bluuebunny/crossref_metadata_2025 huggingface dataset:
An Experimental Comparison of a Document Deception Detection Policy using Real and Artificial Deception
Authors: Yang Yanjuan , Mannino Michael
Published: August 2012

Developing policies to screen documents for deception is often hampered by the cost of data collection and the inability to evaluate policy alternatives due to lack of data. To lower data collection costs and increase the amount of data, artificially generated deception data can be used, but the impact of using artificially generated deception data is not well understood. This article studies the impact of artificially generated deception on document screening policies. The deception and truth data were collected from financial aid applications, a document-centric area with limited resources for screening. Real deception was augmented with artificial data generated by noise and deception generation models. Using the real data and artificially generated data, we designed an innovative experiment with deception type and deception rate as factors, and harmonic mean and cost as outcome variables. We used two budget models (fixed and variable) typically employed by financial aid offices to measure the cost of noncompliance in financial aid applications. The analysis included an evaluation of a common policy for deception screening using both fixed and varying screening rates. The results of the experiment provided evidence of similar performance of screening policy with real and artificial deception, suggesting the possibility of using artificially generated deception to reduce the costs associated with obtaining training data.
Practical Approach to Emergencies in Lung Transplant Recipients: How We Do It
Authors: Schuurmans Macé M. , Tini Gabrielo M. , Zuercher Alice , Hofer Markus , Benden Christian , Boehler Annette
Published: August 2012

Lung transplant recipients (LTRs) are prone to medical complications and emergencies due to the transplanted organ being in constant direct contact with the environment and the need for life-long profound immunosuppression (IS). As a result of these specific circumstances, the medical and surgical management of LTRs frequently differs from usual standard care. Therefore, we outline here some of the principles we take into account when dealing with the most frequent medical emergencies encountered in our lung transplant cohort in Zurich. The main topics dealt with are: diagnostics and treatment of infections, gastrointestinal emergencies, IS and other medication issues as well as work-up of unclear inflammatory signs and peri-operative precautions in LTRs. Early post-operative transplant complications, rare medical emergencies and surgical problems are not covered. Our report is intended to help internists and pulmonologists new to the field to obtain a better understanding of the peculiarities of LTRs and their management.
Endobronchial Ultrasound-Guided Transbronchial Biopsy of Peripheral Pulmonary Lesions: How Many Specimens Are Necessary?
Authors: Huang Chun-Ta , Tsai Yi-Ju , Liao Wei-Yu , Wu Pei-Chen , Ho Chao-Chi , Yu Chong-Jen , Yang Pan-Chyr
Published: August 2012

Background: Although endobronchial ultrasound (EBUS)-guided transbronchial biopsy (TBB) has been shown to increase the diagnostic yield over conventional bronchoscopic techniques, an important issue regarding the optimal number of biopsy specimens required has not been thoroughly investigated. Objectives: We sought to examine whether the number of biopsy specimens taken was associated with the diagnostic yield of EBUS-guided TBB and, if this was the case, to determine the optimal number of specimens required for the maximum diagnostic yield in peripheral pulmonary lesions. Methods: The medical records of patients undergoing EBUS-guided TBB for the diagnosis of peripheral pulmonary lesions from 2008 to 2010 were retrospectively reviewed. The association of clinical and radiological features, including the number of biopsy specimens, with the diagnostic yield was analysed. Results: A total of 384 patients were included for analysis. The overall diagnostic yield of EBUS-guided TBB was 73%, and the only factor influencing the diagnostic yield was the position of the probe. Patients in which the EBUS probe was placed within the lesions had a significantly higher yield (85%) than those in which the probe was adjacent to or outside the lesions (38%; p < 0.001). When the number of biopsy specimens was determined based on their adequacy, it was an insignificant factor in predicting the diagnostic yield. Conclusions: Probe position independently predicts the diagnostic yield of EBUS-guided TBB. In real-world practice, the optimal number of biopsy specimens should be decided on a case-by-case basis.
Epstein-Barr Virus Infection and Altered Control of Apoptotic Pathways in Posttransplant Lymphoproliferative Disorders
Authors: Ghigna Maria-Rosa , Reineke Tanja , Rincé Patricia , Schüffler Peter , El Mchichi Bouchra , Fabre Monique , Jacquemin Emmanuel , Durrbach Antoine , Samuel Didier , Joab Irène , Guettier Catherine , Lucioni Marco , Paulli Marco , Tinguely Marianne , Raphael Martine
Published: August 2012

Posttransplant lymphoproliferative disorders (PTLD) represent a spectrum of lymphoid diseases complicating the clinical course of transplant recipients. Most PTLD are Epstein-Barr virus (EBV) associated with viral latency type III. Several in vitro studies have revealed an interaction between EBV latency proteins and molecules of the apoptosis pathway. Data on human PTLD regarding an association between Bcl-2 family proteins and EBV are scarce. We analyzed 60 primary PTLD for expression of 8 anti- (Bcl-2, Bcl-XL, and Mcl-1) and proapoptotic proteins (Bak and Bax), the so-called BH3-only proteins (Bad, Bid, Bim, and Puma), as well as the apoptosis effector cleaved PARP by immunohistochemistry. Bim and cleaved PARP were both significantly (p = 0.001 and p = 5.251e-6) downregulated in EBV-positive compared to EBV-negative PTLD [Bim: 6/40 (15%), cleaved PARP: 10/43 (23%), vs. Bim: 13/16 (81%), cleaved PARP: 12/17 (71%)]. Additionally, we observed a tendency toward increased Bcl-2 protein expression (p = 0.24) in EBV-positive PTLD. Hence, we provide evidence of a distinct regulation of Bcl-2 family proteins in EBV-positive versus negative PTLD. The low-expression pattern of the proapoptotic proteins Bim and cleaved PARP together with the high-expression pattern of the antiapoptotic protein Bcl-2 by trend in EBV-positive tumor cells suggests disruption of the apoptotic pathway by EBV in PTLD, promoting survival signals in the host cells.
Circulation
Editors' Picks
Authors:   The Editors
Published: August 2012

