Aggregation number distributions and mesoglobules in dilute solutions of diblock and triblock copolymers

We investigate the aggregation number and size distributions for inter-molecular clusters of amphiphilic diblock and triblock copolymers in poor solvent at very low concentrations. Diblocks and triblocks with hydrophilic ends are shown to possess narrow distributions corresponding to formation of monodispersed mesoglobules. Diblocks with hydrophobic ends are found to produce inter-cluster multimers due to bridging by the hydrophilic middle blocks, resulting in polydisperse distributions. Implications of these observations for preparation of monodispersed nanoparticles and, potentially, understanding of the quaternary structure of proteins are discussed.Comment: 4 pages, 4 PS figures. Accepted for publication in EP

Unusual Presentation Chronic Pulmonary Embolism due to Calcified Right Ventricular Mass

Cardiac calcified amorphous tumors (CATs) can arise in all four chambers of the heart. Cardiac CATs can cause diverse symptoms according to their locations, and mass or embolic effects. Pulmonary emboli arising from cardiac CATs have been reported, but the true incidence is unknown due to their rarity. Herein we report a rare case with diffuse CATs in the right ventricle which caused a calcific pulmonary embolism and right-sided heart failure. Echocardiography, chest non-contrast computed tomography, and cardiac magnetic resonance imaging helped us diagnose the CATs. We recommend the usefulness of a multimodality imaging approach to characterize intracardiac masses and their complications accurately

A System for Worldwide COVID-19 Information Aggregation

The global pandemic of COVID-19 has made the public pay close attention to related news, covering various domains, such as sanitation, treatment, and effects on education. Meanwhile, the COVID-19 condition is very different among the countries (e.g., policies and development of the epidemic), and thus citizens would be interested in news in foreign countries. We build a system for worldwide COVID-19 information aggregation (http://lotus.kuee.kyoto-u.ac.jp/NLPforCOVID-19 ) containing reliable articles from 10 regions in 7 languages sorted by topics for Japanese citizens. Our reliable COVID-19 related website dataset collected through crowdsourcing ensures the quality of the articles. A neural machine translation module translates articles in other languages into Japanese. A BERT-based topic-classifier trained on an article-topic pair dataset helps users find their interested information efficiently by putting articles into different categories.Comment: Poster on NLP COVID-19 Workshop at ACL 2020, 4 pages, 3 figures, 7 table

A facility to Search for Hidden Particles (SHiP) at the CERN SPS

A new general purpose fixed target facility is proposed at the CERN SPS accelerator which is aimed at exploring the domain of hidden particles and make measurements with tau neutrinos. Hidden particles are predicted by a large number of models beyond the Standard Model. The high intensity of the SPS 400~GeV beam allows probing a wide variety of models containing light long-lived exotic particles with masses below ${\cal O}$(10)~GeV/c$^2$, including very weakly interacting low-energy SUSY states. The experimental programme of the proposed facility is capable of being extended in the future, e.g. to include direct searches for Dark Matter and Lepton Flavour Violation.Comment: Technical Proposa

Silibinin induces mitochondrial NOX4-mediated endoplasmic reticulum stress response and its subsequent apoptosis

Background: Silibinin, a biologically active compound of milk thistle, has chemopreventive effects on cancer cell lines. Recently it was reported that silibinin inhibited tumor growth through activation of the apoptotic signaling pathway. Although various evidences showed multiple signaling pathways of silibinin in apoptosis, there were no reports to address the clear mechanism of ROS-mediated pathway in prostate cancer PC-3 cells. Several studies suggested that reactive oxygen species (ROS) play an important role in various signaling cascades, but the primary source of ROS was currently unclear. Methods: The effect of silibinin was investigated on cell growth of prostate cell lines by MTT assay. We examined whether silibinin induced apoptosis through production of ROS using flow cytometry. Expression of apoptosis-, endoplasmic reticulum (ER)-related protein and gene were determined by western blotting and RT-PCR, respectively. Results: Results showed that silibinin triggered mitochondrial ROS production through NOX4 expression and finally led to induce apoptosis. In addition, mitochondrial ROS caused ER stress through disruption of Ca2+ homeostasis. Co-treatment of ROS inhibitor reduced the silibinin-induced apoptosis through the inhibition of NOX4 expression, resulting in reduction of both Ca2+ level and ER stress response. Conclusions: Taken together, silibinin induced mitochondrial ROS-dependent apoptosis through NOX4, which is associated with disruption of Ca2+ homeostasis and ER stress response. Therefore, the regulation of NOX4, mitochondrial ROS producer, could be a potential target for the treatment of prostate cancer.ope

Mitochondrial abnormalities in spinal and bulbar muscular atrophy

Spinal and bulbar muscular atrophy (SBMA) is a motor neuron disease caused by polyglutamine expansion mutation in the androgen receptor (AR). We investigated whether the mutant protein alters mitochondrial function. We found that constitutive and doxycycline-induced expression of the mutant AR in MN-1 and PC12 cells, respectively, are associated with depolarization of the mitochondrial membrane. This was mitigated by cyclosporine A, which inhibits opening of the mitochondrial permeability transition pore. We also found that the expression of the mutant protein in the presence of ligand results in an elevated level of reactive oxygen species, which is blocked by the treatment with the antioxidants co-enzyme Q10 and idebenone. The mutant protein in MN-1 cells also resulted in increased Bax, caspase 9 and caspase 3. We assessed the effects of mutant AR on the transcription of mitochondrial proteins and found altered expression of the peroxisome proliferator-activated receptor γ coactivator 1 and the mitochondrial specific antioxidant superoxide dismutase-2 in affected tissues of SBMA knock-in mice. In addition, we found that the AR associates with mitochondria in cultured cells. This study thus provides evidence for mitochondrial dysfunction in SBMA cell and animal models, either through indirect effects on the transcription of nuclear-encoded mitochondrial genes or through direct effects of the mutant protein on mitochondria or both. These findings indicate possible benefit from mitochondrial therapy for SBMA

