bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV patients treated with low-dose prednisolone exhibit lower immune activation than untreated patients
Authors: Kasang Christa , Ulmer Albrecht , Donhauser Norbert , Schmidt Barbara , Stich August , Klinker Hartwig , Kalluvya Samuel , Koutsilieri Eleni , Rethwilm Axel , Scheller Carsten 
Published: January 2012

AbstractBackgroundHIV-associated general immune activation is a strong predictor for HIV disease progression, suggesting that chronic immune activation may drive HIV pathogenesis. Consequently, immunomodulating agents may decelerate HIV disease progression.MethodsIn an observational study, we determined immune activation in HIV patients receiving low-dose (5 mg/day) prednisolone with or without highly-active antiretroviral therapy (HAART) compared to patients without prednisolone treatment. Lymphocyte activation was determined by flow cytometry detecting expression of CD38 on CD8(+) T cells. The monocyte activation markers sCD14 and LPS binding protein (LBP) as well as inflammation markers soluble urokinase plasminogen activated receptor (suPAR) and sCD40L were determined from plasma by ELISA.ResultsCD38-expression on CD8+ T lymphocytes was significantly lower in prednisolone-treated patients compared to untreated patients (median 55.40% [percentile range 48.76-67.70] versus 73.34% [65.21-78.92],p= 0.0011, Mann-Whitney test). Similarly, we detected lower levels of sCD14 (3.6 μg/ml [2.78-5.12] vs. 6.11 μg/ml [4.58-7.70];p= 0.0048), LBP (2.18 ng/ml [1.59-2.87] vs. 3.45 ng/ml [1.84-5.03];p= 0.0386), suPAR antigen (2.17 μg/ml [1.65-2.81] vs. 2.56 μg/ml [2.24-4.26];p= 0.0351) and a trend towards lower levels of sCD40L (2.70 pg/ml [1.90-4.00] vs. 3.60 pg/ml [2.95-5.30];p= 0.0782). Viral load in both groups was similar (0.8 × 105ng/ml [0.2-42.4 × 105] vs. 1.1 × 105[0.5-12.2 × 105];p= 0.3806). No effects attributable to prednisolone were observed when patients receiving HAART in combination with prednisolone were compared to patients who received HAART alone.ConclusionsPatients treated with low-dose prednisolone display significantly lower general immune activation than untreated patients. Further longitudinal studies are required to assess whether treatment with low-dose prednisolone translates into differences in HIV disease progression.
Soluble RAGE as a severity marker in community acquired pneumonia associated sepsis
Authors: Narvaez-Rivera Rodrigo M , Rendon Adrian , Salinas-Carmona Mario C , Rosas-Taraco Adrian G 
Published: January 2012

Abstract

Background
Community-acquired pneumonia (CAP) is considered the most important cause of death from infectious disease in developed countries. Severity assessment scores partially address the difficulties in identifying high-risk patients. A lack of specific and valid pathophysiologic severity markers affect early and effective sepsis therapy. HMGB-1, sRAGE and RAGE have been involved in sepsis and their potential as severity markers has been proposed. The aim of this study was to evaluate HMGB-1, RAGE and sRAGE levels in patients with CAP-associated sepsis and determine their possible association with clinical outcome.

Method
We evaluated 33 patients with CAP-associated sepsis admitted to the emergency room and followed in the medical wards. Severity assessment scores (CURB-65, PSI, APACHE II, SOFA) and serologic markers (HMGB-1, RAGE, sRAGE) were evaluated on admission.

Results
Thirty patients with a diagnosis of CAP-associated sepsis were enrolled in the study within 24 hours after admission. Fourteen (46.6%) had pandemic (H1N1) influenza A virus, 2 (6.6%) had seasonal influenza A and 14 other diagnoses. Of the patients in the study group, 16 (53.3%) had a fatal outcome. ARDS was observed in 17 (56.6%) and a total of 22 patients had severe sepsis on admission (73%). The SOFA score showed the greatest difference between surviving and non-surviving groups (P = .003) with similar results in ARDS patients (P = .005). sRAGE levels tended to be higher in non-surviving (P = .058) and ARDS patients (P = .058). Logistic regression modeling demonstrated that SOFA (P = .013) and sRAGE (P = .05) were the only variables that modified the probability of a fatal outcome.

