bluuebunny/crossref_metadata_2025_split huggingface dataset:
An internal deletion in MTH1 enables growth on glucose of pyruvate-decarboxylase negative, non-fermentative Saccharomyces cerevisiae
Authors: Oud Bart , Flores Carmen-Lisset , Gancedo Carlos , Zhang Xiuying , Trueheart Joshua , Daran Jean-Marc , Pronk Jack T , van Maris Antonius JA 
Published: September 2012

Abstract

Background
Pyruvate-decarboxylase negative (Pdc-) strains of Saccharomyces cerevisiae combine the robustness and high glycolytic capacity of this yeast with the absence of alcoholic fermentation. This makes Pdc-
S. cerevisiae an interesting platform for efficient conversion of glucose towards pyruvate-derived products without formation of ethanol as a by-product. However, Pdc- strains cannot grow on high glucose concentrations and require C2-compounds (ethanol or acetate) for growth under conditions with low glucose concentrations, which hitherto has limited application in industry.

Results
Genetic analysis of a Pdc- strain previously evolved to overcome these deficiencies revealed a 225bp in-frame internal deletion in MTH1, encoding a transcriptional regulator involved in glucose sensing. This internal deletion contains a phosphorylation site required for degradation, thereby hypothetically resulting in increased stability of the protein. Reverse engineering of this alternative MTH1 allele into a non-evolved Pdc- strain enabled growth on 20 g l-1 glucose and 0.3% (v/v) ethanol at a maximum specific growth rate (0.24 h-1) similar to that of the evolved Pdc- strain (0.23 h-1). Furthermore, the reverse engineered Pdc- strain grew on glucose as sole carbon source, albeit at a lower specific growth rate (0.10 h-1) than the evolved strain (0.20 h-1). The observation that overexpression of the wild-type MTH1 allele also restored growth of Pdc-
S. cerevisiae on glucose is consistent with the hypothesis that the internal deletion results in decreased degradation of Mth1. Reduced degradation of Mth1 has been shown to result in deregulation of hexose transport. In Pdc- strains, reduced glucose uptake may prevent intracellular accumulation of pyruvate and/or redox problems, while release of glucose repression due to the MTH1 internal deletion may contribute to alleviation of the C2-compound auxotrophy.

Conclusions
In this study we have discovered and characterised a mutation in MTH1 enabling Pdc- strains to grow on glucose as the sole carbon source. This successful example of reverse engineering not only increases the understanding of the glucose tolerance of evolved Pdc-
S. cerevisiae, but also allows introduction of this portable genetic element into various industrial yeast strains, thereby simplifying metabolic engineering strategies.
Coronin 3 promotes gastric cancer metastasis via the up-regulation of MMP-9 and cathepsin K
Authors: Ren Gui , Tian Qifei , An Yanxin , Feng Bin , Lu Yuanyuan , Liang Jie , Li Kai , Shang Yulong , Nie Yongzhan , Wang Xin , Fan Daiming 
Published: September 2012

AbstractBackgroundCoronins are a family of highly evolutionary conserved proteins reportedly involved in the regulation of actin cytoskeletal dynamics, although only coronin 3 has been shown to be related to cancer cell migration. In glioblastoma cells, the knockdown of coronin 3 inhibits cell proliferation and invasion. Coronin 3 is also associated with the aggression and metastasis of hepatocellular carcinoma. In this paper, we analyze the migration, invasion and metastasis abilities of gastric cancer cells after up- or down-regulation of coronin 3, and explore the mechanism of coronin 3 in the process of gastric cancer metastasis.ResultsThe expression of coronin 3 was higher in the highly metastatic sub-cell line MKN28-M, which we established in our laboratory. We also demonstrated that the expression of coronin 3 was remarkably higher in lymph lode metastases than in primary gastric cancer tissues, and over-expression of coronin 3 was correlated with the increased clinical stage and lymph lode metastasis. Recombinant lentiviral vectors encoding shRNAs were designed to down-regulate coronin 3 expression in gastric cancer cell lines. Stable knockdown of coronin 3 by this lentiviral vector could efficiently inhibit the migration and invasion of MKN45 gastric cancer cells. In contrast, up-regulation of coronin 3 significantly enhanced migration and invasion of MKN28-NM cells. In addition, knockdown of coronin 3 significantly reduced liver metastasis in mice after tail vein injection of gastric cancer cells. The Human Tumor Metastasis PCR Array was used to screen the metastasis-associated genes identified by the down-regulation of coronin 3, and the results suggested that, following the knockdown of coronin 3, the tumor cell migration and invasion were inhibited by the reduced expression of MMP-9 and cathepsin K.ConclusionCoronin 3 is highly expressed in gastric cancer metastases and can promote the metastatic behaviors of gastric cancer cells, including their migration and invasion.
Development of a new humanized mouse model to study acute inflammatory arthritis
Authors: Misharin Alexander V , Haines G Kenneth , Rose Shawn , Gierut Angelical K , Hotchkiss Richard S , Perlman Harris 
Published: September 2012

