bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blockade of XBP1 splicing by inhibition of IRE1α is a promising therapeutic option in multiple myeloma
Authors: Mimura Naoya , Fulciniti Mariateresa , Gorgun Gullu , Tai Yu-Tzu , Cirstea Diana , Santo Loredana , Hu Yiguo , Fabre Claire , Minami Jiro , Ohguchi Hiroto , Kiziltepe Tanyel , Ikeda Hiroshi , Kawano Yutaka , French Maureen , Blumenthal Martina , Tam Victor , Kertesz Nathalie L. , Malyankar Uriel M. , Hokenson Mark , Pham Tuan , Zeng Qingping , Patterson John B. , Richardson Paul G. , Munshi Nikhil C. , Anderson Kenneth C. 
Published: April 2012

Abstract
Multiple myeloma (MM) cells are characterized by high protein synthesis resulting in chronic endoplasmic reticulum (ER) stress, which is adaptively managed by the unfolded protein response. Inositol-requiring enzyme 1α (IRE1α) is activated to splice X-box binding protein 1 (XBP1) mRNA, thereby increasing XBP1s protein, which in turn regulates genes responsible for protein folding and degradation during the unfolded protein response. In this study, we examined whether IRE1α-XBP1 pathway is a potential therapeutic target in MM using a small-molecule IRE1α endoribonuclease domain inhibitor MKC-3946. MKC-3946 triggered modest growth inhibition in MM cell lines, without toxicity in normal mononuclear cells. Importantly, it significantly enhanced cytotoxicity induced by bortezomib or 17-AAG, even in the presence of bone marrow stromal cells or exogenous IL-6. Both bortezomib and 17-AAG induced ER stress, evidenced by induction of XBP1s, which was blocked by MKC-3946. Apoptosis induced by these agents was enhanced by MKC-3946, associated with increased CHOP. Finally, MKC-3946 inhibited XBP1 splicing in a model of ER stress in vivo, associated with significant growth inhibition of MM cells. Taken together, our results demonstrate that blockade of XBP1 splicing by inhibition of IRE1α endoribonuclease domain is a potential therapeutic option in MM.
Genome-wide linkage analyses identify Hfhl1 and Hfhl3 with frequency-specific effects on the hearing spectrum of NIH Swiss mice
Authors: Keller James M , Noben-Trauth Konrad 
Published: April 2012

Abstract

Background
The mammalian cochlea receives and analyzes sound at specific places along the cochlea coil, commonly referred to as the tonotopic map. Although much is known about the cell-level molecular defects responsible for severe hearing loss, the genetics responsible for less severe and frequency-specific hearing loss remains unclear. We recently identified quantitative trait loci (QTLs) Hfhl1 and Hfhl2 that affect high-frequency hearing loss in NIH Swiss mice. Here we used 2f1-f2 distortion product otoacoustic emissions (DPOAE) measurements to refine the hearing loss phenotype. We crossed the high frequency hearing loss (HFHL) line of NIH Swiss mice to three different inbred strains and performed linkage analysis on the DPOAE data obtained from the second-generation populations.

Results
We identified a QTL of moderate effect on chromosome 7 that affected 2f1-f2 emissions intensities (Hfhl1), confirming the results of our previous study that used auditory brainstem response (ABR) thresholds to identify QTLs affecting HFHL. We also identified a novel significant QTL on chromosome 9 (Hfhl3) with moderate effects on 2f1-f2 emissions intensities. By partitioning the DPOAE data into frequency subsets, we determined that Hfhl1 and Hfhl3 affect hearing primarily at frequencies above 24 kHz and 35 kHz, respectively. Furthermore, we uncovered additional QTLs with small effects on isolated portions of the DPOAE spectrum.

