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323.
Anna N. Panek Maximilian G. Posch Natalia Alenina Santhosh K. Ghadge Bettina Erdmann Elena Popova Andreas Perrot Christian Geier Rainer Dietz Ingo Morano Michael Bader Cemil ?zcelik 《PloS one》2009,4(8)
Connective tissue growth factor (CTGF) is a secreted protein that is strongly induced in human and experimental heart failure. CTGF is said to be profibrotic; however, the precise function of CTGF is unclear. We generated transgenic mice and rats with cardiomyocyte-specific CTGF overexpression (CTGF-TG). To investigate CTGF as a fibrosis inducer, we performed morphological and gene expression analyses of CTGF-TG mice and rat hearts under basal conditions and after stimulation with angiotensin II (Ang II) or isoproterenol, respectively. Surprisingly, cardiac tissues of both models did not show increased fibrosis or enhanced gene expression of fibrotic markers. In contrast to controls, Ang II treated CTGF-TG mice displayed preserved cardiac function. However, CTGF-TG mice developed age-dependent cardiac dysfunction at the age of 7 months. CTGF related heart failure was associated with Akt and JNK activation, but not with the induction of natriuretic peptides. Furthermore, cardiomyocytes from CTGF-TG mice showed unaffected cellular contractility and an increased Ca2+ reuptake from sarcoplasmatic reticulum. In an ischemia/reperfusion model CTGF-TG hearts did not differ from controls.Our data suggest that CTGF itself does not induce cardiac fibrosis. Moreover, it is involved in hypertrophy induction and cellular remodeling depending on the cardiac stress stimulus. Our new transgenic animals are valuable models for reconsideration of CTGF''s profibrotic function in the heart. 相似文献
324.
Natalia Gomez Jun Ouyang Mary D. H. Nguyen Abigail R. Vinson Andy A. Lin Inn H. Yuk 《Biotechnology progress》2010,26(5):1438-1445
THIOMABs are recombinant antibodies with reactive cysteine residues used for forming THIOMAB–drug conjugates (TDCs). We recently reported a new impurity associated with THIOMABs: one of the engineered cysteines forms a disulfide bond with an extra light chain (LC) to generate a triple light chain antibody (3LC). In our previous investigations, increased LC expression increased 3LC levels, whereas increased glutathione (GSH) production decreased 3LC levels. In this work, on three stably transfected CHO cell lines, we investigated the effects of temperature, pH, dissolved oxygen (DO), and hydrolysate on 3LC formation during THIOMAB fed‐batch cell culture production. Although pH between 6.8 and 7.0 had no significant impact on 3LC formation, temperature at 35°C instead of 33 or 31°C generated the lowest 3LC values for two cell lines. The decreased 3LC level correlated with increased GSH production. We implemented a 35°C temperature process for large‐scale (2,000 L) production of a THIOMAB. This process reduced 3LC levels by ~50% compared with a 33°C temperature process. By contrast, DO and hydrolysate had modest effect on 3LC levels for the model cell line studied. Overall, we did not find significant changes in LC expression under the conditions tested, whereas changes in GSH production were more evident. By investigating the impact of bioreactor process and medium conditions on 3LC levels, we identified strategies that reduced 3LC levels. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010 相似文献
325.
Landon LA Peletskaya EN Glinsky VV Karasseva N Quinn TP Deutscher SL 《Journal of Protein Chemistry》2003,22(2):193-204
Thomsen-Friedenreich (TF) antigen occurs on approximately 90% of human carcinomas, is likely involved in carcinoma cell homotypic aggregation, and has clinical value as a prognostic indicator and marker of metastasized cells. Previously, we isolated anti-TF antigen peptides from bacteriophage display libraries. These bound to TF antigen on carcinoma cells but were of low affinity and solubility. We hypothesized that peptide amino acid sequence changes would result in increased affinity and solubility, which would translate into improved carcinoma cell binding and increased inhibition of aggregation. The new peptides were more soluble and exhibited up to fivefold increase in affinity (Kd 60 nM). They bound cultured human breast and prostate carcinoma cells at low concentrations, whereas the earlier peptides did not. Moreover, the new peptides were potent inhibitors of homotypic aggregation. The maturated peptides will have expanded applications in basic studies of the TF antigen and particular utility as clinical carcinoma-targeting agents. 相似文献
326.
