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An immune signature characterized by activated antigen-specific CD8 T cells is identified in the brain and blood of mice with amyotrophic lateral sclerosis-4 (ALS4), suggesting that the immune system is involved in ALS4 neurodegeneration.

The crystal structure of the Frizzled 4 receptor transmembrane domain is reported to a resolution of 2.4 Å in a ligand-free state.

Here, the authors identify B lymphocyte antigen CD20 as a marker for HIV-infected T cells and provide evidence for the potential use of anti-CD20 antibodies in combination with latency reversing agents for depletion of viral reactivated CD4 T cells in patients on antiretroviral therapy.

Using cervical explant models and cervical tissue from ART-suppressed HIV⁺ women, the authors here show that resident memory T cells (T_RM) in the cervical mucosa are preferentially infected and harbor more viral DNA, RNA and protein than non-T_RM, suggesting that T_RM may serve as viral reservoir in the cervical mucosa.

Stabilization of an active and inactive conformation of the β₂-adrenergic receptor by allosteric nanobodies reveals differential ligand-dependent regulation of receptor states to control G-protein-coupled receptor activation.

A biomedical application of a nanoconjugate is now shown in vivo. Sealed carbon nanotubes filled with a radionuclide are functionalized with carbohydrate molecules without prompting cargo release. The stability and biocompatibility of the capsule together with the radioactive payload enables in vivo imaging of the system and delivery of a high-density radiodose.

Binding modes and molecular mechanisms of several allosteric modulators of a prototypical G-protein-coupled receptor are revealed using atomic-level simulations and validated by the rational design of a modulator with substantially altered effects.

Tropomyosin receptor kinase B (TrkB), encoded by the neurotrophic tyrosine receptor kinase 2 (NTRK2) gene, exhibits intricate splicing patterns and post-translational modifications. Here, the authors perform whole gene and transcript-level analyses and report the TrkB.T1 splice variant enhances PDGF-driven gliomas in vivo and augments PI3K signaling cascades in vitro.

The crystal structure of CCR2 chemokine receptor in a complex with two different antagonists—one orthosteric the other allosteric—which functionally cooperate to inhibit CCR2.

Biological applications of x-ray fluorescence (XRF) imaging are currently limited to mapping naturally occurring elements in tissues. Here, the authors encapsulate toxic elements in functionalized single walled nanotubes, and use them as non-toxic XRF contrast agents for imaging specific cellular organelles.

Serial femtosecond crystallography of the human δ-opioid receptor in complex with an endomorphin-derived peptide reveals interactions that are important for understanding the pharmacology of opioid peptides and developing analgesics with reduced side effects.

By examining Latin American individuals of mixed European, Native American and African ancestry, Adhikari et al. identify novel loci influencing various features of facial and scalp hair. The study also provides experimental evidence that one of the implicated genes (PRSS53) is expressed in the hair follicle and that the top associated variant alters processing of this enzyme.

It remains incompletely understood how cytokines shape T_H1 cell differentiation to central memory T (T_CM) and follicular T helper (T_FH) cells. Here the authors show that T_H1 cells can co-initiate the expression of both T_FH and T_CM gene programs and that IL-7 signalling represses T_FH-associated but not T_CM-associated genes.

Here, the authors show that reticulocytes derived from immortalized erythroblasts support invasion and development of Plasmodium falciparum and use CRISPR-mediated gene knockout and complementation of an invasion receptor to demonstrate utility of this model system for research in malaria invasion.

Analysis of the InvaCost database shows that the costs of biological invasions have markedly increased between 1970 and 2017 and show no sign of slowing down, highlighting the importance of evidence-based and cost-effective management actions.

Different neoadjuvant therapies have been proposed to improve immunotherapy for cancer treatment. Here, the authors perform a phase Ib clinical trial where an agonist OX40 antibody provided prior to surgery is well tolerated and increases proliferation and activation of tumor antigen-specific T cells in head and neck cancer patients.

The shape of the pinna varies widely in the general human population but the genetic basis of this variation is unknown. Here Adhikari et al. conduct a genome-wide association study in Latin Americans and discover seven gene regions influencing pinna morphology, including EDAR and TBX15.

Genome-wide data from 400 individuals indicate that the initial spread of the Beaker archaeological complex between Iberia and central Europe was propelled by cultural diffusion, but that its spread into Britain involved a large-scale migration that permanently replaced about ninety per cent of the ancestry in the previously resident population.

Single-molecule FRET experiments with human A2A adenosine receptor in its apo and agonist-bound states in lipid nanodiscs provide insights into its conformational dynamics and activation.

Yu Chen and colleagues describe a new constitutively activating mutation in the G-protein-coupled receptor CYSLTR2 in patients with uveal melanoma lacking mutations in the G-protein-encoding genes GNAQ and GNA11. They find that expression of the mutant leads to increased expression of melanocyte-lineage signature genes and promotes tumorigenesis in vivo.

The epidermal growth factor receptor (EGFR) signalling is regulated at multiple levels. Here the authors show that the importin RanBP6 acts as a tumor suppressor in Glioblastoma and  regulates EGFR signalling through promoting translocation of STAT3 to the nuclei and repressing EGFR transcription.

In this study, the authors use a dataset of stable isotope compositions of otoliths from Atlantic bluefin tuna to infer the thermal sensitivity of metabolic performance in their first year of life. They then assess the likely trajectories of tuna production until end century under differing emission scenarios in their two main spawning grounds, the western Atlantic and Mediterranean Sea.

Pigmentation variation in humans is influenced by complex genetic architecture in different populations. Here, the authors perform a genome-wide association analysis involving > 6,000 Latin Americans for pigmentation of skin and eyes, and identify known and novel genetic associations.

Analysing spatial association networks among >300 terrestrial and aquatic assemblages, the authors find that the majority of negative associations involve abundant species. In contrast, rare species form mostly positive associations, potentially explaining their persistence in natural communities.

The International Mouse Phenotyping Consortium (IMPC) aims to identify the function of all protein-coding genes in the mouse genome. Hayday and colleagues leverage 530 knockout lines from the IPMC to develop the 3i Project, which immunophenotypes mice and leads to the identification of new and unexpected gene influences on immune function and on the structural organization of the immune system.

Cellular metabolism seems to dictate immune responses. Weinmann and colleagues show that the transcription factor Bcl-6 opposes the action of c-Myc and Hif-1α to suppress expression of genes encoding key glycolytic enzymes and transporters.