bluuebunny/crossref_metadata_2025_split huggingface dataset:
Live imaging of neutrophil motility in a zebrafish model of WHIM syndrome
Authors: Walters Kevin B. , Green Julie M. , Surfus Jill C. , Yoo Sa Kan , Huttenlocher Anna 
Published: July 2010

Abstract
CXCR4 is a G protein–coupled chemokine receptor that has been implicated in the pathogenesis of primary immunodeficiency disorders and cancer. Autosomal dominant gain-of-function truncations of CXCR4 are associated with warts, hypo-gammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, a primary immunodeficiency disorder characterized by neutropenia and recurrent infections. Recent progress has implicated CXCR4-SDF1 (stromal cell-derived factor 1) signaling in regulating neutrophil homeostasis, but the precise role of CXCR4-SDF1 interactions in regulating neutrophil motility in vivo is not known. Here, we use the optical transparency of zebrafish to visualize neutrophil trafficking in vivo in a zebrafish model of WHIM syndrome. We demonstrate that expression of WHIM mutations in zebrafish neutrophils induces neutrophil retention in hematopoietic tissue, impairing neutrophil motility and wound recruitment. The neutrophil retention signal induced by WHIM truncation mutations is SDF1 dependent, because depletion of SDF1 with the use of morpholino oligonucleotides restores neutrophil chemotaxis to wounds. Moreover, localized activation of a genetically encoded, photoactivatable Rac guanosine triphosphatase is sufficient to direct migration of neutrophils that express the WHIM mutation. The findings suggest that this transgenic zebrafish model of WHIM syndrome may provide a valuable tool to screen for agents that modify CXCR4-SDF1 retention signals.
Toll-like receptor control of glucocorticoid-induced apoptosis in human plasmacytoid predendritic cells (pDCs)
Authors: Lepelletier Yves , Zollinger Raphaël , Ghirelli Cristina , Raynaud Françoise , Hadj-Slimane Réda , Cappuccio Antonio , Hermine Olivier , Liu Yong-Jun , Soumelis Vassili 
Published: July 2010

AbstractMicrobial infection triggers the endogenous production of immunosuppressive glucocorticoid (GC) hormones and simultaneously activates innate immunity through toll-like receptors (TLRs). How innate immune cells integrate these 2 opposing signals in dictating immunity or tolerance to infection is not known. In this study, we show that human plasmacytoid predendritic cells (pDCs) were highly sensitive to GC-induced apoptosis. Strikingly, they were protected by microbial stimulation through TLR-7 and TLR-9, but not by microbial-independent stimuli, such as interleukin-3, granulocyte macrophage colony-stimulating factor, or CD40-ligand. This protection was dependent on TLR-induced autocrine tumor necrosis factor-α and interferon-α, which collectively increased the expression ratio between antiapoptotic genes (Bcl-2, Bcl-xL, BIRC3, CFLAR) versus proapoptotic genes (Caspase-8, BID, BAD, BAX). In particular, virus-induced Bcl-2 up-regulation was dependent on autocrine interferon-α. Using small interfering RNA technology, we demonstrated that Bcl-2 and CFLAR/c-flip were essential for TLR-induced protection of pDCs from GC-induced caspase-8–mediated apoptosis. Our results demonstrate a novel property of the TLR pathway in regulating the interface between GC and innate immunity and reveal a previously undescribed mechanism of GC resistance.
Proteome-wide survey of phosphorylation patterns affected by nuclear DNA polymorphisms in Arabidopsis thaliana
Authors: Riaño-Pachón Diego Mauricio , Kleessen Sabrina , Neigenfind Jost , Durek Pawel , Weber Elke , Engelsberger Wolfgang R , Walther Dirk , Selbig Joachim , Schulze Waltraud X , Kersten Birgit 
Published: July 2010

