bluuebunny/crossref_metadata_2025_split huggingface dataset:
The high-affinity human IgG receptor FcγRI (CD64) promotes IgG-mediated inflammation, anaphylaxis, and antitumor immunotherapy
Authors: Mancardi David A. , Albanesi Marcello , Jönsson Friederike , Iannascoli Bruno , Van Rooijen Nico , Kang Xiaoqiang , England Patrick , Daëron Marc , Bruhns Pierre 
Published: January 2013

Key Points
Human FcγRI can trigger antibody-induced inflammatory arthritis, thrombocytopenia, airway inflammation, and systemic anaphylaxis. Human FcγRI can trigger antibody-mediated immunotherapy of mouse metastatic melanoma.
Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia
Authors: Gudbrandsdottir Sif , Birgens Henrik Sverre , Frederiksen Henrik , Jensen Bjarne Anker , Jensen Morten Krogh , Kjeldsen Lars , Klausen Tobias Wirenfeldt , Larsen Herdis , Mourits-Andersen Hans Torben , Nielsen Claus Henrik , Nielsen Ove Juul , Plesner Torben , Pulczynski Stanislaw , Rasmussen Inge Helleberg , Rønnov-Jessen Dorthe , Hasselbalch Hans Carl 
Published: January 2013

Key Points
In newly diagnosed ITP, addition of rituximab to dexamethasone yields higher sustained response rates than dexamethasone alone.
Silencing of STIM1 attenuates hypoxia-induced PASMCs proliferation via inhibition of the SOC/Ca2+/NFAT pathway
Authors: Hou Xianhua , Chen Jian , Luo Yongjun , Liu Fuyu , Xu Gang , Gao Yuqi 
Published: January 2013

Abstract

Background
Stromal interaction molecule 1 (STIM1) is a newly discovered Ca2+ sensor on the endoplasmic reticulum which is an indispensable part in the activation of store-operated Ca2+ channels (SOC). Recent studies demonstrate that SOC of pulmonary smooth muscle cells (PASMCs) were upregulated by chronic hypoxia which contribute to the enhanced pulmonary vasoconstriction and vascular remodeling. However, the exact role of STIM1 in the development of chronic hypoxic pulmonary hypertension(HPH) remains unclear.

Methods
In this study we investigated the cellular distribution and expression of STIM1 by immunofluorescence, qRTPCR and Western blotting methods in Wistar rat distal intrapulmonary arteries under normal and chronic hypobaric hypoxic conditions. In vitro, Wistar rat PASMCs were isolated and cultured. PASMCs were transfected with siRNA targeting STIM1 gene by liposome. The expression of STIM1 protein was detected by Western blotting. [3H]-thymidine ([3H]-TdR) incorporation were performed to detect PASMCs proliferation. The cell cycle was analyzed by flow cytometry. The SOC-mediated Ca2+ influx was calculated by Ca2+ fluorescence imaging and the nuclear translocation of NFATc3 was determined by immunofluorescence and Western blot analysis of nuclear extracts.

Results
We found that during the development of HPH and the initiation of vascular remodeling, the mRNA and protein expression levels of STIM1 significantly increased in the distal intrapulmonary arteries. Moderate hypoxia significantly promotes PASMCs proliferation and cell cycle progression. Silencing of STIM1 significantly decreased cellular proliferation and delayed the cell cycle progression induced by hypoxia. Silencing of STIM1 also significantly decreased SOC-mediated Ca2+ influx and inhibited the nuclear translocation of NFATc3 in hypoxic PASMCs.

Conclusion
Our findings suggest that chronic hypobaric hypoxia upregulates the expression of STIM1 in the distal intrapulmonary arteries which plays an important role in the hypoxia-induced PASMCs proliferation via SOC/Ca2+/NFAT pathway and may represent a novel therapeutic target for the prevention of hypoxia pulmonary hypertension.
Identifying targets of the Sox domain protein Dichaete in the Drosophila CNS via targeted expression of dominant negative proteins
Authors: Shen Shih Pei , Aleksic Jelena , Russell Steven 
Published: January 2013

Abstract

Background
Group B Sox domain transcription factors play important roles in metazoan central nervous system development. They are, however, difficult to study as mutations often have pleiotropic effects and other Sox family members can mask phenotypes due to functional compensation. In Drosophila melanogaster, the Sox gene Dichaete is dynamically expressed in the embryonic CNS, where it is known to have functional roles in neuroblasts and the ventral midline. In this study, we use inducible dominant negative proteins in combination with ChIP, immunohistochemistry and genome-wide expression profiling to further dissect the role of Dichaete in these two tissues.

