Repertoire

PURPOSE: Auto-antibodies (auto-abs) to type I interferons (IFNs) have been identified in patients with life-threatening coronavirus disease 2019 (COVID-19), suggesting that the presence of auto-abs may be a risk factor for disease severity. We therefore investigated the mechanism underlying COVID-19 exacerbation induced by auto-abs to type I IFNs. METHODS: We evaluated plasma from 123 patients with COVID-19 to measure auto-abs to type I IFNs. We performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells from the patients with auto-abs and conducted epitope mapping of the auto-abs...

Homology in vertebrate body plans is traditionally ascribed to the high-level conservation of regulatory components within the genetic programs governing them, particularly during the "phylotypic stage." However, advancements in embryology and molecular phylogeny have unveiled the dynamic nature of gene repertoires responsible for early development. Notably, the Nodal and Lefty genes, members of the transforming growth factor-beta superfamily producing intercellular signaling molecules and crucial for left-right (L-R) symmetry breaking, exhibit distinctive features within their gene repertoires...

Dietary analysis in wildlife is fundamental for understanding their flexible response to seasonal changes and developing effective conservation management measures. Taihangshan macaque ( Macaca mulatta tcheliensis ) is the northernmost population of rhesus macaque, currently only distributed in the southern Mt. Taihangshan area. This area belongs to a semi-arid region resulting in limited plant food availability for Taihangshan macaques, with seasonal variation. Herein, we used a chloroplast trnL DNA metabarcoding approach to identify the plant diet diversity and composition from 100 fecal samples of Taihangshan macaque in four seasons (spring, summer, autumn, and winter) from 2020 to 2021...

The biomolecular corona, a complex layer of biological molecules, envelops nanoparticles (NPs) upon exposure to biological fluids including blood. This dynamic interface is pivotal for the advancement of nanomedicine, particularly in areas of therapy and diagnostics. In situ analysis of the biomolecular corona is crucial, as it can substantially improve our ability to accurately predict the biological fate of nanomedicine and, therefore, enable development of more effective, safe, and precisely targeted nanomedicines...

INTRODUCTION: Direct oral anticoagulants (DOACs) reflect anticoagulation agents given to treat or prevent thrombosis, having largely replaced vitamin K antagonists (VKAs) such as warfarin. DOACs are given in fixed daily doses and generally do not need monitoring. However, there may be a variety of reasons that justify measurement of plasma DOAC levels in individual patients. METHODS: We report updated findings for DOAC testing in our geographic region, using recent data from the RCPAQAP, an international external quality assessment (EQA) program, currently with some 40-60 participants in each of the different DOAC (rivaroxaban, apixaban, dabigatran) modules, to assess laboratory performance in this area...

Lupus erythematosus (LE) is a heterogeneous, antibody-mediated autoimmune disease. Isolate discoid LE (IDLE) and systematic LE (SLE) are traditionally regarded as the two ends of the spectrum, ranging from skin-limited damage to life-threatening multi-organ involvement. Both belong to LE, but IDLE and SLE differ in appearance of skin lesions, autoantibody panels, pathological changes, treatments, and immunopathogenesis. Is discoid lupus truly a form of LE or is it a completely separate entity? This question has not been fully elucidated...

PURPOSE: To provide a comprehensive update on the different techniques and outcomes of contemporary Single-Port (SP) Robotic Radical Prostatectomy (RARP) approaches. METHODS: A literature review was performed to identify cohort studies that have utilized the purpose-built SP robotic platform (Intuitive Surgical Inc., Sunnyvale, California) for RARP. All published approaches of SP-RARP were included in our review. Baseline clinical, perioperative, and postoperative oncological and functional outcomes were collected from the included studies...

The immune escape of Omicron variants significantly subsides by the third dose of an mRNA vaccine. However, it is unclear how Omicron variant-neutralizing antibodies develop under repeated vaccination. We analyze blood samples from 41 BNT162b2 vaccinees following the course of three injections and analyze their B-cell receptor (BCR) repertoires at six time points in total. The concomitant reactivity to both ancestral and Omicron receptor-binding domain (RBD) is achieved by a limited number of BCR clonotypes depending on the accumulation of somatic hypermutation (SHM) after the third dose...

BACKGROUND: Rational design of synthetic phage-displayed libraries requires the identification of the most appropriate positions for randomization using defined amino acid sets to recapitulate the natural occurrence. The present study uses position-specific scoring matrixes (PSSMs) for identifying and randomizing Camelidae nanobody (VHH) CDR3. The functionality of a synthetic VHH repertoire designed by this method was tested for discovering new VHH binders to recombinant coagulation factor VII (rfVII)...

N6-methyladenosine (m6 A) is a mRNA modification with important roles in gene expression. In African trypanosomes, this post-transcriptional modification is detected in hundreds of transcripts and it affects the stability of the variant surface glycoprotein (VSG) transcript in the proliferating blood stream form. However, how the m6 A landscape varies across the life cycle remains poorly defined. Using full-length, non-fragmented RNA, we immunoprecipitated and sequenced m6 A-modified transcripts across three life cycle stages of Trypanosoma brucei - slender (proliferative), stumpy (quiescent), and procyclic forms (proliferative)...