Marzi S Knight W Brandi L Caserta E Soboleva N Hill WE Gualerzi CO Lodmell JS 《RNA (New York, N.Y.)》2003,9(8):958-969
Bacterial translation initiation factor IF2 is a GTP-binding protein that catalyzes binding of initiator fMet-tRNA in the ribosomal P site. The topographical localization of IF2 on the ribosomal subunits, a prerequisite for understanding the mechanism of initiation complex formation, has remained elusive. Here, we present a model for the positioning of IF2 in the 70S initiation complex as determined by cleavage of rRNA by the chemical nucleases Cu(II):1,10-orthophenanthroline and Fe(II):EDTA tethered to cysteine residues introduced into IF2. Two specific amino acids in the GII domain of IF2 are in proximity to helices H3, H4, H17, and H18 of 16S rRNA. Furthermore, the junction of the C-1 and C-2 domains is in proximity to H89 and the thiostrepton region of 23S rRNA. The docking is further constrained by the requisite proximity of the C-2 domain with P-site-bound tRNA and by the conserved GI domain of the IF2 with the large subunit's factor-binding center. Comparison of our present findings with previous data further suggests that the IF2 orientation on the 30S subunit changes during the transition from the 30S to 70S initiation complex. 相似文献
327.
Insulation of the chicken beta-globin chromosomal domain from a chromatin-condensing protein,MENT 下载免费PDF全文
Istomina NE Shushanov SS Springhetti EM Karpov VL Krasheninnikov IA Stevens K Zaret KS Singh PB Grigoryev SA 《Molecular and cellular biology》2003,23(18):6455-6468
Active genes are insulated from developmentally regulated chromatin condensation in terminally differentiated cells. We mapped the topography of a terminal stage-specific chromatin-condensing protein, MENT, across the active chicken beta-globin domain. We observed two sharp transitions of MENT concentration coinciding with the beta-globin boundary elements. The MENT distribution profile was opposite to that of acetylated core histones but correlated with that of histone H3 dimethylated at lysine 9 (H3me2K9). Ectopic MENT expression in NIH 3T3 cells caused a large-scale and specific remodeling of chromatin marked by H3me2K9. MENT colocalized with H3me2K9 both in chicken erythrocytes and NIH 3T3 cells. Mutational analysis of MENT and experiments with deacetylase inhibitors revealed the essential role of the reaction center loop domain and an inhibitory affect of histone hyperacetylation on the MENT-induced chromatin remodeling in vivo. In vitro, the elimination of the histone H3 N-terminal peptide containing lysine 9 by trypsin blocked chromatin self-association by MENT, while reconstitution with dimethylated but not acetylated N-terminal domain of histone H3 specifically restored chromatin self-association by MENT. We suggest that histone H3 modification at lysine 9 directly regulates chromatin condensation by recruiting MENT to chromatin in a fashion that is spatially constrained from active genes by gene boundary elements and histone hyperacetylation. 相似文献
328.
Natalia Von Ellenrieder 《Systematic Entomology》2002,27(4):437-467
Abstract A cladistic analysis of the world Aeshnidae is presented, based on fifty-eight characters of adult and larval anatomy. The ingroup taxa include all the extant genera of Aeshnidae, and the austropetaliid genera Phyllopetalia and Hypopetalia were chosen as the outgroup. The strict consensus tree obtained after successive weighting shows that the subgroups defined traditionally for Aeshnidae are paraphyletic or polyphyletic. The previous reclassification derived from analyses based on wing venation is supported in terms of the monophyly of Aeshnidae, Gomphaeschninae and its sister group comprising the remaining Aeshnidae. Gomphaeschninae is confirmed as sister group of the remaining Aeshnidae (= Aeshnodea Bechly). The sister-group relationships between Gomphaeschna + Sarasaeschna and Linaeschna + Oligoaeschna are corroborated. Within Aeshnodea, three monophyletic groups emerged: Boyeria + ( Petaliaeschna + ( Limnetron + Gynacanthaeschna + Periaeschna )) + (( Cephalaeschna + Caliaeschna ) + ( Allopetalia ( Notoaeschna + Spinaeschna ))); Dendroaeschna + ( Epiaeschna + ( Aeschnophlebia + ( Nasiaeschna + ( Tetracanthagyna + Brachytron )))); and Polycanthagyna + ( Basiaeschna + ( Amphiaeschna + ( Indaeschna + ( Oplonaeschna + ( Racenaeschna + Plattycantha + Agyrtacantha + Triacanthagyna + ( Subaeschna + Austrogynacantha + Gynacantha ) + ( Heliaeschna + ( Neuraeschna + Staurophlebia ))) + (( Castoraeschna + Coryphaeschna + Remartinia ) + ( Oreaeschna + ( Aeshna + ( Anaciaeschna + ((' A .' isosceles + Andaeshna ) + ( Anax + Hemianax )))))). Additional informative characters are required to test the relationships suggested here between the main groups of Aeshnodea and some enigmatic basal taxa ( Antipodophlebia , Austroaeschna , Acanthaeschna , Telephlebia , Austrophlebia and Planaeschna ). 相似文献
329.
