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CRISPR-mediated gene knockout and activation are used to identify molecules in cancer cells and macrophages that regulate antibody-dependent cancer cell phagocytosis.

De novo designed interleukin-4 mimetics were engineered that induce biased signaling activation and exhibit high thermal stability. These mimetics offer insight into cytokine signaling and can be directly incorporated into 3D-printed biomaterials

The ligandability of the human proteome can be expanded using covalent chemistry. A multi-tiered chemical proteomic strategy now provides in-depth maps of tryptoline acrylamide–protein interactions in cancer cells. This platform afforded the discovery of stereoselective covalent ligands for hundreds of human proteins, including compounds that disrupt protein–protein interactions regulating the cell cycle.

Single cell RNA sequencing generates short reads from one end of a template, providing incomplete transcript coverage and limiting identification of diverse sequences such as antigen receptors. Here the authors combine long read nanopore sequencing with short read profiling of barcoded libraries to generate full-length antigen receptor sequences.

IgG molecules are glycosylated at a conserved asparagine residue of their constant region, and this modification is essential for the effector functions of their soluble form, such as complement activation and binding to Fcɣ receptors. Here authors show that in a model B-cell line, neither the expression nor the function of the membrane-bound form of IgG depend on glycosylation.

Chimeric antigen receptor T cells represent a breakthrough treatment in hematologic malignancies, but insufficient level of cytotoxicity and persistence of T cells might compromise success. Authors show here that a recombinant long acting form of interleukin-7 enhances proliferation, persistence and cytotoxicity of the engineered T cells, resulting in long term disease remission.

The creation and application of engineered constructs specific for one of two IL-4 coreceptors explain how immune signaling is limited by coreceptor concentration and establish specific roles for type II receptor–specific signaling in dendritic cell differentiation.

Incorporating bioorthogonally-modified amino acids into newly synthesized proteins allows studying the nascent proteome, but current methods often require special conditions or are toxic to cells. Here, the authors develop a method that uses β-ethynylserine to label nascent proteins under standard conditions without harming cells.

A gene therapy method using AAV can help deliver HIV-fighting antibodies long-term, but the body often rejects them. Here the authors show that a short course of the drug rapamycin helps prevent host anti-drug antibody responses, showing successful antibody delivery in mice and monkeys.

Sojka et al. analyse the transcriptomic and epigenomic landscape of human astrocyte maturation and identify an epigenetically regulated intermediate state associated with aberrant development in glioblastoma.

Human B cells can be edited to produce custom heavy-chain antibodies while allowing the cells to respond to immunization with a matched antigen.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

Understanding the mechanisms behind clinical immunity to malaria is crucial for developing effective interventions. Here, the authors demonstrate that clinical immunity to Plasmodium vivax develops rapidly after a single controlled human malaria infection, reducing inflammatory responses and protecting against symptoms, while not significantly affecting parasite load.

Here, Murray-Nerger et al use a genome-wide CRISPR/Cas9 screen to show that the nuclear protein SFPQ suppresses lytic reactivation of Epstein-Barr virus by promoting the expression and accumulation of linker histone H1 on the viral genome.

Antibodies against SARS-CoV-2 continue to evolve 6 to 12 months after infection in patients who have recovered from COVID-19, increasing in potency and breadth with time.

In contrast to direct-targeting monoclonal antibodies, low affinity confers agonistic monoclonal antibodies with more potency.

Genome-wide association meta-analyses of attention-deficit/hyperactivity disorder symptom measures and clinical diagnoses identify new risk loci, highlight putative effector genes and yield improved polygenic risk scores.

KIR2DL2 and KIR2DL3 are two inhibitory members of the killer-cell immunoglobulin-like receptors (KIR) family that share a common HLA-I preference in binding HLA from the C1 group. However, it is still unclear to what extent binding and function is equivalent between KIR2DL2 and 2DL3. Here, the authors present the crystal structures of KIR2DL2 and 2DL3 in complex with HLA-C*07:02 and observe differences in HLA-C recognition between KIR2DL2 and 2DL3, which correlates with differences in HLA-C binding preference as they show with mutagenesis and binding studies.

