Determinants of antimicrobial resistance in biosolids: A systematic review, database, and meta-analysis.

Biosolids can provide a nutrient rich soil amendment, particularly for poor soils and semi-arid or drought-prone areas. However, there are concerns that sludge and biosolids could be a source of propagation and exposure to AMR determinants such as antibiotic resistant bacteria (ARB), and antibiotic resistance genes (ARGs). To inform risk assessment efforts, a systematic literature review was performed to build a comprehensive spreadsheet database of ARB and ARG concentrations in biosolids (and some sludges specified as intended for land application), along with 69 other quantitative and qualitative meta-data fields from 68 published studies describing sampling information and processing methods that can be used for modeling purposes.

What is the Difference between Conventional Drinking Water, Potable Reuse Water, and Nonpotable Reuse Water? A Microbiome Perspective.

As water reuse applications expand, there is a need for more comprehensive means to assess water quality. Microbiome analysis could provide the ability to supplement fecal indicators and pathogen profiling toward defining a "healthy" drinking water microbiota while also providing insight into the impact of treatment and distribution. Here, we utilized 16S rRNA gene amplicon sequencing to identify signature features in the composition of microbiota across a wide spectrum of water types (potable conventional, potable reuse, and nonpotable reuse).

Actin network evolution as a key driver of eukaryotic diversification.

Eukaryotic cells have been evolving for billions of years, giving rise to wildly diverse cell forms and functions. Despite their variability, all eukaryotic cells share key hallmarks, including membrane-bound organelles, heavily regulated cytoskeletal networks and complex signaling cascades. Because the actin cytoskeleton interfaces with each of these features, understanding how it evolved and diversified across eukaryotic phyla is essential to understanding the evolution and diversification of eukaryotic cells themselves.

Synthesis of a -Derived Muropeptide Standard Fragment Library.

The interplay between the human innate immune system and bacterial cell wall components is pivotal in understanding diseases such as Crohn's disease and Lyme arthritis. Lyme disease, caused by , is the most prevalent tick-borne illness in the United States, with a substantial number of cases reported annually. While antibiotic treatments are generally effective, approximately 10% of Lyme disease cases develop persistent arthritis, suggesting a dysregulated host immune response.

Automated design of bone-preserving, insertable, and shape-matching patient-specific acetabular components.

Effective treatment of large acetabular defects remains among the most challenging aspects of revision total hip arthroplasty (THA), due to the deficiency of healthy bone stock and degradation of the support columns. Generic uncemented components, which are favored in primary THA, are often unsuitable in revision cases, where the bone-implant contact may be insufficient for fixation, without significant reaming of the limited residual bone. This study presents a computational design strategy for automatically generating patient-specific implants that simultaneously maximize the bone-implant contact area, and minimize bone reaming while ensuring insertability.

Fluorogenic Probes of the Mycobacterial Membrane as Reporters of Antibiotic Action.

The genus includes species such as , which can cause deadly human diseases. These bacteria have a protective cell envelope that can be remodeled to facilitate their survival in challenging conditions. Understanding how such conditions affect membrane remodeling can facilitate antibiotic discovery and treatment.

To what extent do water reuse treatments reduce antibiotic resistance indicators? A comparison of two full-scale systems.

Water reuse is an essential strategy for reducing water demand from conventional sources, alleviating water stress, and promoting sustainability, but understanding the effectiveness of associated treatment processes as barriers to the spread of antibiotic resistance is an important consideration to protecting human health. We comprehensively evaluated the reduction of antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) in two field-operational water reuse systems with distinct treatment trains, one producing water for indirect potable reuse (ozone/biologically-active carbon/granular activated carbon) and the other for non-potable reuse (denitrification-filtration/chlorination) using metagenomic sequencing and culture. Relative abundances of total ARGs/clinically-relevant ARGs and cultured ARB were reduced by several logs during primary and secondary stages of wastewater treatment, but to a lesser extent during the tertiary water reuse treatments.

Cell constriction requires processive septal peptidoglycan synthase movement independent of FtsZ treadmilling in Staphylococcus aureus.

Bacterial cell division requires recruitment of peptidoglycan (PG) synthases to the division site by the tubulin homologue, FtsZ. Septal PG synthases promote septum growth. FtsZ treadmilling is proposed to drive the processive movement of septal PG synthases and septal constriction in some bacteria; however, the precise mechanisms spatio-temporally regulating PG synthase movement and activity and FtsZ treadmilling are poorly understood.

High-Specificity CRISPR-Mediated Genome Engineering in Anti-BCMA Allogeneic CAR T Cells Suppresses Allograft Rejection in Preclinical Models.

Allogeneic chimeric antigen receptor (CAR) T cell therapies hold the potential to overcome many of the challenges associated with patient-derived (autologous) CAR T cells. Key considerations in the development of allogeneic CAR T cell therapies include prevention of graft-vs-host disease (GvHD) and suppression of allograft rejection. Here, we describe preclinical data supporting the ongoing first-in-human clinical study, the CaMMouflage trial (NCT05722418), evaluating CB-011 in patients with relapsed/refractory multiple myeloma.

Salactin, a dynamically unstable actin homolog in Haloarchaea.

