LH RECEPTORS AND STEROIDOGENESIS IN DISTINCT POPULATIONS OF LEYDIG CELLS *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74634/1/j.1749-6632.1982.tb23168.x.pd

ВИКОРИСТАННЯ ІМПУЛЬСНОГО МЕТОДУ ВИМІРЮВАННЬ ДЛЯ ВИЗНАЧЕННЯ ПОШКОДЖЕННЯ КАБЕЛЬНИХ ЛІНІЙ

В даній роботі розглядаються особливості використання приладу ІКЛ-5 для швидкого визначення точності імпульсних вимірювань в пошкодженнях кабельних ліній і точного знаходження міста пошкодження кабелю. Для досягнення поставленої мети запропонований імпульсний метод, який визначає місце і характер пошкодження кабельних ліній. Обраний у роботі підхід дає можливість вимірювання при будьякому складному характері ушкодження. Завдяки цьому забезпечується зручність, простота і швидкість вимірювань

The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis.

Ferroptosis is a form of regulated cell death that is caused by the iron-dependent peroxidation of lipids1,2. The glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4) prevents ferroptosis by converting lipid hydroperoxides into non-toxic lipid alcohols3,4. Ferroptosis has previously been implicated in the cell death that underlies several degenerative conditions2, and induction of ferroptosis by the inhibition of GPX4 has emerged as a therapeutic strategy to trigger cancer cell death5. However, sensitivity to GPX4 inhibitors varies greatly across cancer cell lines6, which suggests that additional factors govern resistance to ferroptosis. Here, using a synthetic lethal CRISPR-Cas9 screen, we identify ferroptosis suppressor protein 1 (FSP1) (previously known as apoptosis-inducing factor mitochondrial 2 (AIFM2)) as a potent ferroptosis-resistance factor. Our data indicate that myristoylation recruits FSP1 to the plasma membrane where it functions as an oxidoreductase that reduces coenzyme Q10 (CoQ) (also known as ubiquinone-10), which acts as a lipophilic radical-trapping antioxidant that halts the propagation of lipid peroxides. We further find that FSP1 expression positively correlates with ferroptosis resistance across hundreds of cancer cell lines, and that FSP1 mediates resistance to ferroptosis in lung cancer cells in culture and in mouse tumour xenografts. Thus, our data identify FSP1 as a key component of a non-mitochondrial CoQ antioxidant system that acts in parallel to the canonical glutathione-based GPX4 pathway. These findings define a ferroptosis suppression pathway and indicate that pharmacological inhibition of FSP1 may provide an effective strategy to sensitize cancer cells to ferroptosis-inducing chemotherapeutic agents

Coupled evolutions of the stellar obliquity, orbital distance, and planet's radius due to the Ohmic dissipation induced in a diamagnetic hot Jupiter around a magnetic T Tauri star

We revisit the calculation of the Ohmic dissipation in a hot Jupiter presented in Laine et al. (2008) by considering more realistic interior structures, stellar obliquity, and the resulting orbital evolution. In this simplified approach, the young hot Jupiter of one Jupiter mass is modelled as a diamagnetic sphere with a finite resistivity, orbiting across tilted stellar magnetic dipole fields in vacuum. Since the induced Ohmic dissipation occurs mostly near the planet's surface, we find that the dissipation is unable to significantly expand the young hot Jupiter. Nevertheless, the planet inside a small co-rotation orbital radius can undergo orbital decay by the dissipation torque and finally overfill its Roche lobe during the T Tauri star phase. The stellar obliquity can evolve significantly if the magnetic dipole is parallel/anti-parallel to the stellar spin. Our results are validated by the general torque-dissipation relation in the presence of the stellar obliquity. We also run the fiducial model in Laine et al. (2008) and find that the planet's radius is sustained at a nearly constant value by the Ohmic heating, rather than being thermally expanded to the Roche radius as suggested by the authors.Comment: about 40 pages, 10 figures, Accepted for publication in The Astrophysical Journa

The coupled thermal-hydraulic-mechanical behaviour of a large scale in-situ heating experiment

The thermo-hydraulic-mechanical behaviour of a large in situ heating test, the Buffer/Container Experiment (BCE), carried out at Atomic Energy of Canada's underground research laboratory, is considered. The work can be seen as an extension of the authors' previous research, investigating the behaviour of a large-scale test, the so-called ‘isothermal test’, to now include heating effects. Suggestions related to the micro–macro behaviour of bentonitic buffer materials subjected to resaturation in confined non-isothermal conditions are explored. Simulation of pre-heating phases of the experiment demonstrates the ability of the model to describe the hydraulic regime in the host rock and isothermal infiltration into the buffer. Consideration of the heating phase confirms that the temperature field is well understood, with a good correlation between the numerical and experimental results. In the moisture field it is found that the interaction between the emplaced buffer and host rock is of considerable importance. It is found that inclusion of micro–macro interaction effects, by way of consideration of the impact of swelling and micro–macro interactions on the hydraulic conductivity of the material, yielded significantly improved correlations between observed and calculated results in the moisture field. The results of the numerical simulations suggest that the interaction between the emplaced buffer and host rock is strongly influenced by the micro–macro behaviour of the bentonitic buffer material. It is concluded that the consideration of the impact of micro–macro interactions on moisture flow in bentonitic buffers is of considerable importance, and may be of some significance in considering the total resaturation time as part of the performance assessment of a nuclear waste disposal repository

