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Mouse models show that lymphoedema caused by impaired lymphatic drainage is ameliorated by removal of cholesterol deposits, which promotes the regeneration of lymphatic vessels.

Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

EGFR inhibitors are standard of care in patients with EGFR-mutant non-small cell lung cancer (NSCLC) but resistance often develops. Here the authors report that the evolution of EGFR inhibitor resistance in EGFR-mutant NSCLC results in a sensitivity to the compound, MCB-613, and investigate the underlying mechanism of action.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

In mouse brain, neurotensin released into the basolateral amygdala by neurons in the paraventricular nucleus of the thalamus assigns positive or negative valence during associative learning.

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.

Human and mouse astrocytes express the protocadherin PcdhγC3, which promotes self-recognition of individual astrocytes, thereby contributing to normal astrocyte and brain development.

Secretory autophagy (SA) plays a crucial role in neuroinflammation-driven neurodegeneration, through SKA2 and FKBP5. SKA2 regulation of SA can inhibit IL-1β release. Its dysfunction leads to neurodegeneration, and is linked to Alzheimer’s disease.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

The Inflammatory Bowel Disease Multi’omics Database includes longitudinal data encompassing a multitude of analyses of stool, blood and biopsies of more than 100 individuals, and provides a comprehensive description of host and microbial activities in inflammatory bowel diseases.

Fear and fear extinction learning are dynamic. These dynamic changes are underlined by transcriptional changes. Here, the authors translationally profiled Crh neurons in the amygdala and and identified relevant gene networks.

Routes of infection with bovine highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b in cynomolgus macaques are investigated, and in contrast to orogastric inoculation, intranasal or intratracheal inoculation could cause systemic infection resulting in mild and severe respiratory disease, respectively.

Here the authors show that contemporary SARS-CoV-2 Omicron variants are evolving towards the upper respiratory tract while causing less severe disease in the lung. The more antigenically distinct variant JN.1 fails to transmit in the male hamster model and causes reduced pathology.

The role of interferon-γ (IFNγ) in anti-viral immunity has been unclear. Here the authors show that bacterial-induced or intranasally administered IFNγ effectively restricts SARS-CoV-2 infection in mice through effects on non-hematopoietic cells.

Pairing an odor conditioned stimulus (CS) with an unconditioned stimulus (US) induces memory formation. Vetere et al. replace the real CS and US with direct optogenetic stimulation of the brain and create a fully artificial odor memory in mice.

Stroke profoundly disrupts cortical excitability which impedes recovery, but how stroke affects inhibitory interneurons is poorly understood. Here, the authors show that functional impairments after stroke are associated with the disruption of a highly active subpopulation of interneurons expressing vasoactive intestinal peptide (VIP), which could be ameliorated by chemogenetic stimulation.

Transcriptomic, proteomic and immune repertoire profiling reveals distinct peripheral features of MIS-C and pediatric COVID-19, including elevated soluble spike protein levels, more pronounced type II IFN-dependent gene expression and a higher B cell mutation rate in patients with MIS-C.

Taxonomic compositions in bathtub faucet water microbiomes showed household individuality, with differences in the prevalences of non-tuberculous mycobacterial species. A similar antimicrobial resistome was detected.

Activation of Thy-1 expressing neurons in the basolateral amygdala (BLA) has been shown to result in inhibition of fear. Here the authors present a comprehensive workflow to identify genes that are upregulated in this population and can be pharmacologically targeted to enable fear extinction.

Structural changes in the dendrites are mediated in part by a cell adhesion molecule, β-catenin, and are associated with memory formation and maintenance. A new study by Maguschak and Ressler shows that β-catenin has a selective role in fear memory consolidation.

MSK-IMPACT is a clinical sequencing platform able to detect genomic mutations, copy number alterations and structural variants in a panel of cancer-related genes. This assay is implemented prospectively to inform patient enrollment in genomically matched clinical trials at Memorial Sloan Kettering Cancer Center (MSKCC). Sequencing results of tumor and matched normal tissue from a cohort of >10,000 patients with detailed clinical annotation provide an overview of the genomic landscape of advanced solid cancers and bring new insights into molecularly guided cancer therapy.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

This paper proposes a research agenda towards the more just, equitable and effective integration of gender into blue carbon initiatives. It is a call-to-action towards closing the gender gap in the conservation and restoration of these ecosystems.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

A benchtop system for protein synthesis achieves purity and potency comparable to those of marketed drugs.

The neuropeptide CRH is believed to induce aversive, stress-like behavioral responses. Here the authors describe a distinct population of CRH neurons in the extended amygdala that act to suppress anxiety by positively modulating dopamine release.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

This Perspective from the Harvard Chan Microbiome in Public Health Center describes a generalizable and scalable approach to stool and oral microbiome and metadata collection in the Micro-N (Microbiome Among Nurses) study, to show how to carry out prospective studies of the microbiome.

Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

Primary biliary cirrhosis is an autoimmune liver disease with poor therapeutic options. Here Cordell et al. a perform meta-analysis of European genome-wide association studies identifying six novel risk loci and a number of potential therapeutic pathways.

Jayavelu, Samaha et al., apply machine learning models on hospital admission data, including antibody titers and viral load, to identify patients at high risk for Long COVID. Low antibody levels, high viral loads, chronic diseases, and female sex are key predictors, supporting early, targeted interventions.

The immune system of laboratory mice raised in an ultra-hygienic environment resembles that ofnewborn humans, but can be induced to resemble the immune system of adult humans or 'dirty' mice by co-housing with pet store-bought mice.