Results
We generated two dominant negative Dichaete constructs, one lacking a DNA binding domain and the other fused to the Engrailed transcriptional repressor domain. We expressed these tissue-specifically in the midline and in neuroblasts using the UAS/GAL4 system, validating their use at the phenotypic level and with known target genes. Using ChIP and immunohistochemistry, we identified two new likely direct Dichaete target genes, commisureless in the midline and asense in the neuroectoderm. We performed genome-wide expression profiling in stage 8–9 embryos, identifying almost a thousand potential tissue-specific Dichaete targets, with half of these genes showing evidence of Dichaete binding in vivo. These include a number of genes with known roles in CNS development, including several components of the Notch, Wnt and EGFR signalling pathways.

Conclusions
As well as identifying commisureless as a target, our data indicate that Dichaete helps establish its expression during early midline development but has less effect on its established later expression, highlighting Dichaete action on tissue specific enhancers. An analysis of the broader range of candidate Dichaete targets indicates that Dichaete plays diverse roles in CNS development, with the 500 or so Dichaete-bound putative targets including a number of transcription factors, signalling pathway components and terminal differentiation genes. In the early neurectoderm we implicate Dichaete in the lateral inhibition pathway and show that Dichaete acts to repress the proneural gene asense. Our analysis also reveals that dominant negatives cause off-target effects, highlighting the need to use other experimental data for validating findings from dominant negative studies.
Inhibition of COX-2 expression by topical diclofenac enhanced radiation sensitivity via enhancement of TRAIL in human prostate adenocarcinoma xenograft model
Authors: Inoue Takeshi , Anai Satoshi , Onishi Sayuri , Miyake Makito , Tanaka Nobumichi , Hirayama Akihide , Fujimoto Kiyohide , Hirao Yoshihiko 
Published: January 2013

Abstract

Background
COX-2 inhibitors have an antitumor potential and have been verified by many researchers. Treatment of cancer cells with external stressors such as irradiation can stimulate the over-expression of COX-2 and possibly confer radiation resistance. In this study, we tested if topical diclofenac, which inhibits both COX-1 and COX-2, administration rendered prostate tumor cells sensitize to the effects of radiation.

Methods
LNCaP-COX-2 and LNCaP-Neo cells were treated with 0 to 1000 μM diclofenac. Next, a clonogenic assay was performed in which cells were subjected to irradiation (0 to 4 Gy) with or without diclofenac. COX-2 expression and other relevant molecules were measured by real-time PCR and immunohistochemistry after irradiation and diclofenac treatment. In addition, we assessed the tumor volumes of xenograft LNCaP-COX-2 cells treated with topical diclofenac with or without radiation therapy (RT).

Results
LNCaP-COX-2 and LNCaP-Neo cell lines experienced cytotoxic effects of diclofenac in a dose related manner. Clonogenic assays demonstrated that LNCaP-COX-2 cells were significantly more resistant to RT than LNCaP-Neo cells. Furthermore, the addition of diclofenac sensitized LNCaP-COX-2 not but LNCaP-Neo cells to the cytocidal effects of radiation. In LNCaP-COX-2 cells, diclofenac enhanced radiation-induced apoptosis compared with RT alone. This phenomenon might be attributed to enhancement of RT-induced TRAIL expression as demonstrated by real-time PCR analysis. Lastly, tumor volumes of LNCaP-COX-2 cells xenograft treated with diclofenac or RT alone was >4-fold higher than in mice treated with combined diclofenac and radiation (p<0.05).

Conclusions
These in vitro and in vivo findings suggest that conventional COX inhibitor, diclofenac enhances the effect of RT on prostate cancer cells that express COX-2. Thus, diclofenac may have potential as radiosensitizer for treatment of prostate cancer.
Study on nanometric cutting of germanium by molecular dynamics simulation
Authors: Lai Min , Zhang Xiaodong , Fang Fengzhou , Wang Yufang , Feng Min , Tian Wanhui 
Published: January 2013