Rare variant contribution to cholestatic liver disease in a South Asian population in the United Kingdom

This study assessed the contribution of five genes previously known to be involved in cholestatic liver disease in British Bangladeshi and Pakistani people. Five genes (ABCB4, ABCB11, ATP8B1, NR1H4, TJP2) were interrogated by exome sequencing data of 5236 volunteers. Included were non-synonymous or loss of function (LoF) variants with a minor allele frequency < 5%. Variants were filtered, and annotated to perform rare variant burden analysis, protein structure, and modelling analysis in-silico. Out of 314 non-synonymous variants, 180 fulfilled the inclusion criteria and were mostly heterozygous unless specified. 90 were novel and of those variants, 22 were considered likely pathogenic and 9 pathogenic. We identified variants in volunteers with gallstone disease (n = 31), intrahepatic cholestasis of pregnancy (ICP, n = 16), cholangiocarcinoma and cirrhosis (n = 2). Fourteen novel LoF variants were identified: 7 frameshift, 5 introduction of premature stop codon and 2 splice acceptor variants. The rare variant burden was significantly increased in ABCB11. Protein modelling demonstrated variants that appeared to likely cause significant structural alterations. This study highlights the significant genetic burden contributing to cholestatic liver disease. Novel likely pathogenic and pathogenic variants were identified addressing the underrepresentation of diverse ancestry groups in genomic research

Searching for G3G^3 in t \tbar Production

The triple gluon field strength operator $G^3$ represents the only genuinely gluonic CP conserving term which can appear at dimension-6 within an effective strong interaction Lagrangian. Previous studies of this operator have revealed that its effect on gluon scattering is surprisingly difficult to detect. In this article, we analyze the impact of $G^3$ upon top quark pair production. We find that it will generate observable cross section deviations from QCD at the LHC for even relatively small values of its coefficient. Furthermore, $G^3$ affects the transverse momentum distribution of the produced top quarks more strongly at high energies than dimension-6 four-quark and chromomagnetic moment terms in the effective Lagrangian. Top-antitop production at the LHC will therefore provide a sensitive and clean probe for the elusive triple gluon field strength operator.Comment: 20 pages, 8 figures (3 updated figures not included but available upon request), CALT-68-1941, BUHEP-94-18. (Some previously overlooked graphs are now included. Our conclusions remain unchanged.

A Land System representation for global assessments and land-use modeling

Current global scale land-change models used for integrated assessments and climate modeling are based on classifications of land cover. However, land-use management intensity and livestock keeping are also important aspects of land use, and are an integrated part of land systems. This article aims to classify, map, and to characterize Land Systems (LS) at a global scale and analyze the spatial determinants of these systems. Besides proposing such a classification, the article tests if global assessments can be based on globally uniform allocation rules. Land cover, livestock, and agricultural intensity data are used to map LS using a hierarchical classification method. Logistic regressions are used to analyze variation in spatial determinants of LS. The analysis of the spatial determinants of LS indicates strong associations between LS and a range of socioeconomic and biophysical indicators of human-environment interactions. The set of identified spatial determinants of a LS differs among regions and scales, especially for (mosaic) cropland systems, grassland systems with livestock, and settlements. (Semi-)Natural LS have more similar spatial determinants across regions and scales. Using LS in global models is expected to result in a more accurate representation of land use capturing important aspects of land systems and land architecture: the variation in land cover and the link between land-use intensity and landscape composition. Because the set of most important spatial determinants of LS varies among regions and scales, land-change models that include the human drivers of land change are best parameterized at sub-global level, where similar biophysical, socioeconomic and cultural conditions prevail in the specific regions. © 2012 Blackwell Publishing Ltd

A role of SCN9A in human epilepsies, as a cause of febrile seizures and as a potential modifier of Dravet syndrome

A follow-up study of a large Utah family with significant linkage to chromosome 2q24 led us to identify a new febrile seizure (FS) gene, SCN9A encoding Na(v)1.7. In 21 affected members, we uncovered a potential mutation in a highly conserved amino acid, p.N641Y, in the large cytoplasmic loop between transmembrane domains I and II that was absent from 586 ethnically matched population control chromosomes. To establish a functional role for this mutation in seizure susceptibility, we introduced the orthologous mutation into the murine Scn9a ortholog using targeted homologous recombination. Compared to wild-type mice, homozygous Scn9a(N641Y/N641Y) knockin mice exhibit significantly reduced thresholds to electrically induced clonic and tonic-clonic seizures, and increased corneal kindling acquisition rates. Together, these data strongly support the SCN9A p.N641Y mutation as disease-causing in this family. To confirm the role of SCN9A in FS, we analyzed a collection of 92 unrelated FS patients and identified additional highly conserved Na(v)1.7 missense variants in 5% of the patients. After one of these children with FS later developed Dravet syndrome (severe myoclonic epilepsy of infancy), we sequenced the SCN1A gene, a gene known to be associated with Dravet syndrome, and identified a heterozygous frameshift mutation. Subsequent analysis of 109 Dravet syndrome patients yielded nine Na(v)1.7 missense variants (8% of the patients), all in highly conserved amino acids. Six of these Dravet syndrome patients with SCN9A missense variants also harbored either missense or splice site SCN1A mutations and three had no SCN1A mutations. This study provides evidence for a role of SCN9A in human epilepsies, both as a cause of FS and as a partner with SCN1A mutations