Variants and vaccines impact nasal immunity over three waves of SARS-CoV-2.

Viral variant and host vaccination status impact infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet how these factors shift cellular responses in the human nasal mucosa remains uncharacterized. We performed single-cell RNA sequencing (scRNA-seq) on nasopharyngeal swabs from vaccinated and unvaccinated adults with acute Delta and Omicron SARS-CoV-2 infections and integrated with data from acute infections with ancestral SARS-CoV-2. Patients with Delta and Omicron exhibited greater similarity in nasal cell composition driven by myeloid, T cell and SARS-CoV-2 cell subsets, which was distinct from that of ancestral cases.

Induction of the macrolide-resistance efflux pump Mega inhibits intoxication of Staphylococcus aureus strains by Streptococcus pneumoniae.

Streptococcus pneumoniae (Spn) kills Staphylococcus aureus (Sau) through a contact-dependent mechanism that is catalyzed by cations, including iron, to convert hydrogen peroxide (HO) to highly toxic hydroxyl radicals (OH). There are two well-characterized ABC transporters that contribute to the pool of iron in Spn, named Pia and Piu. Some Spn strains have acquired genes mef(E)/mel encoding another ABC trasporter (Mega) that produces an inducible efflux pump for resistance to macrolides.

Increased rates of blood culture contamination during the coronavirus disease 2019 pandemic.

We observed a higher rate of blood-culture contamination during the COVID-19 pandemic at our institution compared to a prepandemic period. Given the potential implications of blood contamination in antibiotic and diagnostic test utilization as well as added cost, it is imperative to continue efforts to minimize these episodes during the pandemic.

Clinical Validation of a SARS-CoV-2 Real-Time Reverse Transcription PCR Assay Targeting the Nucleocapsid Gene.

Background: Detection of SARS-CoV-2 viral RNA is important for the diagnosis and management of COVID-19.

Methods: We present a clinical validation of a reverse transcription PCR (RT-PCR) assay for the SARS-CoV-2 nucleocapsid (N1) gene. Off-board lysis on an automated nucleic acid extraction system was optimized with endemic coronaviruses (OC43 and NL63).

Abbott ARCHITECT Syphilis TP Chemiluminescent Immunoassay Accurately Diagnoses Past or Current Syphilis in Pregnancy.

Objective: We evaluate diagnostic accuracy of the ARCHITECT chemiluminescent immunoassay (CIA) screening test in pregnancy, and evaluate pregnancy outcomes among screen-positive women.

Study Design: Samples from routine prenatal rapid plasma reagin (RPR) tests were collected between June 22 and August 18, 2017 and frozen. Samples were batch-tested with the Abbott ARCHITECT syphilis TP immunoassay (CIA, index test).

Identification via a Parallel Hit Progression Strategy of Improved Small Molecule Inhibitors of the Malaria Purine Uptake Transporter that Inhibit Parasite Proliferation.

Emerging resistance to current antimalarial medicines underscores the importance of identifying new drug targets and novel compounds. Malaria parasites are purine auxotrophic and import purines via the equilibrative nucleoside transporter type 1 (PfENT1). We previously showed that PfENT1 inhibitors block parasite proliferation in culture.

Susceptibility of Cardiac Troponin Assays to Biotin Interference.

Objectives: To investigate biotin interference on three cardiac troponin (cTn) assays and demonstrate a method to overcome biotin interference.

Methods: cTn levels were measured in (1) plasma from healthy volunteers on 10-mg daily biotin supplementation mixed with a plasma with known elevated troponin, (2) plasmas with known elevated cTn after mixing in reagent biotin to simulate supplementation, and (3) biotin-spiked plasma specimens pretreated with streptavidin-agarose beads.

Results: Daily biotin ingestion (10 mg) and studies simulating daily biotin use resulted in significant interference in the Gen5 cardiac troponin T (cTnT) assay; the contemporary Gen 4 cTnT and high-sensitivity cardiac troponin I (hs-cTnI) assays were unaffected.

Impact of Hormone Therapy on Laboratory Values in Transgender Patients.

Background: For transgender individuals taking hormone therapy (HT), data on laboratory values are limited, and the effects on laboratory values cannot be easily predicted. We evaluated the impact on common laboratory analytes in transgender individuals before and after initiation of HT.

Methods: We conducted a retrospective chart review of transgender patients identified at transgender-specific clinics at an urban county hospital and community clinic.

Targeting the Plasmodium vivax equilibrative nucleoside transporter 1 (PvENT1) for antimalarial drug development.

Infection with Plasmodium falciparum and vivax cause most cases of malaria. Emerging resistance to current antimalarial medications makes new drug development imperative. Ideally a new antimalarial drug should treat both falciparum and vivax malaria.

