Negative regulation of urokinase receptor activity by a GPI-specific phospholipase C in breast cancer cells.

The urokinase receptor (uPAR) is a glycosylphosphatidylinositol (GPI)-anchored protein that promotes tissue remodeling, tumor cell adhesion, migration and invasion. uPAR mediates degradation of the extracellular matrix through protease recruitment and enhances cell adhesion, migration and signaling through vitronectin binding and interactions with integrins. Full-length uPAR is released from the cell surface, but the mechanism and significance of uPAR shedding remain obscure. Here we identify transmembrane glycerophosphodiesterase GDE3 as a GPI-specific phospholipase C that cleaves and releases uPAR with consequent loss of function, whereas its homologue GDE2 fails to attack uPAR. GDE3 overexpression depletes uPAR from distinct basolateral membrane domains in breast cancer cells, resulting in a less transformed phenotype, it slows tumor growth in a xenograft model and correlates with prolonged survival in patients. Our results establish GDE3 as a negative regulator of the uPAR signaling network and, furthermore, highlight GPI-anchor hydrolysis as a cell-intrinsic mechanism to alter cell behavior

“Зізнання авантюриста Фелікса Крулля” Томаса Манна як пародія на велику автобіографію

Статтю присвячено розгляду рецепції та відображення “Поезії і правди” Й.-В. Гете в романі Т. Манна “Зізнання авантюриста Фелікса Крулля”. Представлена розвідка продовжує ряд наукових досліджень, присвячених вивченню особливостей рецепції автобіографії Й.-В. Гете, зокрема в німецькомовному літературному просторі. При дослідженні особливостей наявного в аналізованому нами романі пародійного наслідування Й.-В. Гете основна увага зосереджується автором на його стилістичному та тематичному рівнях.Статья посвящена рассмотрению рецепции и отражения “Поэзии и правды” Й.-В. Гете в романе Т. Манна “Признания авантюриста Феликса Крулля”. Представленная статья продолжает ряд научных исследований, посвященных изучению особенностей рецепции автобиографии Й.-В. Гете в частности в немецкоязычном литературном пространстве. При изучении особенностей имеющихся в анализированном нами романе пародийного подражания Й.-В. Гете основное внимание автор сосредотачивает на его стилистическом и тематическом уровнях.The article focuses on the reception of Goethe’s “Poetry and Truth” and its reflection in T. Mann’s novel “The Confession of adventurer Felix Crool”. The given article extends the series of scientific investigations that deal with the peculiarities of Goethe’s reception in German literature. Studying the parody imitation peculiarities of Goethe in the analysed novel, the main attention is paid to the stylistic and theme levels

Efficient Double Fragmentation ChIP-seq Provides Nucleotide Resolution Protein-DNA Binding Profiles

Immunoprecipitated crosslinked protein-DNA fragments typically range in size from several hundred to several thousand base pairs, with a significant part of chromatin being much longer than the optimal length for next-generation sequencing (NGS) procedures. Because these larger fragments may be non-random and represent relevant biology that may otherwise be missed, but also because they represent a significant fraction of the immunoprecipitated material, we designed a double-fragmentation ChIP-seq procedure. After conventional crosslinking and immunoprecipitation, chromatin is de-crosslinked and sheared a second time to concentrate fragments in the optimal size range for NGS. Besides the benefits of increased chromatin yields, the procedure also eliminates a laborious size-selection step. We show that the double-fragmentation ChIP-seq approach allows for the generation of biologically relevant genome-wide protein-DNA binding profiles from sub-nanogram amounts of TCF7L2/TCF4, TBP and H3K4me3 immunoprecipitated material. Although optimized for the AB/SOLiD platform, the same approach may be applied to other platforms

Gauss Law Constraints in Chern-Simons Theory From BRST Quantization

The physical state condition in the BRST quantization of Chern-Simons field theory is used to derive Gauss law constraints in the presence of Wilson loops, which play an important role in explicitly establishing the connection of Chern-Simons field theory with 2-dimensional conformal field theory.Comment: Some typetwritten errors have been corrected. A few formulas have been modified to make the arguments clear. A little English have been re-edite

Impact of Extraction Time during Donation after Circulatory Death Organ Procurement on Kidney Function after Transplantation in the Netherlands

Background:In The Netherlands, 60% of deceased-donor kidney offers are after donation after circulatory death. Cold and warm ischemia times are known risk factors for delayed graft function (DGF) and inferior allograft survival. Extraction time is a relatively new ischemia time. During procurement, cooling of the kidneys is suboptimal with ongoing ischemia. However, evidence is lacking on whether extraction time has an impact on DGF if all ischemic periods are included.Methods:Between 2012 and 2018, 1524 donation after circulatory death kidneys were procured and transplanted in The Netherlands. Donation and transplantation-related data were obtained from the database of the Dutch Transplant Foundation. The primary outcome parameter was the incidence of DGF. Results:In our cohort, extraction time ranged from 14 to 237 min, with a mean of 62 min (SD 32). In multivariate logistic regression analysis, extraction time was an independent risk factor for incidence of DGF (odds ratio per minute increase 1.008; 95% confidence interval, 1.003-1.013; P = 0.001). The agonal phase, hypoperfusion time, and anastomosis time were not independent risk factors for incidence of DGF. Conclusions:Considering all known ischemic periods during the donation after the circulatory death process, prolonged kidney extraction time increased the risk of DGF after kidney transplantation.</p

Variation in tospovirus transmission between populations of Frankliniella occidentalis (Thysanoptera: Thripidae)

Fourteen populations of the western flower thrips Frankliniella occidentalisPergande, originating from different hosts and countries in Asia, Europe, North America and New Zealand, were analysed for their competency and efficiency to transmit tomato spotted wilt virus (TSWV). All populations acquired and subsequently transmitted the virus, and were thus competent to transmit. They show marked differences in their efficiency, expressed as the percentage of transmitting adults. Efficiencies varied from 18 or a F. occidentalis population from the USA (US2) to 75␈r a population from Israel (IS2). The differences between populations were not affected by the amount of virus ingested or by the host plant used. However, the tospovirus species studied and age at which the larvae acquired the virus affected the efficiency to transmit. First instar larvae of the NL3 population from The Netherlands were able to acquire tomato spotted wilt virus, whereas second instar larvae failed to do so. However, both instars of this population acquired impatiens necrotic spot virus (INSV), another tospovirus. This and tomato spotted wilt virus were both acquired by both larval stages of the populations IS2 and US2, although their ability to acquire virus decreased with their age. Hence, it is likely that, in general, both instar larvae of most F. occidentalis populations are competent to acquire both tospoviruses. These results show that large differences exist in the efficiency by which tomato spotted wilt is transmitted by the various F. occidentalis populations and that the ability to acquire tospovirus decreases with the age of the larva