bluuebunny/crossref_metadata_2025_split huggingface dataset:
Qualitative reasoning of dynamic gene regulatory interactions from gene expression data
Authors: Chen Yu , Park Byungkyu , Han Kyungsook 
Published: December 2010

Abstract

Background
A gene regulatory relation often changes over time rather than being constant. But many gene regulatory networks available in databases or literatures are static in the sense that they are either snapshots of gene regulatory relations at a time point or union of successive gene regulations over time. Such static networks cannot represent temporal aspects of gene regulatory interactions such as the order of gene regulations or the pace of gene regulations.

Results
We developed a new qualitative method for representing dynamic gene regulatory relations and algorithms for identifying dynamic gene regulations from the time-series gene expression data using two types of scores. The identified gene regulatory interactions and their temporal properties are visualized as a gene regulatory network. All the algorithms have been implemented in a program called GeneNetFinder (http://wilab.inha.ac.kr/genenetfinder/) and tested on several gene expression data.

Conclusions
The dynamic nature of dynamic gene regulatory interactions can be inferred and represented qualitatively without deriving a set of differential equations describing the interactions. The approach and the program developed in our study would be useful for identifying dynamic gene regulatory interactions from the large amount of gene expression data available and for analyzing the interactions.
Construction of a genetic AND gate under a new standard for assembly of genetic parts
Authors: Ayukawa Shotaro , Kobayashi Akio , Nakashima Yusaku , Takagi Hidemasa , Hamada Shogo , Uchiyama Masahiko , Yugi Katsuyuki , Murata Satoshi , Sakakibara Yasubumi , Hagiya Masami , Yamamura Masayuki , Kiga Daisuke 
Published: December 2010

Abstract

Background
Appropriate regulation of respective gene expressions is a bottleneck for the realization of artificial biological systems inside living cells. The modification of several promoter sequences is required to achieve appropriate regulation of the systems. However, a time-consuming process is required for the insertion of an operator, a binding site of a protein for gene expression, to the gene regulatory region of a plasmid. Thus, a standardized method for integrating operator sequences to the regulatory region of a plasmid is required.

Results
We developed a standardized method for integrating operator sequences to the regulatory region of a plasmid and constructed a synthetic promoter that functions as a genetic AND gate. By standardizing the regulatory region of a plasmid and the operator parts, we established a platform for modular assembly of the operator parts. Moreover, by assembling two different operator parts on the regulatory region, we constructed a regulatory device with an AND gate function.

Conclusions
We implemented a new standard to assemble operator parts for construction of functional genetic logic gates. The logic gates at the molecular scale have important implications for reprogramming cellular behavior.
Gerontome: a web-based database server for aging-related genes and analysis pipelines
Authors: Kwon Jekeun , Lee Byungwook , Chung Haeyoung 
Published: December 2010

Abstract

Background
Aging is a complex and challenging phenomenon that requires interdisciplinary efforts to unravel its mystery. Insight into genes relevant to the aging process would offer the chance to delay and avoid some of deteriorative aspects of aging through the use of preventive methods. To assist basic research on aging, a comprehensive database and analysis platform for aging-related genes is required.

Results
We developed a web-based database server, called Gerontome that contains aging-related gene information and user-friendly analysis pipelines. To construct the Gerontome database, we integrated aging-related genes and their annotation data. The aging-related genes were categorized by a set of structural terms from Gene Ontology (GO). Analysis pipelines for promoter analysis and protein-ligand docking were developed. The promoter analysis pipeline allows users to investigate the age-dependent regulation of gene expression. The protein-ligand docking pipeline provides information on the position and orientation of a ligand in an age-related protein surface.

Conclusion
Gerontome can be accessed through web interfaces for querying and browsing. The server provides comprehensive age-related gene information and analysis pipelines. Gerontome is available free at http://gerontome.kobic.re.kr.
Essential role for ALCAM gene silencing in megakaryocytic differentiation of K562 cells
Authors: Tan Fang , Ghosh Samit , Mbeunkui Flaubert , Thomas Robert , Weiner Joshua A , Ofori-Acquah Solomon F 
Published: December 2010

Abstract

Background
Activated leukocyte cell adhesion molecule (ALCAM/CD166) is expressed by hematopoietic stem cells. However, its role in hematopoietic differentiation has not previously been defined.