The remarkable efficacy of Epstein-Barr virus (EBV) specific T-cells for the treatment of post-transplant lymphomas (PTLD) has not been reproduced for EBV+ malignancies outside the transplant setting. This is due in part to the heterogeneous expression and poor immunogenicity of the viral antigens expressed, namely LMPs 1 and 2, EBNA1, and BARF1 (type-2 (T2) latency). However, EBV lytic cycle proteins are also expressed in certain EBV+ malignancies, and since several EBV lytic cycle proteins are abundantly expressed, have oncogenic activity, and likely contribute to malignancy, we sought and identified viral lytic-cycle transcripts in EBV+ Hodgkin's lymphoma biopsies...

BACKGROUND/AIMS: The physiological phenotype of individuals can influence and shape real-life phenomena in that it can contribute to the development of specific characteristics that can affect the immune response to specific stimuli. In this study we aimed to understand whether the sphingosine/sphingosine-1-phoshate (S1P) axis can modulate the immunotype of circulating cells. METHODS: To pursue this goal, we performed bioinformatic analyses of public datasets. RESULTS: The transcriptomic profile of healthy subjects of GSE192829 dataset identified two clusters with different transcriptional repertoire...

Phosphorylation is a major constituent of the CTD code, which describes the set of post-translational modifications on 52 repeats of a YSPTSPS consensus heptad that orchestrates the binding of regulatory proteins to the C-terminal domain (CTD) of RNA polymerase II. Phospho-specific antibodies are used to detect CTD phosphorylation patterns. However, their recognition repertoire is underexplored due to limitations in the synthesis of long multiphosphorylated peptides. Herein, we describe the development of a synthesis strategy that provides access to multiphosphorylated CTD peptides in high purity without HPLC purification for immobilization onto microtiter plates...

BACKGROUND: High-throughput sequencing is a powerful tool that is extensively applied in biological studies. However, sequencers may produce low-quality bases, leading to ambiguous bases, 'N's. PCR duplicates introduced in library preparation are conventionally removed in genomics studies, and several deduplication tools have been developed for this purpose. Two identical reads may appear different due to ambiguous bases and the existing tools cannot address 'N's correctly or efficiently...

Single-cell T cell and B cell antigen receptor-sequencing data analysis can potentially perform in-depth assessments of adaptive immune cells that inform on understanding immune cell development to tracking clonal expansion in disease and therapy. However, it has been extremely challenging to analyze and interpret T cells and B cells and their adaptive immune receptor repertoires at the single-cell level due to not only the complexity of the data but also the underlying biology. In this Review, we delve into the computational breakthroughs that have transformed the analysis of single-cell T cell and B cell antigen receptor-sequencing data...

OBJECTIVES: We explored the role of metabolic hormones and the B-cell repertoire in the association between nutritional status and vaccine responses. METHODS: In this prospective cohort study, nested within a larger randomized open-label trial, 211 South African children received two doses of measles vaccine and two or three doses of pneumococcal conjugate vaccine (PCV). Metabolic markers (leptin, ghrelin and adiponectin) and distribution of B-cell subsets (n = 106) were assessed at 18 months of age...

The enzymatic repertoire of starter cultures belonging to the Lactococcus genus determines various important characteristics of fermented dairy products but might change in response to the substantial environmental changes in the manufacturing process. Assessing bacterial proteome adaptation in dairy and other food environments is challenging due to the high matrix-protein concentration and is even further complicated in particularly cheese by the high fat concentrations, the semi-solid state of that matrix, and the non-growing state of the bacteria...

Previous mass spectrometry (MS)-based global proteomics studies have detected a combined total of 86% of all Treponema pallidum proteins under infection conditions (in vivo-grown T. pallidum ). Recently, a method was developed for the long-term culture of T. pallidum under in vitro conditions (in vitro-cultured T. pallidum ). Herein, we used our previously reported optimized MS-based proteomics approach to characterize the T. pallidum global protein expression profile under in vitro culture conditions. These analyses provided a proteome coverage of 94%, which extends the combined T...

The jawless vertebrates (agnathans or cyclostomes) are ancestral animals comprising lampreys and hagfishes, which are the only extant representatives. They possess an alternative adaptive immune system (AIS) that uses leucine-rich repeats (LRR)-based variable lymphocyte receptors (VLRs) instead of the immunoglobulin (Ig)-based antigen receptors of jawed vertebrates (gnathostomes). The five VLR types (VLRA-VLRE) are expressed on agnathan lymphocytes and functionally resemble lymphocyte antigen receptors. In particular, VLRB is functionally similar to the B cell receptor expressed and secreted by B-like lymphocytes as VLRB antibodies that bind antigens with high affinity and specificity...

AIM: To implement a culturally-adapted screening program aimed to determine the ability of infant motor repertoire to predict early neurodevelopment on the Hammersmith Infant Neurological Examination (HINE) and improve Australian First Nations families' engagement with neonatal screening. METHODS: A prospective cohort of 156 infants (55 % male, mean (standard deviation [SD]) gestational age 33.8 (4.6) weeks) with early life risk factors for adverse neurodevelopmental outcomes (ad-NDO) participated in a culturally-adapted screening program...