Safety, tolerability, pharmacokinetics, and neutralisation activities of the anti-HIV-1 monoclonal antibody PGT121.414.LS administered alone and in combination with VRC07-523LS in adults without HIV in the USA (HVTN 136/HPTN 092): a first-in-human, open-label, randomised controlled phase 1 trial.

Background: Multiple broadly neutralising monoclonal antibodies (mAbs) are in development for HIV-1 prevention. The aim of this trial was to test the PGT121.414.

Conformational variability in the D2 loop of Apical Membrane antigen 1.

Apical Membrane Antigen 1 (AMA1) plays a vital role in the invasion of the host erythrocyte by the malaria parasite, . It is thus an important target for vaccine and anti-malaria therapeutic strategies that block the invasion process. AMA1, present on the surface of the parasite, interacts with RON2, a component of the parasite's rhoptry neck (RON) protein complex, which is transferred to the erythrocyte membrane during invasion.

Prevalence of detectable HIV-DNA and HIV-RNA in cerebrospinal fluid of youth with perinatal HIV and impaired cognition on antiretroviral therapy.

Objective: Central nervous system (CNS) HIV infection can impact cognition and may be an obstacle to cure in adolescents and young adults with perinatal HIV (AYAPHIV). IMPAACT2015 enrolled AYAPHIV on suppressive antiretroviral therapy (ART) with cognitive impairment to detect and quantify HIV in blood and cerebrospinal fluid (CSF).

Design: IMPAACT2015 was a U.

Inhibition profile of three biological nitrification inhibitors and their response to soil pH modification in two contrasting soils.

Up to 70% of the nitrogen (N) fertilizer applied to agricultural soils is lost through microbially mediated processes, such as nitrification. This can be counteracted by synthetic and biological compounds that inhibit nitrification. However, for many biological nitrification inhibitors (BNIs), the interaction with soil properties, nitrifier specificity, and effective concentrations are unclear.

Learning vs. understanding: When does artificial intelligence outperform process-based modeling in soil organic carbon prediction?

In recent years, machine learning (ML) algorithms have gained substantial recognition for ecological modeling across various temporal and spatial scales. However, little evaluation has been conducted for the prediction of soil organic carbon (SOC) on small data sets commonly inherent to long-term soil ecological research. In this context, the performance of ML algorithms for SOC prediction has never been tested against traditional process-based modeling approaches.

"It's already in your body and it's preventing": a qualitative study of African female adolescent's acceptability and preferences for proxy HIV prevention methods in Cape Town, South Africa.

Background: Advances in biomedical HIV prevention will soon offer young women a choice of HIV prevention methods, including various pre-exposure prophylaxis (PrEP) modalities such as daily oral pills, dapivirine vaginal ring, and long-acting injectable agents. By understanding preferences for contraceptive methods, we may draw analogies for the HIV prevention needs of young women. The UChoose Study was an open-label randomised cross-over study designed to evaluate the acceptability and preference for several contraceptive options as a proxy for HIV prevention methods that use similar types of administration.

Meta-analysis protocol on the effects of cover crops on pool specific soil organic carbon.

Soil organic carbon (SOC) plays an important role in agricultural soils, as it contributes to overall soil health as well as climate change mitigation and adaptation. By conducting a meta-analysis, we aim to quantitatively summarize research studying the effects of cover crops (CC) on SOC pools throughout soil depths in arable cropland. We included global studies located in the climatic zones present in Europe.

Microbial responses to soil cooling might explain increases in microbial biomass in winter.

Unlabelled: In temperate, boreal and arctic soil systems, microbial biomass often increases during winter and decreases again in spring. This build-up and release of microbial carbon could potentially lead to a stabilization of soil carbon during winter times. Whether this increase is caused by changes in microbial physiology, in community composition, or by changed substrate allocation within microbes or communities is unclear.

Scaling eukaryotic cell-free protein synthesis achieved with the versatile and high-yielding tobacco BY-2 cell lysate.

Eukaryotic cell-free protein synthesis (CFPS) can accelerate expression and high-throughput analysis of complex proteins with functionally relevant post-translational modifications (PTMs). However, low yields and difficulties scaling such systems have prevented their widespread adoption in protein research and manufacturing. Here, we provide detailed demonstrations for the capabilities of a CFPS system derived from Nicotiana tabacum BY-2 cell culture (BY-2 lysate; BYL).

The concept of an agroinfiltration kit for recombinant protein production for educational and commercial use-A journey through a forest of regulatory and legal implications.

Recombinant expression using Agrobacterium-mediated transient transformation (ATT) of plants has developed into a robust and versatile method to rapidly produce proteins. The capability of plants to efficiently synthesize even homo- and hetero-multimeric complex folded proteins featuring disulfide bonds and other post-translational modifications such as N-linked glycosylation makes them superior to most of the established microbial, especially prokaryotic expression hosts. Compared to production in mammalian cell cultures, ATT requires lower skills, simple technical equipment and cheaper media components.

Production of Recombinant Proteins by Agrobacterium-Mediated Transient Expression.