Abstract

Background
Substantial advances have been generated in understanding the pathogenesis of rheumatoid arthritis (RA). Current murine models of RA-like disease have provided great insights into the molecular mechanism of inflammatory arthritis due to the use of genetically deficient or transgenic mice. However, these studies are limited by differences that exist between human and murine immune systems. Thus, the development of an animal model that utilizes human immune cells, will afford the opportunity to study their function in the initiation and propagation of inflammatory arthritis.

Methods
One to two-day old irradiated NOD-scid IL2rγ

null
(NSG) mice were reconstituted with human CD34+ cord blood stem cells. Leukocytes were analyzed by flow cytometry and circulating antibodies were determined by ELISA. Arthritis was induced by injecting complete Freund’s adjuvant into knee or ankle joints. Mice were also treated with the TNF inhibitor, Etanercept, or PBS and joints were analyzed histologically.

Results
Humanized mice were established with high reconstitution rates and were able to spontaneously produce human immunoglobulins as well as specific IgG in response to immunization. Intraperitoneal injection of thioglycolate or injection of complete Freund’s adjuvant into joints resulted in migration of human immune cells to the injected sites. Arthritic humanized mice treated with Etanercept had markedly less inflammation, which was associated with decreased total numbers of human CD45+ cells, including human lymphocytes and neutrophils.

Conclusions
The humanized mouse model is a new model to study inflammatory arthritis disease using human leukocytes without rejection of engrafted tissue. Future studies may adapt this system to incorporate RA patient cord blood and develop a chimeric animal model of inflammatory arthritis using genetically predisposed immune cells.
Anomalous luminescence phenomena of indium-doped ZnO nanostructures grown on Si substrates by the hydrothermal method
Authors: Wang Jen-Cheng , Cheng Fang-Ching , Liang Yu-Ting , Chen Hung-Ing , Tsai Chung-Yuan , Fang Chia-Hui , Nee Tzer-En 
Published: September 2012

Abstract
In recent years, zinc oxide (ZnO) has become one of the most popular research materials due to its unique properties and various applications. ZnO is an intrinsic semiconductor, with a wide bandgap (3.37 eV) and large exciton binding energy (60 meV) making it suitable for many optical applications. In this experiment, the simple hydrothermal method is used to grow indium-doped ZnO nanostructures on a silicon wafer, which are then annealed at different temperatures (400°C to 1,000°C) in an abundant oxygen atmosphere. This study discusses the surface structure and optical characteristic of ZnO nanomaterials. The structure of the ZnO nanostructures is analyzed by X-ray diffraction, the superficial state by scanning electron microscopy, and the optical measurements which are carried out using the temperature-dependent photoluminescence (PL) spectra. In this study, we discuss the broad peak energy of the yellow-orange emission which shows tendency towards a blueshift with the temperature increase in the PL spectra. This differs from other common semiconductors which have an increase in their peak energy of deep-level emission along with measurement temperature.
Development of the excretory system in a polyplacophoran mollusc: stages in metanephridial system development
Authors: Baeumler Natalie , Haszprunar Gerhard , Ruthensteiner Bernhard 
Published: September 2012

Abstract

Background
Two types of excretory systems, protonephridia and metanephridial systems are common among bilaterians. The homology of protonephridia of lophotrochozoan taxa has been widely accepted. In contrast, the homology of metanephridial systems – including coelomic cavities as functional units – among taxa as well as the homology between the two excretory systems is a matter of ongoing discussion. This particularly concerns the molluscan kidneys, which are mostly regarded as being derived convergently to the metanephridia of e.g. annelids because of different ontogenetic origin. A reinvestigation of nephrogenesis in polyplacophorans, which carry many primitive traits within molluscs, could shed light on these questions.

