bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infection-associated platelet dysfunction of canine platelets detected in a flow chamber model
Authors: Ferkau Annika , Gillmann Hans-Jörg , Mischke Reinhard , Calmer Simone , Ecklebe Silke , Abid Monia , Minde Jan-Wighard , Echtermeyer Frank , Theilmeier Gregor 
Published: June 2013

Abstract

Background
In the present study, the influence of bacterial infection, lipopolysacharides (LPS) and hydroxyethyl starch (HES) on platelet function in a parallel plate flow chamber were measured. Experiments were performed with non-activated and protease-activating-receptor (PAR) 4 agonist activated platelets. Comparative measurements were in vivo capillary bleeding time, platelet function analyzer and impedance aggregometry.

Results
PAR 4 agonist did not increase platelet adhesion of platelets from dogs with bacterial inflammation in the flow chamber in contrast to platelets of healthy dogs. Except from impedance aggregometry with lower sensitivity and specificity, PFA did not detect platelet dysfunctions in dogs with infection. In vitro addition of LPS or HES significantly reduced platelet covered area after PAR-activation.

Conclusions
The flow chamber detects platelet dysfunctions in dogs with inflammatory diseases. In vitro addition of LPS highlights the inhibiting effect of bacterial wall components on platelet function. Platelet dysfunction induced by infection could possibly also be diagnosed after treatment of sepsis with colloids has commenced. The flow chamber could be a useful tool to detect sepsis associated platelet dysfunction given that larger prospective trials confirm these findings from a proof of concept study.
Acanthamoeba castellanii of the T4 genotype is a potential environmental host for Enterobacter aerogenes and Aeromonas hydrophila
Authors: Yousuf Farzana Abubakar , Siddiqui Ruqaiyyah , Khan Naveed Ahmed 
Published: June 2013

Abstract

Background

Acanthamoeba can interact with a wide range of microorganisms such as viruses, algae, yeasts, protists and bacteria including Legionella pneumophila, Pseudomonas aeruginosa, Vibrio cholerae, Helicobacter pylori, Listeria monocytogenes, Mycobacterium spp., and Escherichia coli. In this capacity, Acanthamoeba has been suggested as a vector in the transmission of bacterial pathogens to the susceptible hosts.

Methods
Here, we used a keratitis isolate of A. castellanii of the T4 genotype and studied its interactions with two bacterial genera which have not been tested before, Enterobacter aerogenes, and Aeromonas hydrophila, as well as E. coli. Assays were performed to determine bacterial association with and invasion of A. castellanii. Additionally, bacterial survival intracellular of A. castellanii trophozoites as well as cysts was determined.

Results
All three bacterial isolates tested, associated, invaded, and survived inside A. castellanii trophozoites as well as A. castellanii cysts. However, E. aerogenes and E. coli exhibited significantly reduced association with and invasion of A. castellanii as compared with A. hydrophila (P < 0.01 using paired T-test, one tail distribution). In the long term survival assays, all three bacterial isolates tested remained viable inside A. castellanii trophozoites, while amoeba remained intact; however A. hydrophila exhibited higher survival inside amoebae (14.54 ± 3.3 bacteria:amoeba ratio) compared with E. aerogenes (3.96 ± 0.7 bacteria:amoeba ratio) and E. coli (5.85 ± 1.1 bacteria:amoeba ratio). A. hydrophila, E. coli, and E. aerogenes remained viable during the encystment process and exhibited higher levels of recovery from mature cysts (14.13 ± 0.89 A. hydrophila:amoeba ratio, 10.13 ± 1.17 E. aerogenes:amoeba ratio, and 11.95 ± 0.7 E. coli:amoeba ratio).

Conclusions

A. hydrophila and E. aerogenes also joined the ranks of other bacteria that could benefit from A. castellanii. Because cysts can be airborne, these findings suggest that Acanthamoeba is a potential vector in the transmission of A. hydrophila and E. aerogenes to susceptible hosts.
Synthesis, docking and acetylcholinesterase inhibitory assessment of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives with potential anti-Alzheimer effects
Authors: Mohammadi-Farani Ahmad , Ahmadi Aram , Nadri Hamid , Aliabadi Alireza 
Published: June 2013

Abstract

Background
Alzheimer’s disease (AD) as neurodegenerative disorder, is the most common form of dementia accounting for about 50-60% of the overall cases of dementia among persons over 65 years of age. Low acetylcholine (ACh) concentration in hippocampus and cortex areas of the brain is one of the main reasons for this disease. In recent years, acetylcholinesterase (AChE) inhibitors like donepezil with prevention of acetylcholine hydrolysis can enhance the duration of action of acetylcholine in synaptic cleft and improve the dementia associated with Alzheimer’s disease.

