The Shu complex interacts with the replicative helicase to prevent mutations and aberrant recombination.

Homologous recombination (HR) is important for DNA damage tolerance during replication. The yeast Shu complex, a conserved homologous recombination factor, prevents replication-associated mutagenesis. Here we examine how yeast cells require the Shu complex for coping with MMS-induced lesions during DNA replication.

Protective antibodies target cryptic epitope unmasked by cleavage of malaria sporozoite protein.

The most advanced monoclonal antibodies (mAbs) and vaccines against malaria target the central repeat region or closely related sequences within the circumsporozoite protein (PfCSP). Here, using an antigen-agnostic strategy to investigate human antibody responses to whole sporozoites, we identified a class of mAbs that target a cryptic PfCSP epitope that is only exposed after cleavage and subsequent pyroglutamylation (pGlu) of the newly formed N terminus. This pGlu-CSP epitope is not targeted by current anti-PfCSP mAbs and is not included in the licensed malaria vaccines.

Daily activity patterns in agoutis ( spp) in response to relaxed predation.

Animals' fitness is determined in a large proportion by the balance in energetic requirements maintained during daily activities, in response to environmental factors. Predation is a major environmental factor influencing the activity patterns of prey, and the deployment of adaptive responses to predation represents a significant cost to prey populations and communities. Experimental removal of predators to study the effect on activity patterns of prey is impractical for vertebrate species.

Structural and functional comparisons of salivary α-glucosidases from the mosquito vectors Aedes aegypti, Anopheles gambiae, and Culex quinquefasciatus.

Mosquito vectors of medical importance both blood and sugar feed, and their saliva contains bioactive molecules that aid in both processes. Although it has been shown that the salivary glands of several mosquito species exhibit α-glucosidase activities, the specific enzymes responsible for sugar digestion remain understudied. We therefore expressed and purified three recombinant salivary α-glucosidases from the mosquito vectors Aedes aegypti, Anopheles gambiae, and Culex quinquefasciatus and compared their functions and structures.

Accumulation of defense systems in phage-resistant strains of .

Prokaryotes encode multiple distinct anti-phage defense systems in their genomes. However, the impact of carrying a multitude of defense systems on phage resistance remains unclear, especially in a clinical context. Using a collection of antibiotic-resistant clinical strains of and a broad panel of phages, we demonstrate that defense systems contribute substantially to defining phage host range and that overall phage resistance scales with the number of defense systems in the bacterial genome.

Disentangling detrimental sand fly-mite interactions in a closed laboratory sand fly colony: implications for vector-borne disease studies and guidelines for overcoming severe mite infestations.

Background: Vector sand fly colonies are a critical component of studies aimed at improving the understanding of the neglected tropical disease leishmaniasis and alleviating its global impact. However, among laboratory-colonized arthropod vectors of infectious diseases, the labor-intensive nature of sand fly rearing coupled with the low number of colonies worldwide has generally discouraged the widespread use of sand flies in laboratory settings. Among the different factors associated with the low productivity of sand fly colonies, mite infestations are a significant factor.

Cryo-EM structures of anti-malarial antibody L9 with circumsporozoite protein reveal trimeric L9 association and complete 27-residue epitope.

Monoclonal antibody L9 recognizes the Plasmodium falciparum circumsporozoite protein (PfCSP) and is highly protective following controlled human malaria challenge. To gain insight into its function, we determined cryoelectron microscopy (cryo-EM) structures of L9 in complex with full-length PfCSP and assessed how this recognition influenced protection by wild-type and mutant L9s. Cryo-EM reconstructions at 3.

SARS-CoV-2-Spike Antibody and T-Cell Responses Elicited by a Homologous Third mRNA COVID-19 Dose in Hemodialysis and Kidney Transplant Recipients.

The effect of a third vaccine dose (3D) of homologous mRNA vaccine on blood levels of SARS-CoV-2-receptor binding domain (RBD)-total antibodies was assessed in 40 hemodialysis patients (HD) and 21 kidney transplant recipients (KTR) at a median of 46 days after 3D. Anti-RBD antibodies were detected in 39/40 HD and 19/21 KTR. Overall, 3D boosted anti-RBD antibody levels (median: 58-fold increase).

Calculating minimum safety distance against wildfires at the wildland-urban interface in Chile and Spain.

