bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-21 inhibits T cell IL-2 production and impairs Treg homeostasis
Authors: Attridge Kesley , Wang Chun Jing , Wardzinski Lukasz , Kenefeck Rupert , Chamberlain Jayne L. , Manzotti Claire , Kopf Manfred , Walker Lucy S. K. 
Published: March 2012

AbstractModulation of regulatory T cell (Treg) suppression has important implications for vaccine development, the effectiveness of tumor surveillance, and the emergence of autoimmunity. We have previously shown that the cytokine IL-21 can counteract Treg suppression. However, whether this reflects an effect of IL-21 on Treg, conventional T cells, or antigen-presenting cells is not known. Here we have used lymphocyte populations from IL-21R–deficient mice to pinpoint which cell type needs to be targeted by IL-21 for Treg suppression to be overcome. We show that IL-21 counteracts suppression by acting on conventional T cells and that this is associated with inhibition of IL-2 production. Despite the lack of IL-2, conventional T-cell responses proceed unimpaired because IL-21 can substitute for IL-2 as a T cell growth factor. However, IL-21 is unable to substitute for IL-2 in supporting the Treg compartment. Thus, IL-21 signaling in conventional T cells indirectly impacts Treg homeostasis by decreasing IL-2 availability. These data demonstrate that IL-21 and IL-2 can have overlapping roles in promoting conventional T-cell responses but play distinct roles in controlling Treg homeostasis and function. The data also suggest a new paradigm whereby cytokines can promote immunity by inhibiting IL-2.
Functionally distinct subsets of human FOXP3+ Treg cells that phenotypically mirror effector Th cells
Authors: Duhen Thomas , Duhen Rebekka , Lanzavecchia Antonio , Sallusto Federica , Campbell Daniel J. 
Published: March 2012

AbstractFOXP3+ regulatory T (Treg) cells are a broadly acting and potent anti-inflammatory population of CD4+ T cells essential for maintaining immune homeostasis and preventing debilitating autoimmunity. Based on chemokine receptor expression, we identified distinct populations of Treg cells in human blood expected to colocalize with different Th cell subsets. Although each population was functionally suppressive, they displayed unique patterns of pro- and anti-inflammatory cytokine production, differentially expressed lineage-specifying transcription factors, and responded differently to antigens associated with Th1 and Th17 responses. These results highlight a previously unappreciated degree of phenotypic and functional diversity in human Treg cells that allows subsets with unique specificities and immunomodulatory functions to be targeted to defined immune environments during different types of inflammatory responses.
DNGR-1 is a specific and universal marker of mouse and human Batf3-dependent dendritic cells in lymphoid and nonlymphoid tissues
Authors: Poulin Lionel F. , Reyal Yasmin , Uronen-Hansson Heli , Schraml Barbara U. , Sancho David , Murphy Kenneth M. , Håkansson Ulf K. , Ferreira Moita Luis , Agace William W. , Bonnet Dominique , Reis e Sousa Caetano 
Published: March 2012

Abstract
Mouse CD8α+ dendritic cells (DCs) in lymphoid organs and CD103+ CD11b− DCs in nonlymphoid tissues share phenotypic and functional similarities, as well as a unique shared developmental dependence on the transcription factor Batf3. Human DCs resembling mouse CD8α+ DCs in phenotype and function have been identified in human blood, spleen, and tonsil. However, it is not clear whether such cells are also present in human nonlymphoid organs, and their equivalence to mouse CD8α+ DC has recently been questioned. Furthermore, the identification of “CD8α+ DC-like” cells across different tissues and species remains problematic because of the lack of a unique marker that can be used to unambiguously define lineage members. Here we show that mouse CD8α+ DCs and CD103+ CD11b− DCs can be defined by shared high expression of DNGR-1 (CLEC9A). We further show that DNGR-1 uniquely marks a CD11b− human DC population present in both lymphoid and nonlymphoid tissues of humans and humanized mice. Finally, we demonstrate that knockdown of Batf3 selectively prevents the development of DNGR-1+ human DCs in vitro. Thus, high expression of DNGR-1 specifically and universally identifies a unique DC subset in mouse and humans. Evolutionarily conserved Batf3 dependence justifies classification of DNGR-1hi DCs as a distinct DC lineage.
Immunohistochemical investigation of Foxp3 expression in the intestine in healthy and diseased dogs
Authors: Junginger Johannes , Schwittlick Ulrike , Lemensieck Frederik , Nolte Ingo , Hewicker-Trautwein Marion 
Published: March 2012

