Obstructive lung diseases are common causes of disability and death worldwide. A hallmark feature is aberrant activation of Gq protein–dependent signaling cascades. Currently, drugs targeting single G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors (GPCRs) are used to reduce airway tone. However, therapeutic efficacy is often limited, because various GPCRs contribute to

Treatment of type 2 diabetes mellitus continues to pose an important clinical challenge, with most existing therapies lacking demonstrable ability to improve cardiovascular outcomes. The atheroprotective peptide apelin (APLN) enhances glucose utilization and improves insulin sensitivity. However, the mechanism of these effects remains poorly defined. We demonstrate that the expression of APLNR (APJ/AGTRL1)

In melanoma, vascular endothelial growth factor–C (VEGF-C) expression and consequent lymphangiogenesis correlate with metastasis and poor prognosis. VEGF-C also promotes tumor immunosuppression, suggesting that lymphangiogenesis inhibitors may be clinically useful in combination with immunotherapy. We addressed this concept in mouse melanoma models with VEGF receptor–3 (VEGFR-3)–blocking antibodies

Reducing IgE with Omalizumab in children with asthma improves the plasmacytoid dendritic cell interferon response to virus in vitro.

A neuronal subpopulation in the central amygdala promotes food consumption.

Mast cell inhibition prevents heterotopic ossification in a model of fibrodysplasia ossificans progressiva.

A gain-of-function mutation in NLRP3 is associated with cochlear inflammation and hearing loss.

Increasing evidence supports the hypothesis that soluble misfolded protein assemblies contribute to the degeneration of postmitotic tissue in amyloid diseases. However, there is a dearth of reliable nonantibody-based probes for selectively detecting oligomeric aggregate structures circulating in plasma or deposited in tissues, making it difficult to scrutinize this hypothesis in patients. Hence, understanding

Creatine metabolism in adipose tissue is necessary to burn off extra dietary calories and helps prevent obesity.

Neutralizing antibodies to the V2 apex antigenic region of the HIV-1 envelope (Env) trimer are among the most prevalent cross-reactive antibodies elicited by natural infection. Two recently described V2-specific antibodies, PGDM1400 and CAP256-VRC26.25, have demonstrated exquisite potency and neutralization breadth against HIV-1. However, little data exist on the protective efficacy of V2-specific

Conventional methods for histopathologic tissue diagnosis are labor- and time-intensive and can delay decision-making during diagnostic and therapeutic procedures. We report the development of an automated and biocompatible handheld mass spectrometry device for rapid and nondestructive diagnosis of human cancer tissues. The device, named MasSpec Pen, enables controlled and automated delivery of a discrete

Low–molecular weight heparin (LMWH) is used clinically to treat clotting disorders. As an animal-sourced product, LMWH is a highly heterogeneous mixture, and its anticoagulant activity is not fully reversible by protamine. Furthermore, the reliability of the LMWH supply chain is a concern for regulatory agencies. We demonstrate the synthesis of heparin dodecasaccharides (12-mers) at the gram scale

Antibiotic resistance in Escherichia coli can be assessed by real-time imaging of bacterial replication in a microfluidics system.

Plasma β-amyloid drives peripheral insulin resistance, which precedes an increase in cerebral neuropathology in a novel mouse model that combines Alzheimer’s and diabetes pathologies.

High throughput, single-cell transcriptomic profiling can rapidly profile frozen mouse and human tissues.

ILCregs are a population of innate lymphoid cells that control innate intestinal inflammation through IL-10.

There is a medical need for antibacterial agents that do not damage the resident gut microbiota or promote the spread of antibiotic resistance. We recently described a prototypic precision bactericidal agent, Av-CD291.2, which selectively kills specific Clostridium difficile strains and prevents them from colonizing mice. We have since selected two Av-CD291.2–resistant mutants that have a surface (S)-layer–null

Whole-genome sequencing (WGS) of maternal plasma cell-free DNA (cfDNA) can potentially evaluate all 24 chromosomes to identify abnormalities of the placenta, fetus, or pregnant woman. Current bioinformatics algorithms typically only report on chromosomes 21, 18, 13, X, and Y; sequencing results from other chromosomes may be masked. We hypothesized that by systematically analyzing WGS data from all

Researchers have edited the genome of human embryos to correct dominant myocardial disease.

