bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fecal calprotectin and alpha-1 antitrypsin predict severity and response to corticosteroids in gastrointestinal graft-versus-host disease
Authors: Rodriguez-Otero Paula , Porcher Raphael , Peffault de Latour Régis , Contreras Margarita , Bouhnik Yoram , Xhaard Aliénor , Andreoli Annalisa , Ribaud Patricia , Kapel Nathalie , Janin Anne , Socié Gérard , Robin Marie 
Published: May 2012

AbstractDiagnosis of gastrointestinal GVHD (GI-GVHD) is based on clinical symptoms and histologic findings. No biomarkers predicting responses to treatment are routinely available even though 30% to 50% of patients will not respond to corticosteroids. In this study, we aimed to evaluate fecal calprotectin, α-1-antitrypsin (α1-AT), and elastase at the time of first symptoms as diagnostic and prognostic tools for GI-GVHD in 72 consecutive patients, of whom 51 developed GI-GVHD. The prognostic value of markers was evaluated by their association with complete response (CR) and steroid-resistant (SR) GVHD. Calprotectin and α1-AT concentrations increased with GI-GVHD initial stages but patients with initial stage 1 GI-GVHD had similar marker levels to patients without GI-GVHD, so sensitivity to diagnose GI-GVHD was weak. In contrast, calprotectin and α1-AT were predictors for SR-GVHD and CR. Multiple regression modeling identified calprotectin and α1-AT concentration as independently predicting SR-GVHD together with initial stage > 2 GI-GVHD. Our results showed that fecal calprotectin and α1-AT levels at the time of diagnosis are predictive for responses to treatment but are not diagnostic markers for initial stage 1 to 3 GI-GVHD.
GeSICA: Genome segmentation from intra-chromosomal associations
Authors: Liu Lin , Zhang Yiqian , Feng Jianxing , Zheng Ning , Yin Junfeng , Zhang Yong 
Published: May 2012

Abstract

Background
Various aspects of genome organization have been explored based on data from distinct technologies, including histone modification ChIP-Seq, 3C, and its derivatives. Recently developed Hi-C techniques enable the genome wide mapping of DNA interactomes, thereby providing the opportunity to study genome organization in detail, but these methods also pose challenges in methodology development.

Results
We developed Genome Segmentation from Intra Chromosomal Associations, or GeSICA, to explore genome organization and applied the method to Hi-C data in human GM06990 and K562 cells. GeSICA calculates a simple logged ratio to efficiently segment the human genome into regions with two distinct states that correspond to rich and poor functional element states. Inside the rich regions, Markov Clustering was subsequently applied to segregate the regions into more detailed clusters. The binding sites of the insulator, cohesion, and transcription complexes are enriched in the boundaries between neighboring clusters, indicating that inferred clusters may have fine organizational features.

Conclusions
Our study presents a novel analysis method, known as GeSICA, which gives insight into genome organization based on Hi-C data. GeSICA is open source and freely available at: http://web.tongji.edu.cn/~zhanglab/GeSICA/
The fetomaternal interface in the placenta of three species of armadillos (Eutheria, Xenarthra, Dasypodidae)
Authors: Rezende Lorenna C , Barbeito Claudio G , Favaron Phelipe O , Mess Andrea , Miglino Maria A 
Published: May 2012

Abstract

Background
Placental characters vary among Xenarthra, one of four supraordinal clades of Eutheria. Armadillos are known for villous, haemochorial placentas similar to humans. Only the nine-banded armadillo has been well studied so far.

Methods
Placentas of three species of armadillos were investigated by means of histology, immunohistochemistry including proliferation marker, and transmission and scanning electron microscopy.

Results
The gross anatomy differed: Euphractus sexcinctus and Chaetophractus villosus had extended, zonary placentas, whereas Chaetophractus vellerosus had a disk. All taxa had complex villous areas within the maternal blood sinuses of the endometrium. Immunohistochemistry indicated the validity of former interpretations that the endothelium of the sinuses was largely intact. Tips of the villi and the columns entering the maternal tissue possessed trophoblast cell clusters with proliferation activity. Elsewhere, the feto-maternal barrier was syncytial haemochorial with fetal vessels near the surface.