Results
In this study, we show that ALCAM expression is silenced in erythromegakaryocytic progenitor cell lines. In agreement with this finding, the ALCAM promoter is occupied by GATA-1 in vivo, and a cognate motif at -850 inhibited promoter activity in K562 and MEG-01 cells. Gain-of-function studies showed that ALCAM clusters K562 cells in a process that requires PKC. Induction of megakaryocytic differentiation in K562 clones expressing ALCAM activated PKC-δ and triggered apoptosis.

Conclusions
There is a lineage-specific silencing of ALCAM in bi-potential erythromegakaryocytic progenitor cell lines. Marked apoptosis of ALCAM-expressing K562 clones treated with PMA suggests that aberrant ALCAM expression in erythromegakaryocytic progenitors may contribute to megakaryocytopenia.
Two distinct regions in the model protein Peb1 are critical for its heterologous transport out of Escherichia coli
Authors: Anton Lena , Majander Katariina , Savilahti Harri , Laakkonen Liisa , Westerlund-Wikström Benita 
Published: December 2010

Abstract

Background

Escherichia coli is frequently the first-choice host organism in expression of heterologous recombinant proteins in basic research as well as in production of commercial, therapeutic polypeptides. Especially the secretion of proteins into the culture medium of E. coli is advantageous compared to intracellular production due to the ease in recovery of the recombinant protein. Since E. coli naturally is a poor secretor of proteins, a few strategies for optimization of extracellular secretion have been described. We have previously reported efficient secretion of the diagnostically interesting model protein Peb1 of Campylobacter jejuni into the growth medium of Escherichia coli strain MKS12 (ΔfliCfliD). To generate a more detailed understanding of the molecular mechanisms behind this interesting heterologous secretion system with biotechnological implications, we here analyzed further the transport of Peb1 in the E. coli host.

Results
When mature Peb1 was expressed without its SecA-YEG -dependent signal sequence and without the putative signal peptidase II recognition sequence in E. coli MKS111ΔHBB lacking the flagellar secretion complex, the protein was found in the periplasm and growth medium which indicated a flagellum-independent translocation. We assessed the Peb1 secretion proficiency by an exhaustive search for transport-affecting regions using a transposition-based scanning mutagenesis strategy. Strikingly, insertion mutagenesis of only two segments, called TAR1 (residues 42 and 43) and TAR2 (residues 173 to 180), prevented Peb1 secretion individually. We confirmed the importance of TAR regions by subsequent site-specific mutagenesis and verified that the secretion deficiency of Peb1 mutants was not due to insolubility or aggregation of the proteins in the cytoplasm. We found by cell fractionation that the mutant proteins were present in the periplasm as well as in the cytoplasm of MKS12. Hence, mutagenesis of TAR regions did not affect export of Peb1 across the cytoplasmic membrane, whereas its export over the outer membrane was markedly impaired.

Conclusions
We propose that the localization of the model protein Peb1 in the growth medium of E. coli is due to active secretion by a still unknown pathway of E. coli. The secretion apparently is a two-step process involving a periplasmic step and the TAR regions.
Targeting the oncogenic protein beta-catenin to enhance chemotherapy outcome against solid human cancers
Authors: Saifo Maher S , Rempinski Donald R , Rustum Youcef M , Azrak Rami G 
Published: December 2010

Abstract

Background
Beta-catenin is a multifunctional oncogenic protein that contributes fundamentally to cell development and biology. Elevation in expression and activity of β-catenin has been implicated in many cancers and associated with poor prognosis. Beta-catenin is degraded in the cytoplasm by glycogen synthase kinase 3 beta (GSK-3β) through phosphorylation. Cell growth and proliferation is associated with β-catenin translocation from the cytoplasm into the nucleus.
This laboratory was the first to demonstrate that selenium-containing compounds can enhance the efficacy and cytotoxicity of anticancer drugs in several preclinical xenograft models. These data provided the basis to identify mechanism of selenium action focusing on β-catenin as a target. This study was designed to: (1) determine whether pharmacological doses of methylseleninic acid (MSeA) have inhibitory effects on the level and the oncogenic activity of β-catenin, (2) investigate the kinetics and the mechanism of β-catenin inhibition, and (3) confirm that inhibition of β-catenin would lead to enhanced cytotoxicity of standard chemotherapeutic drugs.

Results
In six human cancer cell lines, the inhibition of total and nuclear expression of β-catenin by MSeA was dose and time dependent. The involvement of GSK-3β in the degradation of β-catenin was cell type dependent (GSK-3β-dependent in HT-29, whereas GSK-3β-independent in HCT-8). However, the pronounced inhibition of β-catenin by MSeA was independent of various drug treatments and was not reversed after combination therapy.
Knockout of β-catenin by ShRNA and its inhibition by MSeA yielded similar enhancement of cytotoxicity of anticancer drugs.
Collectively, the generated data demonstrate that β-catenin is a target of MSeA and its inhibition resulted in enhanced cytotoxicity of chemotherapeutic drugs.

