bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of ribosomal protein synthesis and protein translation factors by Peg-interferon alpha/ribavirin in HCV patients blood mononuclear cells (PBMC)
Authors: Gupta Rahul , Kim Sun , Taylor Milton W 
Published: March 2012

AbstractBackgroundWe have previously reported the induction of many interferon stimulated genes (ISGs) in PBMC collected from patients infected with HCV at various times after initiation of interferon-ribavirin treatment using DNA microarrays to identify changes in gene expression with time. Almost as many genes are down regulated (suppressed) during interferon-ribavirin treatment as are up regulated.MethodsDNA microarrays were analyzed by different software, including MAS5 (Affymetrix-Kegg) and GSEA (gene set enrichment analysis) to identify specific pathways both up regulated and down regulated. Data was assessed from a clinical trial, which was a microarray analysis from 68 patients.ResultsUp regulated genes included genes associated with NF-kb, toll like receptor cytokine -cytokine interaction, and complement and adhesion pathways. The most prominent pathway down regulated was that for ribosomal structural proteins, and eukaryotic translational factors. Down regulation of ribosomal protein genes continued through the treatment up to the last measurement, which was at day 28.ConclusionsThis suppression of the protein synthetic apparatus might explain the long-term side effects of interferon-ribavirin, and explain a non-specific effect of interferon-ribavirin on viral protein synthesis. There was no evidence for unique transcription factors or micro RNA involvement.
Safety and feasibility of countering neurological impairment by intravenous administration of autologous cord blood in cerebral palsy
Authors: Lee Young-Ho , Choi Kyung Vin , Moon Jin Hwa , Jun Hyun-Joo , Kang Hye-Ryeong , Oh Se-In , Kim Hyung Sun , Um Jang Soo , Kim Mi Jung , Choi Yun Young , Lee Young-Jun , Kim Hee-Jin , Lee Jong-Hwa , Son Su Min , Choi Soo-Jin , Oh Wonil , Yang Yoon-Sun 
Published: March 2012

Abstract

Backgrounds
We conducted a pilot study of the infusion of intravenous autologous cord blood (CB) in children with cerebral palsy (CP) to assess the safety and feasibility of the procedure as well as its potential efficacy in countering neurological impairment.

Methods
Patients diagnosed with CP were enrolled in this study if their parents had elected to bank their CB at birth. Cryopreserved CB units were thawed and infused intravenously over 10~20 minutes. We assessed potential efficacy over 6 months by brain magnetic resonance imaging (MRI)-diffusion tensor imaging (DTI), brain perfusion single-photon emission computed tomography (SPECT), and various evaluation tools for motor and cognitive functions.

Results
Twenty patients received autologous CB infusion and were evaluated. The types of CP were as follows: 11 quadriplegics, 6 hemiplegics, and 3 diplegics. Infusion was generally well-tolerated, although 5 patients experienced temporary nausea, hemoglobinuria, or urticaria during intravenous infusion. Diverse neurological domains improved in 5 patients (25%) as assessed with developmental evaluation tools as well as by fractional anisotropy values in brain MRI-DTI. The neurologic improvement occurred significantly in patients with diplegia or hemiplegia rather than quadriplegia.

Conclusions
Autologous CB infusion is safe and feasible, and has yielded potential benefits in children with CP.
Throughput-optimal scheduling for cooperative relaying in wireless access networks
Authors: Pham Ngoc-Thai , Huynh Thong , Hwang Won-Joo 
Published: March 2012

Abstract
This article considers the cooperation between base station and relay stations to increase system throughput in time-slotted relaying wireless networks, such as dynamic time division multiple access systems. We focus on optimal throughput scheduling policies for the cooperative relaying at the network layer level. It is shown that the resulting policy for this cooperative protocol obtains the optimal throughput region. Random packet queueing at the relay stations may cause a packet-reordering effect, which may be an obstacle for real-time applications. We alter the design for throughput-optimal scheduling to remove this effect and guarantee a near optimal throughput region.
Imbalance of heterologous protein folding and disulfide bond formation rates yields runaway oxidative stress
Authors: Tyo Keith EJ , Liu Zihe , Petranovic Dina , Nielsen Jens 
Published: March 2012

Abstract

Background
The protein secretory pathway must process a wide assortment of native proteins for eukaryotic cells to function. As well, recombinant protein secretion is used extensively to produce many biologics and industrial enzymes. Therefore, secretory pathway dysfunction can be highly detrimental to the cell and can drastically inhibit product titers in biochemical production. Because the secretory pathway is a highly-integrated, multi-organelle system, dysfunction can happen at many levels and dissecting the root cause can be challenging. In this study, we apply a systems biology approach to analyze secretory pathway dysfunctions resulting from heterologous production of a small protein (insulin precursor) or a larger protein (α-amylase).