Conclusions
This study identifies QTLs with effects that are isolated to limited portions of the frequency map. Our results support the hypothesis that frequency-specific hearing loss results from variation in gene activity along the cochlear partition and suggest a strategy for creating a map of cochlear genes that influence differences in hearing sensitivity and/or vulnerability in restricted portions of the cochlea.
Genetic characterization of Plectorhinchus mediterraneus yields important clues about genome organization and evolution of multigene families
Authors: Merlo Manuel A , Pacchiarini Tiziana , Portela-Bens Silvia , Cross Ismael , Manchado Manuel , Rebordinos Laureana 
Published: April 2012

AbstractBackgroundMolecular and cytogenetic markers are of great use for to fish characterization, identification, phylogenetics and evolution. Multigene families have proven to be good markers for a better understanding of the variability, organization and evolution of fish species. Three different tandemly-repeated gene families (45S rDNA, 5S rDNA and U2 snDNA) have been studied inPlectorhinchus mediterraneus(Teleostei: Haemulidae), at both molecular and cytogenetic level, to elucidate the taxonomy and evolution of these multigene families, as well as for comparative purposes with other species of the family.ResultsFour different types of 5S rDNA were obtained; two of them showed a high homology with that ofRaja asterias, and the putative implication of a horizontal transfer event and its consequences for the organization and evolution of the 5S rDNA have been discussed. The other two types do not resemble any other species, but in one of them a putative tRNA-derived SINE was observed for the first time, which could have implications in the evolution of the 5S rDNA. The ITS-1 sequence was more related to a species of another different genus than to that of the same genus, therefore a revision of the Hamulidae family systematic has been proposed. In the analysis of the U2 snDNA, we were able to corroborate that U2 snDNA and U5 snDNA were linked in the same tandem array, and this has interest for tracing evolutionary lines. The karyotype of the species was composed of 2n = 48 acrocentric chromosomes, and each of the three multigene families were located in different chromosome pairs, thus providing three different chromosomal markers.ConclusionsNovel data can be extracted from the results: a putative event of horizontal transfer, a possible tRNA-derived SINE linked to one of the four 5S rDNA types characterized, and a linkage between U2 and U5 snDNA. In addition, a revision of the taxonomy of the Haemulidae family has been suggested, and three cytogenetic markers have been obtained. Some of these results have not been described before in any other fish species. New clues about the genome organization and evolution of the multigene families are offered in this study.
Characterization of host microRNAs that respond to DNA virus infection in a crustacean
Authors: Huang Tianzhi , Xu Dandan , Zhang Xiaobo 
Published: April 2012

Abstract

Background
MicroRNAs (miRNAs) are key posttranscriptional regulators of gene expression that are implicated in many processes of eukaryotic cells. It is known that the expression profiles of host miRNAs can be reshaped by viruses. However, a systematic investigation of marine invertebrate miRNAs that respond to virus infection has not yet been performed.

Results
In this study, the shrimp Marsupenaeus japonicus was challenged by white spot syndrome virus (WSSV). Small RNA sequencing of WSSV-infected shrimp at different time post-infection (0, 6, 24 and 48 h) identified 63 host miRNAs, 48 of which were conserved in other animals, representing 43 distinct families. Of the identified host miRNAs, 31 were differentially expressed in response to virus infection, of which 25 were up-regulated and six down-regulated. The results were confirmed by northern blots. The TargetScan and miRanda algorithms showed that most target genes of the differentially expressed miRNAs were related to immune responses. Gene ontology analysis revealed that immune signaling pathways were mediated by these miRNAs. Evolutionary analysis showed that three of them, miR-1, miR-7 and miR-34, are highly conserved in shrimp, fruit fly and humans and function in the similar pathways.

Conclusions
Our study provides the first large-scale characterization of marine invertebrate miRNAs that respond to virus infection. This will help to reveal the molecular events involved in virus-host interactions mediated by miRNAs and their evolution in animals.
Hypochlorous acid and hydrogen peroxide-induced negative regulation of Salmonella enterica serovar Typhimurium ompW by the response regulator ArcA
Authors: Morales Eduardo H , Calderón Iván L , Collao Bernardo , Gil Fernando , Porwollik Steffen , McClelland Michael , Saavedra Claudia P 
Published: April 2012

Abstract

Background
Hydrogen peroxide (H2O2) and hypochlorous acid (HOCl) are reactive oxygen species that are part of the oxidative burst encountered by Salmonella enterica serovar Typhimurium (S. Typhimurium) upon internalization by phagocytic cells. In order to survive, bacteria must sense these signals and modulate gene expression. Growing evidence indicates that the ArcAB two component system plays a role in the resistance to reactive oxygen species. We investigated the influx of H2O2 and HOCl through OmpW and the role of ArcAB in modulating its expression after exposure to both toxic compounds in S. Typhimurium.