Conclusions
This study demonstrates that β-catenin, a molecule associated with drug resistance, is a target of selenium and its inhibition is associated with increased multiple drugs cytotoxicity in various human cancers. Further, degradation of β-catenin by GSK-3β is not a general mechanism but is cell type dependent.
Prevalence of the GJB2 IVS1+1G >A mutation in Chinese hearing loss patients with monoallelic pathogenic mutation in the coding region of GJB2
Authors: Yuan Yongyi , Yu Fei , Wang Guojian , Huang Shasha , Yu Ruili , Zhang Xin , Huang Deliang , Han Dongyi , Dai Pu 
Published: December 2010

Abstract

Background
Mutations in the GJB2 gene are the most common cause of nonsyndromic recessive hearing loss in China. In about 6% of Chinese patients with severe to profound sensorineural hearing impairment, only monoallelic GJB2 mutations known to be either recessive or of unclear pathogenicity have been identified. This paper reports the prevalence of the GJB2 IVS1+1G>A mutation in a population of Chinese hearing loss patients with monoallelic pathogenic mutation in the coding region of GJB2.

Methods
Two hundred and twelve patients, screened from 7133 cases of nonsyndromic hearing loss in China, with monoallelic mutation (mainly frameshift and nonsense mutation) in the coding region of GJB2 were examined for the GJB2 IVS1+1G>A mutation and mutations in the promoter region of this gene. Two hundred and sixty-two nonsyndromic hearing loss patients without GJB2 mutation and 105 controls with normal hearing were also tested for the GJB2 IVS1+1G>A mutation by sequencing.

Results
Four patients with monoallelic mutation in the coding region of GJB2 were found carrying the GJB2 IVS1+1G>A mutation on the opposite allele. One patient with the GJB2 c.235delC mutation carried one variant, -3175 C>T, in exon 1 of GJB2. Neither GJB2 IVS1+1G>A mutation nor any variant in exon 1 of GJB2 was found in the 262 nonsyndromic hearing loss patients without GJB2 mutation or in the 105 normal hearing controls.

Conclusion
Testing for the GJB2 IVS 1+1 G to A mutation explained deafness in 1.89% of Chinese GJB2 monoallelic patients, and it should be included in routine testing of patients with GJB2 monoallelic pathogenic mutation.
CCL2/CCR2 and CX3CL1/CX3CR1 chemokine axes and their possible involvement in age-related macular degeneration
Authors: Raoul William , Auvynet Constance , Camelo Serge , Guillonneau Xavier , Feumi Charles , Combadière Christophe , Sennlaub Florian 
Published: December 2010

Abstract
The causes of age-related macular degeneration (AMD) are not well understood. Due to demographic shifts in the industrialized world a growing number of people will develop AMD in the coming decades. To develop treatments it is essential to characterize the disease's pathogenic process. Over the past few years, numerous studies have focused on the role of chemotactic cytokines, also known as chemokines. Certain chemokines, such as CCL2 and CX3CL1, appear to be crucial in subretinal microglia and macrophage accumulation observed in AMD, and participate in the development of retinal degeneration as well as in choroidal neovascularization. This paper reviews the possible implications of CCL2 and CX3CL1 signaling in AMD. Expression patterns, single nucleotide polymorphisms (SNPs) association studies, chemokine and chemokine receptor knockout models are discussed. Future AMD treatments could target chemokines and/or their receptors.
Lignin monomer composition affects Arabidopsis cell-wall degradability after liquid hot water pretreatment
Authors: Li Xu , Ximenes Eduardo , Kim Youngmi , Slininger Mary , Meilan Richard , Ladisch Michael , Chapple Clint 
Published: December 2010

Abstract

Background
Lignin is embedded in the plant cell wall matrix, and impedes the enzymatic saccharification of lignocellulosic feedstocks. To investigate whether enzymatic digestibility of cell wall materials can be improved by altering the relative abundance of the two major lignin monomers, guaiacyl (G) and syringyl (S) subunits, we compared the degradability of cell wall material from wild-type Arabidopsis thaliana with a mutant line and a genetically modified line, the lignins of which are enriched in G and S subunits, respectively.