Results

HAC1-dependent and independent dysfunctions and cellular responses were apparent across multiple datasets. In particular, processes involving (a) degradation of protein/recycling amino acids, (b) overall transcription/translation repression, and (c) oxidative stress were broadly associated with secretory stress.

Conclusions
Apparent runaway oxidative stress due to radical production observed here and elsewhere can be explained by a futile cycle of disulfide formation and breaking that consumes reduced glutathione and produces reactive oxygen species. The futile cycle is dominating when protein folding rates are low relative to disulfide bond formation rates. While not strictly conclusive with the present data, this insight does provide a molecular interpretation to an, until now, largely empirical understanding of optimizing heterologous protein secretion. This molecular insight has direct implications on engineering a broad range of recombinant proteins for secretion and provides potential hypotheses for the root causes of several secretory-associated diseases.
Characterization and determination of holin protein of Streptococcus suis bacteriophage SMP in heterologous host
Authors: Shi Yibo , Yan Yaxian , Ji Wenhui , Du Bin , Meng Xiangpeng , Wang Hengan , Sun Jianhe 
Published: March 2012

Abstract

Background
Holins are a group of phage-encoded membrane proteins that control access of phage-encoded endolysins to the peptidoglycan, and thereby trigger the lysis process at a precise time point as the 'lysis clock'. SMP is an isolated and characterized Streptococcus suis lytic phage. The aims of this study were to determine the holin gene, HolSMP, in the genome of SMP, and characterized the function of holin, HolSMP, in phage infection.

Results

HolSMP was predicted to encode a small membrane protein with three hydrophobic transmembrane helices. During SMP infections, HolSMP was transcribed as a late gene and HolSMP accumulated harmlessly in the cell membrane before host cell lysis. Expression of HolSMP in Escherichia coli induced an increase in cytoplasmic membrane permeability, an inhibition of host cell growth and significant cell lysis in the presence of LySMP, the endolysin of phage SMP. HolSMP was prematurely triggered by the addition of energy poison to the medium. HolSMP complemented the defective λ S allele in a non-suppressing Escherichia coli strain to produce phage plaques.

Conclusions
Our results suggest that HolSMP is the holin protein of phage SMP and a two-step lysis system exists in SMP.
Kupffer cells ameliorate hepatic insulin resistance induced by high-fat diet rich in monounsaturated fatty acids: the evidence for the involvement of alternatively activated macrophages
Authors: Papackova Zuzana , Palenickova Eliska , Dankova Helena , Zdychova Jana , Skop Vojtech , Kazdova Ludmila , Cahova Monika 
Published: March 2012

Abstract

Background
Resident macrophages (Kupffer cells, KCs) in the liver can undergo both pro- or anti-inflammatory activation pathway and exert either beneficiary or detrimental effects on liver metabolism. Until now, their role in the metabolically dysfunctional state of steatosis remains enigmatic. Aim of our study was to characterize the role of KCs in relation to the onset of hepatic insulin resistance induced by a high-fat (HF) diet rich in monounsaturated fatty acids.

Methods
Male Wistar rats were fed either standard (SD) or high-fat (HF) diet for 4 weeks. Half of the animals were subjected to the acute GdCl3 treatment 24 and 72 hrs prior to the end of the experiment in order to induce the reduction of KCs population. We determined the effect of HF diet on activation status of liver macrophages and on the changes in hepatic insulin sensitivity and triacylglycerol metabolism imposed by acute KCs depletion by GdCl3.

Results
We found that a HF diet rich in MUFA itself triggers an alternative but not the classical activation program in KCs. In a steatotic, but not in normal liver, a reduction of the KCs population was associated with a decrease of alternative activation and with a shift towards the expression of pro-inflammatory activation markers, with the increased autophagy, elevated lysosomal lipolysis, increased formation of DAG, PKCε activation and marked exacerbation of HF diet-induced hepatic insulin resistance.