Results
Design, synthesis and assessment of anticholinesterase activity of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives showed prepared compounds can function as potential acetylcholinesterase inhibitor. Among 12 synthesized derivatives, compound 4a with ortho chlorine moiety as electron withdrawing group exhibited the highest potency in these series (IC50 = 0.91 ± 0.045 μM) compared to donepezil (IC50 = 0.14 ± 0.03 μM). The results of the enzyme inhibition test (Ellman test) showed that electron withdrawing groups like Cl, F and NO2 can render the best effect at position ortho and para of the phenyl ring. But compound 4g with methoxy group at position 3(meta) afforded a favorable potency (IC50 = 5.5 ± 0.7 μM). Furthermore, docking study confirmed a same binding mode like donepezil for compound 4a.

Conclusions
Synthesized compounds 4a-4l could be proposed as potential anticholinesterase agents.
Idiopathic inflammatory myopathies: pathogenic mechanisms of muscle weakness
Authors: Rayavarapu Sree , Coley William , Kinder Travis B , Nagaraju Kanneboyina 
Published: June 2013

AbstractIdiopathic inflammatory myopathies (IIMs) are a heterogenous group of complex muscle diseases of unknown etiology. These diseases are characterized by progressive muscle weakness and damage, together with involvement of other organ systems. It is generally believed that the autoimmune response (autoreactive lymphocytes and autoantibodies) to skeletal muscle-derived antigens is responsible for the muscle fiber damage and muscle weakness in this group of disorders. Therefore, most of the current therapeutic strategies are directed at either suppressing or modifying immune cell activity. Recent studies have indicated that the underlying mechanisms that mediate muscle damage and dysfunction are multiple and complex. Emerging evidence indicates that not only autoimmune responses but also innate immune and non-immune metabolic pathways contribute to disease pathogenesis. However, the relative contributions of each of these mechanisms to disease pathogenesis are currently unknown. Here we discuss some of these complex pathways, their inter-relationships and their relation to muscle damage in myositis. Understanding the relative contributions of each of these pathways to disease pathogenesis would help us to identify suitable drug targets to alleviate muscle damage and also improve muscle weakness and quality of life for patients suffering from these debilitating muscle diseases.
Identification, technological and safety characterization of Lactobacillus sakei and Lactobacillus curvatus isolated from Argentinean anchovies (Engraulis anchoita)
Authors: Belfiore Carolina , Raya Raúl R , Vignolo Graciela M 
Published: June 2013

Abstract
In this study, the identification and characterization of Lactobacillus previously isolated from fresh anchovies (Engraulis anchoita) are investigated. 16S rDNA partial sequencing assigned all the isolates to belong to the Lactobacillus sakei/curvatus group. Fourteen out of 15 isolates were identified as L. sakei by phenotypic traits: they exhibited catalase activity and fermented melibiose, although only 10 of them hydrolyzed arginine. These results were confirmed by multiplex PCR-based restriction enzyme analysis with Hin dIII and by restriction fragment length polymorphic (RFLP) analysis of the 16S-23S rDNA intergenic spacer region with Taq I. Among identified isolates, four L. sakei strains and the sole L. curvatus strain showing sensitivity to chloramphenicol, erythromycin and tetracycline and exhibiting high tolerance to NaCl (10-18%) were unable to produce neither dextran nor biogenic amines. Based on technological and safety features, L. sakei SACB704 and L. curvatus SACB03a naturally present in fresh anchovies may be promising strains for the development of a starter culture to accelerate and control the fermentation of salt fermented anchovy-based products.
Seaweed-mediated synthesis of gold nanoparticles using Turbinaria conoides and its characterization
Authors: Rajeshkumar Shanmugam , Malarkodi Chelladurai , Gnanajobitha Gnanadhas , Paulkumar Kanniah , Vanaja Mahendran , Kannan Chellapandian , Annadurai Gurusamy 
Published: June 2013