Results
Arabidopsis tissue containing G- and S-rich lignins had the same saccharification performance as the wild type when subjected to enzyme hydrolysis without pretreatment. After a 24-hour incubation period, less than 30% of the total glucan was hydrolyzed. By contrast, when liquid hot water (LHW) pretreatment was included before enzyme hydrolysis, the S-lignin-rich tissue gave a much higher glucose yield than either the wild-type or G-lignin-rich tissue. Applying a hot-water washing step after the pretreatment did not lead to a further increase in final glucose yield, but the initial hydrolytic rate was doubled.

Conclusions
Our analyses using the model plant A. thaliana revealed that lignin composition affects the enzymatic digestibility of LHW pretreated plant material. Pretreatment is more effective in enhancing the saccharification of A. thaliana cell walls that contain S-rich lignin. Increasing lignin S monomer content through genetic engineering may be a promising approach to increase the efficiency and reduce the cost of biomass to biofuel conversion.
Nonoxidative Free Fatty Acid Disposal Is Greater in Young Women than Men
Authors: Koutsari Christina , Basu Rita , Rizza Robert A. , Nair K. Sreekumaran , Khosla Sundeep , Jensen Michael D. 
Published: December 2010

abstract

Context:
Large increases in systemic free fatty acid (FFA) availability in the absence of a corresponding increase in fatty acid oxidation can create a host of metabolic abnormalities. These adverse responses are thought to be the result of fatty acids being shunted into hepatic very low-density lipoprotein-triglyceride production and/or intracellular lipid storage and signaling pathways because tissues are forced to increase nonoxidative FFA disposal.

Objective:
The objective of the study was to examine whether variations in postabsorptive nonoxidative FFA disposal within the usual range predict insulin resistance and hypertriglyceridemia.

Design:
We measured: systemic FFA turnover using a continuous iv infusion of [9–10, 3H]palmitate; substrate oxidation with indirect calorimetry combined with urinary nitrogen excretion; whole-body and peripheral insulin sensitivity with the labeled iv glucose tolerance test minimal model.

Setting:
the study was conducted at the Mayo Clinic General Clinical Research Center.

Participants:
Participants included healthy, postabsorptive, nonobese adults (21 women and 21 men).

Interventions:
There were no interventions.

Main Outcome Measures:
Nonoxidative FFA disposal (micromoles per minute), defined as the FFA disappearance rate minus fatty acid oxidation.

Results:
Women had 64% greater nonoxidative FFA disposal rate than men but a better lipid profile and similar insulin sensitivity. There was no significant correlation between nonoxidative FFA disposal and whole-body sensitivity, peripheral insulin sensitivity, or fasting serum triglyceride concentrations in men or women.

Conclusions:
Healthy nonobese women have greater rates of nonoxidative FFA disposal than men, but this does not appear to relate to adverse health consequences. Understanding the sex-specific interaction between adipose tissue lipolysis and peripheral FFA removal will help to discover new approaches to treat FFA-induced abnormalities.
A New Small-Molecule Antagonist Inhibits Graves' Disease Antibody Activation of the TSH Receptor
Authors: Neumann Susanne , Eliseeva Elena , McCoy Joshua G. , Napolitano Giorgio , Giuliani Cesidio , Monaco Fabrizio , Huang Wenwei , Gershengorn Marvin C. 
Published: December 2010

abstract

Context:
Graves' disease (GD) is caused by persistent, unregulated stimulation of thyrocytes by thyroid-stimulating antibodies (TSAbs) that activate the TSH receptor (TSHR). We previously reported the first small-molecule antagonist of human TSHR and showed that it inhibited receptor signaling stimulated by sera from four patients with GD.

Objective:
Our objective was to develop a better TSHR antagonist and use it to determine whether inhibition of TSAb activation of TSHR is a general phenomenon.

Design:
We aimed to chemically modify a previously reported small-molecule TSHR ligand to develop a better antagonist and determine whether it inhibits TSHR signaling by 30 GD sera. TSHR signaling was measured in two in vitro systems: model HEK-EM293 cells stably overexpressing human TSHRs and primary cultures of human thyrocytes. TSHR signaling was measured as cAMP production and by effects on thyroid peroxidase mRNA.

