Communication between DNA polymerases and Replication Protein A within the archaeal replisome.

Replication Protein A (RPA) plays a pivotal role in DNA replication by coating and protecting exposed single-stranded DNA, and acting as a molecular hub that recruits additional replication factors. We demonstrate that archaeal RPA hosts a winged-helix domain (WH) that interacts with two key actors of the replisome: the DNA primase (PriSL) and the replicative DNA polymerase (PolD). Using an integrative structural biology approach, combining nuclear magnetic resonance, X-ray crystallography and cryo-electron microscopy, we unveil how RPA interacts with PriSL and PolD through two distinct surfaces of the WH domain: an evolutionarily conserved interface and a novel binding site.

Disparities in Evaluation, Treatment, and Outcomes of Pediatric Knee Injuries.

Similar to other fields, there is growing evidence of disparities in pediatric sports medicine. For children and adolescents with knee injuries, disparities persist along the lines of sex, gender, race, ethnicity, insurance, socioeconomic status, and other determinants. These factors influence the evaluation, treatment, and outcomes for a variety of knee pathologies, including anterior cruciate ligament ruptures, meniscus tears, osteochondritis dissecans, cartilage injuries, and tibial spine fractures.

Characteristics, clinical care, and outcomes of sepsis among patients boarding in the emergency department.

Background: Patients who first meet clinical criteria for sepsis while boarding in the emergency department (ED) may not receive optimal sepsis care.

Objective: Assess the association between ED boarding status and sepsis quality of care and outcomes.

Methods: We conducted a retrospective cohort study of adult patients admitted to a large academic hospital from July 2021 to October 2023 who had clinical features consistent with sepsis present while physically in the ED.

Anti-S-layer monoclonal antibodies impact physiology.

(), a gram-positive anaerobic and spore-forming bacterium, is the leading cause of nosocomial antibiotic-associated diarrhea in adults which is characterized by high levels of recurrence and mortality. Surface (S)-layer Protein A (SlpA), the most abundantly expressed protein on the bacterial surface, plays a crucial role in the early stages of infection although the nature of its involvement in physiology is yet to be fully understood. Anti-S-layer antibodies have been identified in the sera of convalescent patients and have been correlated with improved outcomes of infection (CDI).

A monoclonal antibody collection for C. difficile typing ?

Clostridioides difficile is the leading cause of antibiotic-associated diarrhea and pseudomembranous colitis in adults. Various C. difficile strains circulate currently, associated with different outcomes and antibiotic resistance profiles.

PvDBPII elicits multiple antibody-mediated mechanisms that reduce growth in a Plasmodium vivax challenge trial.

The receptor-binding domain, region II, of the Plasmodium vivax Duffy binding protein (PvDBPII) binds the Duffy antigen on the reticulocyte surface to mediate invasion. A heterologous vaccine challenge trial recently showed that a delayed dosing regimen with recombinant PvDBPII SalI variant formulated with adjuvant Matrix-M reduced the in vivo parasite multiplication rate (PMR) in immunized volunteers challenged with the Thai P. vivax isolate PvW1.

Antigen self-anchoring onto bacteriophage T5 capsid-like particles for vaccine design.

The promises of vaccines based on virus-like particles stimulate demand for universal non-infectious virus-like platforms that can be efficiently grafted with large antigens. Here, we harnessed the modularity and extreme affinity of the decoration protein pb10 for the capsid of bacteriophage T5. SPR experiments demonstrated that pb10 fused to mCherry or to the model antigen ovalbumin (Ova) retained picomolar affinity for DNA-free T5 capsid-like particles (T5-CLPs), while cryo-EM studies attested to the full occupancy of the 120 capsid binding sites.

Focused Cardiac Ultrasound Findings of Fluid Tolerance and Fluid Resuscitation in Septic Shock.

Objectives: Compliance with the fluid bonus component of the SEP-1 (severe sepsis and septic shock management) bundle remains poor due to concerns for iatrogenic harm from fluid overload. We sought to assess whether patients who received focused cardiac ultrasound (FCU) and were found to be fluid tolerant (FT) were more likely to receive the recommended 30 mL/kg fluid bolus within 3 hours of sepsis identification.

Design: Retrospective, observational cohort study.

Institutional Structures and Processes to Support Sepsis Care: A Multihospital Study.

Objectives: To identify opportunities for improving hospital-based sepsis care and to inform an ongoing statewide quality improvement initiative in Michigan.

Design: Surveys on hospital sepsis processes, including a self-assessment of practices using a 3-point Likert scale, were administered to 51 hospitals participating in the Michigan Hospital Medicine Safety Consortium, a Collaborative Quality Initiative sponsored by Blue Cross Blue Shield of Michigan, at two time points (2020, 2022). Forty-eight hospitals also submitted sepsis protocols for structured review.

SCRIB controls apical contractility during epithelial differentiation.

Although mutations in the SCRIB gene lead to multiple morphological organ defects in vertebrates, the molecular pathway linking SCRIB to organ shape anomalies remains elusive. Here, we study the impact of SCRIB-targeted gene mutations during the formation of the gut epithelium in an organ-on-chip model. We show that SCRIB KO gut-like epithelia are flatter with reduced exposed surface area.

Interrogating Aptamer Chemical Space Through Modified Nucleotide Substitution Facilitated by Enzymatic DNA Synthesis.

Chemical modification of aptamers is an important step to improve their performance and stability in biological media. This can be performed either during their identification (mod-SELEX) or after the in vitro selection process (post-SELEX). In order to reduce the complexity and workload of the post-SELEX modification of aptamers, we have evaluated the possibility of improving a previously reported, chemically modified aptamer by combining enzymatic synthesis and nucleotides bearing bioisosteres of the parent cubane side-chains or substituted cubane moieties.