The agroinfiltration of plant tissue is a robust method that allows the rapid and transient expression of recombinant proteins. Using wild-type plants as biomass, agroinfiltration exploits the ability of plants to synthesize even complex multimeric proteins that require oxidative folding and/or post-translational modifications, while avoiding the expensive and time-consuming creation of stably transformed plant lines. Here we describe a generic method for the transient expression of recombinant proteins in Nicotiana benthamiana at the small to medium laboratory scale, including appropriate binary vectors, the design and cloning of expression constructs, the transformation, selection, and cultivation of recombinant Agrobacterium tumefaciens, the infiltration of plants using a syringe or vacuum device, and finally the extraction of recombinant proteins from plant tissues.

Recombinant Protein Production in Plants: A Brief Overview of Strengths and Challenges.

The first recombinant proteins were produced in microbes and animal cells cultivated in bioreactors. These systems have become the standard for industrial-scale recombinant protein manufacturing. Later, the production of recombinant proteins was demonstrated in whole plants, which differ morphologically from cell-based systems and require completely different cultivation conditions.

LEDitSHAKE: a lighting system to optimize the secondary metabolite content of plant cell suspension cultures.

Plant secondary metabolites are widely used in the food, cosmetic and pharmaceutical industries. They can be extracted from sterile grown plant cell suspension cultures, but yields and quality strongly depend on the cultivation environment, including optimal illumination. Current shaking incubators do not allow different light wavelengths, intensities and photoperiods to be tested in parallel.

A Randomized Trial of Point-of-Care Early Infant Human Immunodeficiency Virus (HIV) Diagnosis in Zambia.

Background: Point-of-care (POC) early infant diagnosis (EID) provides same-day results and the potential for immediate initiation of antiretroviral therapy (ART).

Methods: We conducted a pragmatic trial at 6 public clinics in Zambia. HIV-exposed infants were individually randomized to either (1) POC EID (onsite testing with the Alere q HIV-1/2 Detect) or (2) enhanced standard of care (SOC) EID (off-site testing at a public laboratory).

Microsurgical training course for clinicians and scientists: a 10-year experience at the Münster University Hospital.

Background: Microsurgical techniques are an important part of clinical and experimental research. Here we present our step-by-step microsurgery training course developed at the Münster University Hospital. The goal of this course was to create a short, modular curriculum with clearly described and easy to follow working steps in accordance with the Guidelines for Training in Surgical Research in Animals by the Academy of Surgical Research.

Safety, acceptability, and pharmacokinetics of a monoclonal antibody-based vaginal multipurpose prevention film (MB66): A Phase I randomized trial.

Background: MB66 film is a multipurpose prevention technology (MPT) product with monoclonal antibodies (mAbs) against HIV-1 (VRC01-N) and HSV-1 and 2 (HSV8-N). The mAbs were produced by transient expression in Nicotiana benthamiana (N). We conducted a Phase I clinical trial to assess the safety, pharmacokinetics (PK), and ex vivo efficacy of single and repeated doses of MB66 when used intravaginally.

Isolation and light chain shuffling of a Plasmodium falciparum AMA1-specific human monoclonal antibody with growth inhibitory activity.

Background: Plasmodium falciparum, the parasite causing malaria, affects populations in many endemic countries threatening mainly individuals with low malaria immunity, especially children. Despite the approval of the first malaria vaccine Mosquirix™ and very promising data using cryopreserved P. falciparum sporozoites (PfSPZ), further research is needed to elucidate the mechanisms of humoral immunity for the development of next-generation vaccines and alternative malaria therapies including antibody therapy.

Tenofovir Diphosphate Concentrations in Dried Blood Spots From Pregnant and Postpartum Adolescent and Young Women Receiving Daily Observed Pre-exposure Prophylaxis in Sub-Saharan Africa.

Background: Intracellular tenofovir diphosphate (TFV-DP) concentration in dried blood spots (DBSs) is used to monitor cumulative pre-exposure prophylaxis (PrEP) adherence. We evaluated TFV-DP in DBSs following daily oral PrEP (emtricitabine 200 mg/tenofovir diphosphate 300 mg) among pregnant and postpartum adolescent girls and young women (AGYW).

Methods: Directly observed PrEP was administered for 12 weeks in a pregnancy (14-24 weeks' gestation, n = 20) and postpartum (6-12 weeks postpartum, n = 20) group of AGYW aged 16-24 years in sub-Saharan Africa.

A Novel Method for Antibiotic Detection in Milk Based on Competitive Magnetic Immunodetection.

The misuse of antibiotics as well as incorrect dosage or insufficient time for detoxification can result in the presence of pharmacologically active molecules in fresh milk. Hence, in many countries, commercially available milk has to be tested with immunological, chromatographic or microbiological analytical methods to avoid consumption of antibiotic residues. Here a novel, sensitive and portable assay setup for the detection and quantification of penicillin and kanamycin in whole fat milk (WFM) based on competitive magnetic immunodetection (cMID) is described and assay accuracy determined.

Acceptability, safety, and patterns of use of oral tenofovir disoproxil fumarate and emtricitabine for HIV pre-exposure prophylaxis in South African adolescents: an open-label single-arm phase 2 trial.

Background: HIV incidence among adolescents in southern Africa remains unacceptably high. Pre-exposure prophylaxis (PrEP) is an effective HIV prevention intervention but there are few data on its implementation among adolescents. We aimed to investigate the safety, feasibility, and acceptability of PrEP with oral tenofovir disoproxil fumarate and emtricitabine as part of a comprehensive HIV prevention package in an adolescent population in South Africa.