Modeling memory B cell responses in a lymphoid organ-chip to evaluate mRNA vaccine boosting.

Predicting the immunogenicity of candidate vaccines in humans remains a challenge. To address this issue, we developed a lymphoid organ-chip (LO chip) model based on a microfluidic chip seeded with human PBMC at high density within a 3D collagen matrix. Perfusion of the SARS-CoV-2 spike protein mimicked a vaccine boost by inducing a massive amplification of spike-specific memory B cells, plasmablast differentiation, and spike-specific antibody secretion.

Clonal succession after prolonged antiretroviral therapy rejuvenates CD8 T cell responses against HIV-1.

Human immunodeficiency virus 1 (HIV-1) infection is characterized by a dynamic and persistent state of viral replication that overwhelms the host immune system in the absence of antiretroviral therapy (ART). The impact of prolonged treatment on the antiviral efficacy of HIV-1-specific CD8 T cells has nonetheless remained unknown. Here, we used single-cell technologies to address this issue in a cohort of aging individuals infected early during the pandemic and subsequently treated with continuous ART.

Development of resident and migratory three-spined stickleback, Gasterosteus aculeatus.

The three-spined stickleback (Gasterosteus aculeatus) is a teleost fish and a model organism in evolutionary ecology, useful for both laboratory and natural experiments. It is especially valued for the substantial intraspecific variation in morphology, behaviour and genetics. Classic work of Swarup (1958) has described the development in the laboratory of embryos from a single freshwater population, but this was carried out at higher temperature than many stickleback would encounter in the wild and variation between populations was not addressed.

Corrigendum: Acute imidacloprid exposure alters mitochondrial function in bumblebee flight muscle and brain.

[This corrects the article DOI: 10.3389/finsc.2021.

Simplifying stable CHO cell line generation with high probability of monoclonality by using microfluidic dispensing as an alternative to fluorescence activated cell sorting.

Single cell cloning is a critical step for cell line development (CLD) for therapeutic protein production, with proof of monoclonality being compulsorily sought in regulatory filings. Among the different single cell deposition technologies, we found that fluorescence activated cell sorting (FACS) offers high probability of monoclonality and can allow selective enrichment of the producer cells. However, FACS instruments are expensive and resource-intensive, have a large footprint, require highly skilled operators and take hours for setup, thereby complicating the cell line generation process.

Second-generation antipsychotics and metabolic syndrome: a role for mitochondria.

Psychosis is a known risk factor for developing metabolic syndrome (MetS). The risk is even greater in patients who are taking second-generation antipsychotics (SGAs). SGAs exacerbate metabolic abnormalities and lead to a 3-fold increased risk of severe weight gain, type 2 diabetes, and cardiovascular disease in patients.

Engineered CHO cells as a novel AAV production platform for gene therapy delivery.

The Herpes simplex virus (HSV)-based platform for production of recombinant adeno-associated viral vectors (rAAVs) yields higher titers and increased percentage of full capsids when compared to the triple transient transfection (TTT) method. However, this platform currently faces two major challenges. The first challenge is the reliance on commercial media, sometimes supplemented with serum, leading to costly manufacturing and a high risk for introduction of adventitious agents.

Neutralization of African enterovirus A71 genogroups by antibodies to canonical genogroups.

Enterovirus 71 (EV-A71) is a major public health problem, causing a range of illnesses from hand-foot-and-mouth disease to severe neurological manifestations. EV-A71 strains have been phylogenetically classified into eight genogroups (A to H), based on their capsid-coding genomic region. Genogroups B and C have caused large outbreaks worldwide and represent the two canonical circulating EV-A71 subtypes.

Universal DNA methylation age across mammalian tissues.

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.

DNA methylation networks underlying mammalian traits.

Using DNA methylation profiles ( = 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels in subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors.

SARS-CoV-2 hijacks neutralizing dimeric IgA for nasal infection and injury in Syrian hamsters.

Prevention of robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) requires evaluation of IgA neutralizing antibodies. Here, we report the efficacy of receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1, B8-dIgA2 and TH335-dIgA1 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparable neutralization potency against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding.