Current challenges in prostate cancer: an interview with Prostate Cancer UK.

In this video Q&A, we talk to Iain Frame and Sarah Cant from Prostate Cancer UK about the current challenges in prostate cancer research and policy and how these are being addressed.

Yeast-based high-throughput screen identifies Plasmodium falciparum equilibrative nucleoside transporter 1 inhibitors that kill malaria parasites.

Equilibrative transporters are potential drug targets; however, most functional assays involve radioactive substrate uptake that is unsuitable for high-throughput screens (HTS). We developed a robust yeast-based growth assay that is potentially applicable to many equilibrative transporters. As proof of principle, we applied our approach to Equilibrative Nucleoside Transporter 1 of the malarial parasite Plasmodium falciparum (PfENT1).

Purine import into malaria parasites as a target for antimalarial drug development.

Infection with Plasmodium species parasites causes malaria. Plasmodium parasites are purine auxotrophs. In all life cycle stages, they require purines for RNA and DNA synthesis and other cellular metabolic processes.

Biography: Dr Iain Frame, director of research, prostate cancer UK.

Sophia Maprayil, Commissioning Editor for Expert Review of Anticancer Therapy, talks to Dr Iain Frame, Director of Research for Prostate Cancer UK. Iain is Prostate Cancer UK's first Director of Research, responsible for overseeing the development and implementation of the charity's ambitious new research strategy. He joined Prostate Cancer UK in 2012 from Diabetes UK where he held the post of Research Director for 5 years.

UV-triggered affinity capture identifies interactions between the Plasmodium falciparum multidrug resistance protein 1 (PfMDR1) and antimalarial agents in live parasitized cells.

A representative of a new class of potent antimalarials with an unknown mode of action was recently described. To identify the molecular target of this class of antimalarials, we employed a photo-reactive affinity capture method to find parasite proteins specifically interacting with the capture compound in living parasitized cells. The capture reagent retained the antimalarial properties of the parent molecule (ACT-213615) and accumulated within parasites.

Malaria parasite type 4 equilibrative nucleoside transporters (ENT4) are purine transporters with distinct substrate specificity.

Malaria, caused by Plasmodia parasites, affects hundreds of millions of people. As purine auxotrophs, Plasmodia use transporters to import host purines for subsequent metabolism by the purine salvage pathway. Thus purine transporters are attractive drug targets.

Transmembrane segment 11 appears to line the purine permeation pathway of the Plasmodium falciparum equilibrative nucleoside transporter 1 (PfENT1).

Purine transport is essential for malaria parasites to grow because they lack the enzymes necessary for de novo purine biosynthesis. The Plasmodium falciparum Equilibrative Nucleoside Transporter 1 (PfENT1) is a member of the equilibrative nucleoside transporter (ENT) gene family. PfENT1 is a primary purine transport pathway across the P.

New tools to support collaboration and virtual organizations.

We describe the use of new eScience tools to support collaboration, including the use of XML data representations to support shared viewing of the information content of data, metadata tools for documenting data and Web 2.0 social networking tools for documenting ideas and the collaboration process. This latter work has led to the development of the http://SciSpace.

eScience for molecular-scale simulations and the eMinerals project.

We review the work carried out within the eMinerals project to develop eScience solutions that facilitate a new generation of molecular-scale simulation work. Technological developments include integration of compute and data systems, developing of collaborative frameworks and new researcher-friendly tools for grid job submission, XML data representation, information delivery, metadata harvesting and metadata management. A number of diverse science applications will illustrate how these tools are being used for large parameter-sweep studies, an emerging type of study for which the integration of computing, data and collaboration is essential.

Identifying the impact of diabetes research.

Aims: Assessment of the impact of health research is a growing but problematic field. We examined how a combination of approaches might together inform assessment of the impact of a body of diabetes research published in 1981 and help identify factors behind success.

Methods: Three broad approaches were applied to the work of one team leader of acknowledged influence.

Mechanism of genetic exchange in American trypanosomes.

The kinetoplastid Protozoa are responsible for devastating diseases. In the Americas, Trypanosoma cruzi is the agent of Chagas' disease--a widespread disease transmissible from animals to humans (zoonosis)--which is transmitted by exposure to infected faeces of blood-sucking triatomine bugs. The presence of genetic exchange in T.

Genetic affinities of the Andaman Islanders, a vanishing human population.

Background: The Andaman Islands in the Bay of Bengal are inhabited by hunter-gatherers of unknown origin, now on the verge of extinction. The Andamanese and other Asian small-statured peoples, traditionally known as "Negritos," resemble African pygmies. However, it is generally believed that they descend from the early Australo-Melanesian settlers of Southeast Asia and that their resemblance to some Africans is due to adaptation to a similar environment, rather than shared origins.