Abstract
Three-dimensional molecular dynamics simulations are conducted to study the nanometric cutting of germanium. The phenomena of extrusion, ploughing, and stagnation region are observed from the material flow. The uncut thickness which is defined as the depth from bottom of the tool to the stagnation region is in proportion to the undeformed chip thickness on the scale of our simulation and is almost independent of the machined crystal plane. The cutting resistance on (111) face is greater than that on (010) face due to anisotropy of germanium. During nanometric cutting, both phase transformation from diamond cubic structure to β-Sn phase and direct amorphization of germanium occur. The machined surface presents amorphous structure.
Anti-inflammatory and anti-amyloidogenic
effects of a small molecule, 2,4-bis(p-hydroxyphenyl)-2-butenal in Tg2576 Alzheimer’s
disease mice model
Authors: Jin Peng , Kim Jin-A , Choi Dong-Young , Lee Young-Jung , Jung Heon Sang , Hong Jin Tae 
Published: January 2013

Abstract

Background
Alzheimer’s disease (AD) is pathologically characterized by excessive
accumulation of amyloid-beta (Aβ) fibrils within the brain and activation of
astrocytes and microglial cells. In this study, we examined anti-inflammatory
and anti-amyloidogenic effects of 2,4-bis(p-hydroxyphenyl)-2-butenal (HPB242),
an anti-inflammatory compound produced by the tyrosine-fructose Maillard
reaction.

Methods
12-month-old Tg2576 mice were treated with HPB242 (5 mg/kg) for 1 month and
then cognitive function was assessed by the Morris water maze test and passive
avoidance test. In addition, western blot analysis, Gel electromobility shift
assay, immunostaining, immunofluorescence staining, ELISA and enzyme activity
assays were used to examine the degree of Aβ deposition in the brains of Tg2576
mice. The Morris water maze task was analyzed using two-way ANOVA with repeated
measures. Otherwise were analyzed by one-way ANOVA followed by Dunnett’s post
hoc test.

Results
Treatment of HPB242 (5 mg/kg for 1 month) significantly attenuated cognitive
impairments in Tg2576 transgenic mice. HPB242 also prevented amyloidogenesis in
Tg2576 transgenic mice brains. This can be evidenced by Aβ accumulation, BACE1,
APP and C99 expression and β-secretase activity. In addition, HPB242 suppresses
the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2
(COX-2) as well as activation of astrocytes and microglial cells. Furthermore,
activation of nuclear factor-kappaB (NF-κB) and signal transducer and activator
of transcription 1/3 (STAT1/3) in the brain was potently inhibited by
HPB242.

Conclusions
Thus, these results suggest that HPB242 might be useful to intervene in
development or progression of neurodegeneration in AD through its
anti-inflammatory and anti-amyloidogenic effects.
Notch1 is required for hypoxia-induced proliferation, invasion and chemoresistance of T-cell acute lymphoblastic leukemia cells
Authors: Zou Jie , Li Peng , Lu Fei , Liu Na , Dai Jianjian , Ye Jingjing , Qu Xun , Sun Xiulian , Ma Daoxin , Park Jino , Ji Chunyan 
Published: January 2013

Abstract

Background
Notch1 is a potent regulator known to play an oncogenic role in many malignancies including T-cell acute lymphoblastic leukemia (T-ALL). Tumor hypoxia and increased hypoxia-inducible factor-1α (HIF-1α) activity can act as major stimuli for tumor aggressiveness and progression. Although hypoxia-mediated activation of the Notch1 pathway plays an important role in tumor cell survival and invasiveness, the interaction between HIF-1α and Notch1 has not yet been identified in T-ALL. This study was designed to investigate whether hypoxia activates Notch1 signalling through HIF-1α stabilization and to determine the contribution of hypoxia and HIF-1α to proliferation, invasion and chemoresistance in T-ALL.

Methods
T-ALL cell lines (Jurkat, Sup-T1) transfected with HIF-1α or Notch1 small interference RNA (siRNA) were incubated in normoxic or hypoxic conditions. Their potential for proliferation and invasion was measured by WST-8 and transwell assays. Flow cytometry was used to detect apoptosis and assess cell cycle regulation. Expression and regulation of components of the HIF-1α and Notch1 pathways and of genes related to proliferation, invasion and apoptosis were assessed by quantitative real-time PCR or Western blot.

Results
Hypoxia potentiated Notch1 signalling via stabilization and activation of the transcription factor HIF-1α. Hypoxia/HIF-1α-activated Notch1 signalling altered expression of cell cycle regulatory proteins and accelerated cell proliferation. Hypoxia-induced Notch1 activation increased the expression of matrix metalloproteinase-2 (MMP2) and MMP9, which increased invasiveness. Of greater clinical significance, knockdown of Notch1 prevented the protective effect of hypoxia/HIF-1α against dexamethasone-induced apoptosis. This sensitization correlated with losing the effect of hypoxia/HIF-1α on Bcl-2 and Bcl-xL expression.