Results
The metanephridial system of Lepidochitona corrugata develops rapidly in the early juvenile phase. It is formed from a coelomic anlage that soon achieves endothelial organization. The pericardium and heart are formed from the central portion of the anlage. The nephridial components are formed by outgrowth from lateral differentiations of the anlage. Simultaneously with formation of the heart, podocytes appear in the atrial wall of the pericardium. In addition, renopericardial ducts, kidneys and efferent nephroducts, all showing downstream ciliation towards the internal lumen, become differentiated (specimen length: 0.62 mm). Further development consists of elongation of the kidney and reinforcement of filtration and reabsorptive structures.

Conclusions
During development and in fully formed condition the metanephridial system of Lepidochitona corrugata shares many detailed traits (cellular and overall organization) with the protonephridia of the same species. Accordingly, we suggest a serial homology of various cell types and between the two excretory systems and the organs as a whole. The formation of the metanephridial system varies significantly within Mollusca, thus the mode of formation cannot be used as a homology criterion. Because of similarities in overall organization, we conclude that the molluscan metanephridial system is homologous with that of the annelids not only at the cellular but also at the organ level.
Sulforaphane prevention of diabetes-induced aortic damage was associated with the up-regulation of Nrf2 and its down-stream antioxidants
Authors: Miao Xiao , Bai Yang , Sun Weixia , Cui Wenpeng , Xin Ying , Wang Yuehui , Tan Yi , Miao Lining , Fu Yaowen , Su Guanfang , Cai Lu 
Published: September 2012

Abstract

Background
Oxidative stress plays an important role in diabetes-induced vascular inflammation and pathogenesis. Nuclear factor E2-related factor-2 (Nrf2) is a transcription factor orchestrating antioxidant and cyto-protective responses to oxidative stress. In the present study, we tested whether sulforaphane (SFN) can protect the aorta from diabetes and, if so, whether the aortic protection is associated with up-regulation of Nrf2 and its down-stream antioxidants.

Methods
Type 1 diabetes was induced in FVB mice by multiple low-dose streptozotocin. Diabetic and age-matched control mice were treated with or without SFN at 0.5 mg/kg daily in five days of each week for three months. At the end of 3 months treatment of SFN one set of mice were sacrificed to perform the experimental measurements. The second set of both diabetic and control mice were aged for additional 3 months without further SFN treatment and then sacrificed to perform the experimental measurements. Aortas from these mice were assessed for fibrosis, inflammation, oxidative damage, and Nrf2 expression and transcription by immunohistochemical staining and real-time PCR method, respectively.

Results
Diabetes induced significant increases in oxidative stress and inflammation in the aorta at both 3 and 6 months, and fibrotic response at 6 months. SFN completely prevented these diabetic pathogenic changes and also significantly up-regulated the expression of Nrf2 and its down-stream antioxidants.

Conclusions
These results suggest that diabetes-induced aortic fibrosis, inflammation, and oxidative damage can be prevented by SFN. The aortic protection from diabetes by SFN was associated with the up-regulation of Nrf2 and its downstream antioxidants.
Impact of different exercise training modalities on the coronary collateral circulation and plaque composition in patients with significant coronary artery disease (EXCITE trial): study protocol for a randomized controlled trial
Authors: Uhlemann Madlen , Adams Volker , Lenk Karsten , Linke Axel , Erbs Sandra , Adam Jennifer , Thiele Holger , Hilberg Thomas , Gutberlet Matthias , Grunze Martin , Schuler Gerhard C , Möbius-Winkler Sven 
Published: September 2012

Abstract

Background
Exercise training (ET) in addition to optimal medical therapy (OMT) in patients with stable coronary artery disease (CAD) has been demonstrated to be superior to percutaneous coronary interventions (PCI) with respect to the composite endpoint of death, myocardial infarction, stroke, revascularization and hospitalization due to worsening of angina. One mechanism leading to this superiority discussed in the literature is the increase in coronary collateral blood flow due to ET. Until now, data demonstrating the positive effect of ET on the collateral blood flow and the functional capacity of the coronary collateral circulation are still lacking.

