Immune response to SARS-CoV-2 in severe disease and long COVID-19

COVID-19 is mild to moderate in otherwise healthy individuals but may nonetheless cause life-threatening disease and/or a wide range of persistent symptoms. The general determinant of disease severity is age mainly because the immune response declines in aging patients. Here, we developed a mathematical model of the immune response to SARS-CoV-2 and revealed that typical age-related risk factors such as only a several 10% decrease in innate immune cell activity and inhibition of type-I interferon signaling by autoantibodies drastil ally increased the viral load. It was reported that the numbers of certain dendritic cell subsets remained less than half those in healthy donors even seven months after infection. Hence, the inflammatory response was ongoing. Our model predicted the persistent DC reduction and showed that certain patients with severe and even mild symptoms could not effectively eliminate the virus and could potentially develop long COVID

Mechanism underlying hippocampal long-term potentiation and depression based on competition between endocytosis and exocytosis of AMPA receptors

N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) and long-term depression (LTD) of signal transmission form neural circuits and thus are thought to underlie learning and memory. These mechanisms are mediated by AMPA receptor (AMPAR) trafficking in postsynaptic neurons. However, the regulatory mechanism of bidirectional plasticity at excitatory synapses remains unclear. We present a network model of AMPAR trafficking for adult hippocampal pyramidal neurons, which reproduces both LTP and LTD. We show that the induction of both LTP and LTD is regulated by the competition between exocytosis and endocytosis of AMPARs, which are mediated by the calcium-sensors synaptotagmin 1/7 (Syt1/7) and protein interacting with C-kinase 1 (PICK1), respectively. Our result indicates that recycling endosomes containing AMPAR are always ready for Syt1/7-dependent exocytosis of AMPAR at peri-synaptic/synaptic membranes. This is because molecular motor myosin V-b constitutively transports the recycling endosome toward the membrane in a Ca2+-independent manner

Kinetics of the ancestral carbon metabolism pathways in deep-branching bacteria and archaea

The origin of life is believed to be chemoautotrophic, deriving all biomass components from carbon dioxide, and all energy from inorganic redox couples in the environment. The reductive tricarboxylic acid cycle (rTCA) and the Wood-Ljungdahl pathway (WL) have been recognized as the most ancient carbon fixation pathways. The rTCA of the chemolithotrophic Thermosulfidibacter takaii, which was recently demonstrated to take place via an unexpected reverse reaction of citrate synthase, was reproduced using a kinetic network model, and a competition between reductive and oxidative fluxes on rTCA due to an acetyl coenzyme A (ACOA) influx upon acetate uptake was revealed. Avoiding ACOA direct influx into rTCA from WL is, therefore, raised as a kinetically necessary condition to maintain a complete rTCA. This hypothesis was confirmed for deep-branching bacteria and archaea, and explains the kinetic factors governing elementary processes in carbon metabolism evolution from the last universal common ancestor

Muscarinic acetylcholine receptor-dependent and NMDA receptor-dependent LTP and LTD share the common AMPAR trafficking pathway

The forebrain cholinergic system promotes higher brain function in part by signaling through the M1 muscarinic acetylcholine receptor (mAChR). Long-term potentiation (LTP) and long-term depression (LTD) of excitatory synaptic transmis-sion in the hippocampus are also induced by mAChR. An AMPA receptor (AMPAR) trafficking model for hippocampal neurons has been proposed to simulate N-methyl-D-aspartate receptor (NMDAR)-dependent synaptic plasticity in the early phase. In this study, we demonstrated the validity of the hypothesis that the mAChR-dependent LTP/LTD shares a common AMPAR trafficking pathway associated with NMDAR-dependent LTP/LTD. However, unlike NMDAR, Ca2+ influx into the spine cytosol occurs owing to the Ca2+ stored inside the ER and is induced via the activation of inositol 1,4,5-trisphosphate (IP3) receptors during M1 mAChR activation. Moreover, the AMPAR trafficking model implies that alterations in LTP and LTD observed in Alzheimer's disease could be attributed to age-dependent reductions in AMPAR expression levels

Levels of Octachlorostyrene in Mothers' Milk and Potential Exposure Among Infants in Sendai City, Japan 2012

