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21.
Phillipp Kirfel Marisa Skaljac Jens Grotmann Tobias Kessel Maximilian Seip Katja Michaelis Andreas Vilcinskas 《Archives of insect biochemistry and physiology》2020,103(3):e21614
Histone acetylation is an evolutionarily conserved epigenetic mechanism of eukaryotic gene regulation which is tightly controlled by the opposing activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). In insects, life-history traits such as longevity and fecundity are severely affected by the suppression of HAT/HDAC activity, which can be achieved by RNA-mediated gene silencing or the application of chemical inhibitors. We used both experimental approaches to investigate the effect of HAT/HDAC inhibition in the pea aphid (Acyrthosiphon pisum) a model insect often used to study complex life-history traits. The silencing of HAT genes (kat6b, kat7, and kat14) promoted survival or increased the number of offspring, whereas targeting rpd3 (HDAC) reduced the number of viviparous offspring but increased the number of premature nymphs, suggesting a role in embryogenesis and eclosion. Specific chemical inhibitors of HATs/HDACs showed a remarkably severe impact on life-history traits, reducing survival, delaying development, and limiting the number of offspring. The selective inhibition of HATs and HDACs also had opposing effects on aphid body weight. The suppression of HAT/HDAC activity in aphids by RNA interference or chemical inhibition revealed similarities and differences compared to the reported role of these enzymes in other insects. Our data suggest that gene expression in A. pisum is regulated by multiple HATs/HDACs, as indicated by the fitness costs triggered by inhibitors that suppress several of these enzymes simultaneously. Targeting multiple HATs or HDACs with combined effects on gene regulation could, therefore, be a promising approach to discover novel targets for the management of aphid pests. 相似文献
22.
Dola Das Ehsan Fayazzadeh Xin Li Nischal Koirala Akshay Wadera Min Lang Maximilian Zernic Catherine Panick Pete Nesbitt Gordon McLennan 《Journal of cellular physiology》2020,235(9):6167-6182
Hepatocellular carcinoma (HCC) is a major health problem worldwide and in the United States as its incidence has increased substantially within the past two decades. HCC therapy remains a challenge, primarily due to underlying liver disorders such as cirrhosis that determines treatment approach and efficacy. Activated hepatic stellate cells (A-HSCs) are the key cell types involved in hepatic fibrosis/cirrhosis. A-HSCs are important constituents of HCC tumor microenvironment (TME) and support tumor growth, chemotherapy resistance, cancer cell migration, and escaping immune surveillance. This makes A-HSCs an important therapeutic target in hepatic fibrosis/cirrhosis as well as in HCC. Although many studies have reported the role of A-HSCs in cancer generation and investigated the therapeutic potential of A-HSCs reversion in cancer arrest, not much is known about inactivated or quiescent HSCs (Q-HSCs) in cancer growth or arrest. Here we report that Q-HSCs resist cancer cell growth by inducing cytotoxicity and enhancing chemotherapy sensitivity. We observed that the conditioned media from Q-HSCs (Q-HSCCM) induces cancer cell death through a caspase-independent mechanism that involves an increase in apoptosis-inducing factor expression, nuclear localization, DNA fragmentation, and cell death. We further observed that Q-HSCCM enhanced the efficiency of doxorubicin, as measured by cell viability assay. Exosomes present in the conditioned media were not involved in the mechanism, which suggests the role of other factors (proteins, metabolites, or microRNA) secreted by the cells. Identification and characterization of these factors are important in the development of effective HCC therapy. 相似文献
23.
24.
Nikolai Petrovsky Maximilian Larena Venkatraman Siddharthan Natalie A. Prow Roy A. Hall Mario Lobigs John Morrey 《Journal of virology》2013,87(18):10324-10333
West Nile virus (WNV), currently the cause of a serious U.S. epidemic, is a mosquito-borne flavivirus and member of the Japanese encephalitis (JE) serocomplex. There is currently no approved human WNV vaccine, and treatment options remain limited, resulting in significant mortality and morbidity from human infection. Given the availability of approved human JE vaccines, this study asked whether the JE-ADVAX vaccine, which contains an inactivated cell culture JE virus antigen formulated with Advax delta inulin adjuvant, could provide heterologous protection against WNV infection in wild-type and β2-microglobulin-deficient (β2m−/−) murine models. Mice immunized twice or even once with JE-ADVAX were protected against lethal WNV challenge even when mice had low or absent serum cross-neutralizing WNV titers prior to challenge. Similarly, β2m−/− mice immunized with JE-ADVAX were protected against lethal WNV challenge in the absence of CD8+ T cells and prechallenge WNV antibody titers. Protection against WNV could be adoptively transferred to naive mice by memory B cells from JE-ADVAX-immunized animals. Hence, in addition to increasing serum cross-neutralizing antibody titers, JE-ADVAX induced a memory B-cell population able to provide heterologous protection against WNV challenge. Heterologous protection was reduced when JE vaccine antigen was administered alone without Advax, confirming the importance of the adjuvant to induction of cross-protective immunity. In the absence of an approved human WNV vaccine, JE-ADVAX could provide an alternative approach for control of a major human WNV epidemic. 相似文献
25.
