ON THE COVER
Luk et al. find that injection of brain lysate from symptomatic aged mice into the brains of asymptomatic young mice is sufficient to initiate spreading of α-synuclein aggregates and to accelerate the onset of Parkinson’s disease–like symptoms. Original image shows α-synuclein (green) and microtubule-associated protein 2 (red) in the brain of a mouse injected 90 d prior with symptomatic brain lysate. Artwork by Lewis Long (firstname.lastname@example.org).
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Prion-like spread of protein aggregates in neurodegeneration
A growing body of evidence suggests that cell-to-cell spread of misfolded protein aggregates represents a mechanism underlying the pathogenesis of several neurodegenerative diseases.
Brief Definitive Report
A role for GPx3 in activity of normal and leukemia stem cells
High levels of glutathione peroxidase 3 (GPx3) expression correlate with adverse prognosis in acute myeloid leukemia, and enhance activity of long-term repopulating hematopoietic stem cells in mice.
Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation
GVHD is associated with significant shifts in the composition of the intestinal microbiota in human and mouse models; manipulating the microbiota can alter the severity of GVHD in mice.
Expansion of somatically reverted memory CD8+ T cells in patients with X-linked lymphoproliferative disease caused by selective pressure from Epstein-Barr virus
In patients with XLP, a primary immunodeficiency caused by mutations in SH2D1A, EBV infection can lead to somatic reversion of the disease-causing mutation selectively in effector memory CD8 T cells; reverted CD8 cells are better able to respond to and kill EBV-infected cells.
Autotaxin expression from synovial fibroblasts is essential for the pathogenesis of modeled arthritis
Synovial fibroblasts from patients and mice with arthritis express autotaxin, and ablation of autotaxin in fibroblasts ameliorates disease.
Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation
Human skin-resident IL-10+ regulatory dendritic cells induce T reg cells that suppress allogeneic skin graft inflammation.
Proinflammatory cytokine signaling required for the generation of natural killer cell memory
Responsiveness to interleukin-12, but not interferon-γ, is essential for the generation of long-lived natural killer cells capable of responding to secondary viral infection.
Artemis C-terminal region facilitates V(D)J recombination through its interactions with DNA Ligase IV and DNA-PKcs
Interactions of Artemis with DNA Ligase IV and DNA-PKcs are required for efficient coding joint formation.
Ectopic restriction of DNA repair reveals that UNG2 excises AID-induced uracils predominantly or exclusively during G1 phase
As revealed using an UNG2 inhibitor peptide fused to cell cycle–regulated degradation motifs, the cell cycle phase during which uracil residues are processed determines the fidelity of repair.
Intracerebral inoculation of pathological α-synuclein initiates a rapidly progressive neurodegenerative α-synucleinopathy in mice
Synthetic a-Synuclein fibrils injected into the brain spread far beyond the injection site and are sufficient to accelerate Parkinson’s disease–like pathology in mice.
Human invariant natural killer T cells acquire transient innate responsiveness via histone H4 acetylation induced by weak TCR stimulation
Weak TCR stimulation of iNKT cells, such as that resulting from self-antigen recognition, induces histone modifications at the IFNG locus that allow the iNKT cells to subsequently produce IFN-γ in response to proinflammatory cytokines alone.
B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells
IL-6–producing B cells contribute to EAE pathology and possibly human MS, whereas ablation of B cell IL-6 is associated with a reduced Th17 response.
Dll4–Notch signaling in Flt3-independent dendritic cell development and autoimmunity in mice
Blocking Dll4–Notch signaling can reverse established diabetes via Flt3-independent induction of immature thymic DCs that enhance Treg cell generation in mice.
Chikungunya virus–induced autophagy delays caspase-dependent cell death
Chikungunya virus induces autophagy by triggering ER and oxidative stress, and this autophagy restricts apoptosis and viral propagation.
Apicoplast isoprenoid precursor synthesis and the molecular basis of fosmidomycin resistance in Toxoplasma gondii