Propolis Components and Biological Activities from Stingless Bees Collected on South Sulawesi, Indonesia

Three new compounds, namely sulabiroins A (1) and B (2), and 2',3'-dihydro-3'-hydroxypapuanic acid (3), were isolated from the propolis of stingless bees (Tetragonula aff. biroi) collected on South Sulawesi, Indonesia. In addition, ten known compounds, (–)-papuanic acid (4), (–)-isocalolongic acid (5), isopapuanic acid (6), isocalopolyanic acid (7), glyasperin A (8), broussoflavonol F (9), (2S)-5,7-dihydroxy-4'-methoxy-8-prenylflavanone (10), isorhamnetin (11), (1'S)-2-trans,4-trans-abscisic acid (12), and (1'S)-2-cis,4-trans-abscisic acid (13) were identified. The structures of the new and known compounds were determined by spectroscopic analysis. The absolute configurations of sulabiroins A (1) and B (2) were determined by X-ray crystallography analysis and ECD calculation, respectively. The propolis from stingless bee (Tetragonula aff. biroi) collected on South Sulawesi contained compounds not present in propolis from other regions. Sulabiroin A (1) and isorhamnetin (11) were examined for xanthine oxidase (XO) inhibitory activity as one of biological activities; isorhamnetin (11) exhibited potent XO inhibitory activity, with an IC50 value of 3.9 µm

Conflicting actions of 4-vinylcatechol in rat lymphocytes under oxidative stress induced by hydrogen peroxide

4-Vinylcatechol (4VC) has been identified as an aroma compound in roasted foods, especially coffee. It is also a component in traditional herbal medicines. This compound may be subconsciously ingested through foods and herbs. Recent experimental evidence has shown that 4VC possesses an antioxidative action. However, the antioxidative action of 4VC at cellular levels is not well characterized. The effects of 4VC (0.1–100 μM) were examined on rat thymic lymphocytes without and with oxidative stress induced by 300 μM hydrogen peroxide (H2O2). Cell treatment with 100 μM 4VC alone for 4 hr significantly increased the population of dead cells. Thus, 4VC at 100 μM or above elicits cytotoxicity. However, 4VC at sublethal concentrations (1–10 μM) significantly attenuated the H2O2-induced increase in cell lethality in a concentration-dependent manner. While application of 10 μM 4VC slowed the process of cell death induced by H2O2, 4VC did not antagonize the H2O2-induced reduction of cellular nonprotein thiols. Although 4VC at 10 μM did not affect intracellular Ca2+ and Zn2+ levels, the agent potentiated the H2O2-induced increases in these levels. These actions of 10 μM 4VC are adverse to the cells under the oxidative stress. However, 10 μM 4VC partly attenuated the cell death induced by 100 nM A23187, a calcium ionophore. There are conflicting actions of 4VC at 1–100 μM on the cells under oxidative stress although the agent is used for an antioxidant. Thus, caution is required when using 4VC as a therapeutic agent

Nonivamide, a natural analog of capsaicin, affects intracellular Ca2+ level in rat thymic lymphocytes

Effect of nonivamide, a natural analog of capsaicin, on intracellular Ca2+ level of rat thymocytes was examined using a flow-cytometric technique with appropriate fluorescent probes in order to further characterize the cytotoxicity because nonivamide can be used as an active intergradient of antifouling paints. Nonivamide at concentrations ranging from 30 μM to 300 μM significantly increased the intensity of Fluo-3 fluorescence. The potency of 100 μM nonivamide to increase the fluorescence was similar to that of 100 μM capsaicin. The increase in Fluo-3 fluorescence by 100 μM nonivamide was attenuated under an external Ca2+-free condition. Nonivamide at 100 μM also increased the intensity of Fluo-3 fluorescence in the continued presence of 100 μM capsaicin. It is suggested that nonivamide at high micromolar concentrations increases intracellular Ca2+ level via the activation of vanilloid receptors. Nonivamide concentrations (30 μM or more) that increase intracellular Ca2+ level in rat thymocytes are comparable to those in algal cells. However, it is something hard to argue the implications in environmental science because nonivamide doesn’t seem to be released into environment in such a high concentration, and because bioaccumulation of nonivamide has not been reported

Hydroxyhydroquinone, a by-product of coffee bean roasting, increases intracellular Ca2+ concentration in rat thymic lymphocytes