Conclusions
Notch1 signalling is required for hypoxia/HIF-1α-induced proliferation, invasion and chemoresistance in T-ALL. Pharmacological inhibitors of HIF-1α or Notch1 signalling may be attractive interventions for T-ALL treatment.
Crosstalk between SET7/9-dependent methylation and ARTD1-mediated ADP-ribosylation of histone H1.4
Authors: Kassner Ingrid , Barandun Marc , Fey Monika , Rosenthal Florian , Hottiger Michael O 
Published: January 2013

Abstract

Background
Different histone post-translational modifications (PTMs) fine-tune and integrate different cellular signaling pathways at the chromatin level. ADP-ribose modification of histones by cellular ADP-ribosyltransferases such as ARTD1 (PARP1) is one of the many elements of the histone code. All 5 histone proteins were described to be ADP-ribosylated in vitro and in vivo. However, the crosstalk between ADP-ribosylation and other modifications is little understood.

Results
In experiments with isolated histones, it was found that ADP-ribosylation of H3 by ARTD1 prevents H3 methylation by SET7/9. However, poly(ADP-ribosyl)ation (PARylation) of histone H3 surprisingly allowed subsequent methylation of H1 by SET7/9. Histone H1 was thus identified as a new target for SET7/9. The SET7/9 methylation sites in H1.4 were pinpointed to the last lysine residues of the six KAK motifs in the C-terminal domain (K121, K129, K159, K171, K177 and K192). Interestingly, H1 and the known SET7/9 target protein H3 competed with each other for SET7/9-dependent methylation.

Conclusions
The results presented here identify H1.4 as a novel SET7/9 target protein, and document an intricate crosstalk between H3 and H1 methylation and PARylation, thus implying substrate competition as a regulatory mechanism. Thereby, these results underline the role of ADP-ribosylation as an element of the histone code.
Isolation and characterization of exopolysaccharide with immunomodulatory activity from fermentation broth of Morchella conica
Authors: Su Chao-an , Xu Xiao-yan , Liu De-yun , Wu Ming , Zeng Fan-qing , Zeng Meng-yao , Wei Wei , Jiang Nan , Luo Xia 
Published: January 2013

Abstract

Background and the purpose of this study
Mushroom polysaccharides have traditionally been used for the prevention and treatment of a multitude of disorders like infectious illnesses, cancers and various autoimmune diseases. In vitro and in vivo studies suggest that certain polysaccharides affect immune system function. Morchella conica (M. conica) is a species of rare edible mushroom whose multiple medicinal functions have been proven. Thus, the objective of this study is to isolate and characterize of exopolysaccharide from submerged mycelial culture of M. conica, and to evaluate its immunomodulatory activity.

Methods
A water-soluble Morchella conica Polysaccharides (MCP) were extracted and isolated from the fermentation broth of M. conica through a combination of DEAE-cellulose and Sephacryl S-300 HR chromatograph. NMR and IR spectroscopy has played a developing role in identification of polysaccharide with different structure and composition from fungal and plant sources, as well as complex glycosaminoglycans of animal origin. Thus, NMR and IR spectroscopy were used to analyze the chemical structure and composition of the isolated polysaccharide. Moreover, the polysaccharide was tested for its immunomodulatory activity at different concentrations using in vitro model.

Results
The results showed that MCP may significantly modulate nitric oxide production in macrophages, and promote splenocytes proliferation. Analysis from HPLC, infrared spectra and nuclear magnetic resonance spectroscopy showed that MCP was a homogeneous mannan with an average molecular weight of approximately 81.2 kDa. The glycosidic bond links is →6)-α-D-Man p-(1→.