Nifedipin ublažava djelovanje kokaina na enzimsku aktivnost u mozgu i jetri te smanjuje njegovo izlučivanje putem mokraće

The aim of this study was to see how nifedipine counters the effects of cocaine on hepatic and brain enzymatic activity in rats and whether it affects urinary excretion of cocaine. Male Wistar rats were divided in four groups of six: control, nifedipine group (5 mg kg-1 i.p. a day for five days); cocaine group (15 mg kg-1 i.p. a day for five days), and the nifedipine+cocaine group. Twenty-four hours after the last administration, we measured neuronal nitric oxide synthase (nNOS) activity in the brain and cytochrome P450 quantity, ethylmorphine-N-demethylase, and anilinehydroxylase activity in the liver. Urine samples were collected 24 h after the last cocaine and cocaine+nifedipine administration. Urinary cocaine concentration was determined using the GC/MS method. Cocaine administration increased brain nNOS activity by 55 % (p<0.05) in respect to control, which indicates the development of tolerance and dependence. In the combination group, nifedipine decreased the nNOS activity in respect to the cocaine-only group. In the liver, cocaine significantly decreased and nifedipine significantly increased cytochrome P450, ethylmorphine-N-demethylase, and anilinehydroxylase in respect to control. In combination, nifedipine successfully countered cocaine effects on these enzymes. Urine cocaine excretion in the cocaine+nifedipine group significantly dropped (by 35 %) compared to the cocaine-only group. Our results have confirmed the effects of nifedipine against cocaine tolerance and development of dependence, most likely due to metabolic interactions between them.Cilj je ovoga istraživanja bio utvrditi kako nifedipin ublažava djelovanje kokaina na enzimsku aktivnost u mozgu i jetri Wistar štakora te utječe li na njegovo izlučivanje putem mokraće. Mužjaci su podijeljeni u četiri skupine po šest jedinki: kontrolnu skupinu, nifedipinsku skupinu koja je pet dana intraperitonealno primala nifedipin u dozi od 5 mg kg-1; skupinu koja je pet dana primala kokain u dozi od 15 mg kg-1 na dan te skupinu koja je zajedno primala nifedipin i kokain u odgovarajućim dozama. Dvadeset i četiri sata nakon posljednje doze izmjerena je enzimska aktivnost sintaze dušičnoga oksida (nNOS) u mozgu, razina citokroma P450 te aktivnosti enzima etilmorfi n-N-demetilaze i anilinhidroksilaze u jetri štakora. Uzorci mokraće prikupljeni su 24 sata nakon posljednje doze kokaina odnosno kombinacije nifedipina i kokaina. Koncentracija kokaina u mokraći izmjerena je s pomoću vezanog sustava plinske kromatografi je i spektrometrije masa. Kokain je povećao aktivnost nNOS-a u mozgu za 55 % (p<0,05) u odnosu na kontrolnu skupinu, što upućuje na stvaranje tolerancije i ovisnosti. U kombiniranoj skupini nifedipin je značajno smanjio aktivnost nNOS-a u odnosu na skupinu koja je primila samo kokain. Kokain je značajno snizio, a nifedipin značajno povisio razinu citokroma P450 u jetri te aktivnost etilmorfi n-N-demetilaze i anilinhidroksilaze u odnosu na kontrolnu skupinu. U kombiniranoj skupini nifedipin je uspješno ublažio djelovanje kokaina na aktivnost spomenutih enzima. Izlučivanje kokaina putem mokraće u kombiniranoj skupini bilo je značajno manje (35 %) nego u skupini koja je primala samo kokain. Ovi rezultati potvrđuju da nifedipin štiti od djelovanja kokaina i stvaranja ovisnosti, najvjerojatnije zbog interakcija u metabolizmu dvaju spojeva

Experience-Driven Axon Retraction in the Pharmacologically Inactivated Visual Cortex Does Not Require Synaptic Transmission

BACKGROUND: Experience during early postnatal development plays an important role in the refinement of specific neural connections in the brain. In the mammalian visual system, altered visual experiences induce plastic adaptation of visual cortical responses and guide rearrangements of afferent axons from the lateral geniculate nucleus. Previous studies using visual deprivation demonstrated that the afferents serving an open eye significantly retract when cortical neurons are pharmacologically inhibited by applying a gamma-aminobutyric acid type A receptor agonist, muscimol, whereas those serving a deprived eye are rescued from retraction, suggesting that presynaptic activity can lead to the retraction of geniculocortical axons in the absence of postsynaptic activity. Because muscimol application suppresses the spike activity of cortical neurons leaving transmitter release intact at geniculocortical synapses, local synaptic interaction may underlie the retraction of active axons in the inhibited cortex. METHOD AND FINDINGS: New studies reported here determined whether experience-driven axon retraction can occur in the visual cortex inactivated by blocking synaptic inputs. We inactivated the primary visual cortex of kittens by suppressing synaptic transmission with cortical injections of botulinum neurotoxin type E, which cleaves a synaptic protein, SNAP-25, and blocks transmitter release, and examined the geniculocortical axon morphology in the animals with normal vision and those deprived of vision binocularly. We found that afferent axons in the animals with normal vision showed a significant retraction in the inactivated cortex, as similarly observed in the muscimol-treated cortex, whereas the axons in the binocularly deprived animals were preserved. CONCLUSIONS: Therefore, the experience-driven axon retraction in the inactivated cortex can proceed in the absence of synaptic transmission. These results suggest that presynaptic mechanisms play an important role in the experience-driven refinement of geniculocortical axons