Conclusions
We propose that in the presence of a high MUFA content the population of alternatively activated resident liver macrophages may mediate beneficial effects on liver insulin sensitivity and alleviate the metabolic disturbances imposed by HF diet feeding and steatosis. Our data indicate that macrophage polarization towards an alternative state might be a useful strategy for treating type 2 diabetes.
IMRT for locally advanced anal cancer: clinical experience of the Montpellier Cancer Center
Authors: Vieillot Sabine , Fenoglietto Pascal , Lemanski Claire , Moscardo Carmen Llacer , Gourgou Sophie , Dubois Jean-Bernard , Aillères Norbert , Azria David 
Published: March 2012

Abstract

Purpose
To assess outcomes of patients with carcinoma of the anal canal (CAC) treated with intensity-modulated radiation therapy (IMRT).

Method and materials
From August 2007 to January 2011, seventy-two patients suffering from CAC were treated with IMRT. Concurrent chemotherapy was added in case of locally advanced tumors. Radiation course consisted in delivering an initial plan to the PTV1 defined as the primary tumor and the risk area including pelvic and inguinal nodes. Forty-five Gy in daily 1.8 Gy-daily fractions were delivered five days a week. A second plan of 14.4-20 Gy to the primary tumor (PTV2) was administered in 1.8-2 Gy-daily fractions, 5 days a week. We present here the results of dosimetry, toxicities, and clinical outcome of the first 39 patients with a median follow-up of 24 months.

Results
Thirty-one women and eight men were included in the present analysis. Tumors were classified as stages I, II, III and IV in 2, 7, 27 and 2 patients, respectively. Median age was 59 years (range, 38-85). Radiotherapy alone (RT) or combined with chemotherapy (RCT) were delivered in 6 (15%) and 33 (85%) patients, respectively.
Six patients (15%) required a treatment break ≥ 3 days, and median time for treatment break was 8 days (range, 3-14 days). Acute grade 3 gastrointestinal (GI) and genitourinary (GU) toxicities were seen in 10 and 5% of patients, respectively. Grade 4 toxicity was only hematologic and occurred in 12% patients receiving RCT. With a median follow-up of 24 months, no patient experienced any late grade 4 toxicity. The 2-year overall survival rate was 89%, the 2-year local relapse free survival was 77% and the 2-year colostomy-free survival rate was 85%.

Conclusion
IMRT is well tolerated with acceptable treatment interruption allowing dose escalation.
Neuregulin repellent signaling via ErbB4 restricts GABAergic interneurons to migratory paths from ganglionic eminence to cortical destinations
Authors: Li Hao , Chou Shen-Ju , Hamasaki Tadashi , Perez-Garcia Carlos G , O'Leary Dennis DM 
Published: March 2012

Abstract

Background
Cortical GABAergic interneurons (INs) are generated in the medial ganglionic eminence (MGE) and migrate tangentially into cortex. Because most, if not all, migrating MGE-derived INs express the neuregulin (NRG) receptor, ErbB4, we investigated influences of Nrg1 isoforms and Nrg3 on IN migration through ventral telencephalon (vTel) and within cortex.

Results
During IN migration, NRG expression domains and distributions of ErbB4-expressing, MGE-derived INs are complementary with minimal overlap, both in vTel and cortex. In wild-type mice, within fields of NRG expression, these INs are focused at positions of low or absent NRG expression. However, in ErbB4-/- HER4heart mutant mice in which INs lack ErbB4, these complementary patterns are degraded with considerable overlap evident between IN distribution and NRG expression domains. These findings suggest that NRGs are repellents for migrating ErbB4-expressing INs, a function supported by in vitro and in vivo experiments. First, in collagen co-cultures, MGE-derived cells preferentially migrate away from a source of secreted NRGs. Second, cells migrating from wild-type MGE explants on living forebrain slices from wild-type embryonic mice tend to avoid endogenous NRG expression domains, whereas this avoidance behavior is not exhibited by ErbB4-deficient cells migrating from MGE explants and instead they have a radial pattern with a more uniform distribution. Third, ectopic NRG expression in the IN migration pathway produced by in utero electroporation blocks IN migration and results in cortex distal to the blockade being largely devoid of INs. Finally, fewer INs reach cortex in ErbB4 mutants, indicating that NRG-ErbB4 signaling is required for directing IN migration from the MGE to cortex.