The following articles are being highlighted as part of
Circulation's
Topic Review series. This series will summarize the most important manuscripts, as selected by the editors, published in
Circulation
and the
Circulation
subspecialty journals. The studies included in this article represent the most read manuscripts published on the topic of arrhythmia and electrophysiology within the last year.
Should We Teach Semantic Prosody Awareness?
Authors: McGee Iain
Published: August 2012

While considerable attention has been paid to collocation, and the development of the collocational competence of L2 learners in recent years, very little has been said about a related concept in teaching journals, namely semantic prosody, and L2 learner awareness of this phenomenon. In this paper the concept of semantic prosody is introduced, and then discussed, before an experiment is reported investigating the semantic prosody awareness of three different sets of participants (university undergraduate Arab students, Arab English teachers, and native speaker (NS) English teachers) for seven lexical items for which specific semantic prosody claims have been made by corpus linguists. The results show that the data from the NS Group (when considered as a group) concurred with corpus observed semantic prosody tendencies for all seven items, but for the other two sets of participants the results were mixed regarding agreement. It would appear that for some items non-native users of English of different language levels appreciated the typical semantic prosody. For other items this was clearly not the case, and it appears that semantic prosody awareness can be incremental, or may not actually develop. Given the mixed data, it is suggested that explicit instruction about semantic prosody in the classroom may be of some value to learners.
Six Functions of Bilingual EFL Teacher Talk: Animating, Translating, Explaining, Creating, Prompting and Dialoguing
Authors: Forman Ross
Published: August 2012

‘Teacher talk’, which remains a primary feature of much education, plays a crucial role in EFL contexts where exposure to the L2 is often confined to the language classroom, and where local teachers generally share L1 with their students. The present study explores fresh ways of describing the major pedagogic functions of teacher talk across both L1 and L2 in such environments. It seeks to establish broad descriptive categories which can be directly applied by teachers and teacher-educators to the analysis of bilingual classroom practices.
Reading Aloud Activity in L2 and Cerebral Activation
Authors: Takeuchi Osamu , Ikeda Maiko , Mizumoto Atsushi
Published: August 2012

This article explores the cerebral mechanism of reading aloud activities in L2 learners. These activities have been widely used in L2 learning and teaching, and its effect has been reported in various Asian L2 learning contexts. However, the reasons for its effectiveness have not been examined. In order to fill in this gap, two studies using a brain-imaging technique, near-infrared spectroscopy, were conducted in order to determine a cerebral basis for the effectiveness of reading aloud activities. Study 1 investigated learners with high L2 proficiency to show the difference in cerebral activation between L2 and L1 learners as they read a passage aloud. The effect of material difficulty was also examined in this study. Study 2 then examined learners with both high and low L2 proficiency to show the effect of material difficulty vis-à-vis the learners’ L2 proficiency. The effect of repeated reading aloud activities was also investigated in this study. These studies show that: Reading aloud in L2 results in a higher degree of cerebral activation than reading aloud in L1. Reading material beyond learners’ L2 ability aloud results in low brain activation. Repetition of the same normal reading aloud activity in L2 does not necessarily increase (or decrease) the level of cerebral activation. However, including a repetitive cognitively demanding reading aloud activity does cause high brain activation.

On the basis of these findings, this article provides a cerebral basis for the effectiveness of reading aloud activities in L2 learning.
Planned Focus on Form: Automatization of Procedural Knowledge
Authors: Khatib Mohammad , Nikouee Majid
Published: August 2012

The present study is premised on Anderson’s ACT model that proposes declarative knowledge is automatizable through practice (1982). The research examined the extent to which declarative knowledge of one morphosyntactic structure, namely present perfect, can be automatized 2 days after practice and can be retained 2 weeks after practice. Twenty intermediate students participated in the study. They were randomly assigned to experimental (G1) and comparison (G2) groups. G1 received rule explanation, mechanical practice, meaningful practice, and planned communicative practice. G2, however, received rule explanation, mechanical practice, and meaningful practice. Overall, the results indicated more automatization measured in terms of reduction in error rate and reaction time on the part of G1than G2. The results obtained two weeks later showed the superiority of G1, too. The findings can be insightful for teachers who wish to have a communicative class not at the expense of discarding a focus on grammar.
Tuning In to Vocabulary Frequency in Coursebooks
Authors: O’Loughlin Richard
Published: August 2012

For second language learners vocabulary growth is of major importance, and for many learners commercially published coursebooks will be the source of this vocabulary learning. In this preliminary study, input from three levels of the coursebook series New English File (Oxenden and Latham-Koenig, 2006; Oxenden, Latham-Koenig, and Seligson, 2004, 2005) was analyzed using the computer program VocabProfile (Cobb, 2009). The results suggest that learners who complete three coursebook levels will receive exposure to fewer than the first 1,500 most frequent words in English. This has important pedagogical implications for learners, teachers and materials writers. Supplementary sources of suitable reading input are recommended, as is instruction in effective vocabulary learning strategies, if learners are to have regular opportunities to meet the most frequent 2,000 words of English.
The Potency of ‘READS’ to Inform Students’ Reading Ability
Authors: Mohamed Abdul Rashid , Siew Eng Lin , Mohamed Ismail Shaik Abdul Malik
Published: August 2012