AbstractIntestinal immune regulation including development of oral tolerance is of great importance for the maintenance of intestinal homeostasis. Concerning this, regulatory T cells (Tregs) occupy a pivotal role in cell-mediated immunosuppression. Dysregulation of mucosal immunology leading to an abnormal interaction with commensal bacteria is suggested to play a key role in the pathogenesis of Inflammatory Bowel Disease (IBD) in men and dogs. The aim of this study was to characterise the expression of Foxp3 in the normal canine gut of 18 dogs (mean age: 6.03 years), in 16 dogs suffering from IBD (mean age: 5.05 years), and of 6 dogs with intestinal nematode infection (mean age: 0.87 years) using immunohistochemistry. In the duodenum, Tregs in healthy dogs declined from villi (median: 10.67/62 500 μm2) to crypts (median: 1.89/62 500 μm2). Tregs were further increased in the villi of middle-aged dogs (median: 18.92/62 500 μm2) in contrast to juvenile (median: 3.50/62 500 μm2) and old (median: 9.56/62 500 μm2) individuals. Compared to healthy controls, animals suffering from IBD revealed reduced numbers of Tregs in duodenal villi (median: 4.13/62 500 μm2). Dogs with intestinal nematode infection displayed increased numbers of Tregs (median: 21.06/62 500 μm2) compared to healthy animals.Age-related changes indicate a progressive establishment of oral tolerance and immunosenescence in the canine elderly. The results further suggest that a defect in Treg homeostasis may be involved in the pathogenesis of canine IBD. In contrast, increased numbers of Tregs in the duodenum may be due to nematode infection.
Amelioration of diet-induced nonalcoholic steatohepatitis in rats by Mn-salen complexes via reduction of oxidative stress
Authors: Rezazadeh Alireza , Yazdanparast Razieh , Molaei Mahsa 
Published: March 2012

Abstract

Background
Nonalcoholic steatohepatitis (NASH), a progressive stage of nonalcoholic fatty liver disease (NAFLD), is characterized by steatosis (accumulation of triacylglycerols within hepatocytes) along with inflammation and ballooning degeneration. It has been suggested that oxidative stress may play an important role in the progress of NAFLD to NASH. The aim of present study was to determine whether antioxidant supplementations using EUK-8, EUK-134 and vitamin C could improve the biochemical and histological abnormalities associated with diet-induced NASH in rats.

Methods
NASH was induced in male N-Mary rats by feeding a methionine - choline deficient (MCD) diet. The rats were fed either normal chow or MCD diet for 10 weeks. After NASH development, the MCD-fed rats were randomly divided into four groups of six: the NASH group that received MCD diet, the EUK-8 group which was fed MCD diet plus EUK-8, the EUK-134 group which was fed MCD diet plus EUK-134 and the vitamin C group which received MCD diet plus vitamin C. EUK-8, EUK-134 and vitamin C (30 mg/kg body weight/day) were administered by gavage for eight weeks.

Results
Treatment of MCD-fed rats with salens reduced the sera aminotransferases, cholesterol, low density lipoprotein contents, the extent of lipid peroxidation and protein carbonylation whereas the HDL-C cholesterol levels were significantly increased. In addition, EUK-8 and EUK-134 improved steatosis, ballooning degeneration and inflammation in liver of MCD-fed rats.

Conclusion
Antioxidant (EUK-8, EUK-134 and vitamin C) supplementation reduces NASH-induced biochemical and histological abnormalities, pointing out that antioxidant strategy could be beneficial in treatment of NASH.
Loss of nonsense mediated decay suppresses mutations in Saccharomyces cerevisiae TRA1
Authors: Kvas Stephanie , Gloor Gregory B , Brandl Christopher J 
Published: March 2012