Abstract
The synthesis of metal nanoparticles using algae has been unexplored, but it is a more biocompatible method than the other biological methods. Metal nanoparticle synthesis using algae extract shows rapid and non-toxic process which resulted to nano sizes having the greatest potential for biomedical applications. In this investigation, we studied the green synthesis of gold nanoparticles using the algae extract of Turbinaria conoides. Green synthesis of gold nanoparticles was preliminarily confirmed by color changing from yellow to dark pink in the reaction mixture, and the broad surface plasmon resonance band was centered at 520 to 525 nm which indicates polydispersed nanoparticles. Transmission electron microscopy and selected-area electron diffraction analysis show the morphology and crystalline structure of synthesized gold nanoparticles with the size range of 6 to 10 nm. The four strong diffraction peaks were observed by X-ray diffraction; it confirmed the crystalline nature of synthesized gold nanoparticles. The carboxylic, amine, and polyphenolic groups were associated with the algae-assisted synthesized gold nanoparticles which was confirmed using Fourier transform-infrared spectroscopy. This study eliminates the use of chemical substances as reducing and stabilizing agent. Because it has natural several constituents which are fucoidan and polyphenolic substances, it does a dual function as both reducing and stabilizing agent for nanoparticles. Thus, algae-mediated synthesis process of biomedically valuable gold nanoparticles is a one-spot, facile, convenient, large-scaled, and eco-friendly method.
Human conditionally immortalized neural stem cells improve locomotor function after spinal cord injury in the rat
Authors: Amemori Takashi , Romanyuk Nataliya , Jendelova Pavla , Herynek Vit , Turnovcova Karolina , Prochazka Pavel , Kapcalova Miroslava , Cocks Graham , Price Jack , Sykova Eva 
Published: June 2013

Abstract
Introduction
A growing number of studies have highlighted the potential of stem cell and more-differentiated neural cell transplantation as intriguing therapeutic approaches for neural repair after spinal cord injury (SCI).

Methods
A conditionally immortalized neural stem cell line derived from human fetal spinal cord tissue (SPC-01) was used to treat a balloon-induced SCI. SPC-01 cells were implanted into the lesion 1 week after SCI. To determine the feasibility of tracking transplanted stem cells, a portion of the SPC-01 cells was labeled with poly-L-lysine-coated superparamagnetic iron-oxide nanoparticles, and the animals grafted with labeled cells underwent magnetic resonance imaging. Functional recovery was evaluated by using the BBB and plantar tests, and lesion morphology, endogenous axonal sprouting and graft survival, and differentiation were analyzed. Quantitative polymerase chain reaction (qPCR) was used to evaluate the effect of transplanted SPC-01 cells on endogenous regenerative processes.

Results
Transplanted animals displayed significant motor and sensory improvement 2 months after SCI, when the cells robustly survived in the lesion and partially filled the lesion cavity. qPCR revealed the increased expression of rat and human neurotrophin and motor neuron genes. The grafted cells were immunohistologically positive for glial fibrillary acidic protein (GFAP); however, we found 25% of the cells to be positive for Nkx6.1, an early motor neuron marker. Spared white matter and the robust sprouting of growth-associated protein 43 (GAP43)+ axons were found in the host tissue. Four months after SCI, the grafted cells matured into Islet2+ and choline acetyltransferase (ChAT)+ neurons, and the graft was grown through with endogenous neurons. Grafted cells labeled with poly-L-lysine-coated superparamagnetic nanoparticles before transplantation were detected in the lesion on T2-weighted images as hypointense spots that correlated with histologic staining for iron and the human mitochondrial marker MTCO2.