Conclusion
The association of elevated sRAGE with a fatal outcome suggests that it may have an independent causal effect in CAP. SOFA scores were the only clinical factor with the ability to identify surviving and ARDS patients.
Inhibition of STAT3 signaling and induction of SHP1 mediate antiangiogenic and antitumor activities of ergosterol peroxide in U266 multiple myeloma cells
Authors: Rhee Yun-Hee , Jeong Soo-Jin , Lee Hyo-Jeong , Lee Hyo-Jung , Koh Wonil , Jung Ji Hoon , Kim Sun-Hee , Sung-Hoon Kim 
Published: January 2012

Abstract

Background
Ergosterol peroxide (EP) derived from edible mushroom has been shown to exert anti-tumor activity in several cancer cells. In the present study, anti-angiogenic activity of EP was investigated with the underlying molecular mechanisms in human multiple myeloma U266 cells.

Results
Despite weak cytotoxicity against U266 cells, EP suppressed phosphorylation, DNA binding activity and nuclear translocalization of signal transducer and activator of transcription 3 (STAT3) in U266 cells at nontoxic concentrations. Also, EP inhibited phosphorylation of the upstream kinases Janus kinase 2 (JAK2) and Src in a time-dependent manner. Furthermore, EP increased the expression of protein tyrosine phosphatase SHP-1 at protein and mRNA levels, and conversely silencing of the SHP-1 gene clearly blocked EP-mediated STAT3 inactivation. In addition, EP significantly decreased vascular endothelial growth factor (VEGF), one of STAT3 target genes at cellular and protein levels as well as disrupted in vitro tube formation assay. Moreover, EP significantly suppressed the growth of U266 cells inoculated in female BALB/c athymic nude mice and immunohistochemistry revealed that EP effectively reduced the expression of STAT3 and CD34 in tumor sections compared to untreated control.

Conclusion
These findings suggest that EP can exert antitumor activity in multiple myeloma U266 cells partly with antiangiogenic activity targeting JAK2/STAT3 signaling pathway as a potent cancer preventive agent for treatment of multiple myeloma cells.
Low-mutation-rate, reduced-genome Escherichia coli: an improved host for faithful maintenance of engineered genetic constructs
Authors: Csörgő Bálint , Fehér Tamás , Tímár Edit , Blattner Frederick R , Pósfai György 
Published: January 2012

AbstractBackgroundMolecular mechanisms generating genetic variation provide the basis for evolution and long-term survival of a population in a changing environment. In stable, laboratory conditions, the variation-generating mechanisms are dispensable, as there is limited need for the cell to adapt to adverse conditions. In fact, newly emerging, evolved features might be undesirable when working on highly refined, precise molecular and synthetic biological tasks.ResultsBy constructing low-mutation-rate variants, we reduced the evolutionary capacity of MDS42, a reduced-genomeE. colistrain engineered to lack most genes irrelevant for laboratory/industrial applications. Elimination of diversity-generating, error-prone DNA polymerase enzymes involved in induced mutagenesis achieved a significant stabilization of the genome. The resulting strain, while retaining normal growth, showed a significant decrease in overall mutation rates, most notably under various stress conditions. Moreover, the error-prone polymerase-free host allowed relatively stable maintenance of a toxic methyltransferase-expressing clone. In contrast, the parental strain produced mutant clones, unable to produce functional methyltransferase, which quickly overgrew the culture to a high ratio (50% of clones in a 24-h induction period lacked functional methyltransferase activity). The surprisingly large stability-difference observed between the strains was due to the combined effects of high stress-induced mutagenesis in the parental strain, growth inhibition by expression of the toxic protein, and selection/outgrowth of mutants no longer producing an active, toxic enzyme.ConclusionsBy eliminating stress-inducible error-prone DNA-polymerases, the genome of the mobile genetic element-freeE. colistrain MDS42 was further stabilized. The resulting strain represents an improved host in various synthetic and molecular biological applications, allowing more stable production of growth-inhibiting biomolecules.
Structure of reverse microemulsion-templated metal hexacyanoferrate nanoparticles
Authors: Gutiérrez-Becerra Alberto , Barcena-Soto Maximiliano , Soto Víctor , Arellano-Ceja Jesús , Casillas Norberto , Prévost Sylvain , Noirez Laurence , Gradzielski Michael , Escalante José I 
Published: January 2012