Mitochondrial Haemoglobin Is Upregulated with Hypoxia in Skeletal Muscle and Has a Conserved Interaction with ATP Synthase and Inhibitory Factor 1.

The globin protein superfamily has diverse functions. Haemoglobin has been found in non-erythroid locations, including within the mitochondria. Using co-immunoprecipitation and in silico methods, we investigated the interaction of mitochondrial haemoglobin with ATP synthase and its associated proteins, including inhibitory factor 1 (IF1).

Accelerated cell culture process development and characterization for cilgavimab/tixagevimab (AZD7442) for the prevention and treatment of COVID-19.

The global COVID-19 pandemic ignited an unprecedented race to develop vaccines and antibody therapeutics. AstraZeneca's pursuit to provide AZD7442 (EVUSHELD), two long-acting, SARS-CoV-2 spike receptor binding domain-specific neutralizing monoclonal antibodies, to individuals at risk on highly accelerated timelines challenged our traditional ways of process development and spurred the rapid adoption of novel approaches. Conventional upstream development processes were replaced by agile strategies that combined technological advances and highly accelerated workflows.

The large numbers of minicolumns in the primary visual cortex of humans, chimpanzees and gorillas are related to high visual acuity.

Minicolumns are thought to be a fundamental neural unit in the neocortex and their replication may have formed the basis of the rapid cortical expansion that occurred during primate evolution. We sought evidence of minicolumns in the primary visual cortex (V-1) of three great apes, three rodents and representatives from three other mammalian orders: Eulipotyphla (European hedgehog), Artiodactyla (domestic pig) and Carnivora (ferret). Minicolumns, identified by the presence of a long bundle of radial, myelinated fibers stretching from layer III to the white matter of silver-stained sections, were found in the human, chimpanzee, gorilla and guinea pig V-1.

The Spike-Stabilizing D614G Mutation Interacts with S1/S2 Cleavage Site Mutations To Promote the Infectious Potential of SARS-CoV-2 Variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remained genetically stable during the first 3 months of the pandemic, before acquiring a D614G spike mutation that rapidly spread worldwide and then generating successive waves of viral variants with increasingly high transmissibility. We set out to evaluate possible epistatic interactions between the early-occurring D614G mutation and the more recently emerged cleavage site mutations present in spike of the Alpha, Delta, and Omicron variants of concern. The P681H/R mutations at the S1/S2 cleavage site increased spike processing and fusogenicity but limited its incorporation into pseudoviruses.

Quantitative Proteomics and Network Analysis of Differentially Expressed Proteins in Proteomes of Icefish Muscle Mitochondria Compared with Closely Related Red-Blooded Species.

Antarctic icefish are extraordinary in their ability to thrive without haemoglobin. We wanted to understand how the mitochondrial proteome has adapted to the loss of this protein. Metabolic pathways that utilise oxygen are most likely to be rearranged in these species.

A close shave: How SARS-CoV-2 induces the loss of cilia.

Wang et al. report in this issue (2022. J.

Proteomic analysis of the ATP synthase interactome in notothenioids highlights a pathway that inhibits ceruloplasmin production.

Antarctic notothenioids have unique adaptations that allow them to thrive in subzero Antarctic waters. Within the suborder Notothenioidei, species of the family Channichthyidae (icefish) lack hemoglobin and in some instances myoglobin too. In studies of mitochondrial function of notothenioids, few have focused specifically on ATP synthase.

Enhanced Cross-Reactive and Polyfunctional Effector-Memory T Cell Responses by ICVAX-a Human PD1-Based Bivalent HIV-1 Gag-p41 Mosaic DNA Vaccine.

Vaccine-induced protective T cell immunity is necessary for HIV-1 functional cure. We previously reported that rhesus PD1-Gag-based DNA vaccination sustained simian-human immunodeficiency virus (SHIV) suppression by inducing effector-memory CD8 T cells. Here, we investigated a human PD1-Gag-based DNA vaccine, namely, ICVAX, for clinical translation.