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Differentiating DCs express ALDH1A2, which produces retinoic acid and suppresses DC activity. Blocking this pathway with a new inhibitor, KyA33, enhances immune responses and boosts the effectiveness of DC cancer vaccines in mouse models.

Proteomic characterization of varicella-zoster virus–host protein interactions and infection-induced changes in a neuronal cell line identifies potential targets for drug discovery and molecular insights into severe disease.

The authors identify a DNA-protein crosslink (DPC) repair pathway orchestrated by poly-ADP-ribosylation. In this process, PARP1 PARylates the DPC, marking it for removal by proteolysis. Consequently, PARP1 facilitates the repair of DPCs located next to DNA breaks, such as topoisomerase 1-DPCs.

Multi-omics profiling of monkeypox virus infected human primary cells was used to characterize the infection process and to prioritize potential antiviral drug targets.

Multi-omics profiling of effects of SARS-CoV-2 and SARS-CoV on A549, a lung-derived human cell line, produces a dataset enabling identification of common and virus-specific mechanisms of infection.

A recent study, published in Nature, identifies the methylcytosine dioxygenase 2 (TET2) as an epigenetic modifier that is regulated in response to glucose availability and mechanistically links higher cancer susceptibility in patients with diabetes to high blood glucose levels.

Colletotrichum tofieldiae is a beneficial root endophyte, whereas the closely related C. incanumis pathogenic. Here the authors compare the genomes and transcriptomes during host plant interaction and demonstrate that the host plant can respond differently to the beneficial endophyte according to phosphate status.

The identification of molecular biomarkers in cancer of unknown primary site (CUP) cases may enable the improvement of prognosis in these patients. Here, the authors integrate whole genome/exome, transcriptome and methylome data in 70 CUP patients, recommend therapies based on their analysis and report clinical outcome data.

Here the authors present improved intramolecular sensors for β-arrestin2 and 1, which enable assessment of conformational changes of both isoforms in living cells. These reveal that the same GPCR induces differential conformational rearrangements that determine the functional diversity between the two β-arrestins.

Disturbances in IP3 receptor-mediated release of Ca²+ from the endoplasmatic reticulum are associated with neurodegenerative disease. Here, the authors identify in four families with hereditary spastic paraplegia biallelic mutations in RNF170 that associate with increased basal levels of IP3 receptors.

Excision of integrated HIV proviruses derived from most HIV-1 strains is achieved with a recombinase evolved in vitro.

Chronic infections are commonly established in the liver. Knolle and colleagues show that cytotoxic T lymphocyte responses can be boosted by TLR-mediated induction of myeloid aggregates (iMATES).

Cushing’s adenoma is associated with somatic mutations in the gene encoding the Cα subunit of protein kinase A. Calebiro et al.reveal that these mutations increase protein kinase A activity by preventing proper assembly of the protein kinase A holoenzyme.

mmPEGC-C22 is a nonsterol glycolipid involved in early Caenorhabditis elegans larval development that can rescue the growth-arrest phenotype caused by sterol deficiency and is controlled by TGF-β to help mobilize internal sterol pools.

A liver-intrinsic mechanism is presented that suppresses effective anti-hepatitis virus B responses in mice and humans by rendering virus-specific CD8 T cells refractory to activation causing loss of effector functions.

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.

Nanobodies (Nbs) coupled to organic dyes are increasingly used for super-resolution cell imaging, but producing gene-specific Nbs is time-consuming. Here the authors present a peptide-tag/Nb combination for dSTORM imaging which can be easily adapted to different targets in fixed and live cells.

Certain bovine antibodies have ultra-long long complementarity-determining regions (CDRs) that contain a knob for antigen interaction, which is connected to the antibody through a stalk. Here, the authors combine biophysical experiments and MD simulations and show that the stalk length is critical for the folding and stability of these antibodies. The authors also demonstrate that ultra-long bovine CDRs can be grafted into human antibodies, and furthermore show that de novo designed mini-domains that bind to the SARS-CoV-2 spike protein with high affinity can be integrated as a knob in ultra-long CDRs in bovine and human antibodies, which neutralize SARS-CoV-2.

A phase 1 dose-escalating trial evaluating CD70 inhibition in combination with hypomethylating therapy results in the elimination of leukemia stem cells and achieves clinical activity in untreated patients with acute myeloid leukemia.