Conclusions
Differences among armadillos occurred in regard to the extension of the placenta, whereas the fine structure was similar. Parallels to the human suggest that armadillos are likely to be useful animal models for human placentation.
Platelet-Activating Factor Antagonists Decrease Follicular Dendritic-Cell Stimulation of Human B Lymphocytes
Authors: Halickman Isaac , Bastien Yolande , Zhuang Qianli , Mazer Monty B , Toledano Baruch , Mazer Bruce D 
Published: May 2012

AbstractBoth B-lymphoblastoid cell lines and tonsillar B lymphocytes express receptors for platelet-activating factor (PAF). In lymph node germinal centres, B lymphocytes interact with follicular dendritic cells (FDCs), which present antigen-containing immune complexes to B lymphocytes. FDCs have phenotypic features that are similar to those of stromal cells and monocytes and may therefore be a source of lipid mediators. In this study, we evaluated the effects of the PAF antagonist WEB 2170 on the activation of tonsillar B lymphocytes by FDCs. FDCs were isolated from tonsils by Bovine Serum Albumin (BSA) gradient centrifugation. After being cultured for 6 to 10 days, they were incubated with freshly isolated B cells in the presence or absence of the specific PAF receptor antagonist WEB 2170. B-lymphocyte proliferation was assessed by [3H]-thymidine incorporation, and immunoglobulin (Ig) G and IgM secretion was assessed by enzyme-linked immunosorbent assay (ELISA). WEB 2170 (10-6to 10-8M) inhibited [3H]-thymidine incorporation by up to 35% ± 3%. Moreover, the secretion of IgG and IgM was inhibited by up to 50% by WEB 2170 concentrations ranging from 10-6to 10-8M. There was no evidence of toxicity by trypan blue staining, and the addition of WEB 2170 to B cells in the absence of FDCs did not inhibit the spontaneous production of IgG or IgM. The effect of the PAF antagonist is primarily on B lymphocytes, as reverse transcription polymerase chain reaction detected little PAF receptor messenger ribonucleic acid (mRNA) from FDCs. These data suggest that endogenous production of PAF may be important in the interaction of B lymphocytes with FDCs.
Potential Adverse and Allergic Reactions from Complementary and Alternative Medicine and Dietary Supplements
Authors: Wong H.C. George 
Published: May 2012

Abstract
Complementary and alternative medicine and dietary supplements are often used by patients. A detailed examination of each preparation used by four patients was carried out. Seven such preparations with the potential to cause bleeding, cardiovascular and central nervous system side effects, and allergic food reactions are described. They were taken by both Asian and Caucasian patients, were purchased locally, and were used for allergic and nonallergic disorders. Inquiry into their use is important to prevent potential adverse and allergic reactions. There should be a higher standard of regulation for such products.
Mechanisms of Degranulation in Neutrophils
Authors: Lacy Paige 
Published: May 2012

AbstractNeutrophils are critical inflammatory cells that cause tissue damage in a range of diseases and disorders. Being bone marrow-derived white blood cells, they migrate from the bloodstream to sites of tissue inflammation in response to chemotactic signals and induce inflammation by undergoing receptor-mediated respiratory burst and degranulation. Degranulation from neutrophils has been implicated as a major causative factor in pulmonary disorders, including severe asphyxic episodes of asthma. However, the mechanisms that control neutrophil degranulation are not well understood. Recent observations indicate that granule release from neutrophils depends on activation of intracellular signalling pathways, including β-arrestins, the Rho guanosine triphosphatase Rac2, soluble NSF attachment protein (SNAP) receptors, thesrcfamily of tyrosine kinases, and the tyrosine phosphatase MEG2. Some of these observations suggest that degranulation from neutrophils is selective and depends on nonredundant signalling pathways. This review focuses on new findings from the literature on the mechanisms that control the release of granule-derived mediators from neutrophils.
Maternal Smoking in Pregnancy: Do the Effects on Innate (Toll-Like Receptor) Function Have Implications for Subsequent Allergic Disease?
Authors: Prescott Susan L. , Noakes Paul S. 
Published: May 2012

