloids are a class of protein aggregates that have been historically characterized by their relationship with human disease. Indeed, amyloids can be the result of misfolded proteins that self-associate to form insoluble, extracellular plaques in diseased tissue. For the first 150 years of their study, the pathogen-first definition of amyloids was sufficient.

Half a century of amyloids: past, present and future.

Amyloid diseases are global epidemics with profound health, social and economic implications and yet remain without a cure. This dire situation calls for research into the origin and pathological manifestations of amyloidosis to stimulate continued development of new therapeutics. In basic science and engineering, the cross-β architecture has been a constant thread underlying the structural characteristics of pathological and functional amyloids, and realizing that amyloid structures can be both pathological and functional in nature has fuelled innovations in artificial amyloids, whose use today ranges from water purification to 3D printing.

Tuning Functional Amyloid Formation Through Disulfide Engineering.

Many organisms produce "functional" amyloid fibers, which are stable protein polymers that serve many roles in cellular biology. Certain Enterobacteriaceae assemble functional amyloid fibers called curli that are the main protein component of the biofilm extracellular matrix. CsgA is the major protein subunit of curli and will rapidly adopt the polymeric amyloid conformation .

A gut bacterial amyloid promotes α-synuclein aggregation and motor impairment in mice.

Amyloids are a class of protein with unique self-aggregation properties, and their aberrant accumulation can lead to cellular dysfunctions associated with neurodegenerative diseases. While genetic and environmental factors can influence amyloid formation, molecular triggers and/or facilitators are not well defined. Growing evidence suggests that non-identical amyloid proteins may accelerate reciprocal amyloid aggregation in a prion-like fashion.

Shotgun metagenomic analysis of microbial communities from the Loxahatchee nature preserve in the Florida Everglades.

Background: Currently, much is unknown about the taxonomic diversity and the mechanisms of methane metabolism in the Florida Everglades ecosystem. The Loxahatchee National Wildlife Refuge is a section of the Florida Everglades that is almost entirely unstudied in regard to taxonomic profiling. This short report analyzes the metagenome of soil samples from this Refuge to investigate the predominant taxa, as well as the abundance of genes involved in environmentally significant metabolic pathways related to methane production (nitrogen fixation and dissimilatory sulfite reduction).

Defining a Theory-Driven Ultrasound Curriculum for Prehospital Providers.

Advances in point-of-care ultrasound technology have allowed for the extension of emergency medicine ultrasound beyond the walls of the emergency department. Emergency medical system providers may benefit from the use of ultrasound. It has previously been shown that with a brief introductory course, novices can obtain and correctly interpret focused ultrasound examinations.

Bacterial functional amyloids: Order from disorder.

The discovery of intrinsic disorderness in proteins and peptide regions has given a new and useful insight into the working of biological systems. Due to enormous plasticity and heterogeneity, intrinsically disordered proteins or regions in proteins can perform myriad of functions. The flexibility in disordered proteins allows them to undergo conformation transition to form homopolymers of proteins called amyloids.

Curli Biogenesis: Bacterial Amyloid Assembly by the Type VIII Secretion Pathway.

In 1989, Normark and coworkers reported on fibrous surface structures called curli on strains of that were suspected of causing bovine mastitis. Subsequent work by many groups has revealed an elegant and highly regulated curli biogenesis pathway also referred to as the type VIII secretion system. Curli biogenesis is governed by two divergently transcribed operons, and .

Benefits and Risks of High-Intensity Interval Training in Patients With Coronary Artery Disease.

Exercise-based cardiac rehabilitation is integral to secondary prevention in patients with coronary artery disease. Recently, the effectiveness and "superiority" of high-intensity interval training (HIIT) is a purported time-saving alternative to "traditional" moderate-intensity continuous training (MICT) in cardiac rehabilitation. The rationale for HIIT adoption is, however, not fully substantiated in the scientific literature.

Physical Determinants of Amyloid Assembly in Biofilm Formation.

A wide range of bacterial pathogens have been shown to form biofilms, which significantly increase their resistance to environmental stresses, such as antibiotics, and are thus of central importance in the context of bacterial diseases. One of the major structural components of these bacterial biofilms are amyloid fibrils, yet the mechanism of fibril assembly and its importance for biofilm formation are currently not fully understood. By studying fibril formation , in a model system of two common but unrelated biofilm-forming proteins, FapC from and CsgA from , we found that the two proteins have a common aggregation mechanism.

Nanoparticle-Laden Macrophages for Tumor-Tropic Drug Delivery.

Macrophages hold great potential in cancer drug delivery because they can sense chemotactic cues and home to tumors with high efficiency. However, it remains a challenge to load large amounts of therapeutics into macrophages without compromising cell functions. This study reports a silica-based drug nanocapsule approach to solve this issue.

Discovery of New Genes Involved in Curli Production by a Uropathogenic Escherichia coli Strain from the Highly Virulent O45:K1:H7 Lineage.

Curli are bacterial surface-associated amyloid fibers that bind to the dye Congo red (CR) and facilitate uropathogenic (UPEC) biofilm formation and protection against host innate defenses. Here we sequenced the genome of the curli-producing UPEC pyelonephritis strain MS7163 and showed it belongs to the highly virulent O45:K1:H7 neonatal meningitis-associated clone. MS7163 produced curli at human physiological temperature, and this correlated with biofilm growth, resistance of sessile cells to the human cationic peptide cathelicidin, and enhanced colonization of the mouse bladder.