Cancer cells alter their nutrition metabolism to cope the stressful environment. One important metabolism adjustment is that cancer cells activate glutaminolysis in response to the reduced carbon from glucose entering into the TCA cycle due to inactivation of several enzymes in glycolysis. An important question is how the cancer cells coordinate the changes of glycolysis and glutaminolysis. In this report, we demonstrate that the pyruvate kinase inactive dimer PKM2 facilitates activation of glutaminolysis. Our experiments show that growth stimulations promote PKM2 dimer. The dimer PKM2 plays a role in regulation of glutaminolysis by upregulation of mitochondrial glutaminase I (GLS-1). PKM2 dimer regulates the GLS-1 expression by controlling internal ribosome entry site (IRES)-dependent c-myc translation. Growth stimulations promote PKM2 interacting with c-myc IRES-RNA, thus facilitating c-myc IRES-dependent translation. Our study reveals an important linker that coordinates the metabolism adjustment in cancer cells.
The trend of e-cigarette use among teens is ever increasing. Here we show the dysbiotic oral microbial ecology in e-cigarette users influencing the local host immune environment compared with non-smoker controls and cigarette smokers. Using 16S rRNA high-throughput sequencing, we evaluated 119 human participants, 40 in each of the three cohorts, and found significantly altered beta-diversity in e-cigarette users (p = 0.006) when compared with never smokers or tobacco cigarette smokers. The abundance of Porphyromonas and Veillonella (p = 0.008) was higher among vapers. Interleukin (IL)-6 and IL-1β were highly elevated in e-cigarette users when compared with non-users. Epithelial cell-exposed e-cigarette aerosols were more susceptible for infection. In vitro infection model of premalignant Leuk-1 and malignant cell lines exposed to e-cigarette aerosol and challenged by Porphyromonas gingivalis and Fusobacterium nucleatum resulted in elevated inflammatory response. Our findings for the first time demonstrate that e-cigarette users are more prone to infection.
Little is known about the effect of latent-phase herpesviruses on their host. Human herpesvirus 6B (HHV-6B) is one of the most ubiquitous herpesviruses, and olfactory astrocytes are one of the most important sites of its latency. Here, we identified SITH-1, an HHV-6B latent protein specifically expressed in astrocytes. Mice induced to produce SITH-1 in their olfactory astrocytes exhibited olfactory bulb apoptosis, a hyper-activated hypothalamic-pituitary-adrenal (HPA) axis and depressive symptoms. The binding of SITH-1 to the host protein calcium-modulating ligand (CAML) to form an activated complex promoted the influx of extracellular calcium. The serum antibody titers for depressive patients with respect to this activated complex were significantly higher than for normal controls (p = 1.78 × 10-15), when the antibody positive rates were 79.8% and 24.4%, respectively, and the odds ratio was 12.2. These results suggest that, in the latent phase, HHV-6B may be involved in the onset of depression.
Mechanical forces are known to be involved in various biological processes. However, it remains unclear whether brain functions are mechanically regulated under physiological conditions. Here, we demonstrate that treadmill running and passive head motion (PHM), both of which produce mechanical impact on the head, have similar effects on the hallucinogenic 5-hydroxytryptamine (5-HT) receptor subtype 2A (5-HT2A) signaling in the prefrontal cortex (PFC) of rodents. PHM generates interstitial fluid movement that is estimated to exert shear stress of a few pascals on cells in the PFC. Fluid shear stress of a relevant magnitude on cultured neuronal cells induces ligand-independent internalization of 5-HT2A receptor, which is observed in mouse PFC neurons after treadmill running or PHM. Furthermore, inhibition of interstitial fluid movement by introducing polyethylene glycol hydrogel eliminates the effect of PHM on 5-HT2A receptor signaling in the PFC. Our findings indicate that neuronal cell function can be physiologically regulated by mechanical forces in the brain.