Results
H2O2 and HOCl influx was determined both in vitro and in vivo. A S. Typhimurium ompW mutant strain (∆ompW) exposed to sub-lethal levels of H2O2 and HOCl showed a decreased influx of both compounds as compared to a wild type strain. Further evidence of H2O2 and HOCl diffusion through OmpW was obtained by using reconstituted proteoliposomes. We hypothesized that ompW expression should be negatively regulated upon exposure to H2O2 and HOCl to better exclude these compounds from the cell. As expected, qRT-PCR showed a negative regulation in a wild type strain treated with sub-lethal concentrations of these compounds. A bioinformatic analysis in search for potential negative regulators predicted the presence of three ArcA binding sites at the ompW promoter region. By electrophoretic mobility shift assay (EMSA) and using transcriptional fusions we demonstrated an interaction between ArcA and one site at the ompW promoter region. Moreover, qRT-PCR showed that the negative regulation observed in the wild type strain was lost in an arcA and in arcB mutant strains.

Conclusions
OmpW allows the influx of H2O2 and HOCl and is negatively regulated by ArcA by direct interaction with the ompW promoter region upon exposure to both toxic compounds.
Genome-wide association mapping of flowering time and northern corn leaf blight (Setosphaeria turcica) resistance in a vast commercial maize germplasm set
Authors: Van Inghelandt Delphine , Melchinger Albrecht E , Martinant Jean-Pierre , Stich Benjamin 
Published: April 2012

AbstractBackgroundSetosphaeria turcicais a fungal pathogen that causes northern corn leaf blight (NCLB) which is a serious foliar disease in maize. In order to unravel the genetic architecture of the resistance against this disease, a vast association mapping panel comprising 1487 European maize inbred lines was used to (i) identify chromosomal regions affecting flowering time (FT) and northern corn leaf blight (NCLB) resistance, (ii) examine the epistatic interactions of the identified chromosomal regions with the genetic background on an individual molecular marker basis, and (iii) dissect the correlation between NCLB resistance and FT.ResultsThe single marker analyses performed for 8 244 single nucleotide polymorphism (SNP) markers revealed seven, four, and four SNP markers significantly (α=0.05, amplicon wise Bonferroni correction) associated with FT, NCLB, and NCLB resistance corrected for FT, respectively. These markers explained individually between 0.36 and 14.29% of the genetic variance of the corresponding trait.ConclusionsThe very well interpretable pattern of SNP associations observed for FT suggested that data from applied plant breeding programs can be used to dissect polygenic traits. This in turn indicates that the associations identified for NCLB resistance might be successfully used in marker-assisted selection programs. Furthermore, the associated genes are also of interest for further research concerning the mechanism of resistance to NCLB and plant diseases in general, because some of the associated genes have not been mentioned in this context so far.
Including mixed methods research in systematic reviews: Examples from qualitative syntheses in TB and malaria control
Authors: Atkins Salla , Launiala Annika , Kagaha Alexander , Smith Helen 
Published: April 2012

Abstract

Background
Health policy makers now have access to a greater number and variety of systematic reviews to inform different stages in the policy making process, including reviews of qualitative research. The inclusion of mixed methods studies in systematic reviews is increasing, but these studies pose particular challenges to methods of review. This article examines the quality of the reporting of mixed methods and qualitative-only studies.

Methods
We used two completed systematic reviews to generate a sample of qualitative studies and mixed method studies in order to make an assessment of how the quality of reporting and rigor of qualitative-only studies compares with that of mixed-methods studies.

Results
Overall, the reporting of qualitative studies in our sample was consistently better when compared with the reporting of mixed methods studies. We found that mixed methods studies are less likely to provide a description of the research conduct or qualitative data analysis procedures and less likely to be judged credible or provide rich data and thick description compared with standalone qualitative studies. Our time-related analysis shows that for both types of study, papers published since 2003 are more likely to report on the study context, describe analysis procedures, and be judged credible and provide rich data. However, the reporting of other aspects of research conduct (i.e. descriptions of the research question, the sampling strategy, and data collection methods) in mixed methods studies does not appear to have improved over time.