AbstractSubtle increases in immaturity of immune function in early infancy have been implicated in the rising susceptibility to allergic disease, particularly relative impairment of type 1 interferon (IFN)-γ responses in the neonatal period. Although genetic predisposition is a clear risk factor, the escalating rates of allergic disease in infancy suggest that environmental factors are also implicated. We previously showed that maternal smoking in pregnancy may impair neonatal IFN-γ responses. Our more recent studies now indicate that this common avoidable toxic exposure is also associated with attenuation of innate immune function, with attenuated Toll-like receptor (TLR)-mediated microbial responses (including TLR-2, -3, -4, and -9 responses). Most notably, the effects were more marked if the mothers were also allergic. In this review, we discuss the significance of these observations in the context of the emerging hypothesis that variations in TLR function in early life may be implicated in allergic propensity. There is now growing evidence that many of the key pathways involved in subsequent T-cell programming and regulation (namely, antigen-presenting cells and regulatory T cells) rely heavily on microbe-driven TLR activation for maturation and function. Factors that influence the function and activity of these innate pathways in early life may contribute to the increasing predisposition for allergic disease. Although "cleaner" environments have been implicated, here we explore the possibility that other common environmental exposures (such as maternal smoking) could also play a role.
Progress and Challenges in the Understanding of Chronic Urticaria
Authors: Ferrer Marta , Kaplan Allen P 
Published: May 2012

AbstractChronic urticaria is a skin disorder characterized by transient pruritic weals that recur from day to day for 6 weeks or more. It has a great impact on patients' quality of life. In spite of this prevalence and morbidity, we are only beginning to understand its physiopathology and we do not have a curative treatment. Moreover, a patient with chronic urticaria may undergo extensive laboratory evaluations seeking a cause only to be frustrated when none is found. In recent years there have been significant advances in our understanding of some of the molecular mechanisms responsible for hive formation. The presence and probable role of IgG autoantibodies directed against epitopes expressed on the alpha-chain of the IgE receptor and to lesser extent, to IgE in a subset of patients is generally acknowledged. These autoantibodies activate complement to release C5a, which augments histamine release, and IL4 and leukotriene C4 are released as well. A perivascular cellular infiltrate results without predominance of either Th1 or Th2 lymphocyte subpopulations. Basophils of all chronic urticaria patients (autoimmune or idiopathic) are hyperresponsive to serum, regardless of source, but poorly responsive to anti IgE. In this review we will summarize the recent contributions to this field and try to provide insights to possible future directions for research on this disease.
Variation in HIV-1 R5 macrophage-tropism correlates with sensitivity to reagents that block envelope: CD4 interactions but not with sensitivity to other entry inhibitors
Authors: Peters Paul J , Duenas-Decamp Maria J , Sullivan W Matthew , Brown Richard , Ankghuambom Chiambah , Luzuriaga Katherine , Robinson James , Burton Dennis R , Bell Jeanne , Simmonds Peter , Ball Jonathan , Clapham Paul R 
Published: May 2012

AbstractBackgroundHIV-1 R5 viruses cause most of the AIDS cases worldwide and are preferentially transmitted compared to CXCR4-using viruses. Furthermore, R5 viruses vary extensively in capacity to infect macrophages and highly macrophage-tropic variants are frequently identified in the brains of patients with dementia. Here, we investigated the sensitivity of R5 envelopes to a range of inhibitors and antibodies that block HIV entry. We studied a large panel of R5 envelopes, derived by PCR amplification without culture from brain, lymph node, blood and semen. These R5 envelopes conferred a wide range of macrophage tropism and included highly macrophage-tropic variants from brain and non-macrophage-tropic variants from lymph node.ResultsR5 macrophage-tropism correlated with sensitivity to inhibition by reagents that inhibited gp120:CD4 interactions. Thus, increasing macrophage-tropism was associated with increased sensitivity to soluble CD4 and to IgG-CD4 (PRO 542), but with increased resistance to the anti-CD4 monoclonal antibody (mab), Q4120. These observations were highly significant and are consistent with an increased affinity of envelope for CD4 for macrophage-tropic envelopes. No overall correlations were noted between R5 macrophage-tropism and sensitivity to CCR5 antagonists or to gp41 specific reagents. Intriguingly, there was a relationship between increasing macrophage-tropism and increased sensitivity to the CD4 binding site mab, b12, but decreased sensitivity to 2G12, a mab that binds a glycan complex on gp120.ConclusionVariation in R5 macrophage-tropism is caused by envelope variation that predominantly influences sensitivity to reagents that block gp120:CD4 interactions. Such variation has important implications for therapy using viral entry inhibitors and for the design of envelope antigens for vaccines.
Mouse T-cells restrict replication of human immunodeficiency virus at the level of integration
Authors: Tervo Hanna-Mari , Goffinet Christine , Keppler Oliver T 
Published: May 2012

