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Genetic vaccines can be quickly formulated and tested but require multiple administrations to generate a durable antibody response, as in the case of protein subunit vaccines. Here SpyTag/SpyCatcher technology is used to develop a genetic vaccine encoding antigen-displaying capsid virus-like particles to enhance the immune response against the Pfs25 malaria antigen.

Kucharska, Ivanochko and Hailemariam and colleagues solved cryo-EM structures of Pfs48/45, needed for Plasmodium falciparum development, with potent antibodies. The work revealed conformational epitopes, with implications for design of therapies against malaria.

Delivering immunomodulatory compounds to myeloid cells can activate innate immunity for cancer immunotherapy. Here the authors design a polymersome-based nanocarrier for delivering β-glucan to red pulp myeloid cells in the spleen and show that their strategy achieves tumour growth reduction in a melanoma model.

The human cytomegalovirus protein US11 downregulates host immune responses by redirecting HLA class I molecules for endoplasmic reticulum-associated protein degradation. Using a high-coverage genome-wide shRNA screen, the authors identify TMEM129 as an E3 ubiquitin ligase essential for this process.

Type 2 diabetes (T2D) is a heterogeneous disorder characterized by insulin resistance and impaired insulin secretion. Here Axelssonet al. show that Sox5, which is reduced in diabetes, regulates a set of differentially expressed genes in T2D and its genetic and pharmacological induction improves insulin secretion by diabetic islets.

Wendrich, Gallant and colleagues find that USP53 and USP54 are active deubiquitinases, with USP53 removing ubiquitin chains from substrate proteins in a chain-linkage-directed manner, and provide biochemical and structural insights into their mechanism, cellular substrates and disease implications.

A multimodal imaging approach using a high-density lipoprotein-derived nanotracer with a perfluoro-crown ether payload enables myeloid cell dynamics to be studied in vivo in mouse models of atherosclerosis and myocardial infarction.

Warming affects forest soil denitrification and nitrogen losses. The authors show that temperature enhances nitrous oxide and dinitrogen but varies by soil; temperature sensitivities are similar across soils but are higher for dinitrogen, suggesting complete denitrification in a warmer climate.

Myeloid cells contribute to the tumor microenvironment of thyroid cancers, but their functional relevance is lesser known. Here authors show that myeloid cells infiltrating non-medullary thyroid carcinomas upregulate their antigen presentation-related genes, release less cytokines and over-produce reactive oxygen species, with transcriptional changes already present in extra-tumoral myeloid cells.

The mechanisms underpinning the variability in methylphenidate’s effects on cognition remain unclear. Here, the authors show that such effects reflect changes in striatal dopamine-related output gating of task-relevant cortical signals, and that these changes depend on baseline dopamine synthesis capacity.

CD47 is a promising new target in cancer immunotherapy and recently the pro-phagocytic signal SLAMF7 has been shown to have a crucial role in phagocytosis induced by CD47-blocking antibody in hematological tumors. In this study, the authors demonstrate that SLAMF7 expressed by cancer cells is not required for phagocytosis suggesting that, in contrast to CD47 expression, SLAMF7 should not be used as selection criterion for CD47-targeted therapy.

Detecting proteins and post-translational modifications is important for drug screens, but the number of proteins measurable simultaneously is limited. Here the authors use antibodies tagged with DNA barcodes and high-throughput sequencing to detect up to 70 (phospho-)proteins in stem cells.

Functional human atrial myocytes derived from foetal atrial tissue can be massively expanded via a conditional cell-immortalization method, and used in in vitro models of atrial fibrillation.

A large-scale single-cell transcriptomic atlas of the non-human primate Macaca fascicularis encompasses over 1 million cells from 45 adult tissues.

Peptides presented to cytotoxic T lymphocytes are typically generated by proteasome action. Kessler and colleagues show that the cytosolic endopeptidases nardilysin and thimet oligopeptidase generate the C termini of tumor-relevant epitopes.

Pigs are important large animal models for biomedical research. Here, the authors construct a single-cell landscape of pig tissues, unravelling the phenotypic heterogeneity of blood endothelial cells in adipose tissues and the evolutionally conserved regulons of microglia in brains.

David van Heel and colleagues report results of a large genome-wide association study of celiac disease. Most of the associated loci contain genes with immune functions, and over half harbor risk variants that are correlated with variation in cis gene expression.

The hypothalamus is a brain region rich in functionally segregated neurons. Here Romanov and colleagues use single-cell RNA sequencing to distinguish 62 neuronal subtypes and define their neuropeptide and neurotransmitter makeup. They then show that onecut-3-containing dopamine neurons populate the periventricular area and are wired into the circadian circuitry.

With acquisition the most likely exit for today's biotech investors, it pays to keep current with the tastes of pharmaceutical firms when launching a venture.

Will your orphan drug startup draw acquisition interest?

Pre-clinical cell culture models capturing the heterogeneity of childhood kidney tumours are limited. Here, the authors establish and characterise an organoid biobank of tumour and matched normal organoid cultures from over 50 children with different subtypes of kidney cancer.

This work shows that treatments used for acute myeloid leukaemia and targeted therapies could be used for early T-cell precursor acute lymphoblastic leukaemia.

The etiology of acute biliary pancreatitis is complex and, as outlined in this Review, involves multiple factors including anatomy, genetics, gallstones, bile and pancreatic juice exclusion and ampullary obstruction. In this article, the authors also discuss the importance of establishing a biliary origin in acute pancreatitis and how both serum biochemistry and imaging investigations are vital to confirm a diagnosis of acute biliary pancreatitis.

Illumination of thin liquid-crystal polymer films that contain azobenzene derivatives with short thermal relaxation times induces a continuous wave motion throughout the films, owing to a feedback loop driven by material self-shadowing.

Disorders caused by abnormal β-globin, such as β-thalassaemia, are the most prevalent inherited disorders worldwide. For treatment, many patients are dependent on blood transfusions; thus far the only cure has involved matched transplantation of haematopoietic stem cells. Here it is shown that lentiviral β-globin gene transfer can be an effective substitute for regular transfusions in a patient with severe β-thalassaemia.

A carcinogen-induced mouse tumour model is used here to show that mutant tumour-specific antigens are targets for CD8⁺ T-cell responses, mediating tumour regression after checkpoint blockade immunotherapy, and that these antigens can be used effectively in therapeutic vaccines; this advance potentially opens the door to personalized cancer vaccines.

The International Childhood Cancer Outcome Project group, involving survivors and other relevant stakeholders, develop a set of core outcomes to measure the quality of care for 17 types of childhood cancers.

The GenoMEL consortium reports a genome-wide association study of melanoma based on imputation and identifies a variant in the FTO gene associated with susceptibility to melanoma.