UBR2 of the N-end rule pathway is required for chromosome stability via histone ubiquitylation in spermatocytes and somatic cells

The N-end rule pathway is a proteolytic system in which its recognition components (N-recognins) recognize destabilizing N-terminal residues of short-lived proteins as an essential element of specific degrons, called N-degrons. The RING E3 ligases UBR2 and UBR1 are major N-recognins that share size (200 kDa), conserved domains and substrate specificities to N-degrons. Despite the known function of the N-end rule pathway in degradation of cytosolic proteins, the major phenotype of UBR2-deficient male mice is infertility caused by arrest of spermatocytes at meiotic prophase I. UBR2-deficient spermatocytes are impaired in transcriptional silencing of sex chromosome-linked genes and ubiquitylation of histone H2A. In this study we show that the recruitment of UBR2 to meiotic chromosomes spatiotemporally correlates to the induction of chromatin-associated ubiquitylation, which is significantly impaired in UBR2-deficient spermatocytes. UBR2 functions as a scaffold E3 that promotes HR6B/UbcH2-dependent ubiquitylation of H2A and H2B but not H3 and H4, through a mechanism distinct from typical polyubiquitylation. The E3 activity of UBR2 in histone ubiquitylation is allosterically activated by dipeptides bearing destabilizing N-terminal residues. Insufficient monoubiquitylation and polyubiquitylation on UBR2-deficient meiotic chromosomes correlate to defects in double strand break (DSB) repair and other meiotic processes, resulting in pachytene arrest at stage IV and apoptosis. Some of these functions of UBR2 are observed in somatic cells, in which UBR2 is a chromatin-binding protein involved in chromatin-associated ubiquitylation upon DNA damage. UBR2-deficient somatic cells show an array of chromosomal abnormalities, including hyperproliferation, chromosome instability, and hypersensitivity to DNA damage-inducing reagents. UBR2-deficient mice enriched in C57 background die upon birth with defects in lung expansion and neural development. Thus, UBR2, known as the recognition component of a major cellular proteolytic system, is associated with chromatin and controls chromatin dynamics and gene expression in both germ cells and somatic cells. © 2012 Kwon et al

Improved Charge Separation and Photovoltaic Performance of BiI3 Absorber Layers by Use of an In Situ Formed BiSI Interlayer

Stable and nontoxic bismuth iodide (BiI3) is emerging as a promising absorber material for solar cell applications as it possesses favorable optical properties such as a narrow bandgap (1.7 eV) and a high absorption coefficient (105 cm–1) in the visible region. Despite these promising features, solar cells employing this material have only achieved power conversion efficiencies in the region of 1% as of yet, which is distant from the theoretical efficiency limit of 28%. It is reasonable to suppose that the relatively low performance of BiI3-based solar cells may originate from very short carrier lifetimes (180–240 ps) in BiI3, which makes efficient separation of mobile charges a crucial factor for the improvement of the photovoltaic performance of this material. Herein, transient optical spectroscopy is employed to show that the use of a bismuth sulfide iodide interlayer between the electron transport layer (ETL) and the bismuth iodide absorber promotes efficient charge separation. On the basis of this knowledge, we report BiI3 solar cells with a power conversion efficiency of 1.21% using a solar cell architecture comprised of ITO/SnO2/BiSI/BiI3/organic HTM/Au

Reduction in CO2 uptake rates of red tide dinoflagellates due to mixotrophy

We investigated a possible reduction in CO2 uptake rate by phototrophic red tide dinoflagellates arising from mixotrophy. We measured the daily ingestion rates of Prorocentrum minimum by Prorocentrum micans over 5 days in 10 L experimentalbottles, and the uptake rates of total dissolved inorganic carbon (CT) by a mixture of P. micans and P. minimum(mixotrophic growth), and for the predator P. micans (phototrophic growth; control) and prey P. minimum (phototrophicgrowth; control) alone. To account for the effect of pH on the phototrophic growth rates of P. micans and P. minimum,measurements of CT and pH in the predator and prey control bottles were continued until the pH reached the same level(pH 9.5) as that in the experimental bottles on the final day of incubation. The measured total CT uptake rate by the mixtureof P. micans and P. minimum changed from 123 to 161 μmol CT kg-1 d-1 over the course of the experiment, and waslower than the CT uptake rates shown by P. micans and P. minimum in the predator and prey control bottles, respectively,which changed from 132 to 176 μmol CT kg-1 d-1 over the course of the experiment. The reduction in total CT uptake ratearising from the mixotrophy of P. micans was 7-31% of the daily CT uptake rate seen during photosynthesis. The resultssuggest that red tide dinoflagellates take up less CT during mixotrophy.1131Ysciescopuskc