Arrayed nanochannels efficiently transfect skin for local in vivo genetic reprogramming.

Germline mutations in RNA polymerase III cause susceptibility to life-threatening varicella zoster infection.

D-cycloserine ameliorates breathing abnormalities and survival rate in a mouse model of Rett syndrome.

Clinical symptoms of dengue virus (DENV) infection, the most prevalent arthropod-borne viral disease, range from classical mild dengue fever to severe, life-threatening dengue shock syndrome. However, most DENV infections cause few or no symptoms. Asymptomatic DENV-infected patients provide a unique opportunity to decipher the host immune responses leading to virus elimination without negative impact

In HIV infection, persistent inflammation despite effective antiretroviral therapy is linked to increased risk of noninfectious chronic complications such as cardiovascular and thromboembolic disease. A better understanding of inflammatory and coagulation pathways in HIV infection is needed to optimize clinical care. Markers of monocyte activation and coagulation independently predict morbidity and

The regenerative capacity of lung and liver is sometimes impaired by chronic or overwhelming injury. Orthotopic transplantation of parenchymal stem cells to damaged organs might reinstate their self-repair ability. However, parenchymal cell engraftment is frequently hampered by the microenvironment in diseased recipient organs. We show that targeting both the vascular niche and perivascular fibroblasts

Recent advances in subcutaneous drug delivery and device design are transforming the biopharmaceutical sector and improving patient care.

Current therapies for reducing raised intracranial pressure (ICP) under conditions such as idiopathic intracranial hypertension or hydrocephalus have limited efficacy and tolerability. Thus, there is a pressing need to identify alternative drugs. Glucagon-like peptide-1 receptor (GLP-1R) agonists are used to treat diabetes and promote weight loss but have also been shown to affect fluid homeostasis

An open-top light-sheet microscope enables rapid high-resolution panoramic imaging of intact clinical samples to increase the accuracy and reproducibility of clinical histology.

Aged mice preconditioned with a running routine were resistant to acute systemic sepsis compared with non-runner.

In patients with nonhematologic cancers, clonal hematopoiesis is prevalent and associated with poor prognoses.

Primary cilia-based signaling provides critical infrastructure for formation of striatal neuronal networks.

Alterations in gene dosage due to copy number variation are associated with autism spectrum disorder, intellectual disability (ID), and other psychiatric disorders. The nervous system is so acutely sensitive to the dose of methyl-CpG–binding protein 2 (MeCP2) that even a twofold change in MeCP2 protein—either increased or decreased—results in distinct disorders with overlapping features including ID

Oncolytic virotherapy is rapidly progressing through clinical evaluation. However, the therapeutic efficacy of oncolytic viruses in humans has been less than expected from preclinical studies. We describe an anticancer drug screen for compounds that enhance M1 oncolytic virus activity in hepatocellular carcinoma (HCC). An inhibitor of the valosin-containing protein (VCP) was identified as the top sensitizer

The ability to walk contributes considerably to physical health and overall well-being, particularly in children with motor disability, and is therefore prioritized as a rehabilitation goal. However, half of ambulatory children with cerebral palsy (CP), the most prevalent childhood movement disorder, cease to walk in adulthood. Robotic gait trainers have shown positive outcomes in initial studies,

Hallmarks of chronic neurodegenerative disease include progressive synaptic loss and neuronal cell death, yet the cellular pathways that underlie these processes remain largely undefined. We provide evidence that dual leucine zipper kinase (DLK) is an essential regulator of the progressive neurodegeneration that occurs in amyotrophic lateral sclerosis and Alzheimer’s disease. We demonstrate that DLK/c-Jun

Early detection and intervention are likely to be the most effective means for reducing morbidity and mortality of human cancer. However, development of methods for noninvasive detection of early-stage tumors has remained a challenge. We have developed an approach called targeted error correction sequencing (TEC-Seq) that allows ultrasensitive direct evaluation of sequence changes in circulating cell-free

Lyme disease, the most commonly reported vector-borne disease in the United States, results from infection with Borrelia burgdorferi. Early clinical diagnosis of this disease is largely based on the presence of an erythematous skin lesion for individuals in high-risk regions. This, however, can be confused with other illnesses including southern tick−associated rash illness (STARI), an illness that

Combining tandem peptides that localize toxins to bacterial membranes with scaffolds that target these payloads to the lungs combats drug resistant bacteria without off-target effects.