Conclusions
The transplantation of SPC-01 cells produced significant early functional improvement after SCI, suggesting an early neurotrophic action associated with long-term restoration of the host tissue, making the cells a promising candidate for future cell therapy in patients with SCI.
B7-1/B7-2 blockade overrides the activation of protective CD8 T cells stimulated in the absence of Foxp3+ regulatory T cells
Authors: Ertelt James M , Buyukbasaran Esra Z , Jiang Tony T , Rowe Jared H , Xin Lijun , Way Sing Sing 
Published: June 2013

ABSTRACTAlthough T cell activation has been classically described to require distinct, positive stimulation signals that include B7-1 (CD80) and B7-2 (CD86) costimulation, overriding suppression signals that avert immune-mediated host injury are equally important. How these opposing stimulation and suppression signals work together remains incompletely defined. Our recent studies demonstrate that CD8 Teff activation in response to cognate peptide stimulation is actively suppressed by the Foxp3+ subset of CD4 cells, called Tregs. Here, we show that the elimination of Treg suppression does not bypass the requirement for positive B7-1/B7-2 costimulation. The expansion, IFN-γ cytokine production, cytolytic, and protective features of antigen-specific CD8 T cells stimulated with purified cognate peptide in Treg-ablated mice were each neutralized effectively by CTLA-4-Ig that blocks B7-1/B7-2. In turn, given the efficiency whereby CTLA-4-Ig overrides the effects of Treg ablation, the role of Foxp3+ cell-intrinsic CTLA-4 in mitigating CD8 Teff activation was also investigated. With the use of mixed chimera mice that contain CTLA-4-deficient Tregs exclusively after the ablation of WT Foxp3+ cells, a critical role for Treg CTLA-4 in suppressing the expansion, cytokine production, cytotoxicity, and protective features of peptide-stimulated CD8 T cells is revealed. Thus, the activation of protective CD8 T cells requires positive B7-1/B7-2 costimulation even when suppression by Tregs and in particular, Treg-intrinsic CTLA-4 is circumvented.
RIG-I activation inhibits HIV replication in macrophages
Authors: Wang Yizhong , Wang Xu , Li Jieliang , Zhou Yu , Ho Wenzhe 
Published: June 2013

ABSTRACTThe RIG-I signaling pathway is critical in the activation of the type I IFN-dependent antiviral innate-immune response. We thus examined whether RIG-I activation can inhibit HIV replication in macrophages. We showed that the stimulation of monocyte-derived macrophages with 5′ppp-dsRNA, a synthetic ligand for RIG-I, induced the expression of RIG-I, IFN-α/β, and several IRFs, key regulators of the IFN signaling pathway. In addition, RIG-I activation induced the expression of multiple intracellular HIV-restriction factors, including ISGs, several members of the APOBEC3 family, tetherin and CC chemokines, the ligands for HIV entry coreceptor (CCR5). The inductions of these factors were associated with the inhibition of HIV replication in macrophages stimulated by 5′ppp-dsRNA. These observations highlight the importance of RIG-I signaling in macrophage innate immunity against HIV, which can be beneficial for the treatment of HIV disease, where intracellular immune defense is compromised by the virus.
MGL signaling augments TLR2-mediated responses for enhanced IL-10 and TNF-α secretion
Authors: van Vliet Sandra J , Bay Sylvie , Vuist Ilona M , Kalay Hakan , García-Vallejo Juan J , Leclerc Claude , van Kooyk Yvette 
Published: June 2013

ABSTRACTDCs orchestrate immune responses to infectious pathogens and disturbances in tissue integrity. Equipped with C-type lectins, DCs can respond to environmental changes in glycosylation. Many C-type lectins are capable of modulating TLR activation, thereby facilitating tailor-made immune reactions. Here, we investigated the signaling properties of the C-type lectin MGL and show that MGL engagement by agonistic antibodies or carbohydrate ligands couples to TLR signal transduction for increased IL-10 and TNF-α secretion by human monocyte-derived DCs. MGL triggering especially synergized with TLR2-induced pathways, leading to elevated IL-10 mRNA levels and enhanced TNF-α mRNA stability. In addition, MGL signaling promoted phosphorylation of the MAPK ERK and the transcription factor CREB. Whereas specific inhibitors of p90RSK blocked the MGL-induced cytokine secretion, AP-1 was not involved. Strikingly, NF-κB was only crucial for the IL-10 response and dispensable for TNF-α production. Together, our results demonstrate that MGL activation of the ERK-p90RSK-CREB axis converges with TLR2-induced pathways, thereby fine-tuning the DC maturation phenotype.
Inhibition of geranylgeranyltransferase attenuates neutrophil accumulation and tissue injury in severe acute pancreatitis
Authors: Merza Mohammed , Wetterholm Erik , Zhang Su , Regner Sara , Thorlacius Henrik 
Published: June 2013

