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Primary cutaneous B-cell lymphoma encompass clinically heterogeneous entities, including indolent and aggressive subtypes. Here, the authors show that the two indolent subtypes exhibit a persistent germinal centre reaction and thus may be driven by (a yet unknown) antigen.

By increasing NAD⁺ consumption in various organelles, mitochondria are revealed to act as buffers that help maintain subcellular NAD⁺ levels. At the same time, cells are found to be particularly sensitive to a decline in NAD⁺ levels originating from mitochondria themselves.

Double-positive αβ thymocytes undergo negative selection on thymic epithelial cells. Ziegler and colleagues show that TGF-β limits numbers and function of medullary thymic epithelial cells, thus influencing the resultant T cell repertoire.

Modulating mitochondrial NAD⁺ levels by changing the expression of the mitochondrial NAD⁺ transporter, SLC25A51, Mukherjee et al. demonstrate that mitochondrial, rather than cytosolic or nuclear, NAD⁺ levels are a key determinant of the rate of liver regeneration.

The herbicide propyzamide increases inflammation in the small and large intestine, and the AHR–NF-κB–C/EBPβ signalling axis—which operates in T cells and dendritic cells to promote intestinal inflammation—is targeted by propyzamide.

Infection with SARS-COV-2 can result in self-limited upper airway infection or progress to a more systemic inflammatory condition including pneumonic COVID-19. Here the authors utilise a multi-omics approach to interrogate the immune response of patients with self-limiting upper respiratory SARS-CoV-2 infection and reveal a temporal immune trajectory they associate with viral containment and restriction from pneumonic progressive disease.

Local microbiome composition influences treatment efficacy of chemotherapy in colon cancer via modulation of tolerogenic versus immunogenic ileal intestinal epithelial cell death, which in turn influences follicular helper T cell priming.

Here, using ribosomal profiling, the authors characterize the translatome of HIV-1 revealing tens of alternative open reading frames (ARF) that encode conserved viral antigens and show that ARF-derived peptides elicit potent HIV-specific poly-functional immune responses mediated by both CD4⁺ and CD8⁺ T cells.

A mass-spectrometry-based draft of the human proteome and a public database for analysis of proteome data are presented; assembled information is used to estimate the size of the protein-coding genome, to identify organ-specific proteins, proteins predicting drug resistance or sensitivity, and many translated long intergenic non-coding RNAs, and to reveal conserved control of protein abundance.

Some bacterial pathogens release NADase enzymes into the host cell that deplete the host’s NAD⁺ pool, thereby causing rapid cell death. Here, Strømland et al. identify NADases on the surface of fungal spores, and show that the enzymes display unique biochemical and structural properties.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

A rapid cellular response to interferons (IFNs) is critical for establishing antimicrobial immunity, but how cells switch from from homeostasis to IFN signaling is not fully understood. Here, the authors provide evidence that IFNs induce gene expression by alternating subunits of transcription factor ISGF3.

Maintaining cellular NAD levels through supplementation with intermediates of NAD synthesis has considerable health benefits. A new study demonstrates that the reduced form of nicotinamide riboside, NRH, can be converted to NAD in a biosynthetic pathway that involves adenosine kinase, thus strongly boosting NAD levels in cells and tissues.

Laser-produced plasma can be used for particle acceleration in different schemes. Here the authors demonstrate proton acceleration from the intense ultrashort laser pulse interaction with micron-sized cryogenic hydrogen jet.

NAD and NADP play fundamentally different roles in cellular metabolism, and yet these pyridine nucleotides cannot be distinguished spectroscopically in living cells. Blacker et al.demonstrate that fluorescence lifetime imaging can be used to quantify NADPH/NADH balance in cultured cells and in the mammalian cochlea.

The genetic architecture underlying brainstem regions and how this links to common brain disorders is not well understood. Here, the authors use MRI and GWAS data from 27,034 individuals to identify genetic and morphological brainstem features that influence common brain disorders.

SLC25A51 is identified as a transporter of intact NAD⁺ into mammalian mitochondria and is required to maintain the mitochondrial NAD⁺ pool and respiratory function.

Levels of the metabolic coenzyme NAD⁺ decline during aging, which is linked to many age-related diseases. Zhang et al. review recent clinical and translational evidence testing NAD⁺ supplementation in age-related diseases, highlighting therapeutic challenges and opportunities.

NAD is a vital molecule in all organisms and is a key component of both energy and signal transduction — processes that undergo crucial changes in cancer cells. NAD⁺-dependent signalling reactions involve the degradation of the molecule, so permanent nucleotide resynthesis through different biosynthetic pathways is crucial for incessant cancer cell proliferation. Is targeting of NAD metabolism a new therapeutic strategy for cancer treatment?

The Mouse Intestinal Bacterial Collection (miBC) is a public repository of bacterial strains and associated genomes from the mouse gut. A minimal consortium of 18 species covered 50–75% of the known functional potential.

Nicotinamide adenine dinucleotide (NAD⁺) has essential roles in metabolism and can be readily supplemented, potentially to benefit human health. This Review discusses recent insights into the roles of the microbiome and cellular compartments in regulating NAD⁺ metabolism, and the promise and pitfalls of NAD⁺ supplementation.

Using structural MRI data from 45,615 individuals aged 3–96 years, Kaufmann and colleagues reveal that common brain disorders are associated with heritable patterns of apparent aging of the brain.