Insect defensin-1 improves wound healing by inducing production of matrix metalloproteinase-9.

Adverse childhood experiences epigenetically regulate expression of kappa opioid receptors.

A small-molecule inhibitor blocks the interaction of the androgen receptor with DNA to target drug-resistant prostate cancer.

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene. The cognitive impairments seen in mouse models of RTT correlate with deficits in long-term potentiation (LTP) at Schaffer collateral (SC)–CA1 synapses in the hippocampus. Metabotropic glutamate receptor 7 (mGlu7) is the predominant mGlu receptor expressed presynaptically at SC-CA1

Broadly neutralizing antibodies (BnAbs) protect macaques from cell-free simian/human immunodeficiency virus (SHIV) challenge, but their efficacy against cell-associated SHIV is unclear. Virus in cell-associated format is highly infectious, present in transmission-competent bodily fluids, and potentially capable of evading antibody-mediated neutralization. The PGT121 BnAb, which recognizes an epitope

Imaging and electroencephalography help to detect covert consciousness after acute brain injury.

Circadian disturbances that accompany tuberous sclerosis Complex are explored in mouse models.

Systematic identification of gene dependencies in cancer cells teaches us some lessons.

Skeletal muscle may communicate with pancreatic beta cells through irisin, a muscle-derived hormone that promotes beta cell survival and insulin release.

Immunotherapy using short immunogenic peptides of disease-related autoantigens restores immune tolerance in preclinical disease models. We studied safety and mechanistic effects of injecting human leukocyte antigen–DR4(DRB1*0401)–restricted immunodominant proinsulin peptide intradermally every 2 or 4 weeks for 6 months in newly diagnosed type 1 diabetes patients. Treatment was well tolerated with no

Inhibition of proliferation in estrogen receptor–positive (ER+) breast cancers after short-term antiestrogen therapy correlates with long-term patient outcome. We profiled 155 ER+/human epidermal growth factor receptor 2–negative (HER2−) early breast cancers from 143 patients treated with the aromatase inhibitor letrozole for 10 to 21 days before surgery. Twenty-one percent of tumors remained highly

We describe an approach to inhibit chemotherapy-induced myelosuppression. We found that short-term exposure of mice to the FLT3 inhibitor quizartinib induced the transient quiescence of multipotent progenitors (MPPs). This property of quizartinib conferred marked protection to MPPs in mice receiving fluorouracil or gemcitabine. The protection resulted in the rapid recovery of bone marrow and blood

Corruption is a critical challenge to global health efforts, and combating it requires international action, advocacy, and research.

A new proinflammatory subtype of antigen-specific TH2 cell that expresses CD161 emerges as the pathogenic cell type in allergic disease and is deleted during allergen-specific immunotherapy (Wambre et al., this issue).

Methicillin-resistant Staphylococcus aureus likely evolved before the introduction of methicillin into clinical use.

A new approach may help to explore the genetic levers that control intelligence.

Neutrophil extraceullar traps (NETs) cause secondary expansion of tissue necrosis in local and remote tissues due to microvascular hypercoagulation.

Severe pneumonia predisposes to recurrent infection by functionally impairing antigen presenting cells.

A recent study showed how geospatial mapping can be used to improve Lesotho’s HIV treatment program to achieve the 90-90-90 targets set by the United Nations but incorrectly describes “treatment as prevention” as the UN’s strategy for a successful national AIDS response.

Alterations in the balance between neuronal excitation and inhibition (E:I balance) have been implicated in the neural circuit activity–based processes that contribute to autism phenotypes. We investigated whether acutely reducing E:I balance in mouse brain could correct deficits in social behavior. We used mice lacking the CNTNAP2 gene, which has been implicated in autism, and achieved a temporally

The development of BH3 mimetics, which antagonize prosurvival proteins of the BCL-2 family, represents a potential breakthrough in cancer therapy. Targeting the prosurvival member MCL-1 has been an area of intense interest because it is frequently deregulated in cancer. In breast cancer, MCL-1 is often amplified, and high expression predicts poor patient outcome. We tested the MCL-1 inhibitor S63845

Detailed geospatial mapping of a generalized HIV epidemic in sub-Saharan Africa shows that implementing the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 strategy could potentially exacerbate urban-rural health care disparities.