Protein filaments play important roles in many biological processes. We discovered an actin homolog in halophilic archaea, which we call Salactin. Just like the filaments that segregate DNA in eukaryotes, Salactin grows out of the cell poles towards the middle, and then quickly depolymerizes, a behavior known as dynamic instability.

Single-molecule dynamics show a transient lipopolysaccharide transport bridge.

Gram-negative bacteria are surrounded by two membranes. A special feature of the outer membrane is its asymmetry. It contains lipopolysaccharide (LPS) in the outer leaflet and phospholipids in the inner leaflet.

Combined GLP-1 Receptor Agonist and Amylin Analogue Pharmacotherapy to Treat Obesity Comorbid With Type 1 Diabetes.

Type 1 diabetes mellitus (T1DM) with obesity is increasingly common, prompting effective clinical interventions to induce weight loss in this population. We present 3 patients with T1DM and obesity prescribed a glucagon-like peptide 1 receptor agonist (GLP-1RA) and pramlintide. A 32-year-old male with obstructive sleep apnea (OSA) who lost -20.

An exhaustive multiple knockout approach to understanding cell wall hydrolase function in .

In order to grow, bacterial cells must both create and break down their cell wall. The enzymes that are responsible for these processes are the target of some of our best antibiotics. Our understanding of the proteins that break down the wall- cell wall hydrolases-has been limited by redundancy among the large number of hydrolases many bacteria contain.

Combination anti-obesity medications to effectively treat bariatric surgery weight regain at an academic obesity center.

Background: Combination anti-obesity medications (AOMs) to treat postoperative bariatric surgery weight regain have limited data on their use in the clinical setting. Understanding the optimal treatment protocol in this cohort will maximize weight loss outcomes.

Methods: A retrospective review of bariatric surgery patients ( = 44) presenting with weight regain at a single academic multidisciplinary obesity center who were prescribed AOM(s) plus intensive lifestyle modification for 12 months.

Allogeneic chimeric antigen receptor-T cells with CRISPR-disrupted programmed death-1 checkpoint exhibit enhanced functional fitness.

Background Aims: Therapeutic disruption of immune checkpoints has significantly advanced the armamentarium of approaches for treating cancer. The prominent role of the programmed death-1 (PD-1)/programmed death ligand-1 axis for downregulating T cell function offers a tractable strategy for enhancing the disease-modifying impact of CAR-T cell therapy.

Methods: To address checkpoint interference, primary human T cells were genome edited with a next-generation CRISPR-based platform (Cas9 chRDNA) by knockout of the PDCD1 gene encoding the PD-1 receptor.

Mycobacterial nucleoid-associated protein Lsr2 is required for productive mycobacteriophage infection.

Mycobacteriophages are a diverse group of viruses infecting Mycobacterium with substantial therapeutic potential. However, as this potential becomes realized, the molecular details of phage infection and mechanisms of resistance remain ill-defined. Here we use live-cell fluorescence microscopy to visualize the spatiotemporal dynamics of mycobacteriophage infection in single cells and populations, showing that infection is dependent on the host nucleoid-associated Lsr2 protein.

Growth rate is modulated by monitoring cell wall precursors in Bacillus subtilis.

How bacteria link their growth rate to external nutrient conditions is unknown. To investigate how Bacillus subtilis cells alter the rate at which they expand their cell walls as they grow, we compared single-cell growth rates of cells grown under agar pads with the density of moving MreB filaments under a variety of growth conditions. MreB filament density increases proportionally with growth rate.

Microbial source tracking to elucidate the impact of land-use and physiochemical water quality on fecal contamination in a mixed land-use watershed.

Escherichia coli has been widely used as a fecal indicator bacterium (FIB) for monitoring water quality in drinking water sources and recreational water. However, fecal contamination sources remain difficult to identify and mitigate, as millions of cases of infectious diseases are reported yearly due to swimming and bathing in recreational water. The objective of this study was to apply molecular techniques for microbial source tracking (MST) to identify sources of fecal contamination in a representative mixed land-use watershed located in the Appalachian Mountains of the United States of America (USA).

Tuberculosis treatment failure associated with evolution of antibiotic resilience.

The widespread use of antibiotics has placed bacterial pathogens under intense pressure to evolve new survival mechanisms. Genomic analysis of 51,229 ()clinical isolates has identified an essential transcriptional regulator, , herein called for resilience regulator, as a frequent target of positive (adaptive) selection. mutants do not show canonical drug resistance or drug tolerance but instead shorten the post-antibiotic effect, meaning that they enable to resume growth after drug exposure substantially faster than wild-type strains.

Comparative effects of weight loss and incretin-based therapies on vascular endothelial function, fibrinolysis and inflammation in individuals with obesity and prediabetes: A randomized controlled trial.

Aim: To test the hypothesis that glucagon-like peptide-1 receptor (GLP-1R) agonists have beneficial effects on vascular endothelial function, fibrinolysis and inflammation through weight loss-independent mechanisms.

Materials And Methods: Individuals with obesity and prediabetes were randomized to 14 weeks of the GLP-1R agonist liraglutide, hypocaloric diet or the dipeptidyl peptidase-4 inhibitor sitagliptin in a 2:1:1 ratio. Treatment with drug was double blind and placebo-controlled.