Conclusions
Our results show that NRGs act as repellents for migrating ErbB4-expressing, MGE-derived GABAergic INs and that the patterned expression of NRGs funnels INs as they migrate from the MGE to their cortical destinations.
Development of marker-free transgenic Jatrophaplants with increased levels of seed oleic acid
Authors: Qu Jing , Mao Hui-Zhu , Chen Wen , Gao Shi-Qiang , Bai Ya-Nan , Sun Yan-Wei , Geng Yun-Feng , Ye Jian 
Published: March 2012

Abstract

Background

Jatropha curcas is recognized as a new energy crop due to the presence of the high amount of oil in its seeds that can be converted into biodiesel. The quality and performance of the biodiesel depends on the chemical composition of the fatty acids present in the oil. The fatty acids profile of the oil has a direct impact on ignition quality, heat of combustion and oxidative stability. An ideal biodiesel composition should have more monounsaturated fatty acids and less polyunsaturated acids. Jatropha seed oil contains 30% to 50% polyunsaturated fatty acids (mainly linoleic acid) which negatively impacts the oxidative stability and causes high rate of nitrogen oxides emission.

Results
The enzyme 1-acyl-2-oleoyl-sn-glycero-3-phosphocholine delta 12-desaturase (FAD2) is the key enzyme responsible for the production of linoleic acid in plants. We identified three putative delta
12
fatty acid desaturase genes in Jatropha (JcFAD2s) through genome-wide analysis and downregulated the expression of one of these genes, JcFAD2-1, in a seed-specific manner by RNA interference technology. The resulting JcFAD2-1 RNA interference transgenic plants showed a dramatic increase of oleic acid (> 78%) and a corresponding reduction in polyunsaturated fatty acids (< 3%) in its seed oil. The control Jatropha had around 37% oleic acid and 41% polyunsaturated fatty acids. This indicates that FAD2-1 is the major enzyme responsible for converting oleic acid to linoleic acid in Jatropha. Due to the changes in the fatty acids profile, the oil of the JcFAD2-1 RNA interference seed was estimated to yield a cetane number as high as 60.2, which is similar to the required cetane number for conventional premium diesel fuels (60) in Europe. The presence of high seed oleic acid did not have a negative impact on other Jatropha agronomic traits based on our preliminary data of the original plants under greenhouse conditions. Further, we developed a marker-free system to generate the transgenic Jatropha that will help reduce public concerns for environmental issues surrounding genetically modified plants.

Conclusion
In this study we produced seed-specific JcFAD2-1 RNA interference transgenic Jatropha without a selectable marker. We successfully increased the proportion of oleic acid versus linoleic in Jatropha through genetic engineering, enhancing the quality of its oil.
Highly pathogenic avian influenza viruses inhibit effective immune responses of human blood-derived macrophages
Authors: Friesenhagen Judith , Boergeling Yvonne , Hrincius Eike , Ludwig Stephan , Roth Johannes , Viemann Dorothee 
Published: March 2012

AbstractHuman blood-derived macrophages are non-permissive for influenza virus propagation, and fail to elicit inflammatory and antiviral responses upon infection with high pathogenic avian influenza viruses.Systemic infections with HPAIVs, such as H5N1, are characterized by cytokine burst and sepsis. We investigated the role of human monocyte-derived macrophages in these events after infection with different influenza virus strains. Macrophages were infected with low pathogenic H1N1 (PR8) or high pathogenic H7N7 (FPV) and H5N1 (KAN-1) subtypes. Macrophages were found to be nonpermissive for influenza virus propagation. Surprisingly, transcriptome analysis revealed an insufficient innate immune response of macrophages only to HPAIV infections. Induction of inflammatory cytokines, as well as type I IFNs, was significantly attenuated in H5N1- and H7N7-infected cells, contradicting a primary role of macrophages for the cytokine burst. Furthermore, inflammasome activation was impaired significantly in HPAIV-infected macrophages. Interestingly, this finding correlated with a complete suppression of viral protein M2 expression after HPAIV infection, which is known to be involved in influenza viral inflammasome activation. In summary, our data provide first evidences for a strategy of how HPAIVs avoid initial inflammatory responses of macrophages facilitating virus spreading and progression to the systemic stage of disease.
Extrapyramidal motor side-effects of first- and
second-generation antipsychotic drugs
Authors: Peluso Michael J. , Lewis Shôn W. , Barnes Thomas R. E. , Jones Peter B. 
Published: March 2012