Methods/design
The EXCITE trial is a three-armed randomized, prospective, single-center, open-label, controlled study enrolling 60 patients with stable CAD and at least one significant coronary stenosis (fractional flow reserve ≤0.75). The study is designed to compare the influence and efficacy of two different 4-week ET programs [high-intensity interval trainings (IT) versus moderate-intensity exercise training (MT) in addition to OMT] versus OMT only on collateral blood flow (CBF). The primary efficacy endpoint is the change of the CBF of the target vessel after 4 weeks as assessed by coronary catheterization with a pressure wire during interruption of the antegrade flow of the target vessel by balloon occlusion. Secondary endpoints include the change in plaque composition as assessed by intravascular ultrasound (IVUS) after 4 weeks, myocardial perfusion as analyzed in MRI after 4 weeks and 12 months, peak oxygen uptake (V02 peak), change in endothelial function and biomarkers after 4 weeks, 3, 6 and 12 months. The safety endpoint addresses major adverse cardiovascular events (death from cardiovascular cause, myocardial infarction, stroke, TIA, target vessel revascularization or hospitalization) after 12 months.

Discussion
The trial investigates whether ET for 4 weeks increases the CBF in patients with significant CAD compared to a sedentary control group. It also examines the impact of two intensities of ET on the CBF as well as the histological plaque composition. The trial started recruitment in June 2009 and will complete recruitment until June 2012. First results are expected in December 2012 (4-week follow-up), final results (12-month long-term secondary endpoint) in December 2013.

Trial registration
Clinical trial registration information-URL: http://www.clinicaltrials.gov.
Unique identifier: NCT01209637
20-HETE Induces Hyperglycemia through the cAMP/PKA-PhK-GP Pathway
Authors: Lai Guangrui , Wu Jingjing , Liu Xiaoliang , Zhao Yanyan 
Published: September 2012

Abstract
We previously generated cytochrome P450 4F2 (CYP4F2) transgenic mice and showed high 20-hydroxyeicosatetraenoic acid (20-HETE) production, which resulted in an elevation of blood pressure. However, it was unclear whether 20-HETE affected glucose metabolism. We measured fasting plasma glucose, insulin, hepatic CYP4F2 expression, and 20-HETE production by hepatic microsomes, and hepatic 20-HETE levels in transgenic mice. We also assessed glycogen phosphorylase (GP) activity and the cAMP/protein kinase A (PKA)-phosphorylase kinase (PhK)-GP pathway, as well as expressions of insulin receptor substrate 1 and glucose transporters in vivo and in vitro. The transgenic mice had overexpressed hepatic CYP4F2, high hepatic 20-HETE and fasting plasma glucose levels but normal insulin level. The GP activity was increased and the cAMP/PKA-PhK-GP pathway was activated in the transgenic mice compared with wild-type mice. Moreover, these alterations were eliminated with the addition of N-hydroxy-N′-(4-butyl-2 methylphenyl) formamidine, which is a selective 20-HETE inhibitor. The results were further validated in Bel7402 cells. In addition, the transgenic mice had functional insulin signaling, and 20-HETE had no effect on insulin signaling in Bel7402 cells, excluding that the observed hyperglycemia in CYP4F2 transgenic mice resulted from insulin dysfunction, because the target tissues were sensitive to insulin. Our study suggested that 20-HETE can induce hyperglycemia, at least in part, through the cAMP/PKA-PhK-GP pathway but not through the insulin-signaling pathway.
DrosophilaCep135/Bld10 maintains proper centriole structure but is dispensable for cartwheel formation
Authors: Roque Hélio , Wainman Alan , Richens Jennifer , Kozyrska Kasia , Franz Anna , Raff Jordan W. 
Published: September 2012

