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Selection of an optimum treatment regimen for patients with ulcerative colitis depends on several factors, including the natural history of the disease. A new study indicates that prognosis for patients with newly diagnosed ulcerative colitis might not be as bad as typically thought—an important finding that should be taken into account when the risks and benefits of future treatment strategies are discussed.

Sepsis induces a period of immunosuppression which can be problematic in the face of subsequent infectious challenge. Here the authors show the presence of PD-L1 expressing regulatory plasma cells that can inhibit T cells in a murine model and in patients with sepsis.

This study documents the evolution of antibiotic resistance and major growth defects in Yersinia enterocolitica in a patient over 14 years, revealing genetic changes that shed light on bacterial adaptation to infection and therapy.

Both environmental factors and genetic factors influence human immunity. Albert and colleagues leverage data from the Milieu Intérieur Consortium to comprehensively describe the effects of lifestyle, environment and genetics on human innate and adaptive immunity.

Despite many recent advances in silicon photonics for optical telecommunications and on-chip optical interconnects, the issue of power consumption has not been fully addressed. Here, Virot et al. propose a waveguide avalanche germanium photodiode suitable for low power consumption interconnects.

Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but seems to be largely redundant physiologically.

Inborn errors of the alternative NF-κB pathway in humans impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

A comparison of the evolutionary history and geographical spread of the antimicrobial-resistant pathogen Staphylococcus capitis in neonatal intensive care units indicates that acquisition of antibiotic resistance and increased competitiveness have led to the success of the NRCS-A S. capitis clone.

A species-level phylogenetic analysis of the high-elevation flora of the European Alps reveals that the flora is young and colonist rich. Its assembly was primarily driven by the Pleistocene climatic cycles, rather than ancient orogenic events.

The BabyDetect project offered expanded newborn genomic screening covering more than 400 genes to 4,260 families, leading to 71 clinical diagnoses.

Understanding the corrosion mechanism of aqueous silicate glass is crucial for the long-term durability of nuclear waste glasses. This mechanism is generally thought to be associated with chemical affinity, but it is now demonstrated that morphological transformations also have an important role in the leaching kinetics of these glasses.

Gene editing strategies for cystic fibrosis are challenging. Here the authors improve on their previously reported shuttle peptide noncovalently combined with Cas ribonucleoprotein (RNP), and derive the S315 peptide for delivery: they show base editing in the respiratory tract of the rhesus macaques.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Sequencing of nested branches from a 234-year-old oak tree reveals a low number of somatic mutations accumulating during its lifetime, implying that mechanisms are in place to reduce these potentially deleterious mutations during ageing.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Earthquakes rarely affect hydrothermal systems in non-magmatic context. Here the authors report outbursts of CO₂ and hydrothermal disturbances triggered by the 2015 Nepal earthquake, revealing high sensitivity of Himalayan hydrothermal systems to co-, post- and possibly pre- seismic deformation.

Methicillin-resistant strains of Staphylococcus aureus appeared in European hedgehogs in the pre-antibiotic era as a co-evolutionary adaptation to antibiotic-producing dermatophytes and have spread within the local hedgehog populations and between hedgehogs and secondary hosts.

Primary immunodeficiency can predispose patients to mycobacterial disease. Casanova and colleagues identify novel human mutations in the enzyme SPPL2A that result in selective accumulation of CD74 in a dendritic cell subset and lead to their death and the failure to mount effective T_H1 responses.

The RNA-binding ubiquitin E3 ligase TRIM25 plays a critical role in antiviral immunity. Here the authors identify key RNA-binding residues of TRIM25, link RNA binding to antiviral activity, reveal RNA structural and sequence preferences, and investigate binding to the viral genome.

Microtubule tracks are important for the transport of molecules within axons. Here, the authors show that ATAT1, the enzyme responsible for acetylating a-tubulin, receives acetyl groups from ATP citrate lyase whose stability is regulated by Elongator, a protein mutated in the neuronal disease Familial dysautonomia.

Mechanical cues can induce morphogenetic processes during development. Here the authors show that mechanical changes during embryonic development in both zebrafish and Drosophilalead to nuclear localization of β-catenin, which regulates genes required for early mesoderm development in both species.

Blockade of the C5a–C5aR1 axis using anti-C5aR1 monoclonal antibodies prevented inflammation associated with COVID-19.

Combined hepatocellular-cholangiocarcinomas (cHCC-CCA) are challenging to diagnose, as they exhibit features of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICCA). Here, the authors use deep learning to re-classify cHCC-CCA tumours into HCC or ICCA based on histopathology images.

Autoantibodies targeting glutamatergic N-methyl-d-aspartic acid receptors (NMDARs) are found in people with anti-NMDAR encephalitis. Two studies reveal that patient-derived autoantibodies are diverse in their epitope binding and modes of action on the NMDAR, providing insights into the mechanisms behind autoantibody-induced NMDAR hypofunction.

HRO761 is a potent, selective, allosteric WRN inhibitor that binds at the interface of the D1 and D2 helicase domains, locking WRN in an inactive conformation.

Discovering disease genes on the X chromosome can be particularly challenging. Here, the authors use features of known disease genes and machine learning to predict genes that remain to be associated with disorders on this chromosome.

In a rat model of spinal cord injury, calpain-dependent cleavage of motoneuron sodium channels can be pharmacologically targeted to achieve long-lasting amelioration of spasticity.

SARS-CoV-2 evolved into several sublineages harboring different mutations in spike. Here, the authors isolate and characterize nine SARS-CoV-2 variants and show that EG.5.1.3 has highest fitness in nasal epithelial cells, while JN.1 shows lower affinity to ACE2 and higher immune evasion compared to BA.2.86.1.

Analysis of a multicenter cohort of kidney transplants shows that mismatches in the MICA locus and the presence of anti-MICA donor-specific antibodies are associated with reduced graft survival and increased rejection.

The structures of three distinct human transcription factor IID (TFIID) protein assemblies are solved using cryo-electron microscopy; by incorporating TAF8 and TAF10, the key structural changes that remodel TFIID during assembly are determined, particularly the transition from a symmetric core-TFIID to an asymmetric holo-complex.

An isolate of the Omicron variant of SARS-COV-2 was completely or partially resistant to neutralization by all nine clinically approved monoclonal antibodies tested.

Micrometre scale simulation of the trajectory of sunlight as it reaches the snowpack shows what snow looks like from the photon’s perspective, providing a more universal representation of snow in optical models.

Genomic analysis uncovers global prevalence of three multidrug-resistant Staphylococcus epidermidis lineages encoding rifampicin resistance and reduced susceptibility to glycopeptide antibiotics.

High-resolution imaging techniques show that aromatic amino acids such as tryptophan formed abiotically and were subsequently preserved at depth beneath the Atlantis Massif of the Mid-Atlantic Ridge, supporting the hydrothermal theory for the origin of life.

A global dataset of the satellite-tracked movements of pelagic sharks and fishing fleets show that sharks—and, in particular, commercially important species—have limited spatial refuge from fishing effort.

Growing evidence indicates that YAP/TAZ transcriptional regulators promote autophagy. Here, the authors characterize the role of YAP against Staphyloccocus aureus infection of synovial organoids and describe the role staphylococcal toxins have in antagonizing YAP-mediated functions.

Staphylococcus aureus is increasingly recognized as a facultative intracellular pathogen, but it is unclear whether the intracellular lifestyle is a general feature or is restricted to some isolates. Here, Rodrigues Lopes et al. profile the interaction of 191 clinical isolates with four host cell types over time, showing that almost all isolates are internalized and that a large fraction replicate and persist within host cells.