Conclusions
Mixed methods research makes an important contribution to health research in general, and could make a more substantial contribution to systematic reviews. Through our careful analysis of the quality of reporting of mixed methods and qualitative-only research, we have identified areas that deserve more attention in the conduct and reporting of mixed methods research.
Dietary L-arginine supplementation reduces Methotrexate-induced intestinal mucosal injury in rat
Authors: Koppelmann Tal , Pollak Yulia , Mogilner Jorge , Bejar Jacob , Coran Arnold G , Sukhotnik Igor 
Published: April 2012

Abstract

Background
Arginine (ARG) and nitric oxide maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluated the effects of oral ARG supplementation on intestinal structural changes, enterocyte proliferation and apoptosis following methotrexate (MTX)-induced intestinal damage in a rat.

Methods
Male rats were divided into four experimental groups: Control rats, CONTR-ARG rats, were treated with oral ARG given in drinking water 72 hours before and 72 hours following vehicle injection, MTX rats were treated with a single dose of methotrexate, and MTX-ARG rats were treated with oral ARG following injection of MTX. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 72 hours following MTX injection. RT-PCR was used to determine bax and bcl-2 mRNA expression.

Results
MTX-ARG rats demonstrated greater jejunal and ileal bowel weight, greater ileal mucosal weight, greater ileal mucosal DNA and protein levels, greater villus height in jejunum and ileum and crypt depth in ileum, compared to MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-ARG rats (vs MTX) was accompanied by decreased bax mRNA and protein expression and increased bcl-2 protein levels.

Conclusions
Treatment with oral ARG prevents mucosal injury and improves intestinal recovery following MTX- injury in the rat.
Whole cell biosynthesis of a functional oligosaccharide, 2′-fucosyllactose, using engineered Escherichia coli
Authors: Lee Won-Heong , Pathanibul Panchalee , Quarterman Josh , Jo Jung-Hyun , Han Nam Soo , Miller Michael J , Jin Yong-Su , Seo Jin-Ho 
Published: April 2012

Abstract

Background
2'-Fucosyllactose (2-FL) is a functional oligosaccharide present in human milk which protects against the infection of enteric pathogens. Because 2-FL can be synthesized through the enzymatic fucosylation of lactose with guanosine 5′-diphosphate (GDP)-l-fucose by α-1,2-fucosyltransferase (FucT2), an 2-FL producing Escherichia coli can be constructed through overexpressing genes coding for endogenous GDP- l-fucose biosynthetic enzymes and heterologous fucosyltransferase.

Results
The gene for FucT2 from Helicobacter pylori was introduced to the GDP- l-fucose producing recombinant E. coli BL21 star(DE3) strain. However, only small amount of 2-FL was produced in a batch fermentation because the E. coli BL21star(DE3) strain assimilated lactose instead of converting to 2-FL. As an alternative host, the E. coli JM109(DE3) strain which is incapable of assimilating lactose was chosen as a 2-FL producer. Whole cell biosynthesis of 2-FL from lactose was investigated in a series of batch fermentations using various concentrations of lactose. The results of batch fermentations showed that lactose was slowly assimilated by the engineered E. coli JM109(DE3) strain and 2-FL was synthesized without supplementation of another auxiliary sugar for cell growth. A maximum 2-FL concentration of 1.23 g/l was obtained from a batch fermentation with 14.5 g/l lactose. The experimentally obtained yield (g 2-FL/g lactose) corresponded to 20% of the theoretical maximum yield estimated by the elementary flux mode (EFM) analysis.

Conclusions
The experimental 2-FL yield in this study corresponded to about 20% of the theoretical maximum yield, which suggests further modifications via metabolic engineering of a host strain or optimization of fermentation processes might be carried out for improving 2-FL yield. Improvement of microbial production of 2-FL from lactose by engineered E. coli would increase the feasibility of utilizing 2-FL as a prebiotic in various foods.
A rapid low-cost real-time PCR for the detection of klebsiella pneumonia carbapenemase genes
Authors: Wang Lijun , Gu Haitong , Lu Xinxin 
Published: April 2012

Abstract

Background

Klebsiella pneumonia carbapenemases (KPCs) are able to hydrolyze the carbapenems, which cause many bacteria resistance to multiple classes of antibiotics, so the rapid dissemination of KPCs is worrisome. Laboratory identification of KPCs-harboring clinical isolates would be a key to limit the spread of the bacteria. This study would evaluate a rapid low-cost real-time PCR assay to detect KPCs.