Results:
We tested analogs of a previously reported small-molecule TSHR inverse agonist and selected the best NCGC00229600 for further study. In the model system, NCGC00229600 inhibited basal and TSH-stimulated cAMP production. NCGC00229600 inhibition of TSH signaling was competitive even though it did not compete for TSH binding; that is, NCGC00229600 is an allosteric inverse agonist. NCGC00229600 inhibited cAMP production by 39 ± 2.6% by all 30 GD sera tested. In primary cultures of human thyrocytes, NCGC00229600 inhibited TSHR-mediated basal and GD sera up-regulation of thyroperoxidase mRNA levels by 65 ± 2.0%.

Conclusion:
NCGC00229600, a small-molecule allosteric inverse agonist of TSHR, is a general antagonist of TSH receptor activation by TSAbs in GD patient sera.
Concentration Determination of Individual Components in Methanol–Raffinose Mixtures Using Diffusion through Agar Membrane Attached to a Surface Plasmon Resonance Sensor
Authors: Montecillo Menchie E , Yoshidome Toshifumi , Yamagata Toshiyuki , Yamasaki Tatsuya , Mitsushio Masaru , Sarno Brian John , Higo Morihide 
Published: December 2010

Abstract
A surface plasmon resonance (SPR) sensor with agar membrane was developed and applied to aqueous solutions containing methanol and raffinose. The concentrations of the components in the mixture were determined by fitting diffusion-based equations to the SPR time chart. Good agreement between the measured and expected concentrations was observed.
Stationary Behavior in Effective Magnetic Moment and Magnetization of 2,3,6-Trifluorophenyl Nitronyl Nitroxide Radical Crystals
Authors: Kanzawa Tsuneki , Nishihara Sadafumi , Nojiri Hiroyuki , Hosokoshi Yuko 
Published: December 2010

Abstract
A new stable organic radical, 2,3,6-trifluorophenyl nitronyl nitroxide (=2-(2,3,6-trifluorophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1-oxyl 3-oxide) was synthesized, and its crystal structure and magnetic properties were examined. The magnetization curve measured at 0.4 K in magnetic field up to 30 T revealed two-step saturation. A magnetization plateau was observed when the magnetization was one half the value of the saturation magnetization. The temperature dependence of the product of paramagnetic susceptibility (χp) and temperature (T), χpT (χpT ∝ μeff2, square of the effective magnetic moment) showed stationary behavior in the range 2–4 K at two-thirds the value at room temperature. The magnetic structure of this material could be elucidated on the basis of magnetization (M) measurements. Complementary analysis of χpT and M revealed the formation of magnetic clusters comprising triplet (S = 1) and singlet (S = 0) species in the ground state. The intradimer interactions were attributed to the special molecular overlaps, as reported previously. Interdimer interactions were also investigated: the difference in the molecular overlap between the trifluorophenyl groups was responsible for the difference in the sign of the magnetic coupling. This is the first experimental evidence for the molecular overlap between the phenyl groups being responsible for the strong magnetic interactions.
Preparation and Characterization of Phase-Segregated Vesicles of Photopolymerizable Diacetylene Mixed with Nonpolymerizable Amphiphiles
Authors: Matsumoto Jin , Yoneda Koshiro , Tasaka Jun , Shiragami Tsutomu , Yasuda Masahide 
Published: December 2010

Abstract
A mixture of sodium 1,2-di(hexadecyloxycarbonyl)ethanesulfonate (2C16S) with photopolymerizable 1,2-di(10,12-tricosadiynoyl)-sn-glycerol 3-phosphocholine (DTPC) in a 2:100 ratio was treated by modified thin-film hydration to give an aggregate which became polymerized giant vesicles (GVs) under irradiation at 254 nm. The autofluorescence of the GVs was analyzed with a confocal laser scanning microscope at the cross section, revealing a 3.8-µm diameter ring shape and the presence of a dark part of ca. 1 µm in the ring. When octadecylrhodamine B (RhB) as an amphiphilic fluorescence probe was added to the GV, the fluorescence of RhB was emitted from the whole ring. Therefore, phase segregation of 2C16S from DTPC was confirmed. Similarly, mixed vesicles of N,N-di(2-hexadecanoyloxyethyl)dimethylammonium iodide with DTPC were found to be 3.7-µm diameter phase-segregated vesicles with a dark portion of ca. 1 µm on the ring in the cross sectional image. On the other hand, DTPC vesicles mixed with 1,2-di(dodecyloxycarbonyl)ethanesulfonate, N,N-di(2-dodecanoyloxyethyl)dimethylammonium iodide, and N,N-di(2-tetradecanoyloxyethyl)dimethylammonium iodide formed sphere structures filling the inside of the vesicles. The segregation mechanism was explained by the difference in the main phase transition temperature of each amphiphile.