This paper shares an initiative conducted in Malaysia in terms of knowledge to gauge students’ Reading Age and to inform teachers of their students’ reading progress and learning. Ensuring teachers understand the needs of students’ reading ability and preparing students to read and comprehend texts are the two most fundamental parallel tasks in today’s classroom setting. Consequently, determining students’ Reading Age has become an important endeavour in recent years by many education authorities throughout the world. This study aims at incorporating the Reading Evaluation and Decoding System (READS), to ascertain students’ Reading Age and comprehension skills at macro and micro levels. This study employed a stratified sample of high school students who were in Secondary 1 through Secondary 5. Data was gathered through a generic standardized reading comprehension developed test. With a precise Reading Matrix, ESL teachers can appraise their students’ reading ability at any level by referring to the Performance Standards to distinguish whether their students are at Meet Reading Age, Below Reading Age or Above Reading Age status. Subsequently, teachers can refer to the Descriptors of Students’ Reading Abilities to find out what the students have achieved so far and what the struggling readers lacked. Accordingly, ESL teachers will be well informed of their students reading ability and accordingly can focus on reading skills development of their students. The ripple effects of READS may enhance students’ reading ability as teachers are now better informed of their students’ reading abilities and thus teachers will be able to prepare reading lessons appropriately according to their students’ reading needs.
Final Report of the Cosmetic Ingredient Review Expert Panel on the Safety Assessment of Cocamidopropyl betaine (CAPB)
Authors: Burnett Christina L. , Bergfeld Wilma F. , Belsito Donald V. , Hill Ronald A. , Klaassen Curtis D. , Liebler Daniel , Marks James G. , Shank Ronald C. , Slaga Thomas J. , Snyder Paul W. , Andersen F. Alan
Published: August 2012

Cocamidopropyl betaine (CAPB) and related amidopropyl betaines are zwitterions used mainly as surfactants in cosmetics. These cosmetic ingredients are similar in their chemistry, in particular with respect to the presence of 3,3-dimethylamino-propylamine (DMAPA) and fatty acid amidopropyl dimethylamine (amidoamine) impurities, which are known as sensitizers. The CIR Expert Panel concluded that because these ingredients present no other significant toxicity, when formulated to be nonsensitizing (which may be based on a quantitative risk assessment), these ingredients are safe for use as cosmetic ingredients in the practices of use and concentration of this safety assessment.
Final Report of the Cosmetic Ingredient Review Expert Panel on the Safety Assessment of Dicarboxylic Acids, Salts, and Esters
Authors: Fiume Monice M. , eldreth HBart , Bergfeld Wilma F. , Belsito Donald V. , Hill Ronald A. , Klaassen Curtis D. , Liebler Daniel , Marks James G. , Shank Ronald C. , Slaga Thomas J. , Snyder Paul W. , Andersen F. Alan
Published: August 2012

The CIR Expert Panel assessed the safety of dicarboxylic acids and their salts and esters as used in cosmetics. Most dicarboxylic acids function in cosmetics as pH adjusters or fragrance ingredients, but the functions of most of the salts in cosmetics are not reported. Some of the esters function as skin conditioning or fragrance ingredients, plasticizers, solvents, or emollients. The Expert Panel noted gaps in the available safety data for some of the dicarboxylic acid and their salts and esters in this safety assessment. The available data on many of the ingredients are sufficient, however, and similar structural activity relationships, biologic functions, and cosmetic product usage suggest that the available data may be extrapolated to support the safety of the entire group. The Panel concluded that the ingredients named in this report are safe in the present practices of use and concentration.
Statistical summability "Equation missing" and a Korovkin type approximation theorem
Authors: Mohiuddine Syed Abdul , Alotaibi Abdullah , Mursaleen Mohammad
Published: August 2012

The concept of statistical summability

(
C
,
1
)

has recently been introduced by Móricz [Jour. Math. Anal. Appl. 275, 277-287 (2002)]. In this paper, we use this notion of summability to prove the Korovkin type approximation theorem by using the test functions 1,

e

−
x

,

e

−
2
x

. We also give here the rate of statistical summability

(
C
,
1
)

and apply the classical Baskakov operator to construct an example in support of our main result.

MSC:41A10, 41A25, 41A36, 40A30, 40G15.
Hyers-Ulam-Rassias stability of the additive-quadratic mappings in non-Archimedean Banach spaces
Authors: Park C , Azadi Kenary H , Rassias TM
Published: August 2012

Using the fixed point and direct methods, we prove the generalized Hyers-Ulam stability of the following additive-quadratic functional equation in non-Archimedean normed spaces

r

[
f

(

x
+
y
+
z

s

)

+
f

(

x
−
y
+
z

s

)

+
f

(

x
+
y
−
z

s

)

+
f

(

−
x
+
y
+
z

s

)

]

=
γ
f
(
x
)
+
γ
f
(
y
)
+
γ
f
(
z
)
,

where r, s, γ are positive real numbers.