Abstract
The droplet phase of a reverse microemulsion formed by the surfactant cetyltrimethylammonium ferrocyanide was used as a matrix to synthesize nanoparticles of nickel hexacyanoferrate by adding just a solution of NiCl2 to the microemulsion media. Dynamic light scattering and small-angle neutron scattering measurements show that the reverse microemulsion droplets employed have a globular structure, with sizes that depend on water content. Transmission electron microscopy and electron diffraction are used to obtain information about the structure of the synthesized nanoparticles. The results show that the size and shape of the coordination compound nanoparticles correspond with the size and shape of the droplets, suggesting that the presented system constitutes an alternative method of the synthesis of metal hexacyanoferrate nanoparticles.
Phylogenetic analysis of Chinese sheeppox and goatpox virus isolates
Authors: Zhou Tao , Jia Huaijie , Chen Guohua , He Xiaobing , Fang Yongxiang , Wang Xiaoxia , Guan Qisai , Zeng Shuang , Cui Qing , Jing Zhizhong 
Published: January 2012

AbstractBackgroundSheeppox virus (SPPV) and goatpox virus (GTPV), members of theCapripoxvirusgenus of thePoxviridaefamily are causative agents of sheep pox and goat pox respectively, which are important contagious diseases and endemic in central and northern Africa, the Middle and Far East, and the Indian sub-continent. Both sheep pox and goat pox can cause wool and hide damage, and reduce the production of mutton and milk, which may result in significant economic losses and threaten the stockbreeding. In this study, three SPPVs and two GTPVs were collected from China in 2009 and 2011. We described the sequence features and phylogenetic analysis of the P32 gene, GPCR gene and RPO30 gene of the SPPVs and GTPVs to reveal their genetic relatedness.ResultsSequence and phylogenetic analysis showed that there was a close relationship among SPPV/GanS/2/2011/China, SPPV/GanS/1/2011/China and SPPV/NingX/2009/China. They were clustered on the same SPPV clade. GTPV/HuB/2009/China and GS-V1 belonged to the GTPV lineage. GS-V1 was closely related to other GTPV vaccine strains. GTPV/HuB/2009/China and GS-V1 were clustered with GTPVs from China and some southern Asian countries.ConclusionThis study may expand the datum for spread trend research of Chinese SPPVs and GTPVs, meanwhile provide theoretical references to improve the preventive and control strategy.
A mixture of anatase and rutile TiO2 nanoparticles induces histamine secretion in mast cells
Authors: Chen Eric Y , Garnica Maria , Wang Yung-Chen , Mintz Alexander J , Chen Chi-Shuo , Chin Wei-Chun 
Published: January 2012

Abstract

Background
Histamine released from mast cells, through complex interactions involving the binding of IgE to FcεRI receptors and the subsequent intracellular Ca2+ signaling, can mediate many allergic/inflammatory responses. The possibility of titanium dioxide nanoparticles (TiO2 NPs), a nanomaterial pervasively used in nanotechnology and pharmaceutical industries, to directly induce histamine secretion without prior allergen sensitization has remained uncertain.

Results
TiO2 NP exposure increased both histamine secretion and cytosolic Ca2+ concentration ([Ca2+]C) in a dose dependent manner in rat RBL-2H3 mast cells. The increase in intracellular Ca2+ levels resulted primarily from an extracellular Ca2+ influx via membrane L-type Ca2+ channels. Unspecific Ca2+ entry via TiO2 NP-instigated membrane disruption was demonstrated with the intracellular leakage of a fluorescent calcein dye. Oxidative stress induced by TiO2 NPs also contributed to cytosolic Ca2+ signaling. The PLC-IP3-IP3 receptor pathways and endoplasmic reticulum (ER) were responsible for the sustained elevation of [Ca2+]C and histamine secretion.