Conclusion
The results suggested that the extracted MCP may modulate nitric oxide production in macrophages and promote splenocytes proliferation, and it may act as a potent immunomodulatory agent.
Characterization of two antimicrobial peptides produced by a halotolerant Bacillus subtilis strain SK.DU.4 isolated from a rhizosphere soil sample
Authors: Baindara Piyush , Mandal Santi M , Chawla Niharika , Singh Pradip Kumar , Pinnaka Anil Kumar , Korpole Suresh 
Published: January 2013

Abstract
A bacterial strain producing two antimicrobial peptides was isolated from a rhizosphere soil sample and identified as Bacillus subtilis based on both phenotypic and 16S rRNA gene sequence phylogenetic analysis. It grew optimally up to 14% NaCl and produced antimicrobial peptide within 24 h of growth. The peptides were purified using a combination of chemical extraction and chromatographic techniques. The MALDI-TOF analysis of HPLC purified fractions revealed that the strain SK.DU.4 secreted a bacteriocin-like peptide with molecular mass of 5323.9 Da and a surface-active lipopeptide (m/z 1056 Da). The peptide mass fingerprinting of low-molecular-weight bacteriocin exhibited significant similarity with stretches of secreted lipoprotein of Methylomicrobium album BG8 and displayed 70% sequence coverage. MALDI MS/MS analysis elucidated the lipopeptide as a cyclic lipopeptide with a β-hydroxy fatty acid linked to Ser of a peptide with seven α-amino acids (Asp-Tyr-Asn-Gln-Pro-Asn-Ser) and assigned it to iturin-like group of antimicrobial biosurfactants. However, it differed in amino acid composition with other members of the iturin family. Both peptides were active against Gram-positive bacteria, suggesting that they had an additive effect.
OPN gene polymorphisms influence the risk of knee OA and OPN levels in synovial fluid in a Chinese population
Authors: Jiang Yongqing , Yao Meng , Liu Qingpeng , Zhou Changwei 
Published: January 2013

Abstract
Introduction
A body of studies suggests the role of osteopontin (OPN) in onset and development of osteoarthritis (OA), however, the association between OPN polymorphisms and OA susceptibility as well as its clinical features has not been reported.

Methods
A total of 750 patients with primary knee OA and 794 healthy volunteer were enrolled as controls. Both OA and control groups were interviewed to obtain demographic and clinical data. Three polymorphisms of OPN gene, namely, -156GG/G, -443C/T and -66T/G were determined. The levels of the full length and the thrombin-cleaved OPN in synovial fluid (SF) from OA subjects were measured.

Results
We found the polymorphisms of the -443C/T and the -66/T/G were significantly associated with the OA risk and the radiographic severity. The -443TT and -66GG showed protective effect against developing OA and were associated with lower Kellgren-Lawrence grade. Besides, the polymorphisms of -443C/T and -66T/G significantly affected the thrombin-cleaved OPN levels in SF from OA subjects. Subjects with -443TT and -66GG genotypes had lower thrombin-cleaved OPN levels in SF. The thrombin-cleaved OPN levels in SF were positively correlated to the radiographic severity of OA.

Conclusions
Our findings suggest that certain OPN gene polymorphisms may be used as molecular markers for the susceptibility and severity of OA.
Hypothalamic obesity: prevalence, associations and longitudinal trends in weight in a specialist adult neuroendocrine clinic
Authors: Steele Caroline A , Cuthbertson Daniel J , MacFarlane Ian A , Javadpour Mohsen , Das Kumar S V , Gilkes Catherine , Wilding John P , Daousi Christina 
Published: January 2013

ObjectiveObesity is highly prevalent among adults with acquired, structural hypothalamic damage. We aimed to determine hormonal and neuroanatomical variables associated with weight gain and obesity in patients following hypothalamic damage and to evaluate the impact of early instigation of weight loss measures to prevent or limit the severity of obesity in these patients.DesignRetrospective study of 110 adults with hypothalamic tumours attending a specialist neuroendocrine clinic. BMI was calculated at diagnosis and at last follow-up clinic visit. Endocrine data, procedures, treatments and weight loss measures were recorded and all available brain imaging reviewed.ResultsAt last follow-up, 82.7% of patients were overweight or heavier (BMI≥25 kg/m2), 57.2% were obese (BMI≥30 kg/m2) and 14.5% were morbidly obese (BMI≥40 kg/m2). Multivariate analysis revealed that use of desmopressin (odds ratio (OR)=3.5;P=0.026), GH (OR=2.7;P=0.031) and thyroxine (OR=3.0;P=0.03) was associated with development of new or worsened obesity. Neuroimaging features were not associated with weight gain. Despite proactive treatments offered in clinic in recent years (counselling, dietetic and physical activity advice, and anti-obesity medications), patients have continued to gain weight.ConclusionsDespite increased awareness, hypothalamic obesity is difficult to prevent and to treat. Improved understanding of the underlying pathophysiologies and multicentre collaboration to examine efficacy of novel obesity interventions are warranted.