AbstractBackgroundProtein phosphorylation is an important post-translational modification influencing many aspects of dynamic cellular behavior. Site-specific phosphorylation of amino acid residues serine, threonine, and tyrosine can have profound effects on protein structure, activity, stability, and interaction with other biomolecules. Phosphorylation sites can be affected in diverse ways in members of any species, one such way is through single nucleotide polymorphisms (SNPs). The availability of large numbers of experimentally identified phosphorylation sites, and of natural variation datasets inArabidopsis thalianaprompted us to analyze the effect of non-synonymous SNPs (nsSNPs) onto phosphorylation sites.ResultsFrom the analyses of 7,178 experimentally identified phosphorylation sites we found that: (i) Proteins with multiple phosphorylation sites occur more often than expected by chance. (ii) Phosphorylation hotspots show a preference to be located outside conserved domains. (iii) nsSNPs affected experimental phosphorylation sites as much as the corresponding non-phosphorylated amino acid residues. (iv) Losses of experimental phosphorylation sites by nsSNPs were identified in 86A. thalianaproteins, among them receptor proteins were overrepresented.These results were confirmed by similar analyses of predicted phosphorylation sites inA. thaliana. In addition, predicted threonine phosphorylation sites showed a significant enrichment of nsSNPs towards asparagines and a significant depletion of the synonymous substitution. Proteins in which predicted phosphorylation sites were affected by nsSNPs (loss and gain), were determined to be mainly receptor proteins, stress response proteins and proteins involved in nucleotide and protein binding. Proteins involved in metabolism, catalytic activity and biosynthesis were less affected.ConclusionsWe analyzed more than 7,100 experimentally identified phosphorylation sites in almost 4,300 protein-coding lociin silico, thus constituting the largest phosphoproteomics dataset forA. thalianaavailable to date. Our findings suggest a relatively high variability in the presence or absence of phosphorylation sites between different natural accessions in receptor and other proteins involved in signal transduction. Elucidating the effect of phosphorylation sites affected by nsSNPs on adaptive responses represents an exciting research goal for the future.
Transcriptional regulation of the grape cytochrome P450 monooxygenase gene CYP736B expression in response to Xylella fastidiosa infection
Authors: Cheng Davis W , Lin Hong , Takahashi Yuri , Walker M Andrew , Civerolo Edwin L , Stenger Drake C 
Published: July 2010

AbstractBackgroundPlant cytochrome P450 monooxygenases (CYP) mediate synthesis and metabolism of many physiologically important primary and secondary compounds that are related to plant defense against a range of pathogenic microbes and insects. To determine if cytochrome P450 monooxygenases are involved in defense response toXylella fastidiosa(Xf) infection, we investigated expression and regulatory mechanisms of the cytochrome P450 monooxygenaseCYP736Bgene in both disease resistant and susceptible grapevines.ResultsCloning of genomic DNA and cDNA revealed that theCYP736Bgene was composed of two exons and one intron with GT as a donor site and AG as an acceptor site.CYP736Btranscript was up-regulated in PD-resistant plants and down-regulated in PD-susceptible plants 6 weeks afterXfinoculation. However,CYP736Bexpression was very low in stem tissues at all evaluated time points. 5'RACE and 3'RACE sequence analyses revealed that there were three candidate transcription start sites (TSS) in the upstream region and three candidate polyadenylation (PolyA) sites in the downstream region ofCYP736B. Usage frequencies of each transcription initiation site and each polyadenylation site varied depending on plant genotype, developmental stage, tissue, and treatment. These results demonstrate that expression ofCYP736Bis regulated developmentally and in response toXfinfection at both transcriptional and post-transcriptional levels. Multiple transcription start and polyadenylation sites contribute to regulation ofCYP736Bexpression.ConclusionsThis report provides evidence that the cytochrome P450 monooxygenaseCYP736Bgene is involved in defense response at a specific stage ofXfinfection in grapevines; multiple transcription initiation and polyadenylation sites exist forCYP736Bin grapevine; and coordinative and selective use of transcription initiation and polyadenylation sites play an important role in regulation ofCYP736Bexpression during growth, development and response toXfinfection.
Assessment of FAE1 polymorphisms in three Brassica species using EcoTILLING and their association with differences in seed erucic acid contents
Authors: Wang Nian , Shi Lei , Tian Fang , Ning Huicai , Wu Xiaoming , Long Yan , Meng Jinling 
Published: July 2010

Abstract

Background

FAE1 (fatty acid elongase1) is the key gene in the control of erucic acid synthesis in seeds of Brassica species. Due to oil with low erucic acid (LEA) content is essential for human health and not enough LEA resource could be available, thus new LEA genetic resources are being sought for Brassica breeding. EcoTILLING, a powerful genotyping method, can readily be used to identify polymorphisms in Brassica.