Hydroxyhydroquinone (HHQ) is generated during coffee bean roasting. A cup of coffee contains 0.1–1.7 mg of HHQ. The actions of HHQ on mammalian DNA were examined because HHQ is a metabolite of benzene, which causes leukemia. Currently, information on the cellular actions of HHQ is limited. We examined the effects of sublethal levels of HHQ on the concentration of intracellular Ca2+ in rat thymic lymphocytes by using a flow cytometric technique with fluorescent probes. HHQ at 10 μM or more significantly elevated intracellular Ca2+ levels by increasing the membrane permeability of divalent cations, resulting in hyperpolarization via the activation of Ca2+-dependent K+ channels. HHQ-induced changes in the intracellular Ca2+ concentration and membrane potential may affect the cell functions of lymphocytes. HHQ-reduced coffee may be preferable in order to avoid the possible adverse effects of HHQ

Time evolution of probability density function of gamma ray burst (GRB) - a possible indication of turbulence origin of GRB

Gamma ray burst (GRB) time series is a non-stationary time series with all its statistical properties varying with time. Considering that each GRB is a different manifestation of the same stochastic process we studied the time dependent as well as time averaged probability density function (\emph{pdf}) characterizing the underlying stochastic process. The \emph{pdf}s are fitted with Gaussian distribution function and it has been argued that the Gaussian \emph{pdf}s possibly indicate the turbulence origin of GRB. The spectral and temporal evolution of GRBs are also studied through the evolution of spectral forms, color-color diagrams and hysteresis loops. The results do not contradict the turbulence interpretation of GRB.Comment: Accepted for publication in MNRA

Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994

Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve.Peer reviewe

Quantum critical behavior of the hyperkagome magnet Mn3CoSi

β-Mn-type family alloys Mn3TX (T = Co, Rh, and Ir; X = Si and Ge) have a three-dimensional antiferromagnetic (AF) corner-shared triangular network, i.e., the hyperkagome lattice. The antiferromagnet Mn3RhSi shows magnetic short-range order over a wide temperature range of approximately 500 K above the Néel temperature TN of 190 K. In this family of compounds, as the lattice parameter decreases, the long-range magnetic ordering temperature decreases. Mn3CoSi has the smallest lattice parameter and the lowest TN in the family. The quantum critical point (QCP) from AF to the quantum paramagnetic state is expected near a cubic lattice parameter of 6.15 Å. Although the Néel temperature of Mn3CoSi is only 140 K, the emergence of the quantum critical behavior in Mn3CoSi is discussed. We study how the magnetic short-range order appears in Mn3CoSi by using neutron scattering, μSR, and bulk characterization such as specific heat capacity. According to the results, the neutron scattering intensity of the magnetic short-range order in Mn3CoSi does not change much at low temperatures from that of Mn3RhSi, although the μSR short-range order temperature of Mn3CoSi is largely suppressed to 240 K from that of Mn3RhSi. Correspondingly, the volume fraction of the magnetic short-range order regions, as shown by the initial asymmetry drop ratio of μSR above TN, also becomes small. Instead, the electronic-specific heat coefficient γ of Mn3CoSi is the largest in this Mn3T Si system, possibly due to the low-energy spin fluctuation near the quantum critical point

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Noise-resistant developmental reproducibility in vertebrate somite formation

いいかげんに働く細胞たちが協調してからだを作る仕組みを解明 --リズムを刻む体内時計によるノイズキャンセル機構--. 京都大学プレスリリース. 2019-02-06.The reproducibility of embryonic development is remarkable, although molecular processes are intrinsically stochastic at the single-cell level. How the multicellular system resists the inevitable noise to acquire developmental reproducibility constitutes a fundamental question in developmental biology. Toward this end, we focused on vertebrate somitogenesis as a representative system, because somites are repeatedly reproduced within a single embryo whereas such reproducibility is lost in segmentation clock gene-deficient embryos. However, the effect of noise on developmental reproducibility has not been fully investigated, because of the technical difficulty in manipulating the noise intensity in experiments. In this study, we developed a computational model of ERK-mediated somitogenesis, in which bistable ERK activity is regulated by an FGF gradient, cell-cell communication, and the segmentation clock, subject to the intrinsic noise. The model simulation generated our previous in vivo observation that the ERK activity was distributed in a step-like gradient in the presomitic mesoderm, and its boundary was posteriorly shifted by the clock in a stepwise manner, leading to regular somite formation. Here, we showed that this somite regularity was robustly maintained against the noise. Removing the clock from the model predicted that the stepwise shift of the ERK activity occurs at irregular timing with irregular distance owing to the noise, resulting in somite size variation. This model prediction was recently confirmed by live imaging of ERK activity in zebrafish embryos. Through theoretical analysis, we presented a mechanism by which the clock reduces the inherent somite irregularity observed in clock-deficient embryos. Therefore, this study indicates a novel role of the segmentation clock in noise-resistant developmental reproducibility