Persistent organic pollutants can accumulate inside the human body, including in mothers’ milk, which may affect infant development. This cross-sectional study aimed to examine selected persistent organic pollutants in the milk of 100 mothers in Sendai city, Miyagi Prefecture, Japan. We used gas-chromatography-electron capture negative chemical ionization-mass spectrometry to check for octachlorostyrene, dechlorane (Dec) plus, Dec 602, Dec 603, and Dec 604. Octachlorostyrene was detected in 86 samples at more than the method detection limit (84 pg g-lipid⁻¹) but no dechloranes were above the method detection limit (1 ng mL⁻¹ for dechlorane plus, Dec 602, and Dec 603; 20 ng mL⁻¹ for Dec 604). The mean octachlorostyrene concentration was 461 pg g-lipid−1, the median was 337 pg g-lipid⁻¹, and the standard deviation 450 pg g-lipid⁻¹. No baseline characteristics were associated with octachlorostyrene level except for mother’s occupation (stay-at-home mother, 353 ± 327 pg g-lipid⁻¹; others, 531 ± 509 pg g-lipid⁻¹). Octachlorostyrene was also significantly negatively correlated with lipid content (r = −0.35, p = 0.0004). However, the maximum intake of octachlorostyrene among infants in this study (3.5 ng/kg/day) was under the acceptable daily intake (30 ng/kg/day, derived from 12−month study in rats), and is therefore unlikely to pose a health risk

The incidence of diabetes among the non-diabetic residents in Kawauchi village, Fukushima, who experienced evacuation after the 2011 Fukushima Daiichi nuclear power plant disaster

OBJECTIVES: After the Fukushima Daiichi nuclear power plant disaster in 2011, residents of Kawauchi village who experienced evacuation had a high risk of suffering from diabetes and metabolic syndrome compared with non-evacuees. In addition to evacuation, lifestyle characteristics can be important factors influencing the development and prognosis of diabetes or glucose tolerance. The current study aimed to evaluate the effects of evacuation (i.e., lifestyle changes) on the incidence of diabetes among the non-diabetic residents of Kawauchi village. METHODS: Design is retrospective cohort study. Annual health examination data of residents of Kawauchi village and control area (Ono town) in Fukushima prefecture from 2008 to 2017, as available from the Japanese National Health Insurance system. Participants were classified into three groups: "Diabetes (DM)" (FBG ≥ 126 mg/dL or HbA1c ≥ 6.5% or hospital visit for DM or usage of diabetic medication), "Borderline DM" (126 mg/dL > FBG ≥ 110 mg/dL or 6.5% > HbA1c ≥ 6.0%, and without hospital visit, and without diabetic medication), and "Normoglycemic" (FBG < 110 mg/dL and HbA1c < 6.0%, and without hospital visit, and without diabetic medication). New onset of diabetes was evaluated and the events or missing data were occurred at health checkup. For this survival analysis, 339 residents in Kawauchi and 598 residents in Ono were included. Average follow-up periods after 2010 were 3.9 years in Kawauchi village and 3.6 years in Ono town. RESULTS: Compared with the normoglycemic group, incidence of DM was much greater in the borderline DM group, where DM occurred among 38.2% of the group in 2012 and increased to over 60% cumulatively through 2017 in Kawauchi village. DM had a prevalence of 16.3% in 2012, and below 30% in 2017 in borderline DM group of Ono town. Cox proportional hazard regression analysis was applied to non-DM groups at both study sites separately to evaluate the effects of lifestyle changes at each site. While BMI, BMI change, and the lack of regular exercise (HR = 1.29, 1.72, and 5.04, respectively) showed significant associations with the onset of diabetes in Ono town, only BMI and late-night dinner (HR = 1.21 and 4.86, respectively) showed significant associations with diabetes onset in Kawauchi village. CONCLUSIONS: The current results confirmed that diabetes incidence was increased 6 years after the Daiichi nuclear power plant disaster in Kawauchi. We also found changes in lifestyle habits, suggesting that diabetes prevention with promotion of healthy lifestyle behaviors is an urgent priority

PRIMARY OVARIAN MYXOMA

Primary ovarian myxoma is exceedingly rare, with only five cases known to be reported. We present an 18-year-old female with an ovarian myxoma

Conflict-related environmental damages on health: lessons learned from the past wars and ongoing Russian invasion of Ukraine

On 24 February 2022, Russian military forces invaded Ukraine. The fighting has already caused unimaginable conditions and millions of people were forced to flee their homes. For decades, conflicts have been linked to environmental pollution, exposure to radioactivity and heavy metals as well as infectious diseases. The invasion may cause specific environmental risks, like the release of radioactive substances from nuclear power plants and contaminated soils. Because international collaboration is one of the most effective ways to address environmental problems, it is critical to establish scientific bodies within a global framework to identify concrete actions and tangible measures to provide immediate assistance to citizens. This commentary discusses the above issues from lessons learned from the past wars and the way forward in the Russian invasion of Ukraine