BackgroundSecond-generation antipsychotics have been thought to cause fewer
extrapyramidal side-effects (EPS) than first-generation antipsychotics,
but recent pragmatic trials have indicated equivalence.AimsTo determine whether second-generation antipsychotics had better outcomes
in terms of EPS than first-generation drugs.MethodWe conducted an intention-to-treat, secondary analysis of data from an
earlier randomised controlled trial (n = 227). A
clinically significant difference was defined as double or half the
symptoms in groups prescribed first- v.
second-generation antipsychotics, represented by odds ratios greater than
2.0 (indicating advantage for first-generation drugs) or less than 0.5
(indicating advantage for the newer drugs). We also examined EPS in terms
of symptoms emergent at 12 weeks and 52 weeks, and symptoms that had
resolved at these time points.ResultsAt baseline those randomised to the first-generation antipsychotic group
(n = 118) had similar EPS to the second-generation
group (n = 109). Indications of resolved Parkinsonism
(OR = 0.5) and akathisia (OR = 0.4) and increased tardive dyskinesia (OR
= 2.2) in the second-generation drug group at 12 weeks were not
statistically significant and the effects were not present by 52 weeks.
Patients in the second-generation group were dramatically (30-fold) less
likely to be prescribed adjunctive anticholinergic medication, despite
equivalence in terms of EPS.ConclusionsThe expected improvement in EPS profiles for participants randomised to
second-generation drugs was not found; the prognosis over 1 year of those
in the first-generation arm was no worse in these terms. The place of
careful prescription of first-generation drugs in contemporary practice
remains to be defined, potentially improving clinical effectiveness and
avoiding life-shortening metabolic disturbances in some patients
currently treated with the narrow range of second-generation
antipsychotics used in routine practice. This has educational
implications because a generation of psychiatrists now has little or no
experience with first-generation antipsychotic prescription.
Research Resource: Whole-Genome Estrogen Receptor α Binding in Mouse Uterine Tissue Revealed by ChIP-Seq
Authors: Hewitt Sylvia C. , Li Leping , Grimm Sara A. , Chen Yu , Liu Liwen , Li Yin , Bushel Pierre R. , Fargo David , Korach Kenneth S. 
Published: March 2012

Abstract
To advance understanding of mechanisms leading to biological and transcriptional endpoints related to estrogen action in the mouse uterus, we have mapped ERα and RNA polymerase II (PolII) binding sites using chromatin immunoprecipitation followed by sequencing of enriched chromatin fragments. In the absence of hormone, 5184 ERα-binding sites were apparent in the vehicle-treated ovariectomized uterine chromatin, whereas 17,240 were seen 1 h after estradiol (E2) treatment, indicating that some sites are occupied by unliganded ERα, and that ERα binding is increased by E2. Approximately 15% of the uterine ERα-binding sites were adjacent to (&lt;10 kb) annotated transcription start sites, and many sites are found within genes or are found more than 100 kb distal from mapped genes; however, the density (sites per base pair) of ERα-binding sites is significantly greater adjacent to promoters. An increase in quantity of sites but no significant positional differences were seen between vehicle and E2-treated samples in the overall locations of ERα-binding sites either distal from, adjacent to, or within genes. Analysis of the PolII data revealed the presence of poised promoter-proximal PolII on some highly up-regulated genes. Additionally, corecruitment of PolII and ERα to some distal enhancer regions was observed. A de novo motif analysis of sequences in the ERα-bound chromatin confirmed that estrogen response elements were significantly enriched. Interestingly, in areas of ERα binding without predicted estrogen response element motifs, homeodomain transcription factor-binding motifs were significantly enriched. The integration of the ERα- and PolII-binding sites from our uterine sequencing of enriched chromatin fragments data with transcriptional responses revealed in our uterine microarrays has the potential to greatly enhance our understanding of mechanisms governing estrogen response in uterine and other estrogen target tissues.