The narwhal (Monodon monoceros) is a highly specialized endemic Arctic cetacean, restricted to the Arctic seas bordering the North Atlantic. Low levels of genetic diversity have been observed across several narwhal populations using mitochondrial DNA and microsatellites. Despite this, the global abundance of narwhals was recently estimated at ∼170,000 individuals. However, the species is still considered vulnerable to changing climates due to its high specialization and restricted Arctic distribution. We assembled and annotated a genome from a narwhal from West Greenland. We find relatively low diversity at the genomic scale and show that this did not arise by recent inbreeding, but rather has been stable over an extended evolutionary timescale. We also find that the current large global abundance most likely reflects a recent rapid expansion from a much smaller founding population.
How does our body affect the way we think about our personality? We addressed this question by eliciting the perceptual illusion that pairs of friends swapped bodies with each other. We found that during the illusion, the participants rated their own personality characteristics more similarly to the way they previously rated their friend’s personality, and this flexible adjustment of self-concept to the “new” bodily self was related to the strength of illusory ownership of the friend’s body. Moreover, a subsequent memory test showed that personality traits rated during the friend-body-swap illusion were generally remembered worse than traits rated during the control conditions; importantly, however, this impairment of episodic recognition memory was reduced for the participants who considerably adjusted their self-concept during the illusory body swapping. These findings demonstrate that our beliefs about own personality are dynamically shaped by the perception of our body and that coherence between the bodily and conceptual self-representations is important for the normal encoding of episodic memories.
Carbon capture, utilization, and sequestration technologies have been extensively studied to utilize carbon dioxide (CO2), a greenhouse gas, as a resource. So far, however, effective technologies have not been proposed owing to the low efficiency conversion rate and high energy requirements. Here, we present a hybrid Na-CO2 cell that can continuously produce electrical energy and hydrogen through efficient CO2 conversion with stable operation for over 1,000 hr from spontaneous CO2 dissolution in aqueous solution. In addition, this system has the advantage of not regenerating CO2 during charging process, unlike aprotic metal-CO2 cells. This system could serve as a novel CO2 utilization technology and high-value-added electrical energy and hydrogen production device.
Varying levels of numerical cognition have been found in several animal species. Bees, in particular, have been argued to be able to count up to four items and solve complex numerical tasks. Here we present an exceedingly simple neural circuit that, when provided with the actual visual input that the bee is receiving while carrying out the task, can make reliable estimates on the number of items in the display. Thus we suggest that the elegance of numerical problem solving in bees might not lie in the formation of numerical concepts (such as “more,” “less,” or “zero”), but in the use of specific flight movements to scan targets, which streamlines the visual input and so renders the task of counting computationally inexpensive. Careful examination of the actual inspection strategies used by animals might reveal that animals often employ active scanning behaviors as shortcuts to simplify complex visual pattern discrimination tasks.
Caregivers hug their infants to express affection and joy. However, it remains unknown how infants react to being hugged. Here we examined heart rate responses in first-year infants during a hug, hold, and tight hug from parents. Infants older than four months showed an increased R-R interval (RRI) during a hug, indicating reduced heart rates and pronounced parasympathetic activity. Few head movements predicted a higher RRI increase in infants during a parental hug compared with that during a hold and tight hug. Infants did not show an increased RRI during a hug from a female stranger. Infants younger than four months did not show RRI increase during parental hug but exhibited a decreased RRI correlated with contact pressure. Parents showed an increased RRI during hugging their infants. These results suggest the parent-infant hug underlies the parent-infant bonding and psychophysiological development of infants.
We have developed and integrated several technologies including whole-organ imaging and software development to support an initial precise 3D neuroanatomical mapping and molecular phenotyping of the intracardiac nervous system (ICN). While qualitative and gross anatomical descriptions of the anatomy of the ICN have each been pursued, we here bring forth a comprehensive atlas of the entire rat ICN at single-cell resolution. Our work precisely integrates anatomical and molecular data in the 3D digitally reconstructed whole heart with resolution at the micron scale. We now display the full extent and the position of neuronal clusters on the base and posterior left atrium of the rat heart, and the distribution of molecular phenotypes that are defined along the base-to-apex axis, which had not been previously described. The development of these approaches needed for this work has produced method pipelines that provide the means for mapping other organs.