MSC:39B55, 46S10.
Heterozygosity for E292V in ABCA3, lung function and COPD in 64,000 individuals
Authors: Bækvad-Hansen Marie , Nordestgaard Børge G , Dahl Morten
Published: August 2012

Background

Mutations in ATP-binding-cassette-member A3 (ABCA3) are related to severe chronic lung disease in neonates and children, but frequency of chronic lung disease due to ABCA3 mutations in the general population is unknown. We tested the hypothesis that individuals heterozygous for ABCA3 mutations have reduced lung function and increased risk of COPD in the general population.

Methods

We screened 760 individuals with extreme pulmonary phenotypes and identified three novel (H86Y, A320T, A1086D) and four previously described mutations (E292V, P766S, S1262G, R1474W) in the ABCA3 gene. We genotyped the entire Copenhagen City Heart study (n = 10,604) to assess the clinical importance of these mutations. To validate our findings we genotyped an additional 54,395 individuals from the Copenhagen General Population Study.

Results

In the Copenhagen City Heart Study individuals heterozygous for E292V had 5% reduced FEV1 % predicted compared with noncarriers (t-test: p = 0.008), and an increased odds ratio for COPD of 1.9 (95% CI: 1.1-3.1). In contrast, the A1086D mutation was associated with increased FEV1 % predicted (p = 0.03). None of the other ABCA3 mutations associated with lung function or COPD risk in the Copenhagen City Heart Study. In the larger Copenhagen General Population Study, and in the two studies combined, E292V heterozygotes did not have reduced lung function or increased risk of COPD (p = 0.11-0.98), while this was the case for the positive controls, surfactant protein-B 121ins2 heterozygotes and α

1

-antitrypsin ZZ homozygotes.

Conclusion

Our results indicate that partially reduced ABCA3 activity due to E292V is not a major risk factor for reduced lung function and COPD in the general population. This is an important finding as 1.3% in the Danish population has partially reduced ABCA3 function due to E292V.
Loss of muscleblind-like 1 promotes invasive mesenchyme formation in endocardial cushions by stimulating autocrine TGFβ3
Authors: LeMasters Kathryn E , Blech-Hermoni Yotam , Stillwagon Samantha J , Vajda Natalie A , Ladd Andrea N
Published: August 2012

Background

Valvulogenesis and septation in the developing heart depend on the formation and remodeling of endocardial cushions in the atrioventricular canal (AVC) and outflow tract (OFT). These cushions are invaded by a subpopulation of endocardial cells that undergo an epithelial-mesenchymal transition in response to paracrine and autocrine transforming growth factor β (TGFβ) signals. We previously demonstrated that the RNA binding protein muscleblind-like 1 (MBNL1) is expressed specifically in the cushion endocardium, and knockdown of MBNL1 in stage 14 embryonic chicken AVC explants enhances TGFβ-dependent endocardial cell invasion.

Results

In this study, we demonstrate that the effect of MBNL1 knockdown on invasion remains dependent on TGFβ3 after it is no longer required to induce basal levels of invasion. TGFβ3, but not TGFβ2, levels are elevated in medium conditioned by MBNL1-depleted AVC explants. TGFβ3 is elevated even when the myocardium is removed, indicating that MBNL1 modulates autocrine TGFβ3 production in the endocardium. More TGFβ3-positive cells are observed in the endocardial monolayer following MBNL1 knockdown. Addition of exogenous TGFβ3 to AVC explants recapitulates the effects of MBNL1 knockdown. Time course experiments demonstrate that knockdown of MBNL1 induces precocious TGFβ3 secretion, and early exposure to excess TGFβ3 induces precocious invasion. MBNL1 expression precedes TGFβ3 in the AVC endocardium, consistent with a role in preventing precocious autocrine TGFβ3 signaling. The stimulatory effects of MBNL1 knockdown on invasion are lost in stage 16 AVC explants. Knockdown of MBNL1 in OFT explants similarly enhances cell invasion, but not activation. TGFβ is necessary and sufficient to mediate this effect.

Conclusions

Taken together, these data support a model in which MBNL1 negatively regulates cell invasion in the endocardial cushions by restricting the magnitude and timing of endocardial-derived TGFβ3 production.
Fine mapping of copy number variations on two cattle genome assemblies using high density SNP array
Authors: Hou Yali , Bickhart Derek M , Hvinden Miranda L , Li Congjun , Song Jiuzhou , Boichard Didier A , Fritz Sébastien , Eggen André , DeNise Sue , Wiggans George R , Sonstegard Tad S , Van Tassell Curtis P , Liu George E
Published: August 2012

Background

Btau_4.0 and UMD3.1 are two distinct cattle reference genome assemblies. In our previous study using the low density BovineSNP50 array, we reported a copy number variation (CNV) analysis on Btau_4.0 with 521 animals of 21 cattle breeds, yielding 682 CNV regions with a total length of 139.8 megabases.

Results

In this study using the high density BovineHD SNP array, we performed high resolution CNV analyses on both Btau_4.0 and UMD3.1 with 674 animals of 27 cattle breeds. We first compared CNV results derived from these two different SNP array platforms on Btau_4.0. With two thirds of the animals shared between studies, on Btau_4.0 we identified 3,346 candidate CNV regions representing 142.7 megabases (~4.70%) of the genome. With a similar total length but 5 times more event counts, the average CNVR length of current Btau_4.0 dataset is significantly shorter than the previous one (42.7 kb vs. 205 kb). Although subsets of these two results overlapped, 64% (91.6 megabases) of current dataset was not present in the previous study. We also performed similar analyses on UMD3.1 using these BovineHD SNP array results. Approximately 50% more and 20% longer CNVs were called on UMD3.1 as compared to those on Btau_4.0. However, a comparable result of CNVRs (3,438 regions with a total length 146.9 megabases) was obtained. We suspect that these results are due to the UMD3.1 assembly's efforts of placing unplaced contigs and removing unmerged alleles. Selected CNVs were further experimentally validated, achieving a 73% PCR validation rate, which is considerably higher than the previous validation rate. About 20-45% of CNV regions overlapped with cattle RefSeq genes and Ensembl genes. Panther and IPA analyses indicated that these genes provide a wide spectrum of biological processes involving immune system, lipid metabolism, cell, organism and system development.

