DOT1L modulates the senescence-associated secretory phenotype through epigenetic regulation of IL1A

Oncogene-induced senescence (OIS) is a stable cell cycle arrest that occurs in normal cells upon oncogene activation. Cells undergoing OIS express a wide variety of secreted factors that affect the senescent microenvironment termed the senescence-associated secretory phenotype (SASP), which is beneficial or detrimental in a context-dependent manner. OIS cells are also characterized by marked epigenetic changes. We globally assessed histone modifications of OIS cells and discovered an increase in the active histone marks H3K79me2/3. The H3K79 methyltransferase disruptor of telomeric silencing 1-like (DOT1L) was necessary and sufficient for increased H3K79me2/3 occupancy at the IL1A gene locus, but not other SASP genes, and was downstream of STING. Modulating DOT1L expression did not affect the cell cycle arrest. Together, our studies establish DOT1L as an epigenetic regulator of the SASP, whose expression is uncoupled from the senescence-associated cell cycle arrest, providing a potential strategy to inhibit the negative side effects of senescence while maintaining the beneficial inhibition of proliferation.     

A distributed lumped parameter model of blood flow with fluid-structure interaction

Biomechanics and Modeling in Mechanobiology - A distributed lumped parameter (DLP) model of blood flow was recently developed that can be simulated in minutes while still incorporating complex...     

Physical factors increased quantity and quality of micropropagated shoots of Cannabis sativa L. in a repeated harvest system with ex vitro rooting

In Vitro Cellular & Developmental Biology - Plant - Micropropagation is a preferred method to propagate clean, clonal stock plants. Subculture is labor intensive and costly. In vitro hedging...     

Honest signals and sexual conflict: Female lizards carry undesirable indicators of quality

Sex differences in animal coloration often result from sex‐dependent regulatory mechanisms. Still, some species exhibit incomplete sexual dimorphism as females carry a rudimentary version of a costly male trait, leading to intralocus sexual conflict. The underlying physiology and condition dependence of these traits can inform why such conflicts remain unresolved. In eastern fence lizards (Sceloporus undulatus), blue iridophore badges are found in males and females, but melanin pigmentation underneath and surrounding badges is male‐exclusive. We track color saturation and area of badges across sexual maturity, and their relationship to individual quality (body condition and immunocompetence) and relevant hormones (testosterone and corticosterone). Saturation and testosterone were positively correlated in both sexes, but hormone and trait had little overlap between males and females. Saturation was correlated with body condition and immunocompetence in males but not in females. Co‐regulation by androgens may have released females from resource allocation costs of color saturation, even when in high condition. Badge area was independent of testosterone, but associated with low corticosterone in females, indicating that a nonsex hormone underlies incomplete sexual dimorphism. Given the evidence in this species for female reproductive costs associated with ornamentation, this sex‐nonspecific regulation of an honest signal may underlie intralocus sexual conflict.     

Supervillin binding to myosin II and synergism with anillin are required for cytokinesis

Cytokinesis, the process by which cytoplasm is apportioned between dividing daughter cells, requires coordination of myosin II function, membrane trafficking, and central spindle organization. Most known regulators act during late cytokinesis; a few, including the myosin II–binding proteins anillin and supervillin, act earlier. Anillin''s role in scaffolding the membrane cortex with the central spindle is well established, but the mechanism of supervillin action is relatively uncharacterized. We show here that two regions within supervillin affect cell division: residues 831–1281, which bind central spindle proteins, and residues 1–170, which bind the myosin II heavy chain (MHC) and the long form of myosin light-chain kinase. MHC binding is required to rescue supervillin deficiency, and mutagenesis of this site creates a dominant-negative phenotype. Supervillin concentrates activated and total myosin II at the furrow, and simultaneous knockdown of supervillin and anillin additively increases cell division failure. Knockdown of either protein causes mislocalization of the other, and endogenous anillin increases upon supervillin knockdown. Proteomic identification of interaction partners recovered using a high-affinity green fluorescent protein nanobody suggests that supervillin and anillin regulate the myosin II and actin cortical cytoskeletons through separate pathways. We conclude that supervillin and anillin play complementary roles during vertebrate cytokinesis.     

Viscoelastic creep induced by repetitive spine flexion and its relationship to dynamic spine stability

Repetitive trunk flexion elicits passive tissue creep, which has been hypothesized to compromise spine stability. The current investigation determined if increased spine flexion angle at the onset of flexion relaxation (FR) in the lumbar extensor musculature was associated with altered dynamic stability of spine kinematics. Twelve male participants performed 125 consecutive cycles of full forward trunk flexion. Spine kinematics and lumbar erector spinae (LES) electromyographic (EMG) activity were obtained throughout the repetitive trunk flexion trial. Dynamic stability was evaluated with maximum finite-time Lyapunov exponents over five sequential blocks of 25 cycles. Spine flexion angle at FR onset, and peak LES EMG activity were determined at baseline and every 25th cycle. Spine flexion angle at FR increased on average by 1.7° after baseline with significant increases of 1.7° and 2.4° at the 50th and 100th cycles. Maximum finite-time Lyapunov exponents demonstrated a transient, non-statistically significant, increase between cycles 26 and 50 followed by a recovery to baseline over the remainder of the repetitive trunk flexion cycles. Recovery of dynamic stability may be the consequence of increased active spine stiffness demonstrated by the non-significant increase in peak LES EMG that occurred as the repetitive trunk flexion progressed.