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A pharmacological screen has identified the histone methyltransferase G9a as a target to reactivate imprinted genes in a mouse model of Prader–Willi Syndrome that improves growth and survival.
Genetic deletion of HDAC3, a circadian epigenome regulator, specifically in skeletal muscle alters amino acid metabolism, leading to increased muscle endurance but at the cost of whole-body insulin resistance.
New vaccine approaches that safely elicit immunity are needed to protect against infectious disease. Erasmus et al. report their development of an insect-virus-based platform that they use to engineer a protective vaccine against chikungunya fever.
In leukemic mice, fasting reduces the development of acute lymphoblastic leukemia, but not acute myeloid leukemia, via upregulation of leptin receptor expression and signaling in the leukemic cells.
Proteasomal degradation of EZH2 in AML patients in response to therapy triggers the expression of stem cell markers and has been identified as an epigenetic pathway leading to acquired drug resistance. Treatments aimed to restore EZH2 expression in relapsed AML patients have shown clinical efficacy and constitute a viable approach to re-sensitize tumors to chemotherapy.
Using functional MRI in a large multisite sample of more that 1,000 patients, four distinct neurophysiological biotypes of depression are defined. These biotypes are used to develop diagnostic classifiers that distinguish patients with depression from controls in separate multisite validation and replication cohorts, and can predict patient responsiveness to therapy.
The Wnt pathway inhibitor Dkk1, which is produced by bone marrow osteolineage cells, promotes hematopoietic recovery after radiation injury by both direct effects on hematopoietic cells and indirect effects on bone marrow endothelial cells.
The thalamus-enriched microRNA miR-338-3p is depleted in mouse models of 22q11.2 deletion syndrome and in humans with schizophrenia, leading to a late-onset dysfunction of auditory thalamocortical synaptic transmission, behavioral abnormalities and altered sensitivity to antipsychotics.
A genome-wide CRISPR screen reveals that FZD5, but none of the other nine Frizzled receptors encoded in the human genome, is a therapeutic vulnerability of pancreatic and colorectal tumors bearing RNF43 mutations.
Organoids formed by combining pluripotent-stem-cell-derived human neural crest cells with pluripotent-stem-cell-derived intestinal tissue show functional interstitial cells of Cajal and undergo waves of contraction; these tissues reveal insights into the molecular defects characterizing Hirschsprung's disease.
Blockade of cIAP1 and cIAP2 induces a tumor cell-autonomous type-I IFN response that activates myeloid cells and potentiates anti-tumor immunity in pre-clinical models and patients with multiple myeloma.
Using induced pluripotent stem cells from patients with familial dysautonomia, the authors show that in vitro models can recapitulate patient-specific differences in disease severity.
Spermidine, a naturally occurring polyamine, extends the lifespan of mice and is cardioprotective in both aged mice and hypertensive rats. In humans, high dietary spermidine intake is associated with reduced blood pressure and a lower incidence of cardiovascular disease.
Antibodies that bind to both H1 and H3 influenza strains exist in the pre-vaccination serum repertoire of healthy adults; most vaccine-elicited clonotypes bind either H1 or H3 strains.
Surender Khurana and colleagues analyzed the antibody repertoire in healthy individuals after vaccination against Ebola virus using a VSV-Ebola vaccine and identify a strong contribution of IgM antibodies to the virus-neutralizing response.
In triple-negative breast cancer, the kinase PIM1, which is highly expressed, functions through the transcription factor c-MYC to promote tumor cell survival and growth.
An immunotherapy consisting of a tumor-antigen targeting antibody, PD-1 blocking antibody, extended half-life recombinant IL-2 and a lymph-node-targeted T cell vaccine mobilized innate and adaptive immunity and eradicated large established tumors in a variety of mouse models.
Poor responses of liver metastases to the anti-angiogenic agent bevacizumab in patients with colorectal and breast cancer correlate with tumor co-option of pre-existing blood vessels, a mechanism of tumor resistance that might be targeted by the inhibition of cancer cell motility.
Caspase-2-mediated cleavage of tau is shown to generate a fibrillation-resistant truncation product (Δtau314) that contributes to the missorting of tau into dendritic spines, synaptic dysfunction, neurodegeneration and cognitive impairments in mice.
Both rhesus and cynomolgus macaques are susceptible to subcutaneous infection with Zika virus; longitudinal studies of infected animals provide information about the temporal dynamics of Zika virus in distinct cells, tissues and body fluids, as well as the immune response to the virus.