Browse Articles

Cao et al. show that human papillomavirus-positive, head and neck squamous cell carcinoma patients are associated with better survival when T-cells are activated. This study suggests that viral infection may recruit immune effector cells and that it may activate PD-1 and CTLA-4 immunosuppressive pathways.

Markel Olabarria et al. show that the loss of Ube3A plays a critical role in synaptic dysfunction, using an Alzheimer’s disease mouse model. This study establishes a molecular pathway that maintains a synaptic function and suggests Ube3A as a potential therapeutic target for Alzheimer’s disease.

Nepon-Sixt, Bryant, and Alexandrow show that Myc increases the chromatin accessibility through Myc-Box II, activating Cdc45-MCM-GINS helicases at Myc-targeted sites. This study highlights a non-transcriptional role for Myc in over-activating DNA replication, providing insight into Myc-driven tumorigenesis.

Jung-A A. Woo et al. show that activated cofilin competes with Tau for microtubule biding in primary neuronal cultures and a C.elegans model. This direct binding decreases microtubule stability and promotes tauopathy, suggesting an important role for cofilin in neurotoxic signaling.

Mona Tonn et al. propose a stochastic model to elucidate the mechanisms by which non-genetic heterogeneity arises in metabolic reactions. They find that even unimodal enzyme expression fluctuations can lead to highly heterogeneous metabolite profiles with two or more metabolically distinct subpopulations of cells.

Fabien Pifferi et al. discuss the latest research in using caloric restriction for promoting healthspan and lifespan in primates. Their Comment touches on their previous study, addressing how to combine nutrition-based clinical protocols with interventions to delay the onset of age-related diseases.

Matthew Quinn et al showed diminished hepatic stress responses in pregnant mice due to epigenetic-mediated decreases in glucocorticoid receptor expression. This decrease is necessary for fetal development and highlights the importance of understanding the tissue-specific effects of glucocorticoid activation in models of maternal stress.

Cheng Luan et al. report that the voltage-gated calcium channel Ca_Vγ4 is necessary for maintaining pancreatic beta-cell function. They find that MafA, a transcription factor required for beta-cell maturation, directly regulates the gene encoding Ca_Vγ4 and suggest that restoration of Ca_Vγ4 may be a potential treatment for type 2 diabetes.

Tsan-Jan Chen, Hung-Jung Wang et al. report the crystal structures of tumor-related mutant forms of pyruvate kinase M2 (PKM2). They show that these mutations lead to increased interaction with the PKM2 binding partner KDM8, suggesting a mechanism for their oncogenic action.

Everly Conway de Macario et al. present a review of microbial models of human chaperonopathies. They discuss the recent progress in using microbes to model human pathogenic mutations and to elucidate disease mechanisms.

Parashkev Nachev et al. investigate the neural basis of meta-volition, the ability to choose to suspend volition. Using diffusion tensor imaging, they find that less optimized right frontal white matter was correlated with improved meta-volition abilities, suggesting meta-volition is controlled by a parallel rather than hierarchical neural organization.

Tomoki Suzuki and Masaki Tanaka measured local field potentials in the caudate nucleus of monkeys performing a time production task and showed that the length of the time interval modified the magnitude of visually-evoked potentials and the spectral power at low frequencies. These changes suggest that neural oscillations within the cortico-basal ganglia pathways regulate timing behavior.

Lingzhao Fang et al. studied the paternal genetic variants that affect gestational length in cattle. They found that paternal genes from pathways involved in embryonic development were associated with gestation length, and that these were often found in differentially methylated regions of the genome.

Yuanyuan Cheng et al. showed that the T-cell repertoire diversity of Tasmanian devils diminishes during their second year of life which may explain the prevalence of devil facial tumor disease in older devils. Infection with this disease also impacts T-cell diversity highlighting a previously unknown effect of the devil facial tumor disease on host immunity.

Krystofiak et al. combined carbon replicas with phase-contrast electron microscopy to overcome the limited fidelity and resolution of metal replicas. This method reveals a double stranded morphology of the tight junction intramembrane fibrils, demonstrating its superiority over conventional freeze-fracture methods.

Yamaguchi et al. investigated evolutionary pressure of 16 pneumococcal choline-binding cell-surface proteins (Cbp) and identified CbpJ as a virulence factor that contributes to pneumococcal evasion of neutrophil killing. This study highlights the utility of molecular evolutionary analysis in discovering virulence factors.

Alvin Acebedo, Kentaro Suzuki et al. show that mesenchymal-derived actomyosin contractility is required for androgen-dependent urethral masculinization in mouse embryos. They also show that actomyosin contractility regulates mesenchymal cell migration during the developmental process.

Huw Colin-York et al. use advanced microscopy techniques to show that the cortical actin network within a model mast cell line undergoes a series of reorganizational events at the basal interface during activation. They find that actin patterns co-localize with zones of Arp2/3 nucleation and myosin-II activity accompanies network reassembly.

Marchetti et al. show that antibodies against Plasmalemma Vesicle Associated Protein (PV1) can be used to efficiently target drugs to lungs and kidneys. In a bleomycin induced lung fibrosis model, mice treated with anti-PV1 antibodies linked to an anti-fibrotic drug exhibited reduced collagen deposition and fibrosis progression compared to control antibodies.