The enzyme activation-induced deaminase (AID) promotes antibody diversification after B-cell activation, by causing mutagenic lesions on DNA. Hence, AID's actions must be tightly controlled. AID is found mainly in the cytosolic compartment and contains a known nuclear export sequence. Now a structural nuclear localization sequence and a cytosolic-retention determinant are identified in AID and found to have a role in localization and function.

Linking transcription factors with disease loci implicates EBNA2, encoded by Epstein–Barr virus, in autoimmune diseases. Applying the method more widely identifies associations for hundreds of transcription factors, illuminating disease mechanisms.

Structural changes in the capping groups of inverted cyanoacrylamide-based kinase inhibitors resulted in alterations in residence time, with some compounds exhibiting sustained pharmacological effects in vivo.

Discovery and exploitation of inherent reaction features of chlorofluoroacetamide (CFA) as a warhead such as low off-target activity and reversible reactivity with cysteine enable specific covalent inhibition of targeted kinases.

To fully understand the potential shortcomings of SARS-CoV-2 vaccination, it is necessary to delineate the properties of the antibodies elicited, during immunization, and also infection. Through investigation of the SARS-CoV-2 spike-reactive B cell repertoire, authors identify following infection, a subset of B cells enriched and almost exclusively target a non-neutralizing S2 epitope present in aberrant forms.

Hypoimmune gene editing in human pluripotent stem cells (hPSCs) provides a promising platform for cellular therapies. Here, the authors report that CRISPR mediated deletion of ICAM-1 in hPSC-derived grafts reduces immune cell adhesion, dampens T cell activation, and protects against immune rejection.

ABPP combined with quantitative MS enabled identification of specific on- and off-targets of covalent kinase inhibitors. Modifications to inhibitors that alter specificity beyond a defined window can promote kinase-independent toxicity.

N-myristoyltransferases (NMTs) target many signaling proteins to membranes. Here the authors show an NMT inhibitor named PCLX-001 selectively kills lymphoma cells by shutting down their main survival signaling pathway and offers an additional treatment strategy for lymphoma patients.

Here, the authors find that BMAL1, best known for controlling the body clock, partners with TRIM28 in naïve pluripotent stem cells to repress retrotransposons.

The authors report Acheulean hominin occupation of eastern Britain during glacial marine isotope stages 17–16 and again in glacial marine isotope stage 12 via stone tools in sediments dated to 712,000 to 424,000 years ago.

Leukocytes are coated with glycans that modulate immune function through interactions with lectins. Here, the authors characterize the N-glycan repertoire of human tonsillar B cells. They report that Gal-9 is an intrinsic regulator of B cell activation that may differentially modulate BCR signaling at steady state and within germinal centers due to expression of I-branched glycans.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

A deep chemical proteomic investigation of diverse aminophilic electrophiles has identified ligandable lysines across a wide range of human proteins. The proteins cover different functional and structural classes, and the aminophilic electrophiles include compounds that disrupt protein–protein and protein–RNA interactions. This dataset provides a proteome-wide atlas of lysine-reactive chemistry.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

A general approach to mask antibodies using coiled-coil domains improves anti-tumor therapeutic efficacy.

Artis and colleagues show that enteric neurons produce CGRP-related ADM2 to promote intestinal tissue-protective functions in ILC2s.

A new computational method for design of pseudosymmetric self-assembling protein nanomaterials has resulted in purification of cage-like protein assemblies containing 960 subunits with a diameter of 96 nm.

The LHCb experiment at CERN has observed significant asymmetries between the decay rates of the beauty baryon and its CP-conjugated antibaryon, thus demonstrating CP violation in baryon decays.