Wildfires in the urban-forest interface constitute a civil protection emergency, causing considerable personal injury and damage to properties. The potential impacts of wildfires on buildings can be minimized by reducing the surrounding fuel and the use of structural materials with low flammability. However, the costs associated with implementing these actions and the responsibility for maintenance usually present conflicts with the property owners.

The Analgesic Museum.

This manuscript uses the perspectives and insights that emerged from the Analgesic Museum conference held virtually on March 11, 2022 as a mechanism for considering the role museums and artists can play in the public health effort to reduce the burden of persistent pain. One hundred and fifty-seven individuals from 22 countries registered for the Analgesic Museum conference. The event explored the intersection of art and pain management practices with presentations centered on three domains of interest: exhibition development, arts experiences and practices, and research and creative scholarship.

Social and environmental determinants of health among children with long-term movement impairment.

The healthcare research community increasingly recognizes the need to address social (SDOH) and environmental determinants of health (EDOH) to optimize health and healthcare. This is particularly relevant to disability and functioning and to those with child onset conditions that impair mobility and impact functioning and participation. Using the World Health Organization (WHO)'s International Classification of Functioning, Disability, and Health (ICF) as a comprehensive framework, this paper aims to discuss our understanding of the relationships between social and EDOH and outcomes among people with impaired mobility that impacts functioning.

Enhancing the Implementation of the Virtual Pediatric Trauma Center Using Practical, Robust, Implementation and Sustainability Model: A Mixed-Methods Study.

Background: This article describes factors related to adoption, implementation, and effectiveness of the Virtual Pediatric Trauma Center intervention, which uses telehealth for trauma specialist consultations for seriously injured children. We aimed at (1) measuring RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) implementation outcomes and (2) identifying PRISM (Practical, Robust, Implementation, and Sustainability Model) contextual factors that influenced the implementation outcomes.

Methods: This interim implementation evaluation of our telehealth trial used a convergent mixed-methods design.

Leveraging Leadership in Child Welfare Systems: Large-scale Trauma- and Resilience-informed Training Initiative.

Strengthening the infrastructure of public health systems around trauma-informed principles is crucial to addressing the needs of traumatized children in the child welfare system. In fact, many local and state initiatives have focused on large-scale evaluation studies to determine the value of training direct service staff on trauma foundations. Less yet is known about the benefits of training leaders on trauma foundations, which is crucial given their unique influence on implementation decisions.

Dynamics of SARS-CoV-2-Spike-reactive antibody and T-cell responses in chronic kidney disease patients within 3 months after COVID-19 full vaccination.

Background: Little is known regarding the dynamics of antibody and T-cell responses in chronic kidney disease (CKD) following coronavirus disease 2019 (COVID-19) vaccination.

Methods: Prospective observational cohort study including 144 participants on haemodialysis (HD) ( = 52) or peritoneal dialysis (PD) ( = 14), those undergoing kidney transplantation (KT) ( = 30) or those with advanced CKD (ACKD) not on dialysis and healthy controls ( = 18). Anti-Spike (S) antibody and T-cell responses were assessed at 15 days (15D) and 3 months (3M) after complete vaccination schedule.

Highly protective antimalarial antibodies via precision library generation and yeast display screening.

The monoclonal antibody CIS43 targets the Plasmodium falciparum circumsporozoite protein (PfCSP) and prevents malaria infection in humans for up to 9 mo following a single intravenous administration. To enhance the potency and clinical utility of CIS43, we used iterative site-saturation mutagenesis and DNA shuffling to screen precise gene-variant yeast display libraries for improved PfCSP antigen recognition. We identified several mutations that improved recognition, predominately in framework regions, and combined these to produce a panel of antibody variants.

COVID-19 Vaccination Improved Psychological Distress (Anxiety and Depression Scores) in Chronic Kidney Disease Patients: A Prospective Study.

The purpose of the study is to analyze the impact of vaccination against SARS-CoV-2 on anxiety and depression scores in patients with different modalities of chronic kidney disease. One hundred and seventeen renal patients (50 hemodialysis patients, 13 peritoneal dialysis patients, 32 kidney transplants, and 22 advanced chronic kidney disease patients at pre-dialysis care) were evaluated for depression, anxiety, health-related quality of life (HRQOL), and perceived fears and resources with standardized (Hospital Anxiety and Depression Scale (HADS)) and self-reported questionnaires. The measure points were before vaccination and 15 days after vaccination.