Abstract

Background
The development of an immunocompetent, genetically modified mouse model to study HIV-1 pathogenesis and to test antiviral strategies has been hampered by the fact that cells from native mice do not or only inefficiently support several steps of the HIV-1 replication cycle. Upon HIV-1 infection, mouse T-cell lines fail to express viral proteins, but the underlying replication barrier has thus far not been unambiguously identified. Here, we performed a kinetic and quantitative assessment of consecutive steps in the early phase of the HIV-1 replication cycle in T-cells from mice and humans.

Results
Both T-cell lines and primary T-cells from mice harbor a severe post-entry defect that is independent of potential species-specTR transactivation. Reverse transcription occurred efficiently following VSV-G-mediated entry of virions into mouse T-cells, and abundant levels of 2-LTR circles indicated successful nuclear import of the pre-integration complex. To probe the next step in the retroviral replication cycle, i.e. the integration of HIV-1 into the host cell genome, we established and validated a nested real-time PCR to specifically quantify HIV-1 integrants exploiting highly repetitive mouse B1 elements. Importantly, we demonstrate that the frequency of integrant formation is diminished 18- to > 305-fold in mouse T-cell lines compared to a human counterpart, resulting in a largely abortive infection. Moreover, differences in transgene expression from residual vector integrants, the transcription off which is cyclin T1-independent, provided evidence for an additional, peri-integrational deficit in certain mouse T-cell lines.

Conclusion
In contrast to earlier reports, we find that mouse T-cells efficiently support early replication steps up to and including nuclear import, but restrict HIV-1 at the level of chromosomal integration.
The effect of earplugs during the night on the onset of delirium and sleep perception: a randomized controlled trial in intensive care patients
Authors: Van Rompaey Bart , Elseviers Monique M , Van Drom Wim , Fromont Veronique , Jorens Philippe G 
Published: May 2012

Abstract
Introduction
This study hypothesised that a reduction of sound during the night using earplugs could be beneficial in the prevention of intensive care delirium. Two research questions were formulated. First, does the use of earplugs during the night reduce the onset of delirium or confusion in the ICU? Second, does the use of earplugs during the night improve the quality of sleep in the ICU?

Methods
A randomized clinical trial included adult intensive care patients in an intervention group of 69 patients sleeping with earplugs during the night and a control group of 67 patients sleeping without earplugs during the night. The researchers were blinded during data collection. Assignment was performed by an independent nurse researcher using a computer program. Eligible patients had an expected length of stay in the ICU of more than 24 hours, were Dutch- or English-speaking and scored a minimum Glasgow Coma Scale of 10. Delirium was assessed using the validated NEECHAM scale, sleep perception was reported by the patient in response to five questions.

Results
The use of earplugs during the night lowered the incidence of confusion in the studied intensive care patients. A vast improvement was shown by a Hazard Ratio of 0.47 (95% confidence interval (CI) 0.27 to 0.82). Also, patients sleeping with earplugs developed confusion later than the patients sleeping without earplugs. After the first night in the ICU, patients sleeping with earplugs reported a better sleep perception.

Conclusions
Earplugs may be a useful instrument in the prevention of confusion or delirium. The beneficial effects seem to be strongest within 48 hours after admission. The relation between sleep, sound and delirium, however, needs further research.

Trial registration
Current Controlled Trials ISRCTN36198138
On the crossing number of semiadequate links
Authors: Stoimenow Alexander 
Published: May 2012

Abstract.
The concept of adequacy of a link was introduced to determine
its crossing number. We give crossing number estimates for the
(much larger) class of semiadequate links, in particular improving
the previously known estimates for positive links. We also give
examples showing that semiadequacy may not be attained in
minimal crossing number diagrams. Our approach uses the
description of links of a given canonical genus, and is related
to skein invariants, the signature, the new concordance
invariants, and hyperbolic volume. It allows to settle the
A/B-adequacy status of many examples, including all knots
up to 10 crossings. As two applications, we describe generic
alternating and positive knots of given genus, determining
the asymptotical behaviour of the number of such knots, and
classify Seifert fibered, and therewith also hyperbolic,
Montesinos links.
On the existence of non-trivial finitely injective modules
Authors: Guil Asensio Pedro A. , Izurdiaga Manuel C. , Torrecillas Blas 
Published: May 2012