The pollen spectra of air and surface soil samples from a rooftop (at 14 m) and from ground level (at 1.6 m) in the suburbs of Vienna (Austria) were compared. Two soil samples and two air samples were taken on four different days to account for possible differences: in winter when no pollination occurred (reference day), in spring during the main flowering of Betula (birch day), in spring/summer during the main flowering of Poaceae (grass day), and in autumn during the main flowering of Ambrosia (ragweed day). Thirty-five different pollen types were used to describe the pollen spectra. Frequencies of certain pollen types reflect a seasonal impact on both the surface soil and air samples and show a similarity between air and soil samples on most of the days. However, the seasonal impact is higher in the air samples and shows a high consistency for ground and rooftop level. Kendall’s tau correlation coefficients further substantiate the similarities of the samples especially for the pollen season days. Exceptions include the winter day when pollination was low and the air samples recorded nearly no pollen at all, and the ragweed day when Ambrosia pollen was abundant in three of four samples but not in the ground surface soil sample. Thus, (1) air and surface pollen samples record similar signals during the pollen season but not during the ragweed and winter season and (2) air and surface pollen samples show the impact of local vegetation also in pollen traps located at different heights. 相似文献
26.
Joanna Szkandera Gudrun Absenger Bernadette Liegl-Atzwanger Martin Pichler Michael Stotz Stefan Gerger Maximilian Zacherl Wilfried Renner Miao Haijun Andreas Leithner Armin Gerger 《Cancer epidemiology》2013,37(6):1003-1009
BackgroundDNA repair mechanisms play a major role in cancer risk and progression. Germline variants in DNA repair genes may result in altered gene function and/or activity, thereby causing inter-individual differences in a patient's tumor recurrence capacity. In genes of the DNA repair pathway the gene variants RAD51 rs1801320 G > C, XRCC2 rs3218536 G > A and XPD rs13181 A > C have been previously related to genetic predisposition and prognosis of various cancer entities. In this study we investigated the association between these polymorphisms and time to recurrence (TTR) and overall survival (OS) in soft-tissue sarcoma (STS) patients after curative surgery.MethodsTwo hundred sixty STS patients were included in this retrospective study. Germline DNA was genotyped by 5′-exonuclease (TaqMan) technology. Kaplan Meier curves and multivariate Cox proportional models were calculated for TTR and OS.ResultsA statistically significant association was observed between tumor grade and adjuvant radiotherapy and TTR and between tumor grade and OS. No association was found between RAD51 rs1801320 G > C, XRCC2 rs3218536 G > A and XPD rs13181 A > C and TTR and OS in univariate and multivariate analysis.ConclusionOur results underline a prognostic effect of tumor grade and adjuvant radiotherapy in STS patients but indicate no association between RAD51 rs1801320 G > C, XRCC2 rs3218536 G > A and XPD rs13181 A > C and clinical outcome in STS patients after curative surgery. 相似文献
27.
Sandra Herout Mattias Mandorfer Florian Breitenecker Thomas Reiberger Katharina Grabmeier-Pfistershammer Armin Rieger Maximilian C. Aichelburg 《PloS one》2016,11(4)
BackgroundIt is unclear whether antiretroviral therapy (ART) should be initiated during acute HIV infection. Most recent data provides evidence of benefits of early ART.MethodsWe retrospectively compared the clinical and immunological course of individuals with acute HIV infection, who received ART within 3 months (group A) or not (group B) after diagnosis.ResultsAmong the 84 individuals with acute HIV infection, 57 (68%) received ART within 3 months (A) whereas 27 (32%) did not receive ART within 3 months (B), respectively. Clinical progression to CDC stadium B or C within 5 years after the diagnosis of HIV was less common in (A) when compared to (B) (P = 0.002). After twelve months, both the mean increase in CD4+ T cell count and the mean decrease in viral load was more pronounced in (A), when compared to (B) (225 vs. 87 cells/μl; P = 0.002 and -4.19 vs. -1.14 log10 copies/mL; P<0.001). Twenty-four months after diagnosis the mean increase from baseline of CD4+ T cells was still higher in group A compared to group B (251 vs. 67 cells/μl, P = 0.004).ConclusionsInitiation of ART during acute HIV infection is associated with a lower probability of clinical progression to more advanced CDC stages and significant immunological benefits. 相似文献
28.