Neither CDK4/6 inhibitors nor oncolytic adenoviruses show high efficiency as monotherapy in the treatment of cancer. Authors show here that when combined, CDK4/6 inhibitors deplete Retinoblastoma protein levels, which leads to more efficient virus replication and an increase in oncolytic virus-producing cancer cells and thus to efficient anti-tumor response in mouse xenograft sarcoma models.

The role of reactive oxygen species (ROS) in signalling and specific targets is not fully understood. Here the authors perform a global proteomic analysis to delineate the yeast redoxome and show that increased levels of intracellular ROS caused by dysfunctional mitochondria decrease global protein synthesis.

Optimized guide RNAs improve RNA editing with endogenous enzymes.

Genome editing using designer nucleases such as TALENs or the CRISPR-Cas9 system is hampered by a lack of methods to detect and quantify the products. Here the authors present GEF-dPCR, a droplet-based digital PCR method for assessing gene-editing frequencies.

Pancreatitis often develops as a consequence of ductal obstruction. Here, the authors show that bicarbonate ions initiate the release of neutrophil extracellular traps (NETs) that form pancreatic ductal aggregates and occlude the ducts, thereby driving pancreatitis in mice and humans.

Transduced hematopoietic stem cells can benefit patients with X-linked chronic granulomatous disease (a genetic immunodeficiency), but it's not risk free. In two treated patients, insertional activation of MDS1–EVI1, PRDM16 and SETBP1 markedly increased the number of transduced cells in the blood, leading to oligoclonal hematopoiesis, monosomy 7 and a myelodysplastic syndrome (pages 163–165).

Fusion of ACE2 to IgM-Fc results in hexameric ACE2-IgM-Fc proteins with potent virus neutralization efficiency of patient-isolated SARS-CoV and SARS-CoV-2 variants.

Biochemical, functional and computational analyses are combined to show that circular RNAs are a large class of animal RNAs with regulatory potency.

In contrast to HIV, simian immunodeficiency viruses (SIV) do not cause disease in their hosts, and the reasons for this are unclear. Here, Joas et al. incorporate two putative HIV virulence factors into SIV and study effects in infected monkeys, suggesting that species-specific host factors are responsible for HIV pathogenesis.

The cyclin D3–CDK6 kinase complex, which is overactive in some cancers, inhibits two key glycolysis enzymes and thereby enhances the levels of antioxidants in cells, promoting tumour cell survival.

Bartok, Pataskar, Nagel et al. show that long-term interferon γ-induced tryptophan degradation interferes with mRNA translation in melanoma. They reveal a mechanism by which indoleamine 2,3-dioxygenase 1 and amino acid starvation-dependent ribosomal frameshifting leads to immunogenic aberrant peptide presentation.

Two private, heterozygous mutations in two functionally related genes, GUCY1A3 and CCT7, are identified in an extended family with myocardial infarction; these genes encode proteins that work together to inhibit platelet activation after nitric oxide stimulation, suggesting a link between impaired nitric oxide signalling and myocardial infarction risk.

Johannes Lemke, Holger Lerche and colleagues report the identification of de novo mutations in the potassium channel gene KCNA2 in patients with epileptic encephalopathies. The authors confirm in vitro that two mutations cause dominant loss of channel function, whereas the other two mutations induce gain-of-function effects, leading to permanently open channels.

A genome-wide association study identifies 17 genetic loci that are associated with the risk of myeloproliferative neoplasms (MPNs), and shows that the modulation of haematopoietic stem cell function drives MPN risk.

Treatment with setmelanotide, a new-generation MC4R agonist, provides durable weight loss in hyperphagic, leptin receptor–deficient patients, suggesting a pharmacological avenue to treat patients with various MC4R pathway defects.

Combined studies in MYC-driven mouse lymphomas and human Burkitt lymphoma unravel an essential role for the B-cell antigen receptor in the control of tumour B-cell fitness both in vitro and in vivo, with possible biological and clinical implications.

Systematic culture and genome sequencing of thoracic airway commensal bacteria finds many potential influences on lung health and disease. Polyomics of differentiated airway epithelium also suggest pathways that may sustain host-microbial interactions.