Methods
Real-time PCR assay based on SYBR GreenIwas designed to amplify a 106 bp product of the bla
KPC gene from the159 clinical Gram-negative isolates resistant to several classes of β-lactam antibiotics through antimicrobial susceptibility testing. We confirmed the results of real-time PCR assay by the conventional PCR-sequencing. At the same time, KPCs of these clinical isolates were detected by the modified Hodge test (MHT). Then we compared the results of real-time PCR assay with those of MHT from the sensitivity and specificity. Moreover, we evaluated the sensitivity of the real-time PCR assay.

Results
The sensitivity and specificity of the results of the real-time PCR assay compared with those of MHT was 29/29(100 %) and 130/130(100 %), respectively. The results of the real-time PCR and the MHT were strongly consistent (Exact Sig. (2-tailed) =1. 000; McNemar test). The real-time PCR detection limit was about 0.8 cfu using clinical isolates.

Conclusion
The real-time PCR assay could rapidly and accurately detect KPCs -harboring strains with high analytical sensitivity and specificity.
A proteomic analysis of liver after ethanol binge in chronically ethanol treated rats
Authors: Aroor Annayya R , Roy Lowery J , Restrepo Ricardo J , Mooney Brian P , Shukla Shivendra D 
Published: April 2012

Abstract

Background
Binge ethanol in rats after chronic ethanol exposure augments necrosis and steatosis in the liver. In this study, two-dimensional gel electrophoresis proteomic profiles of liver of control, chronic ethanol, control-binge, and chronic ethanol- binge were compared.

Results
The proteomic analysis identified changes in protein abundance among the groups. The levels of carbonic anhydrase 3 (CA3) were decreased after chronic ethanol and decreased further after chronic ethanol-binge. Ethanol binge alone in control rats had no effect on this protein suggesting its possible role in increased susceptibility to injury by binge after chonic ethanol treatment. A protein spot, in which both cytosolic isocitrate dehydrogenase (IDH1) and glutamine synthetase (GS) were identified, showed a small decrease after chronic ethanol binge but western blot demonstrated significant decrease only for glutamine synthetase in chronic ethanol treated rats. The level of gluathione S-transferase mu isoform (GSTM1) increased after chronic ethanol but was lower after chronic ethanol-binge compared to chronic ethanol treatment. The protein levels of the basic form of protein disulfide isomerase associated protein 3 (PDIA3) were significantly decreased and the acidic forms were increased after chronic ethanol- binge but not in chronic ethanol treated rats or ethanol binge in control rats. The significant changes in proteome profile in chronic ethanol binge were accompanied by a marked increase in liver injury as evidenced by enhanced steatosis, necrosis, increased 4-hydroxynonenal labeled proteins, CYP2E1 expression, and decreased histone H2AX phosphorylation.

Conclusions
Given the role of CA3, IDH1 and GST in oxidative stress; PDIA3 in protein quality control, apoptosis and DNA repair and decreased glutamine synthetase as a sensitive marker of pericentral liver injury this proteome study of chronic ethanol-binge rat model identifies these proteins for the first time as molecular targets with potential role in progression of liver injury by binge ethanol drinking.
Strong convergence theorems of nonlinear operator equations for countable family of multi-valued total quasi-ϕ-asymptotically nonexpansive mappings with applications
Authors: Chang Shih-Sen , Wang Lin , Tang Yong-Kun , Zhao Yun-He , Ma Zao-Li 
Published: April 2012

Abstract
The purpose of this article is first to introduce the concept of total quasi-ϕ-asymptotically nonexpansive multi-valued mapping which contains many kinds of mappings as its special cases, and then by using the hybrid shrinking technique to propose an iterative algorithm for finding a common element of the set of solutions for a generalized mixed equilibrium problem, the set of solutions for variational inequality problems, and the set of common fixed points for a countable family of multi-valued total quasi-ϕ-asymptotically nonexpansive mappings in a real uniformly smooth and strictly convex Banach space with Kadec-Klee property. The results presented in the article not only generalize some recent results from single-valued mappings to multi-valued mappings, but also improve and extend the main results of Homaeipour and Razani.

2000 AMS Subject Classification: 47J06; 47J25.