Abstract
We develop a technique to construct finitely injective modules which
are non-trivial, in the sense that they are not direct sums of
injective modules. As a consequence, we prove that a ring R is
left noetherian if and only if each finitely injective left
R-module is trivial, thus answering an open question posed by
Salce.
The composite nature of the interaction between nuclear receptors EcR and DHR38
Authors: Zoglowek Anna , Orłowski Marek , Pakuła Szymon , Dutko-Gwóźdź Joanna , Pajdzik Dorota , Gwóźdź Tomasz , Rymarczyk Grzegorz , Wieczorek Elżbieta , Dobrucki Jurek , Dobryszycki Piotr , Ożyhar Andrzej 
Published: May 2012

Abstract
Ecdysteroids coordinate essential biological processes in Drosophila through a complex of two nuclear receptors, the ecdysteroid receptor (EcR) and the ultraspiracle protein (Usp). Biochemical experiments have shown that, in contrast to Usp, the EcR molecule is characterized by high intramolecular plasticity. To investigate whether this plasticity is sufficient to form EcR complexes with nuclear receptors other than Usp, we studied the interaction of EcR with the DHR38 nuclear receptor. Previous in vitro experiments suggested that DHR38 can form complexes with Usp and thus disrupt Usp-EcR interaction with the specific hsp27pal response element. This article provides the experimental evidence that EcR is able to form complexes with DHR38 as well. The recombinant DNA-binding domains (DBDs) of EcR and DHR38 interact specifically on hsp27pal. However, the interaction between the receptors is not restricted to their isolated DBDs. We pre\xadsent data that indicate that the full-length EcR and DHR38 can also form specific complexes within the nuclei of living cells. This interaction is mediated by the hinge region of EcR, which was recently classified as an intrinsically disordered region. Our results indicate that DHR38 might modulate the activity of the Usp-EcR heterodimer by forming complexes with both of its components.
Rab1 interacts directly with the β2-adrenergic receptor to regulate receptor anterograde trafficking
Authors: Hammad Maha M. , Kuang Yi-Qun , Morse Alexa , Dupré Denis J. 
Published: May 2012

Abstract
Very little is understood about the trafficking of G protein-coupled receptors (GPCRs) from the endoplasmic reticulum (ER) to the plasma membrane. Rab guanosine triphosphatases (GTPases) are known to participate in the trafficking of various GPCRs via a direct interaction during the endocytic pathway, but whether this occurs in the anterograde pathway is unknown. We evaluated the potential interaction of Rab1, a GTPase known to regulate β2-adrenergic receptor (β2AR) trafficking, and its effect on export from the ER. Our results show that GTP-bound Rab1 interacts with the F(x)6LL motif of β2AR. Receptors lacking the interaction motif fail to traffic properly, suggesting that a direct interaction with Rab1 is required for β2AR anterograde trafficking.
Tmem27 dimerization, deglycosylation, plasma membrane depletion, and the extracellular Phe-Phe motif are negative regulators of cleavage by Bace2
Authors: Esterházy Daria , Akpinar Pinar , Stoffel Markus 
Published: May 2012

Abstract
The pancreatic β-cell surface protein Tmem27 is promotes the preservation of functional β-cell mass. It is a selective substrate of the protease Bace2, yet the intramolecular features of Tmem27 that regulate its processing by this sheddase have not been characterized. In particular, the importance of homodimerization, glycosylation, trafficking to the plasma membrane (PM), the existence of multiple cleavage sites, and the amino acid residues that govern these features are currently unknown. Using Tmem27 mutational analysis and multiple biochemical approaches, we here show that Tmem27 dimerization is a dynamic process mediated by its intracellular cysteine residue and that prevents Tmem27 cleavage, that extracellular asparagine glycosylation is essential for Tmem27 trafficking to the PM and its processing by Bace2, that the amount of Tmem27 at the PM is proportional to its total cell levels upon glucose stimulation and Bace2 inhibition, and that the double phenylalanine motif in the Tmem27 cleavage site is an intramolecular Bace2 inhibitor. These findings define structural properties of Tmem27 that affect the susceptibility to its protease Bace2 and have implications for the efficiency with which Tmem27 and other Bace2 substrates are cleaved in normal and disease states.