The SET and ankyrin domains of the secreted histone methyltransferase work together to modify host chromatin.

is an intracellular bacterium responsible of Legionnaires' disease, a severe pneumonia that is often fatal when not treated promptly. The pathogen's ability to efficiently colonize the host resides in its ability to replicate intracellularly. Essential for intracellular replication is translocation of many different protein effectors a specialized secretion system.

An original potentiating mechanism revealed by the cryo-EM structures of the human α7 nicotinic receptor in complex with nanobodies.

The human α7 nicotinic receptor is a pentameric channel mediating cellular and neuronal communication. It has attracted considerable interest in designing ligands for the treatment of neurological and psychiatric disorders. To develop a novel class of α7 ligands, we recently generated two nanobodies named E3 and C4, acting as positive allosteric modulator and silent allosteric ligand, respectively.

Disparate Impact: How Does Social Deprivation Affect Patient-reported Outcomes After ACL Reconstruction in Children and Adolescents?

Background: Research has indicated that lower socioeconomic status is associated with delays in the treatment of anterior cruciate ligament (ACL) injuries; however, there is a paucity of literature evaluating its association with patient-reported outcomes (PROs). Using the Area Deprivation Index (ADI), a validated proxy for socioeconomic status, the study aimed to determine how relative socioeconomic disadvantage is related to PROs after primary ACL reconstruction (ACLR) in pediatric patients.

Methods: This retrospective cohort study included all patients 18 years old or above who underwent primary ACLR at an academic institution between 2018 and 2021.

Impact of emergency department-based intensive care unit on outcomes of decompensating boarding emergency department patients.

Objectives: Emergency department (ED) boarding, or remaining in the ED after admission before transfer to an inpatient bed, is prevalent. Boarding patients may decompensate before inpatient transfer, necessitating escalation to the intensive care unit (ICU). We evaluated the impact of an ED-ICU on decompensating boarding ED patients.

Immunogenicity of a Plasmodium vivax vaccine based on the duffy binding protein formulated using adjuvants compatible for use in humans.

The invasion of reticulocytes by Plasmodium vivax merozoites is dependent on the interaction of the Plasmodium vivax Duffy Binding Protein (PvDBP) with the Duffy antigen receptor for chemokines (DARC). The N-terminal cysteine-rich region II of PvDBP (PvDBPII), which binds DARC, is a leading P. vivax malaria vaccine candidate.

New insight into flavivirus maturation from structure/function studies of the yellow fever virus envelope protein complex.

All enveloped viruses enter cells by fusing their envelope with a target cell membrane while avoiding premature fusion with membranes of the producer cell-the latter being particularly important for viruses that bud at internal membranes. Flaviviruses bud in the endoplasmic reticulum, are transported through the TGN to reach the external milieu, and enter other cells via receptor-mediated endocytosis. The trigger for membrane fusion is the acidic environment of early endosomes, which has a similar pH to the TGN of the producer cell.

Raynals, an online tool for the analysis of dynamic light scattering.

Dynamic light scattering (DLS) is routinely employed to assess the homogeneity and size-distribution profile of samples containing microscopic particles in suspension or solubilized polymers. In this work, Raynals, user-friendly software for the analysis of single-angle DLS data that uses the Tikhonov-Phillips regularization, is introduced. Its performance is evaluated on simulated and experimental data generated by different DLS instruments for several proteins and gold nanoparticles.

Part of the gender gap in voting for Democrats arises because a higher proportion of women than men voters are Black.

Women voted for the Democratic candidate more than men did in each US presidential election since 1980. We show that part of the gender gap stems from the fact that a higher proportion of women than men voters are Black, and Black voters overwhelmingly choose Democratic candidates. Past research shows that Black men have especially high rates of death, incarceration, and disenfranchisement due to criminal convictions.

The cell wall lipoprotein CD1687 acts as a DNA binding protein during deoxycholate-induced biofilm formation in Clostridioides difficile.

The ability of bacterial pathogens to establish recurrent and persistent infections is frequently associated with their ability to form biofilms. Clostridioides difficile infections have a high rate of recurrence and relapses and it is hypothesized that biofilms are involved in its pathogenicity and persistence. Biofilm formation by C.

The Epidemiology of Pediatric Basketball Injuries Presenting to US Emergency Departments: 2011-2020.

Objectives: The purpose of this study is to describe the national epidemiology of basketball-related injuries in children and adolescents presenting to US emergency departments (EDs) from 2011 to 2020 and to quantify the effect of the COVID-19 pandemic.

Methods: The National Electronic Injury Surveillance System database was queried for cases of injury in persons aged 0 to 19 years related to product code 1205 (basketball and related equipment) presenting from January 1, 2011 to December 31, 2020. National injury estimates were calculated using National Electronic Injury Surveillance System-recommended weights and strata.

The feasibility and impact of implementing a computer-guided consultation to target health inequality in Asthma.

Greater Manchester has a greater prevalence and worse asthma outcomes than the national average. This study aims to evaluate a digital approach to primary care asthma management and in particular the initial impact of implementing Clinical Decision Support System software in the form of a computer-guided consultation (CGC) in the setting of primary care asthma reviews in deprived areas of Greater Manchester. The CGC (LungHealth Ltd) is an intelligent decision support system ensuring accurate guideline-based staging of asthma and assessment of asthma control with the software subsequently prompting guideline-standard management.

Wealth and Divorce.

In the United States, wealthier couples have lower divorce risk. Wealth may stabilize marriage through its material value, especially by easing financial stress, or by providing symbolic resources, especially signaling that couples meet normative financial standards for marriage. We first show that the negative association between wealth and divorce holds net of a rich set of controls.