SummaryCep135/Bld10 is a conserved centriolar protein required for the formation of the central cartwheel, an early intermediate in centriole assembly. Surprisingly, Cep135/Bld10 is not essential for centriole duplication in Drosophila, suggesting either that Cep135/Bld10 is not essential for cartwheel formation, or that the cartwheel is not essential for centriole assembly in flies. Using electron tomography and super-resolution microscopy we show that centrioles can form a cartwheel in the absence of Cep135/Bld10, but centriole width is increased and the cartwheel appears to disassemble over time. Using 3D structured illumination microscopy we show that Cep135/Bld10 is localized to a region between inner (SAS-6, Ana2) and outer (Asl, DSpd-2 and D-PLP) centriolar components, and the localization of all these component is subtly perturbed in the absence of Cep135/Bld10, although the ninefold symmetry of the centriole is maintained. Thus, in flies, Cep135/Bld10 is not essential for cartwheel assembly or for establishing the ninefold symmetry of centrioles; rather, it appears to stabilize the connection between inner and outer centriole components.
Symbiodinium isolation by NaOH treatment
Authors: Zamoum Thamilla , Furla Paola 
Published: September 2012

Summary
The presence of photosynthetic zooxanthellae (Dinoflagellates) in the tissue of many cnidarians is the main reason for their ecological success (i.e. coral reefs). It could also be their demise, as worldwide reef building coral bleaching is nothing less than the breakdown of this symbiotic association. The stability of this relationship is then the principal marker for the biomonitoring of the cnidarian health. We have therefore developed a new, simple method to isolate zooxanthellae in few steps using a NaOH solution. The protocol was validated in three symbiotic cnidarian species: a sea anemone, a gorgonian and a coral. Our method allows the isolation of intact and viable zooxanthellae with better yields than classic methods, especially for species with calcareous skeleton. Moreover, the isolated zooxanthellae were free of host contaminants, facilitating subsequent specific molecular analyses.
Muscle function during takeoff and landing flight in the pigeon (Columba livia)
Authors: Berg Robertson Angela M. , Biewener Andrew A. 
Published: September 2012

SummaryThis study explored the muscle strain and activation patterns of several key flight muscles of the pigeon (Columba livia) during take-off and landing flight. Using electromyography (EMG) to measure muscle activation, and sonomicrometry to quantify muscle strain, we evaluated the muscle function patterns of the pectoralis, biceps, humerotriceps, and scapulotriceps as pigeons flew between two perches. These recordings were analyzed in the context of three-dimensional wing kinematics. To understand the different requirements of takeoff, midflight, and landing, we compared the activity and strain of these muscles among the three flight modes. The pectoralis and biceps exhibited greater fascicle strain rates during takeoff than during midflight or landing. However, the triceps muscles did not exhibit notable differences in strain among flight modes. All observed strain, activation, and kinematics were consistent with hypothesized muscle functions. The biceps contracted to stabilize and flex the elbow during the downstroke. The humerotriceps contracted to extend the elbow at the upstroke-downstroke transition, followed by scapulotriceps contraction to maintain elbow extension during the downstroke. The scapulotriceps also appeared to contribute to humeral elevation. Greater muscle activation intensity was observed during takeoff, compared to mid-flight and landing, in all muscles except the scapulotriceps. The timing patterns of muscle activation and length change differed among flight modes, yet demonstrated that pigeons do not shift the basic mechanical actions of key flight muscles as they shift from flight activities that demand energy production, such as takeoff and midflight, to maneuvers that require absorbing energy, such as landing. Similarly, joint kinematics were consistent among flight modes. The stereotypy of these neuromuscular and joint kinematic patterns is consistent with previously observed stereotypy of wing kinematics relative to the pigeon's body (in the local body frame) across these flight behaviors. Taken together, these observations suggest that the control of takeoff and landing flight primarily involves modulation of overall body pitch to effect changes in stroke plane angle and resulting wing aerodynamics.