Results
Seven B. rapa, nine B. oleracea and 101 B. napus accessions were collected for identification of FAE1 polymorphisms. Three polymorphisms were detected in the two FAE1 paralogues of B. napus using EcoTILLING and were found to be strongly associated with differences in the erucic acid contents of seeds. In genomic FAE1 sequences obtained from seven B. rapa accessions, one SNP in the coding region was deduced to cause loss of gene function. Molecular evolution analysis of FAE1 homologues showed that the relationship between the Brassica A and C genomes is closer than that between the A/C genomes and Arabidopsis genome. Alignment of the coding sequences of these FAE1 homologues indicated that 18 SNPs differed between the A and C genomes and could be used as genome-specific markers in Brassica.

Conclusion
This study showed the applicability of EcoTILLING for detecting gene polymorphisms in Brassica. The association between B. napus FAE1 polymorphisms and the erucic acid contents of seeds may provide useful guidance for LEA breeding. The discovery of the LEA resource in B. rapa can be exploited in Brasscia cultivation.
Ultrasonographic detection and assessment of the severity of Crohn's disease recurrence after ileal resection
Authors: Pallotta Nadia , Giovannone Maurizio , Pezzotti Patrizio , Gigliozzi Alessandro , Barberani Fausto , Piacentino Daria , Hassan Naima Abdulkadir , Vincoli Giuseppina , Tosoni Mauro , Covotta Alfredo , Marcheggiano Adriana , Di Camillo Mauro , Corazziari Enrico 
Published: July 2010

Abstract

Background
Recurrence and severity of Crohn's disease mucosal lesions after "curative" ileal resection is assessed at endoscopy. Intramural lesions can be detected as increased wall thickness at Small Intestine Contrast Ultrasonography (SICUS).
Aims. To assess after ileal resection whether: 1) SICUS detects recurrence of Crohn's disease lesions, 2) the intestinal wall thickness measured at the level of ileo-colonic anastomosis predicts the severity of endoscopic lesions, 3) the extension of intramural lesions of the neo-terminal ileum is useful for grading severity of the recurrence, 4) the combined measures of wall thickness of the ileo-colonic anastomosis and of the extension of intramural lesions at level of the neo-terminal ileum may predict the endoscopic Rutgeerts score

Methods
Fifty eight Crohn's disease patients (M 37, age range 19-75 yrs) were prospectively submitted at 6-12 months intervals after surgery to endoscopy and SICUS for a total of 111 observations.

Results
Six months or more after surgery wall thickness of ileo-colonic anastomosis > 3.5 mm identified 100% of patients with endoscopic lesions (p < 0.0001). ROC curve analysis, combining wall thickness of ileo-colonic anastomosis and the extension of intramural lesions of neo-terminal ileum, discriminated (0.95) patients with, from those without, endoscopic lesions. Performing two multiple logistic regression analyses only wall thickness of ileo-colonic anastomosis and extension of neo-terminal ileum intramural lesions were significantly associated with absence or presence of endoscopic lesions. An ordinal polychotomus logistic model, considering all investigated variables, confirmed that only SICUS variables were associated with endoscopic grading of severity.

Conclusions
In patients submitted to ileal resection for Crohn's disease non-invasive Small Intestine Contrast Ultrasonography 1) by assessing thickness of ileo-colonic anastomosis accurately detects initial, minimal Crohn's disease recurrence, and 2) by assessing both thickness of ileo-colonic anastomosis and extension of intramural lesions of neo-terminal ileum grades the severity of the post-surgical recurrence.
Circulating cytokines and procalcitonin in acute Q fever granulomatous hepatitis with poor response to antibiotic and short-course steroid therapy: a case report
Authors: Lai Chung-Hsu , Lin Jiun-Nong , Chang Lin-Li , Chen Yen-Hsu , Lin Hsi-Hsun 
Published: July 2010

Abstract

Background
Q fever is a zoonosis distributed worldwide that is caused by Coxiella burnetii infection and the defervescence usually occurs within few days of appropriate antibiotic therapy. Whether the changes of cytokine levels are associated with acute Q fever with persistent fever despite antibiotic therapy had not been investigated before.