Conclusion
Our data suggests that systemic circulation of NPs may prompt histamine release at different locales causing abnormal inflammatory diseases. This study provides a novel mechanistic link between environmental TiO2 NP exposure and allergen-independent histamine release that can exacerbate manifestations of multiple allergic responses.
Sonic hedgehog lineage in the mouse hypothalamus: from progenitor domains to hypothalamic regions
Authors: Alvarez-Bolado Gonzalo , Paul Fabian A , Blaess Sandra 
Published: January 2012

Abstract

Background
The hypothalamus is a brain region with essential functions for homeostasis and energy metabolism, and alterations of its development can contribute to pathological conditions in the adult, like hypertension, diabetes or obesity. However, due to the anatomical complexity of the hypothalamus, its development is not well understood. Sonic hedgehog (Shh) is a key developmental regulator gene expressed in a dynamic pattern in hypothalamic progenitor cells. To obtain insight into hypothalamic organization, we used genetic inducible fate mapping (GIFM) to map the lineages derived from Shh- expressing progenitor domains onto the four rostrocaudally arranged hypothalamic regions: preoptic, anterior, tuberal and mammillary.

Results

Shh- expressing progenitors labeled at an early stage (before embryonic day (E)9.5) contribute neurons and astrocytes to a large caudal area including the mammillary and posterior tuberal regions as well as tanycytes (specialized median eminence glia). Progenitors labeled at later stages (after E9.5) give rise to neurons and astrocytes of the entire tuberal region and in particular the ventromedial nucleus, but not to cells in the mammillary region and median eminence. At this stage, an additional Shh-expressing domain appears in the preoptic area and contributes mostly astrocytes to the hypothalamus. Shh- expressing progenitors do not contribute to the anterior region at any stage. Finally, we show a gradual shift from neurogenesis to gliogenesis, so that progenitors expressing Shh after E12.5 generate almost exclusively hypothalamic astrocytes.

Conclusions
We define a fate map of the hypothalamus, based on the dynamic expression of Shh in the hypothalamic progenitor zones. We provide evidence that the large neurogenic Shh- expressing progenitor domains of the ventral diencephalon are continuous with those of the midbrain. We demonstrate that the four classical transverse zones of the hypothalamus have clearly defined progenitor domains and that there is little or no cell mixing between the tuberal and anterior or the preoptic and anterior hypothalamus. Finally, we show that, in the tuberal hypothalamus, neurons destined for every mediolateral level are produced during a period of days, in conflict with the current 'three-wave' model of hypothalamic neurogenesis. Our work sets the stage for a deeper developmental analysis of this complex and important brain region.
The balance of expression of PTPN22 splice forms is significantly different in rheumatoid arthritis patients compared with controls
Authors: Ronninger Marcus , Guo Yongjing , Shchetynsky Klementy , Hill Andrew , Khademi Mohsen , Olsson Tomas , Reddy Padmalatha S , Seddighzadeh Maria , Clark James D , Lin Lih-Ling , O'Toole Margot , Padyukov Leonid 
Published: January 2012

Abstract
Background
The R620W variant in protein tyrosine phosphatase non-receptor 22 (PTPN22) is associated with rheumatoid arthritis (RA). The PTPN22 gene has alternatively spliced transcripts and at least two of the splice forms have been confirmed to encode different PTPN22 (LYP) proteins, but detailed information regarding expression of these is lacking, especially with regard to autoimmune diseases.

Methods
We have investigated the mRNA expression of known PTPN22 splice forms with TaqMan real-time PCR in relation to ZNF592 as an endogenous reference in peripheral blood cells from three independent cohorts with RA patients (n = 139) and controls (n = 111) of Caucasian origin. Polymorphisms in the PTPN22 locus (25 SNPs) and phenotypic data (gender, disease activity, ACPA and RF status) were used for analysis. Additionally, we addressed possible effects of methotrexate treatment on PTPN22 expression.

Results
We found consistent differences in the expression of the PTPN22 splice forms in unstimulated peripheral blood mononuclear cells between RA patients and normal controls. This difference was more pronounced when comparing the ratio of splice forms and was not affected by methotrexate treatment.

Conclusions
Our data show that RA patients and healthy controls have a shift in balance of expression of splice forms derived from the PTPN22 gene. This balance seems not to be caused by treatment and may be of importance during immune response due to great structural differences in the encoded PTPN22 proteins.
Simultaneous appearance of leukemoid reaction and phlegmasia cerulea dolens
Authors: Kovačević T , Kovačević P , Pecoraro F , Rančić Z 
Published: January 2012