Sensing electric fields using single diamond spins

The ability to sensitively detect charges under ambient conditions would be a fascinating new tool benefitting a wide range of researchers across disciplines. However, most current techniques are limited to low-temperature methods like single-electron transistors (SET), single-electron electrostatic force microscopy and scanning tunnelling microscopy. Here we open up a new quantum metrology technique demonstrating precision electric field measurement using a single nitrogen-vacancy defect centre(NV) spin in diamond. An AC electric field sensitivity reaching ~ 140V/cm/\surd Hz has been achieved. This corresponds to the electric field produced by a single elementary charge located at a distance of ~ 150 nm from our spin sensor with averaging for one second. By careful analysis of the electronic structure of the defect centre, we show how an applied magnetic field influences the electric field sensing properties. By this we demonstrate that diamond defect centre spins can be switched between electric and magnetic field sensing modes and identify suitable parameter ranges for both detector schemes. By combining magnetic and electric field sensitivity, nanoscale detection and ambient operation our study opens up new frontiers in imaging and sensing applications ranging from material science to bioimaging

Noninvasive imaging of radiolabeled exosome-mimetic nanovesicle using Tc-99m-HMPAO

Exosomes known as nano-sized extracellular vesicles attracted recent interests due to their potential usefulness in drug delivery. Amid remarkable advances in biomedical applications of exosomes, it is crucial to understand in vivo distribution and behavior of exosomes. Here, we developed a simple method for radiolabeling of macrophage-derived exosome-mimetic nanovesicles (ENVs) with Tc-99m-HMPAO under physiologic conditions and monitored in vivo distribution of Tc-99m-HMPAO-ENVs using SPECT/CT in living mice. ENVs were produced from the mouse RAW264.7 macrophage cell line and labeled with Tc-99m-HMPAO for 1 hr incubation, followed by removal of free Tc-99m-HMPAO. SPECT/CT images were serially acquired after intravenous injection to BALB/c mouse. When ENVs were labeled with Tc-99m-HMPAO, the radiochemical purity of Tc-99m-HMPAO-ENVs was higher than 90% and the expression of exosome specific protein (CD63) did not change in Tc-99m-HMPAO-ENVs. Tc-99m-HMPAOENVs showed high serum stability (90%) which was similar to that in phosphate buffered saline until 5 hr. SPECT/CT images of the mice injected with Tc-99m-HMPAO-ENVs exhibited higher uptake in liver and no uptake in brain, whereas mice injected with Tc-99m-HMPAO showed high brain uptake until 5 hr. Our noninvasive imaging of radiolabeled-ENVs promises better understanding of the in vivo behavior of exosomes for upcoming biomedical application.114327Ysciescopu

Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD

Fast synthesis of platinum nanopetals and nanospheres for highly-sensitive non-enzymatic detection of glucose and selective sensing of ions

Novel methods to obtain Pt nanostructured electrodes have raised particular interest due to their high performance in electrochemistry. Several nanostructuration methods proposed in the literature use costly and bulky equipment or are time-consuming due to the numerous steps they involve. Here, Pt nanostructures were produced for the first time by one-step template-free electrodeposition on Pt bare electrodes. The change in size and shape of the nanostructures is proven to be dependent on the deposition parameters and on the ratio between sulphuric acid and chloride-complexes (i.e., hexachloroplatinate or tetrachloroplatinate). To further improve the electrochemical properties of electrodes, depositions of Pt nanostructures on previously synthesised Pt nanostructures are also performed. The electroactive surface areas exhibit a two order of magnitude improvement when Pt nanostructures with the smallest size are used. All the biosensors based on Pt nanostructures and immobilised glucose oxidase display higher sensitivity as compared to bare Pt electrodes. Pt nanostructures retained an excellent electrocatalytic activity towards the direct oxidation of glucose. Finally, the nanodeposits were proven to be an excellent solid contact for ion measurements, significantly improving the time-stability of the potential. The use of these new nanostructured coatings in electrochemical sensors opens new perspectives for multipanel monitoring of human metabolism

A nested case–control study of the association of Helicobacter pylori infection with gastric adenocarcinoma in Korea

In a nested case–control study of 86 cases of gastric adenocarcinoma in relation to Helicobactor pylori infection in the Korean Multi-center Cancer Cohort, the H. pylori IgG seropositivity was 83.7% and that of the 344 matched controls was 80.8%, with a matched odds ratio for H. pylori infection of 1.06 (95% CI, 0.80–1.40)

The clock genes Period 2 and Cryptochrome 2 differentially balance bone formation

Background: Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To evaluate the contribution of clock components in this process, we investigated mice mutant in clock genes for a bone volume phenotype. Methodology/Principal Findings: We found that Per2Brdm1 mutant mice as well as mice lacking Cry2-/- displayed significantly increased bone volume at 12 weeks of age, when bone turnover is high. Per2Brdm1 mutant mice showed alterations in parameters specific for osteoblasts whereas mice lacking Cry2-/- displayed changes in osteoclast specific parameters. Interestingly, inactivation of both Per2 and Cry2 genes leads to normal bone volume as observed in wild type animals. Importantly, osteoclast parameters affected due to the lack of Cry2, remained at the level seen in the Cry2-/- mutants despite the simultaneous inactivation of Per2. Conclusions/Significance: This indicates that Cry2 and Per2 affect distinct pathways in the regulation of bone volume with Cry2 influencing mostly the osteoclastic cellular component of bone and Per2 acting on osteoblast parameters