Case Presentation
We report a rare case of acute Q fever granulomatous hepatitis remained pyrexia despite several antibiotic therapy and 6-day course of oral prednisolone. During the 18-month follow-up, the investigation of the serum cytokines profile and procalcitonin (PCT) revealed that initially elevated levels of interleukin-2 (IL-2), IL-8, IL-10, and PCT decreased gradually, but the IL-6 remained in low titer. No evidence of chronic Q fever was identified by examinations of serum antibodies against C. burnetii and echocardiography.

Conclusions
The changes of cytokine levels may be associated with acute Q fever with poor response to treatment and PCT may be an indicator for monitoring the response to treatment.
Repeat hepatectomy for recurrent hepatocellular carcinoma: a local experience and a systematic review
Authors: Zhou Yanming , Sui Chengjun , Li Bin , Yin Zhengfeng , Tan Yunchang , Yang Jiamei , Liu Zhenyu 
Published: July 2010

Abstract

Background
This study aimed to assess the efficacy and safety of repeat hepatectomy for recurrent hepatocellular carcinoma (HCC).

Methods
Thirty-seven patients who underwent a curative repeat hepatectomy in our hospital were retrospectively studied. An extensive database literature search was performed to obtain for all relevant studies.

Results
In our series, there were no perioperative deaths during repeat hepatectomy for recurrent HCC. Patients survival after repeat hepatectomy were similar to 429 patients undergoing initial hepatectomy. A computerized search of the Medline and PubMed databases found 29 retrospective studies providing relevant data in 1149 patients were included for appraisal and data extraction. After the repeat hepatectomy, postoperative morbidity ranged from 6.2% to 68.2% with a median per cohort of 23.5 per cent. There were 7 perioperative deaths (0.7 per cent of 993 for whom mortality data were provided). The overall median survival ranged from 21 to 61.5 months, with 1 -, 3 -, and 5-year survival of 69.0% to 100%, 21.0% to 87.0%, and 25.0% to 87.0%, respectively.

Conclusions
Repeat hepatectomy can be performed safely and is associated with long-term survival in a subset of patients with recurrent HCC. However, the findings have to be carefully interpreted due to the lower level of evidence. A randomized controlled study is needed to compare repeat hepatectomy and other modalities for recurrent HCC.
Unusually young age distribution of primary hepatic leiomyosarcoma: case series and review of the adult literature
Authors: Shamseddine Achraf , Faraj Walid , Mukherji Deborah , El Majzoub Nadim , Khalife Mohamed , Soubra Ayman , Shamseddine Ali 
Published: July 2010

Abstract

Background
Primary hepatic leiomyosarcoma is a rare disease diagnosed in older aged adults with a median age of 58 and occasionally in children with a history of immunosuppression.

Methods
From 1998 to 2009, 215 patients were diagnosed with primary hepatic malignancies at our institution, 4 of which were diagnosed with primary hepatic sarcoma (1.8%). Three cases were primary hepatic leiomyosarcomas (LMS) and one case was primary undifferentiated embryonal sarcoma of the liver; median age 30 (range 20-39) years.

Results
One patient is currently 12 months post-resection with no evidence of recurrence. Two patients passed away at 19 days and 22 months from small for size liver and tumor recurrence respectively.

Conclusion
We have presented 3 cases of primary hepatic leiomyosarcoma diagnosed at our institution with an unusually young age distribution and no evidence of immunosuppression. These cases highlight the diagnostic and therapeutic challenges of this rare tumour.
Acute onset lactobacillus endophthalmitis after trabeculectomy: a case report
Authors: Papaconstantinou Dimitris , Georgalas Ilias , Karmiris Themis , Ladas Ioannis , Droutsas Konstantinos , Georgopoulos Gerasimos 
Published: July 2010

Abstract

Introduction
We report a case of early lactobacillus endophthalmitis which occurred ten days after trabeculectomy.

