Volume 23 Issue 6, June 2017

A new study that uses an integrated single-cell transcriptomics approach to characterize cancer stem cell populations during treatment with molecularly targeted therapies offers insights into disease evolution and points to new therapeutic targets.

A recent study has found that rhinovirus-induced exacerbation of asthma is in part mediated by the release of neutrophil extracellular traps and double-stranded DNA by neutrophils in the airway.

A new study reveals that virus-associated activation of a subset of circulating monocytes results in the release of the proinflammatory cytokine tumor necrosis factor (TNF)-α, which induces increased turnover of synapses in the brain and learning deficits in mice.

New evidence in mouse models reveals that exposure to Δ⁹-tetrahydrocannabinol (THC), the main psychoactive component in Cannabis sativa, might improve cognitive performance in aging animals.

Rubin and colleagues discuss the origin and evolution of poorly differentiated neuroendocrine tumors, and highlight potential new therapeutic strategies.

Metformin treatment for 10 d rescues several behavioral deficits related to fragile X syndrome in adult Fmr1^−/y mice.

Using intracranial electrode recordings in two individuals with Alzheimer's disease, Lam et al. discover hippocampal seizure activity that could not be detected by traditional EEG monitoring.

Targeting NETosis alleviates type-2 immunopathology induced by rhinovirus infection in a mouse model of airway hypersensitivity, and correlative data suggest that a similar mechanism may operate in human rhinovirus-exacerbated asthma.

Applying a new, more sensitive single-cell transcriptomics method to diagnosis, remission and progression samples from patients with chronic myeloid leukemia reveals insight into the heterogeneity of cells that resist treatment with targeted therapy, as well as into the dynamics of disease progression and its effects on nontransformed hematopoietic stem cells.

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.

In a rodent model of viral infection, immune activation causes impairments in motor-learning-dependent cortical synaptic remodeling that are mediated by peripheral monocytes rather than by CNS-resident microglia.

The scavenger receptor MSR1 contributes to the clearance of damage-associated molecular patterns (DAMPs) by infiltrating myeloid cells in the post-stroke rodent brain. Myeloid cell MSR1 deficiency impairs clearance and exacerbates stroke-induced impairments, whereas a pharmacological intervention to boost MSR1 expression improves pathological and functional outcomes.

In rat models of spinal cord injury, the region of the spinal cord below the site of injury becomes hypoxic owing to inadequate blood flow. This effect on blood flow is due to increased production of neurotransmitters known as ‘trace amines,’ which act on pericytes to constrict blood vessels. Alleviation of hypoxia by hyperoxic breathing or inhibition of trace amine synthesis or action improves locomotor function in the injured rats.

Toll-like receptor (TLR) 4 is a key mediator of non-alcoholic fatty liver disease progression. Targeting TLR4 degradation via the lysosome pathway improves outcome in mouse and monkey models of this condition.

Studying patients with long-term diabetes who lack diabetic nephropathy reveals that targeting pyruvate kinase M2 protects against renal disease.

Pei-Yong Shi and colleagues report that a deletion mutant of Zika virus is safe and effective as a live-attenuated vaccine in mice and induces sterilizing immunity. Their results encourage further testing of the candidate vaccine for possible future use in humans.

In mice, sleep loss increases sensitivity to painful stimuli. Restoration of normal sleep or acute treatment with wake-promoting agents can normalize pain sensitivities.

Pharmacological or genetic depletion of senescent cells in the joint ameliorates osteoarthritis in mice.

In mice aged 12–18 months, chronic administration of low-dose Δ⁹-tetrahydrocannabinol (THC) improves performance in behavioral learning and memory tasks, whereas a similar administration in younger mice (aged 2 months) impairs performance.