Conclusion

We present a comprehensive result of cattle CNVs at a higher resolution and sensitivity. We identified over 3,000 candidate CNV regions on both Btau_4.0 and UMD3.1, further compared current datasets with previous results, and examined the impacts of genome assemblies on CNV calling.
Whole-genome microarray analysis and functional characterization reveal distinct gene expression profiles and patterns in two mouse models of ileal inflammation
Authors: Avula Leela Rani , Knapen Dries , Buckinx Roeland , Vergauwen Lucia , Adriaensen Dirk , Van Nassauw Luc , Timmermans Jean-Pierre
Published: August 2012

Background

Although a number of intestinal inflammatory conditions pertain to the ileum, whole-genome gene expression analyses in animal models of ileal inflammation are lacking to date. Therefore, we aimed to identify and characterize alterations in gene expression in the acutely inflamed ileum of two murine models of intestinal inflammation, namely intestinal schistosomiasis and TNBS-induced ileitis, compared to healthy controls. To this end, we used whole-genome microarrays, followed by bioinformatics analyses to detect over-represented Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology categories.

Results

Following screening of almost all known mouse genes and transcripts represented on the array, intestinal schistosomiasis and TNBS-induced ileitis yielded 207 and 1417 differentially expressed genes, respectively, with only 30 overlapping concordantly changed genes. Functional category groups consisting of complement and coagulation cascades, extracellular matrix (ECM)-receptor interaction, Fc epsilon receptor I signaling pathways and protein activation cascade, cell adhesion categories were over-represented in the differential gene list of intestinal schistosomiasis. Antigen processing and presentation, cell adhesion molecules, ABC transporters, Toll-like receptor signaling pathways and response to chemical stimulus categories were over-represented in the differential gene list of TNBS-induced ileitis. Although cytokine-cytokine receptor interaction, intestinal immune network for IgA production, focal adhesion pathways and immune, inflammatory and defense response categories were over-represented in the differential gene lists of both inflammation models, the vast majority of the associated genes and changes were unique to each model.

Conclusions

This study characterized two models of ileal inflammation at a whole-genome level and outlined distinct gene expression profiles and patterns in the two models. The results indicate that intestinal schistosomiasis involves Th2 responses, complement activation, protein activation and enhanced ECM turnover, while TNBS-induced ileitis involves Th17 responses, defective antigen processing and presentation and altered Toll-like receptor-mediated responses. Signs of an impaired epithelial barrier are apparent in both inflammation models. Furthermore, the comprehensive differential gene list and functional groups provided by this study constitute an interesting starting point to explore new targets and extended functional networks dealing with small bowel inflammation.
The peritoneal macrophage inflammatory profile in cirrhosis depends on the alcoholic or hepatitis C viral etiology and is related to ERK phosphorylation
Authors: Tapia-Abellán Ana , Martínez-Esparza María , Ruiz-Alcaraz Antonio J , Hernández-Caselles Trinidad , Martínez-Pascual Cristina , Miras-López Manuel , Such José , Francés Rubén , García-Peñarrubia Pilar
Published: August 2012

Background

The development of ascites in cirrhotic patients generally heralds a deterioration in their clinical status. A differential gene expression profile between alcohol- and hepatitis C virus (HCV)-related cirrhosis has been described from liver biopsies, especially those associated with innate immune responses. The aim of this work was to identify functional differences in the inflammatory profile of monocyte-derived macrophages from ascites in cirrhotic patients of different etiologies in an attempt to extrapolate studies from liver biopsies to immune cells in ascites. To this end 45 patients with cirrhosis and non-infected ascites, distributed according to disease etiology, HCV (n = 15) or alcohol (n = 30) were studied. Cytokines and the cell content in ascites were assessed by ELISA and flow cytometry, respectively. Cytokines and ERK phosphorylation in peritoneal monocyte-derived macrophages isolated and stimulated in vitro were also determined.

Results

A different pattern of leukocyte migration to the peritoneal cavity and differences in the primed status of macrophages in cirrhosis were observed depending on the viral or alcoholic etiology. Whereas no differences in peripheral blood cell subpopulations could be observed, T lymphocyte, monocyte and polymorphonuclear cell populations in ascites were more abundant in the HCV than the alcohol etiology. HCV-related cirrhosis etiology was associated with a decreased inflammatory profile in ascites compared with the alcoholic etiology. Higher levels of IL-10 and lower levels of IL-6 and IL-12 were observed in ascitic fluid from the HCV group. Isolated peritoneal monocyte-derived macrophages maintained their primed status in vitro throughout the 24 h culture period. The level of ERK1/2 phosphorylation was higher in ALC peritoneal macrophages at baseline than in HCV patients, although the addition of LPS induced a greater increase in ERK1/2 phosphorylation in HCV than in ALC patients.