ABSTRACTLeukocyte infiltration and acinar cell necrosis are hallmarks of severe AP, but the signaling pathways regulating inflammation and organ injury in the pancreas remain elusive. In the present study, we investigated the role of geranylgeranyltransferase in AP. Male C57BL/6 mice were treated with a geranylgeranyltransferase inhibitor GGTI-2133 (20 mg/kg) prior to induction of pancreatitis by infusion of taurocholate into the pancreatic duct. Pretreatment with GGTI-2133 reduced plasma amylase levels, pancreatic neutrophil recruitment, hemorrhage, and edema formation in taurocholate-evoked pancreatitis. Moreover, administration of GGTI-2133 decreased the taurocholate-induced increase of MPO activity in the pancreas and lung. Treatment with GGTI-2133 markedly reduced levels of CXCL2 in the pancreas and IL-6 in the plasma in response to taurocholate challenge. Notably, geranylgeranyltransferase inhibition abolished neutrophil expression of Mac-1 in mice with pancreatitis. Finally, inhibition of geranylgeranyltransferase had no direct effect on secretagogue-induced activation of trypsinogen in pancreatic acinar cells in vitro. A significant role of geranylgeranyltransferase was confirmed in an alternate model of AP induced by L-arginine challenge. Our findings show that geranylgeranyltransferase regulates neutrophil accumulation and tissue damage via expression of Mac-1 on neutrophils and CXCL2 formation in AP. Thus, these results reveal new signaling mechanisms in pancreatitis and indicate that targeting geranylgeranyltransferase might be an effective way to ameliorate severe AP.
Childhood maltreatment and methylation of the glucocorticoid receptor geneNR3C1in bipolar disorder
Authors: Perroud Nader , Dayer Alexandre , Piguet Camille , Nallet Audrey , Favre Sophie , Malafosse Alain , Aubry Jean-Michel 
Published: June 2013

BackgroundEarly-life adversities represent risk factors for the development of bipolar affective disorder and are associated with higher severity of the disorder. This may be the consequence of a sustained alteration of the hypothalamic–pituitary–adrenal (HPA) axis resulting from epigenetic modifications of the gene coding for the glucocorticoid receptor (NR3C1).AimsTo investigate whether severity of childhood maltreatment is associated with increased methylation of the exon? 1FNR3C1promoter in bipolar disorder.MethodA sample of people with bipolar disorder (n= 99) were assessed for childhood traumatic experiences. The percentage ofNR3C1methylation was measured for each participant.ResultsThe higher the number of trauma events, the higher was the percentage ofNR3C1methylation (β = 0.52, 95% CI 0.46–0.59,P<<0.0001). The severity of each type of maltreatment (sexual, physical and emotional) was also associated withNR3C1methylation status.ConclusionsEarly-life adversities have a sustained effect on the HPA axis through epigenetic processes and this effect may be measured in peripheral blood. This enduring biological impact of early trauma may alter the development of the brain and lead to adult psychopathological disorder.
Characteristics and rates of mental health problems among Indian and White adolescents in two English cities
Authors: Dogra Nisha , Svirydzenka Nadzeya , Dugard Pat , Singh Swaran P. , Vostanis Panos 
Published: June 2013

BackgroundSampling techniques for national surveys have constrained the statistical power in estimating prevalence rates of child mental health problems in minority ethnic groups.AimsTo establish the prevalence rates of mental health problems in ethnic Indian adolescents in England and compare these with matched White adolescents living in the same areas.MethodA cross-sectional survey with oversampling of Indian adolescents aged 13–15 years of age.ResultsThe sample size was 2900 (71% response rate) with 1087 (37%) Indian and 414 (14%) White adolescents. Ethnically Indian adolescents had lower rates of all types of mentalhealth problems (5% v. 13% and 21% v. 30% for abnormal Strengths and Difficulties Questionnaire and Short Mood and Feelings Questionnaire scores, respectively) and substance misuse (18% v. 57%, 5% v. 15% and 6% v. 9% for regular alcohol, smoking and drug use, respectively), with the exception of eating disorders, compared with their White counterparts. The odds of an abnormal score on the mental health questionnaires were worse for White compared with Indian children irrespective of sociodemographic variables.ConclusionsFactors relating to how Indian adolescents are parented or their social support networks may be influencing their mental health and may warrant further investigation.