A leukemoid reaction is an extreme form of reactive leukocytosis defined as granulocytic leukocytosis above 50 × 109/L produced by normal bone marrow, mostly in response to systemic infection or cancer. The mechanism as to how the haematopoetic system is altered to elevate production of myeloid cells is not known. A 69-year-old man presented with phlegmasia cerulea dolens caused by massive iliofemoral thrombosis. His workout at admission revealed absolute white blood cell count of 73.4 × 109/L, with neutrophil granulocyte of 68.5 × 109/L. The new increase in white blood cell count happened at day 5 after admission, when the haematoma of the anteromedial thigh was evacuated in general anaesthesia. There was a gradual decrease in counts until they reached the normal range. Deteriorated general condition with signs of systemic inflammatory response syndrome improved with supportive therapy, and the patient was discharged from hospital after 30 days. During hospitalization we did not identify any infectious focus, or any malignancy. We could not exclude other occult chronic conditions (malignancy) but the patient did not develop any other condition during 4.5 years of follow-up.
Novel vein closure procedure using a proprietary cyanoacrylate adhesive: 30-day swine model results
Authors: Min Robert J , Almeida Jose I , Mclean Derek J , Madsen Monte , Raabe Rodney 
Published: January 2012

Purpose To conduct a pilot study to demonstrate a novel method of using a proprietary cyanoacrylate (CA) for closure of superficial veins. Materials and Methods Right and left superficial epigastric veins from two swine models were utilized due to the vein's similarities with the human great saphenous vein. Under ultrasound guidance, access was gained and a 5-F delivery catheter was advanced to the junction of the superficial epigastric and abdominus rectus veins. A dispenser gun was then utilized to inject 0.16 mL of CA while compression was applied cephalad to the end of the catheter. Immediately after delivery, the catheter was pulled back 3 cm and manual compression was employed for 30 seconds. After this first injection, the ultrasound probe was repositioned caudad to the injection and cephalad to the catheter tip and another 0.16 mL injection was delivered with immediate 3 cm pullback of the delivery system. Manual compression was applied at the caudad end of the treated vein for 30 seconds. This process was repeated until the entire target segment was treated. Results At 30 days postimplantation, the treated veins were occluded with no evidence of recanalization or migration. Histological findings revealed that the lumen was dilated by coalescing, arborizing clear spaces with entrapped lytic erythrocytes, demarcated by a thin band of granular eosinophilic material. Spindle cells with dense eosinophilic matrix replaced the tunica intima and disrupted the tunica media. Conclusion Results of this initial study demonstrated that intravascular injection of CA is feasible for closure of superficial veins in animal models. These findings warrant further animal studies of this proprietary CA to assess efficacy, safety and its effects on perivenous structures.
Behavioral Phenotype of Fragile X Syndrome in Adolescence and Adulthood
Authors: Smith Leann E , Barker Erin T , Seltzer Marsha Mailick , Abbeduto Leonard , Greenberg Jan S 
Published: January 2012

Abstract
The present study explored the behavioral profile of individuals with fragile X syndrome during adolescence and adulthood. Individuals with both fragile X syndrome and autism (n  =  30) were compared with (a) individuals diagnosed with fragile X syndrome (but not autism; n  =  106) and (b) individuals diagnosed with autism (but not fragile X syndrome; n  =  135) on measures of autism symptoms, adaptive functioning, behavior problems, and psychological symptoms. Results indicated that individuals dually diagnosed with fragile X syndrome and autism displayed greater communication and social reciprocity impairments than individuals with fragile X syndrome only. Individuals in the dually diagnosed group also exhibited higher levels of repetitive and challenging behaviors than either comparison group, suggesting a unique profile of vulnerability for those diagnosed with both fragile X syndrome and autism.
Predictors of Future Caregiving by Adult Siblings of Individuals With Intellectual and Developmental Disabilities
Authors: Burke Meghan M , Taylor Julie Lounds , Urbano Richard , Hodapp Robert M 
Published: January 2012

AbstractWith the growing life expectancy for individuals with intellectual and developmental disabilities, siblings will increasingly assume responsibility for the care of their brother or sister with intellectual and developmental disabilities. Using a 163-item survey completed by 757 siblings, the authors identified factors related to future caregiving expectations. Siblings expected to assume greater caregiving responsibility for their brother or sister with disabilities if they were female, had closer relationships with and lived closer to their brother or sister with intellectual and developmental disabilities, and were the lone sibling without a disability. Siblings who expected to assume higher levels of caregiving had parents who were currently more able to care for their brother or sister with disabilities. With a better understanding of who intends to fulfill future caregiving roles, support can be provided to these siblings.