Conclusions

The macrophage inflammatory status is higher in ascites of alcohol-related cirrhotic patients than in HCV-related patients, which could be related with differences in bacterial translocation episodes or regulatory T cell populations. These findings should contribute to identifying potential prognostic and/or therapeutic targets for chronic liver diseases of different etiology.
Phenotypic and Genomic Analysis of Hypervirulent Human-associated Bordetella bronchiseptica
Authors: Ahuja Umesh , Liu Minghsun , Tomida Shuta , Park Jihye , Souda Puneet , Whitelegge Julian , Li Huiying , Harvill Eric T , Parkhill Julian , Miller Jeff F
Published: August 2012

Background

B. bronchiseptica infections are usually associated with wild or domesticated animals, but infrequently with humans. A recent phylogenetic analysis distinguished two distinct B. bronchiseptica subpopulations, designated complexes I and IV. Complex IV isolates appear to have a bias for infecting humans; however, little is known regarding their epidemiology, virulence properties, or comparative genomics.

Results

Here we report a characterization of the virulence of human-associated complex IV B. bronchiseptica strains. In in vitro cytotoxicity assays, complex IV strains showed increased cytotoxicity in comparison to a panel of complex I strains. Some complex IV isolates were remarkably cytotoxic, resulting in LDH release levels in A549 cells that were 10- to 20-fold greater than complex I strains. In vivo, a subset of complex IV strains was found to be hypervirulent, with an increased ability to cause lethal pulmonary infections in mice. Hypercytotoxicity in vitro and hypervirulence in vivo were both dependent on the activity of the bsc T3SS and the BteA effector. To clarify differences between lineages, representative complex IV isolates were sequenced and their genomes were compared to complex I isolates. Although our analysis showed there were no genomic sequences that can be considered unique to complex IV strains, there were several loci that were predominantly found in complex IV isolates.

Conclusion

Our observations reveal a T3SS-dependent hypervirulence phenotype in human-associated complex IV isolates, highlighting the need for further studies on the epidemiology and evolutionary dynamics of this B. bronchiseptica lineage.
Cellular elements for seeing in the dark: voltage-dependent conductances in cockroach photoreceptors
Authors: Salmela Iikka , Immonen Esa-Ville , Frolov Roman , Krause Stephan , Krause Yani , Vähäsöyrinki Mikko , Weckström Matti
Published: August 2012

Background

The importance of voltage-dependent conductances in sensory information processing is well-established in insect photoreceptors. Here we present the characterization of electrical properties in photoreceptors of the cockroach (Periplaneta americana), a nocturnal insect with a visual system adapted for dim light.

Results

Whole-cell patch-clamped photoreceptors had high capacitances and input resistances, indicating large photosensitive rhabdomeres suitable for efficient photon capture and amplification of small photocurrents at low light levels. Two voltage-dependent potassium conductances were found in the photoreceptors: a delayed rectifier type (KDR) and a fast transient inactivating type (KA). Activation of KDR occurred during physiological voltage responses induced by light stimulation, whereas KA was nearly fully inactivated already at the dark resting potential. In addition, hyperpolarization of photoreceptors activated a small-amplitude inward-rectifying (IR) current mediated at least partially by chloride. Computer simulations showed that KDR shapes light responses by opposing the light-induced depolarization and speeding up the membrane time constant, whereas KA and IR have a negligible role in the majority of cells. However, larger KA conductances were found in smaller and rapidly adapting photoreceptors, where KA could have a functional role.

Conclusions

The relative expression of KA and KDR in cockroach photoreceptors was opposite to the previously hypothesized framework for dark-active insects, necessitating further comparative work on the conductances. In general, the varying deployment of stereotypical K+ conductances in insect photoreceptors highlights their functional flexibility in neural coding.
Testosterone regulation of sex steroid-related mRNAs and dopamine-related mRNAs in adolescent male rat substantia nigra
Authors: Purves-Tyson Tertia D , Handelsman David J , Double Kay L , Owens Samantha J , Bustamante Sonia , Weickert Cynthia Shannon
Published: August 2012

Background

Increased risk of schizophrenia in adolescent males indicates that a link between the development of dopamine-related psychopathology and testosterone-driven brain changes may exist. However, contradictions as to whether testosterone increases or decreases dopamine neurotransmission are found and most studies address this in adult animals. Testosterone-dependent actions in neurons are direct via activation of androgen receptors (AR) or indirect by conversion to 17β-estradiol and activation of estrogen receptors (ER). How midbrain dopamine neurons respond to sex steroids depends on the presence of sex steroid receptor(s) and the level of steroid conversion enzymes (aromatase and 5α-reductase). We investigated whether gonadectomy and sex steroid replacement could influence dopamine levels by changing tyrosine hydroxylase (TH) protein and mRNA and/or dopamine breakdown enzyme mRNA levels [catechol-O-methyl transferase (COMT) and monoamine oxygenase (MAO) A and B] in the adolescent male rat substantia nigra. We hypothesized that adolescent testosterone would regulate sex steroid signaling through regulation of ER and AR mRNAs and through modulation of aromatase and 5α-reductase mRNA levels.

Results

We find ERα and AR in midbrain dopamine neurons in adolescent male rats, indicating that dopamine neurons are poised to respond to circulating sex steroids. We report that androgens (T and DHT) increase TH protein and increase COMT, MAOA and MAOB mRNAs in the adolescent male rat substantia nigra. We report that all three sex steroids increase AR mRNA. Differential action on ER pathways, with ERα mRNA down-regulation and ERβ mRNA up-regulation by testosterone was found. 5α reductase-1 mRNA was increased by AR activation, and aromatase mRNA was decreased by gonadectomy.