Case presentation
A 76-year-old Caucasian diabetic woman underwent uncomplicated trabeculectomy with a collagen implant as an adjunct, in her left phakic eye, for the treatment of uncontrolled open-angle glaucoma. Ten days post-operatively, our patient complained of left phakic eye discharge pain and visual acuity decreased to "light-perception". The anterior chamber had 3+ cells and flare, and there was also 2 mm layered hypopyon. Vitreous involvement was present obscuring visualization of the fundus. On the same day our patient underwent vitrectomy surgery and intra-vitreal and systemic antibiotics were administered. Vitreous cultures grew Lactobacillus brevis. Our patient responded well to treatment and 30 days after vitrectomy visual acuity improved to 1/10. Six months later our patient underwent cataract surgery. Eight months after initial surgery visual acuity was 2/10 and intra-ocular pressure was 14 mmHg without any anti-glaucoma medication.

Conclusions
This is the first report of acute lactobacillus endophthalmitis in the phakic eye of a diabetic patient after trabeculectomy. Glaucoma surgeons should be aware of the potential for acute post-operative endophthalmitis due to rare microorganisms, such as lactobacillus, in glaucoma filtration surgery, especially in diabetic patients. The literature shows an increased risk of endophthalmitis when anti-metabolites are used in conjunction with trabeculectomy. Perhaps, any type of wound healing modulation, such as collagen or mitomycin-C may increase this risk. However, it is unclear at this time and more studies need to be done. In this single case, vitrectomy combined with intra-vitreal and systemic antibiotics were efficient in limiting the devastating sequels of this complication.
Tamoxifen enhances the cytotoxic effects of nelfinavir in breast cancer cells
Authors: Brüning Ansgar , Friese Klaus , Burges Alexander , Mylonas Ioannis 
Published: July 2010

Abstract
Introduction
The HIV protease inhibitor nelfinavir is currently under investigation as a new anti-cancer drug. Several studies have shown that nelfinavir induces cell cycle arrest, endoplasmic reticulum stress, autophagy, and apoptosis in cancer cells. In the present article, the effect of nelfinavir on human breast cancer cells is examined and potential combination treatments are investigated.

Methods
The effects of nelfinavir and tamoxifen on the human breast cancer cell lines MCF7, T47 D, MDA-MB-453, and MDA-MB-435 were tested by analysing their influence on cell viability (via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay), apoptosis (annexin binding, poly(ADP-ribose) polymerase cleavage), autophagy (autophagy marker light chain 3B expression), endoplasmic reticulum stress (binding protein and activating transcription factor 3 expression), and the occurrence of oxidative stress (intracellular glutathione level).

Results
Nelfinavir induced apoptosis in all four breast cancer cell lines tested, although the extent of autophagy and endoplasmic reticulum stress varied among the cell lines. The concentration of nelfinavir needed for an efficient induction of apoptosis in breast cancer cells could be reduced from 15 μg/ml to 6 μg/ml when combined with tamoxifen. At a concentration of 6 μg/ml, tamoxifen substantially enhanced the endoplasmic reticulum stress reaction in those cell lines that responded to nelfinavir with binding protein (BiP) upregulation (MCF7, T47D), and enhanced autophagy in cell lines that responded to nelfinavir treatment with autophagy marker light chain 3B upregulation (MDA-MB-453). Although tamoxifen has been described to be able to induce oxidative stress at concentrations similar to those applied in this study (6 μg/ml), we observed that nelfinavir but not tamoxifen reduced the intracellular glutathione level of breast cancer cells within hours of application by up to 32%, suggesting the induction of oxidative stress was an early event and an additional cause of the apoptosis induced by nelfinavir.

Conclusions
The results demonstrate that nelfinavir may be an effective drug against breast cancer and could be combined with tamoxifen to enhance its efficacy against breast cancer cells. Moreover, the cytotoxic effect of a tamoxifen and nelfinavir combination was independent of the oestrogen receptor status of the analysed breast cancer cells, suggesting a potential benefit of a combination of these two drugs even in patients with no hormone-responsive tumours. We therefore recommend that clinical studies on nelfinavir with breast cancer patients should include this drug combination to analyse the therapeutic efficacy as well as the safety and tolerability of this potential treatment option.