White koji, a solid-state culture of Aspergillus luchuensis mut. kawachii using grains such as rice and barley, is used as a source of amylolytic enzymes and citric acid for the production of shochu, a traditional Japanese distilled spirit. We previously characterized changes in gene expression that affect the properties of white koji during the shochu production process; however, the underlying regulatory mechanisms were not determined. We then characterized the NAD+-dependent histone deacetylase sirtuin, an epigenetic regulator of various biological phenomena, in A. l. mut. kawachii and found that sirtuin SirD is involved in expression of α-amylase activity and citric acid accumulation. In this addendum study, we measured the NAD+/NADH redox state and found that the NAD+ level and NAD+/NADH ratio decrease during koji production, indicating that sirtuin activity declines in the late stages of koji culture. By comparing these results with transcriptomic data obtained in our previous studies, we estimate that approximately 35% of the gene expression changes during white koji production are SirD dependent. This study provides clues to the mechanism of gene expression regulation in A. l. mut. kawachii during the production of white koji.
The Feelings of Knowing - Fundamental Interoceptive Patterns (FoK-FIP) is a transdisciplinary theory developed to explain elusive phenomena suspected to exist that do not easily lend themselves to empirical measurement. The FoK-FIP theory posits that specialized self-generated biomagnetism and "pure mental" process share similarities with the hypothetical elementary particle described in particle physics, magnetic monopoles with a magnetic charge. Feelings of Knowing (FoK) are "awareness charge" that are self-generated events. Fundamental Interoceptive Patterns (FIP) are restricted oscillatory magnetic fields that are FoK caused phenomena. Further, FoK produces "cognitive force," an observing ego representing specialized interoceptive awareness. Through embodied states, FoK-FIP acts as a "biological node," an informational processing unit in which physiological signals and an observing ego's sensations or feelings are centered. An observing ego cognitively broadcasts using specialized small magnetic signals and four phases of a narrowed range of interoceptive signals. By defining interoceptive signals (i.e., signals of the body's internal state) using FoK-FIP through cognitive broadcasting, an observing ego creates a world it projects around itself. This process is understood through the components map with interoceptive markers (IMs), a novel algorithm based on biological evolution. FoK-FIP-related predictions are described as are empirical studies to test aspects of the theory. The FoK-FIP theory details a path to wellbeing based on a sense of control and capacity for self-care. Mental stability is thought to change as a function of an observing ego's volitional reactions.
Despite considerable advances in the past 50 y, the mechanism of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalysis is still not well understood. In particular, the movement and exchange of protons within the active site is not well documented: typically, kinetics of H exchange during the first steps of catalysis, i.e. abstraction of the H3 atom of ribulose 1,5-bisphosphate (RuBP) and enolization, are not clearly established. Here, we took advantage of reaction assays run in heavy water (2H2O) to monitor the appearance of deuterated RuBP and deuterated products (3-phosphoglycerate and 2-phosphoglycolate) with exact mass LC-MS. Enolization was reversible such that de-enolization generated not only monodeuterated RuBP (2H-[H-3]-ribulose 1,5-bisphosphate) but also dideuterated RuBP (2H2-[H-3,O-3]-ribulose 1,5-bisphosphate). Carboxylation yielded about one half deuterated 3-phosphoglycerate (2H-[H-2]-3-phosphoglycerate) and also a small proportion of dideuterated 3-phosphoglycerate (2H2-[H-2,O-2]-3-phosphoglycerate). Oxygenation generated a small amount of monodeuterated, but no dideuterated, products. (Di)deuterated isotopologue abundance depended negatively on gas concentration. We conclude that in addition to the first step of proton exchange at H3 occurring before gas addition (and thus influenced by the competition between de-enolization and gas addition), there is another proton exchange step between solvent water, active site residues, and the 2,3-enediol(ate) leading to deuterated OH groups in products.