Conclusions

We conclude that increased testosterone at adolescence can shift the balance of sex steroid signaling to favor androgenic responses through promoting conversion of T to DHT and increasing AR mRNA. Further, testosterone may increase local dopamine synthesis and metabolism, thereby changing dopamine regulation within the substantia nigra. We show that testosterone action through both AR and ERs modulates synthesis of sex steroid receptor by altering AR and ER mRNA levels in normal adolescent male substantia nigra. Increased sex steroids in the brain at adolescence may alter substantia nigra dopamine pathways, increasing vulnerability for the development of psychopathology.
Pancreatic-specific autoantibodies to glycoprotein 2 mirror disease location and behaviour in younger patients with Crohn’s disease
Authors: Bogdanos Dimitrios P , Roggenbuck Dirk , Reinhold Dirk , Wex Thomas , Pavlidis Polychronis , von Arnim Ulrike , Malfertheiner Peter , Forbes Alastair , Conrad Karsten , Laass Martin W
Published: August 2012

Background

Glycoprotein 2 (GP2) was discovered as the major autoantigen of Crohn’s disease (CD)-specific pancreatic autoantibodies (PAB). We investigated anti-GP2 IgA and IgG antibodies as novel serological parameters in CD and assessed their association with distinct disease phenotypes.

Methods

Anti-GP2 and anti-Saccharomyces cerevisiae (ASCA) IgA and IgG were detected by ELISA employing recombinant human GP2 and phosphopeptidomannan, respectively and PAB by indirect immunofluorescence (IIF) in 271 sera, 169 with CD and 102 with ulcerative colitis (UC). As healthy controls 160 adult blood donors and 65 children were included.

Results

Anti-GP2 IgG and/or IgA were more prevalent in CD (51/169, 30.2%) than in UC (9/102, 8.9%) patients and in controls (9/225, 4%) (p < 0.001 respectively). ASCA IgG and/or IgA were present in 60/169 (35.5%) in CD and in 7/102 (6.9%) in UC patients (p < 0.001). CD patients with ileocolonic location (L3) showed a significantly higher prevalence of anti-GP2 and ASCA IgA and/or IgG (40/113 and 48/113, respectively; p < 0.05 for both comparisons), whereas CD patients with colonic location (L2) revealed a significantly diminished prevalence for these autoantibody specificities (2/32 and 5/32, respectively, p < 0.05 for both). Anti-GP2 IgG were significantly more prevalent in CD patients with stricturing behaviour (B2) and perianal disease (7/11, p < 0.02) and less prevalent in those with penetrating behaviour (B3) and perianal disease (4/31, p < 0.05). The occurrence of anti-GP2 IgA and/or IgG was significantly more prevalent in CD patients with age at diagnosis of ≤16 years (16/31, p < 0.009). Prevalence of one or more anti-GP2 or ASCA IgA and/or IgG was significantly higher in L3, B2, and A1 and lower in L2 (68/113, 27/41, 23/31, 6/32; p < 0.04, respectively).

Conclusions

Anti-GP2 IgG and IgA, constituting novel CD specific autoantibodies, appear to be associated with distinct disease phenotypes identifying patients at a younger age, with ileocolonic location, and stricturing behaviour with perianal disease.
Unexpected recovery from longterm renal failure in severe diffuse proliferative lupus nephritis
Authors: Ross Sophia , Benz Kerstin , Sauerstein Katja , Amann Kerstin , Dötsch Jörg , Dittrich Katalin
Published: August 2012

Background

Severe renal manifestation of systemic lupus erythematosus (SLE) is not uncommon and is associated with an indeterminate prognosis. Complete remission can be obtained, however, at least in the young when chronic lesions are absent and adequate anti-inflammatory therapy is immediately initiated.

Case presentation

We report the unusual case of a 12-year-old girl who presented with severe oliguric renal failure, macrohematuria and skin rash. Renal biopsy revealed the diagnosis of severe diffuse proliferative glomerulonephritis (GN) with cellular crescents in 15 out of 18 glomeruli and full-house pattern in immunofluorescence indicating lupus nephritis IVB according to WHO, IV-G(A) according to ISN/RPS classification. The serological parameters confirmed the diagnosis of SLE and the patient was immediately treated with methylprednisolone, cyclophosphamide and immunoadsorption. Initially, despite rapid amelioration of her general condition, no substantial improvement of renal function could be achieved and the patient needed hemodialysis treatment for 12 weeks. Unexpectedly, in the further follow-up at first diuresis increased and thereafter also creatinine levels substantially declined so that hemodialysis could be discontinued. Today, 6 years after the initial presentation, the patient has normal renal function and a SLEDAI score of 0 under a continuous immunosuppressive therapy with Mycophenolate mofetil (MMF) and low dose steroid.

Conclusion

Despite the severity of the initial renal injury and the unfavourable renal prognosis the kidney apparently has a tremendous capacity to recover in young patients when the damage is acute and adequate anti-inflammatory therapy is initiated without delay.
Determination of the best method to estimate glomerular filtration rate from serum creatinine in adult patients with sickle cell disease: a prospective observational cohort study
Authors: Arlet Jean-Benoît , Ribeil Jean-Antoine , Chatellier Gilles , Eladari Dominique , De Seigneux Sophie , Souberbielle Jean-Claude , Friedlander Gérard , de Montalembert Marianne , Pouchot Jacques , Prié Dominique , Courbebaisse Marie
Published: August 2012

Background

Sickle cell disease (SCD) leads to tissue hypoxia resulting in chronic organ dysfunction including SCD associated nephropathy. The goal of our study was to determine the best equation to estimate glomerular filtration rate (GFR) in SCD adult patients.