The light chain of the L9 antibody is critical for binding circumsporozoite protein minor repeats and preventing malaria.

L9 is a potent human monoclonal antibody (mAb) that preferentially binds two adjacent NVDP minor repeats and cross-reacts with NANP major repeats of the Plasmodium falciparum circumsporozoite protein (PfCSP) on malaria-infective sporozoites. Understanding this mAb's ontogeny and mechanisms of binding PfCSP will facilitate vaccine development. Here, we isolate mAbs clonally related to L9 and show that this B cell lineage has baseline NVDP affinity and evolves to acquire NANP reactivity.

Protective effects of combining monoclonal antibodies and vaccines against the Plasmodium falciparum circumsporozoite protein.

Combinations of monoclonal antibodies (mAbs) against different epitopes on the same antigen synergistically neutralize many viruses. However, there are limited studies assessing whether combining human mAbs against distinct regions of the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) enhances in vivo protection against malaria compared to each mAb alone or whether passive transfer of PfCSP mAbs would improve protection following vaccination against PfCSP. Here, we isolated a panel of human mAbs against the subdominant C-terminal domain of PfCSP (C-CSP) from a volunteer immunized with radiation-attenuated Pf sporozoites.

Vaccination in a humanized mouse model elicits highly protective PfCSP-targeting anti-malarial antibodies.

Repeat antigens, such as the Plasmodium falciparum circumsporozoite protein (PfCSP), use both sequence degeneracy and structural diversity to evade the immune response. A few PfCSP-directed antibodies have been identified that are effective at preventing malaria infection, including CIS43, but how these repeat-targeting antibodies might be improved has been unclear. Here, we engineered a humanized mouse model in which B cells expressed inferred human germline CIS43 (iGL-CIS43) B cell receptors and used both vaccination and bioinformatic analysis to obtain variant CIS43 antibodies with improved protective capacity.

The Shu complex prevents mutagenesis and cytotoxicity of single-strand specific alkylation lesions.

Three-methyl cytosine (3meC) are toxic DNA lesions, blocking base pairing. Bacteria and humans express members of the AlkB enzymes family, which directly remove 3meC. However, other organisms, including budding yeast, lack this class of enzymes.

The structures of two salivary proteins from the West Nile vector reveal a beta-trefoil fold with putative sugar binding properties.

Female mosquitoes require blood meals for egg development. The saliva of blood feeding arthropods contains biochemically active molecules, whose anti-hemostatic and anti-inflammatory properties facilitate blood feeding on vertebrate hosts. While transcriptomics has presented new opportunities to investigate the diversity of salivary proteins from hematophagous arthropods, many of these proteins remain functionally undescribed.

Aedes aegypti SGS1 is critical for Plasmodium gallinaceum infection of both the mosquito midgut and salivary glands.

Background: The invasion of the mosquito salivary glands by Plasmodium sporozoites is a critical step that defines the success of malaria transmission and a detailed understanding of the molecules responsible for salivary gland invasion could be leveraged towards control of vector-borne pathogens. Antibodies directed against the mosquito salivary gland protein SGS1 have been shown to reduce Plasmodium gallinaceum sporozoite invasion of Aedes aegypti salivary glands, but the specific role of this protein in sporozoite invasion and in other stages of the Plasmodium life cycle remains unknown.

Methods: RNA interference and CRISPR/Cas9 were used to evaluate the role of A.

Inactivation of RNA and DNA viruses in water by copper and silver ions and their synergistic effect.

Cu and Ag have been used as bactericidal agents since ancient times, yet their antiviral capacity in water remains poorly understood. This study tested the effect of copper (Cu) and silver (Ag) on model RNA and DNA viruses MS2 and PhiX 174 in solution at pH 6-8. Cu caused MS2 inactivation with similar rates at pH 6 and 7 but was inert towards PhiX 174 regardless of pH.

Biochemical characterization of AeD7L2 and its physiological relevance in blood feeding in the dengue mosquito vector, Aedes aegypti.

Aedes aegypti saliva facilitates blood meal acquisition through pharmacologically active compounds that prevent host hemostasis. Among these salivary proteins are the D7s, which are highly abundant and have been shown to act as scavengers of biogenic amines and eicosanoids. In this work, we performed comparative structural modeling, characterized the binding capabilities, and assessed the physiological functions of the Ae.