The modern telecommunications industry is ubiquitous throughout the world, with a significant percentage of the population using cellular phones on a daily basis. The possible physiological consequences of wireless emissions in the GHz range are therefore of major interest, but remain poorly understood. Here, we show that exposure to a 1.8 GHz carrier frequency in the amplitude range of household telecommunications induces the formation of ROS (Reactive Oxygen Species) in human HEK293 cultured cells. The ROS concentrations detected by fluorescent imaging techniques increased significantly after 15 minutes of RF field exposure, and were localized to both nuclear and cytosolic cellular compartments. qPCR analysis showed altered gene expression of both anti-oxidative (SOD, GPX, GPX, and CAT) and oxidative (Nox-2) enzymes. In addition, multiple genes previously identified as responsive to static magnetic fields were found to also be regulated by RF, suggesting common features in response mechanisms. By contrast, many RF effects showed evidence of hormesis, whereby biological responsivity does not occur linearly as a function of signal amplitude. Instead, biphasic dose response curves occur with 'blind' spots at certain signal amplitudes where no measureable response occurs. We conclude that modulation of intracellular ROS can be a direct consequence of RF exposure dependent on signal frequency and amplitude. Since changes in intracellular ROS may have both harmful and beneficial effects, these could provide the basis for many reported physiological effects of RF exposure.
In reconstructive surgery using artificial materials after wide resection, soft tissues are usually adjacent to metal surfaces or mesh. The purpose of this study was to provide histological evaluation of the soft tissues adjacent to the metal surfaces of megaprostheses and mesh. Tissues from revision surgery of megaprosthesis and from wide resection after recurrent thoracic wall sarcoma were used. Histological analysis was evaluated by hematoxylin/eosin (HE) and Masson's trichrome staining, and by immunohistochemical staining for markers including cluster of differentiation 68 (CD68), vimentin, collagen type and S100A4. Soft tissue adherence to the smooth metal surface of Ti alloy was not observed. On the surface of capsule, CD68- and vimentin-positive cells formed a thin layer. In contrast, soft tissue adherence to a rough-surface cobalt chrome alloy was observed. Capsule was not apparent for this tissue, in which CD68- and vimentin-positive cells were aggregated randomly. In the resected tissues of recurrent chest wall sarcoma, muscles showed connections to connective soft tissues but did not invade to the inside of the mesh. Around the polypropylene mesh, large numbers of CD68- and vimentin-positive cells were seen. On the ePTFE, small numbers of CD68-positive cells were observed, while a larger number of the cells were vimentin positive. High accumulation of S100A4-positive cells was observed at the metal surface and polypropylene surface. Cells were strongly positive for CD68 and vimentin in tissues adjacent to metal and mesh surfaces. Macrophages and vimentin may play important roles in the foreign body reaction to metal and mesh, and so may contribute to encapsulation and fibrosis.
Ciliary extracellular vesicles (ciEVs), released from primary cilia, contain functional proteins that play an important role in cilia structure and functions. We have recently shown that ciEVs and cytosolic extracellular vesicles (cyEVs) have unique and distinct biomarkers. While ciEV biomarkers have shown some interactions with known ciliary proteins, little is known about the interaction of ciEV proteins with proteins involved in ciliopathy and neurodegenerative disorders. Here, we reveal for the first time the protein-protein interaction (PPI) between the top five ciEVs biomarkers with ciliopathy and Alzheimer disease (AD) proteins. These results support the growing evidence of the critical physiological roles of cilia in neurodegenerative disorders.
We consider the effect of non-constant parameters on the human-forest interaction logistic model coupled with human technological growth introduced in [1]. In recent years in fact, a decrease in human population growth rate has emerged which can be measured to about 1.7% drop per year since 1960 value, which coincides with latest UN projections for next decades up to year 2100 [2]. We therefore consider here the effect of decreasing human population growth-rate on the aforementioned model and we evaluate its effect on the probability of survival of human civilization without going through a catastrophic population collapse. We find that for realistic values of the human population carrying capacity of the earth (measured by the parameter β) this decrease would not affect previous results, leading to a low probability of avoiding a catastrophic collapse. For larger more optimistic values of β instead, a decrease in growth-rate would tilt the probability in favor of a positive outcome, i.e. from 10-20% up to even 95% likelihood of avoiding collapse.