Methods

We conducted a prospective observational cohort study. Since 2007, all adult SCD patients in steady state, followed in two medical departments, have had their GFR measured using iohexol plasma clearance (gold standard). The Cockcroft-Gault, MDRD-v4, CKP-EPI and finally, MDRD and CKD-EPI equations without adjustment for ethnicity were tested to estimate GFR from serum creatinine. Estimated GFRs were compared to measured GFRs according to the graphical Bland and Altman method.

Results

Sixty-four SCD patients (16 men, median age 27.5 years [range 18.0-67.5], 41 with SS-genotype were studied. They were Sub-Saharan Africa and French West Indies natives and predominantly lean (median body mass index: 22 kg/m2[16-33]). Hyperfiltration (defined as measured GFR >110 mL/min/1.73 m2) was detected in 53.1% of patients. Urinary albumin/creatinine ratio was higher in patients with hyperfiltration than in patients with normal GFR (4.05 mg/mmol [0.14-60]versus0.4 mg/mmol [0.7-81], p = 0.01). The CKD-EPI equation without adjustment for ethnicity had both the lowest bias and the greatest precision. Differences between estimated GFRs using the CKP-EPI equation and measured GFRs decreased with increasing GFR values, whereas it increased with the Cockcroft-Gault and MDRD-v4 equations.

Conclusions

We confirm that SCD patients have a high rate of glomerular hyperfiltration, which is frequently associated with microalbuminuria or macroalbuminuria. In non-Afro-American SCD patients, the best method for estimating GFR from serum creatinine is the CKD-EPI equation without adjustment for ethnicity. This equation is particularly accurate to estimate high GFR values, including glomerular hyperfiltration, and thus should be recommended to screen SCD adult patients at high risk for SCD nephropathy.
Patient access to complex chronic disease records on the Internet
Authors: Bartlett Cherry , Simpson Keith , Turner A Neil
Published: August 2012

Background

Access to medical records on the Internet has been reported to be acceptable and popular with patients, although most published evaluations have been of primary care or office-based practice. We tested the feasibility and acceptability of making unscreened results and data from a complex chronic disease pathway (renal medicine) available to patients over the Internet in a project involving more than half of renal units in the UK.

Methods

Content and presentation of the Renal PatientView (RPV) system was developed with patient groups. It was designed to receive information from multiple local information systems and to require minimal extra work in units. After piloting in 4 centres in 2005 it was made available more widely. Opinions were sought from both patients who enrolled and from those who did not in a paper survey, and from staff in an electronic survey. Anonymous data on enrolments and usage were extracted from the webserver.

Results

By mid 2011 over 17,000 patients from 47 of the 75 renal units in the UK had registered. Users had a wide age range (<10 to >90 yrs) but were younger and had more years of education than non-users. They were enthusiastic about the concept, found it easy to use, and 80% felt it gave them a better understanding of their disease. The most common reason for not enrolling was being unaware of the system. A minority of patients had security concerns, and these were reduced after enrolling.

Staff responses were also strongly positive. They reported that it aided patient concordance and disease management, and increased the quality of consultations with a neutral effect on consultation length. Neither patient nor staff responses suggested that RPV led to an overall increase in patient anxiety or to an increased burden on renal units beyond the time required to enrol each patient.

Conclusions

Patient Internet access to secondary care records concerning a complex chronic disease is feasible and popular, providing an increased sense of empowerment and understanding, with no serious identified negative consequences. Security concerns were present but rarely prevented participation. These are powerful reasons to make this type of access more widely available.
Enhanced thermostability of a Rhizopus chinensis lipase by in vivo recombination in Pichia pastoris
Authors: Yu Xiao-Wei , Wang Rui , Zhang Meng , Xu Yan , Xiao Rong
Published: August 2012

Background

Lipase from Rhizopus chinensis is a versatile biocatalyst for various bioconversions and has been expressed at high-level in Pichia pastoris. However, the use of R. chinensis lipase in industrial applications is restricted by its low thermostability. Directed evolution has been proven to be a powerful and efficient protein engineering tool for improvement of biocatalysts. The present work describes improvement of the thermostability of R. chinensis lipase by directed evolution using P. pastoris as the host.

Results

An efficient, fast and highly simplified method was developed to create a mutant gene library in P. pastoris based on in vivo recombination, whose recombination efficiency could reach 2.3 × 105 /μg DNA. The thermostability of r27RCL was improved significantly by two rounds of error-prone PCR and two rounds of DNA shuffling in P. pastoris. The S4-3 variant was found to be the most thermostable lipase, under the conditions tested. Compared with the parent, the optimum temperature of S4-3 was two degrees higher, T
m was 22 degrees higher and half-lives at 60°C and 65°C were 46- and 23- times longer. Moreover, the catalytic efficiency k
cat/K
m of S4-3 was comparable to the parent. Stabilizing mutations probably increased thermostability by increasing the hydrophilicity and polarity of the protein surface and creating hydrophobic contacts inside the protein.

Conclusions

P. pastoris was shown to be a valuable cell factory to improve thermostability of enzymes by directed evolution and it also could be used for improving other properties of enzymes. In this study, by using P. pastoris as a host to build mutant pool, we succeeded in obtaining a thermostable variant S4-3 without compromising enzyme activity and making it a highly promising candidate for future applications at high temperatures.