Solar UV‐B radiation and ethylene play a key role in modulating effective defenses against Anticarsia gemmatalis larvae in field‐grown soybean 下载免费PDF全文
Francisco M. Dillon M. Daniela Tejedor Natalia Ilina Hugo D. Chludil Axel Mithöfer Eduardo A. Pagano Jorge A. Zavala 《Plant, cell & environment》2018,41(2):383-394
Solar UV‐B radiation has been reported to enhance plant defenses against herbivore insects in many species. However, the mechanism and traits involved in the UV‐B mediated increment of plant resistance are unknown in crops species, such as soybean. Here, we studied defense‐related responses in undamaged and Anticarsia gemmatalis larvae‐damaged leaves of two soybean cultivars grown under attenuated or full solar UV‐B radiation. We determined changes in jasmonates, ethylene (ET), salicylic acid, trypsin protease inhibitor activity, flavonoids, and mRNA expression of genes related with defenses. ET emission induced by Anticarsia gemmatalis damage was synergistically increased in plants grown under solar UV‐B radiation and was positively correlated with malonyl genistin concentration, trypsin proteinase inhibitor activity and expression of IFS2, and the pathogenesis protein PR2, while was negatively correlated with leaf consumption. The precursor of ET, aminocyclopropane‐carboxylic acid, applied exogenously to soybean was sufficient to strongly induce leaf isoflavonoids. Our results showed that in field‐grown soybean isoflavonoids were regulated by both herbivory and solar UV‐B inducible ET, whereas flavonols were regulated by solar UV‐B radiation only and not by herbivory or ET. Our study suggests that, although ET can modulate UV‐B‐mediated priming of inducible plant defenses, some plant defenses, such as isoflavonoids, are regulated by ET alone. 相似文献
330.
Logan J. Pallin Nick M. Kellar Debbie Steel Natalia Botero-Acosta C. Scott Baker Jack A. Conroy Daniel P. Costa Chris M. Johnson David W. Johnston Ross C. Nichols Doug P. Nowacek Andrew J. Read Oksana Savenko Oscar M. Schofield Sharon E. Stammerjohn Deborah K. Steinberg Ari S. Friedlaender 《Global Change Biology》2023,29(8):2108-2121
The krill surplus hypothesis of unlimited prey resources available for Antarctic predators due to commercial whaling in the 20th century has remained largely untested since the 1970s. Rapid warming of the Western Antarctic Peninsula (WAP) over the past 50 years has resulted in decreased seasonal ice cover and a reduction of krill. The latter is being exacerbated by a commercial krill fishery in the region. Despite this, humpback whale populations have increased but may be at a threshold for growth based on these human-induced changes. Understanding how climate-mediated variation in prey availability influences humpback whale population dynamics is critical for focused management and conservation actions. Using an 8-year dataset (2013–2020), we show that inter-annual humpback whale pregnancy rates, as determined from skin-blubber biopsy samples (n = 616), are positively correlated with krill availability and fluctuations in ice cover in the previous year. Pregnancy rates showed significant inter-annual variability, between 29% and 86%. Our results indicate that krill availability is in fact limiting and affecting reproductive rates, in contrast to the krill surplus hypothesis. This suggests that this population of humpback whales may be at a threshold for population growth due to prey limitations. As a result, continued warming and increased fishing along the WAP, which continue to reduce krill stocks, will likely impact this humpback whale population and other krill predators in the region. Humpback whales are sentinel species of ecosystem health, and changes in pregnancy rates can provide quantifiable signals of the impact of environmental change at the population level. Our findings must be considered paramount in developing new and more restrictive conservation and management plans for the Antarctic marine ecosystem and minimizing the negative impacts of human activities in the region. 相似文献