Achim von Bomhard Alexander Els?sser Lucas Maximilian Ritschl Silke Schwarz Nicole Rotter 《PloS one》2016,11(2)
Vitrification of endothelial cells (MHECT-5) has not previously been compared with controlled slow freezing methods under standardized conditions. To identify the best cryopreservation technique, we evaluated vitrification and standardized controlled-rate -1°C/minute cell freezing in a -80°C freezer and tested four cryoprotective agents (CPA), namely dimethyl sulfoxide (DMSO), ethylene glycol (EG), propylene glycol (PG), and glycerol (GLY), and two media, namely Dulbecco''s modified Eagle medium Ham’s F-12 (DMEM)and K+-modified TiProtec (K+TiP), which is a high-potassium-containing medium. Numbers of viable cells in proliferation were evaluated by the CellTiter 96® AQueous One Solution Cell Proliferation Assay (Promega Corporation, Mannheim, Germany). To detect the exact frozen cell number per cryo vial, DNA content was measured by using Hoechst 33258 dye prior to analysis. Thus, results could be evaluated unconstrained by absolute cell number. Thawed cells were cultured in 25 cm2 cell culture flasks to confluence and examined daily by phase contrast imaging. With regard to cell recovery immediately after thawing, DMSO was the most suitable CPA combined with K+TiP in vitrification (99 ±0.5%) and with DMEM in slow freezing (92 ±1.6%). The most viable cells in proliferation after three days of culture were obtained in cells vitrificated by using GLY with K+TiP (308 ±34%) and PG with DMEM in slow freezing (280 ±27%). 相似文献
29.
Ye Zhu Maximilian Blum Uwe Hoff Tim Wesser Mandy Fechner Christina Westphal Dennis Gürgen Rusan Ali Catar Aurelie Philippe Kaiyin Wu Gordana Bubalo Michael Rothe Steven M. Weldon Duska Dragun Wolf-Hagen Schunck 《PloS one》2016,11(1)
Aim
20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) are cytochrome P450 (CYP)-dependent eicosanoids that play opposite roles in the regulation of vascular tone, inflammation, and apoptosis. 20-HETE aggravates, whereas EETs ameliorate ischemia/reperfusion (I/R)-induced organ damage. EETs are rapidly metabolized to dihydroxyeicosatrienoic acids (DHETs) by the soluble epoxide hydrolase (sEH). We hypothesized that sEH gene (EPHX2) deletion would increase endogenous EET levels and thereby protect against I/R-induced acute kidney injury (AKI).Methods
Kidney damage was evaluated in male wildtype (WT) and sEH-knockout (KO)-mice that underwent 22-min renal ischemia followed by two days of reperfusion. CYP-eicosanoids were analyzed by liquid chromatography tandem mass spectrometry.Results
Contrary to our initial hypothesis, renal function declined more severely in sEH-KO mice as indicated by higher serum creatinine and urea levels. The sEH-KO-mice also featured stronger tubular lesion scores, tubular apoptosis, and inflammatory cell infiltration. Plasma and renal EET/DHET-ratios were higher in sEH-KO than WT mice, thus confirming the expected metabolic consequences of sEH deficiency. However, CYP-eicosanoid profiling also revealed that renal, but not plasma and hepatic, 20-HETE levels were significantly increased in sEH-KO compared to WT mice. In line with this finding, renal expression of Cyp4a12a, the murine 20-HETE-generating CYP-enzyme, was up-regulated both at the mRNA and protein level, and Cyp4a12a immunostaining was more intense in the renal arterioles of sEH-KO compared with WT mice.Conclusion
These results indicate that the potential beneficial effects of reducing EET degradation were obliterated by a thus far unknown mechanism leading to kidney-specific up-regulation of 20-HETE formation in sEH-KO-mice. 相似文献30.
Rhipsalis (Cactaceae): loss and gain of floral rewards is mirrored in range sizes and distribution patterns of species
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Bernadette Grosse‐Veldmann Stefan Abrahamczyk Jens Mutke Wilhelm Barthlott Maximilian Weigend 《Botanical journal of the Linnean Society. Linnean Society of London》2016,180(4):491-503
Autogamous species are usually distinguishable from xenogamous relatives by smaller flowers, fewer or even no floral rewards and lower pollen–ovule (P/O) ratios. Many Rhipsalis spp. are small flowered, selfing and include the most widespread species in Cactaceae. However, Rhipsalis also includes a large number of narrowly endemic species and is most diverse in the Atlantic rainforests of Brazil. To investigate the evolution of floral function and the correlation between floral function and range size, we analysed display size, floral reward and P/O ratios of Rhipsalis and its closest relatives, reconstructed ancestral traits and related these patterns to the distributions and range sizes of the species. Display size and sugar amount are reduced in subgenera Goniorhipsalis and Rhipsalis and secondarily increased in Phyllarthrorhipsalis, whereas the P/O ratio is decreased in subgenera Rhipsalis and Phyllarthrorhipsalis. We interpret this pattern as a switch from a predominantly xenogamous to an autogamous reproductive system, followed by a return to a predominantly xenogamous system. None of the floral parameters shows significant correlations with range size, except for display size. Nevertheless, those species with the smallest flowers, lowest sugar amounts per flower and lowest P/O ratios occur either outside southeastern Brazil and/or have comparatively large distribution ranges. Almost all Rhipsalis spp. occurring outside the Atlantic rainforests are restricted to the clade formed by subgenera Rhipsalis and Phyllarthrorhipsalis. Thus, we believe that the evolution of an autogamous reproduction system enabled this lineage of Rhipsalis to diversify and spread in the Atlantic rainforests, in the rest of the Neotropics and even spread to the Old World, where it is the only member of the family. 相似文献