AbstractBackgroundTra1 is an essential protein inSaccharomyces cerevisiae. It was first identified in the SAGA and NuA4 complexes, both with functions in multiple aspects of gene regulation and DNA repair, and recently found in the ASTRA complex. Tra1 belongs to the PIKK family of proteins with a C-terminal PI3K domain followed by a FATC domain. Previously we found that mutation of leucine to alanine at position 3733 in the FATC domain of Tra1 (tra1-L3733A) results in transcriptional changes and slow growth under conditions of stress. To further define the regulatory interactions of Tra1 we isolated extragenic suppressors of thetra1-L3733Aallele.ResultsWe screened for suppressors of the ethanol sensitivity caused bytra1-L3733A. Eleven extragenic recessive mutations, belonging to three complementation groups, were identified that partially suppressed a subset of the phenotypes caused by tra1-L3733A. Using whole genome sequencing we identified one of the mutations as an opal mutation at tryptophan 165 ofUPF1/NAM7. Partial suppression of the transcriptional defect resulting fromtra1-L3733Awas observed atGAL10, but not atPHO5. Suppression was due to loss of nonsense mediated decay (NMD) since deletion of any one of the three NMD surveillance components (upf1/nam7, upf2/nmd2, orupf3) mediated the effect. Deletion ofupf1suppressed a second FATC domain mutation,tra1-F3744A, as well as a mutation to the PIK3 domain. In contrast, deletions of SAGA or NuA4 components were not suppressed.ConclusionsWe have demonstrated a genetic interaction betweenTRA1and genes of the NMD pathway. The suppression is specific for mutations inTRA1. Since NMD and Tra1 generally act reciprocally to control gene expression, and the FATC domain mutations do not directly affect NMD, we suggest that suppression occurs as the result of overlap and/or crosstalk in these two broad regulatory networks.
Calpain 3 is important for muscle regeneration: Evidence from patients with limb girdle muscular dystrophies
Authors: Hauerslev Simon , Sveen Marie-Louise , Duno Morten , Angelini Corrado , Vissing John , Krag Thomas O 
Published: March 2012

Abstract

Background
Limb girdle muscular dystrophy (LGMD) type 2A is caused by mutations in the CAPN3 gene and complete lack of functional calpain 3 leads to the most severe muscle wasting. Calpain 3 is suggested to be involved in maturation of contractile elements after muscle degeneration. The aim of this study was to investigate how mutations in the four functional domains of calpain 3 affect muscle regeneration.

Methods
We studied muscle regeneration in 22 patients with LGMD2A with calpain 3 deficiency, in five patients with LGMD2I, with a secondary reduction in calpain 3, and in five patients with Becker muscular dystrophy (BMD) with normal calpain 3 levels. Regeneration was assessed by using the developmental markers neonatal myosin heavy chain (nMHC), vimentin, MyoD and myogenin and counting internally nucleated fibers.

Results
We found that the recent regeneration as determined by the number of nMHC/vimentin-positive fibers was greatly diminished in severely affected LGMD2A patients compared to similarly affected patients with LGMD2I and BMD. Whorled fibers, a sign of aberrant regeneration, was highly elevated in patients with a complete lack of calpain 3 compared to patients with residual calpain 3. Regeneration is not affected by location of the mutation in the CAPN3 gene.

Conclusions
Our findings suggest that calpain 3 is needed for the regenerative process probably during sarcomere remodeling as the complete lack of functional calpain 3 leads to the most severe phenotypes.
A proteome map of primary cultured rat Schwann cells
Authors: Shen Mi , Ji Yuhua , Zhang Shuqiang , Shi Haiyan , Chen Gang , Gu Xiaosong , Ding Fei 
Published: March 2012

Abstract

Background
Schwann cells (SCs) are the principal glial cells of the peripheral nervous system with a wide range of biological functions. SCs play a key role in peripheral nerve regeneration and are involved in several hereditary peripheral neuropathies. The objective of this study was to gain new insight into the whole protein composition of SCs.

Results
Two-dimensional liquid chromatography coupled with tandem mass spectrometry (2D LC-MS/MS) was performed to identify the protein expressions in primary cultured SCs of rats. We identified a total of 1,232 proteins, which were categorized into 20 functional classes. We also used quantitative real time RT-PCR and Western blot analysis to validate some of proteomics-identified proteins.

Conclusion
We showed for the first time the proteome map of SCs. Our data could serve as a reference library to provide basic information for understanding SC biology.
Formation polarity dependent improved resistive switching memory characteristics using nanoscale (1.3 nm) core-shell IrOx nano-dots
Authors: Banerjee Writam , Maikap Siddheswar , Lai Chao-Sung , Chen Yi-Yan , Tien Ta-Chang , Lee Heng-Yuan , Chen Wei-Su , Chen Frederick T , Kao Ming-Jer , Tsai Ming-Jinn , Yang Jer-Ren 
Published: March 2012

Abstract
Improved resistive switching memory characteristics by controlling the formation polarity in an IrOx/Al2O3/IrOx-ND/Al2O3/WOx/W structure have been investigated. High density of 1 × 1013/cm2 and small size of 1.3 nm in diameter of the IrOx nano-dots (NDs) have been observed by high-resolution transmission electron microscopy. The IrOx-NDs, Al2O3, and WOx layers are confirmed by X-ray photo-electron spectroscopy. Capacitance-voltage hysteresis characteristics show higher charge-trapping density in the IrOx-ND memory as compared to the pure Al2O3 devices. This suggests that the IrOx-ND device has more defect sites than that of the pure Al2O3 devices. Stable resistive switching characteristics under positive formation polarity on the IrOx electrode are observed, and the conducting filament is controlled by oxygen ion migration toward the Al2O3/IrOx top electrode interface. The switching mechanism is explained schematically based on our resistive switching parameters. The resistive switching random access memory (ReRAM) devices under positive formation polarity have an applicable resistance ratio of > 10 after extrapolation of 10 years data retention at 85°C and a long read endurance of 105 cycles. A large memory size of > 60 Tbit/sq in. can be realized in future for ReRAM device application. This study is not only important for improving the resistive switching memory performance but also help design other nanoscale high-density nonvolatile memory in future.
Carpet-dust chemicals as measures of exposure: Implications of variability
Authors: Whitehead Todd P , Nuckols John R , Ward Mary H , Rappaport Stephen M 
Published: March 2012

Abstract
Background
There is increasing interest in using chemicals measured in carpet dust as indicators of chemical exposures. However, investigators have rarely sampled dust repeatedly from the same households and therefore little is known about the variability of chemical levels that exist within and between households in dust samples.

Results
We analyzed 9 polycyclic aromatic hydrocarbons, 6 polychlorinated biphenyls, and nicotine in 68 carpet-dust samples from 21 households in agricultural communities of Fresno County, California collected from 2003-2005. Chemical concentrations (ng per g dust) ranged from < 2-3,609 for 9 polycyclic aromatic hydrocarbons, from < 1-150 for 6 polychlorinated biphenyls, and from < 20-7,776 for nicotine. We used random-effects models to estimate variance components for concentrations of each of these carpet-dust chemicals and calculated the variance ratio, λ, defined as the ratio of the within-household variance component to the between-household variance component. Subsequently, we used the variance ratios calculated from our data, to illustrate the potential effect of measurement error on the attenuation of odds ratios in hypothetical case-control studies. We found that the median value of the estimated variance ratios was 0.33 (range: 0.13-0.72). Correspondingly, in case-control studies of associations between these carpet-dust chemicals and disease, given the collection of only one measurement per household and a hypothetical odds ratio of 1.5, we expect that the observed odds ratios would range from 1.27 to 1.43. Moreover, for each of the chemicals analyzed, the collection of three repeated dust samples would limit the expected magnitude of odds ratio attenuation to less than 20%.

Conclusions
Our findings suggest that attenuation bias should be relatively modest when using these semi-volatile carpet-dust chemicals as exposure surrogates in epidemiologic studies.
Prevalence and risk factors of feline leukaemia virus and feline immunodeficiency virus in peninsular Malaysia
Authors: Bande Faruku , Arshad Siti Suri , Hassan Latiffah , Zakaria Zunita , Sapian Nurul Asyikin , Rahman Noor Alimah , Alazawy Amer 
Published: March 2012

AbstractBackgroundFeline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) are major causes of morbidity and mortality in domestic and wild felids. Despite the clinical importance of feline retroviruses and the growing interest in cats as pets, information about FeLV and FIV in Malaysia is presently insufficient to properly advise veterinarians and pet owners. A cross-sectional study was carried out from January 2010 to December 2010 to determine the prevalence and risk factors associated with FeLV and FIV among domestic cats in peninsular Malaysia. Plasma samples were harvested from the blood of 368 domestic cats and screened for evidence of FeLV p27 antigen and FIV antibodies, using an immunochromatographic kit. Additionally, data on cat demographics and health were collected using a structured questionnaire, and were evaluated as potential risk factors for FeLV or FIV status.ResultsOf the 368 cats that were evaluated in this study, 12.2% (45/368; 95% CI = 8.88 - 15.58) were positive for FeLV p27 antigen, 31.3%, (115/368; 95% CI = 26.51 - 35.99) were seropositive to FIV antibodies, and 4.3% (16/368; 95% CI = 2.27 - 6.43) had evidence of both viruses. Factors found to significantly increase the risk for FeLV seropositivity include sex, age, behaviour, sickness, and living in a multi-cat household. Seropositive response to FIV was significantly associated with sex, neuter status, age, behaviour, and health status.ConclusionsThe present study indicates that FeLV and FIV are common among domestic cats in peninsular Malaysia, and that factors related to cat demographics and health such as age, sex, behaviour, health status and type of household are important predictors for seropositive status to FeLV or FIV in peninsular Malaysia. High prevalence of FeLV or FIV observed in our study is of concern, in view of the immunosuppressive potentials of the two pathogens. Specific measures for control and prevention such as screening and routine vaccination are needed to ensure that FeLV and FIV are controlled in the cat population of peninsular Malaysia.
Trends in prescriptions and costs of drugs for mental disorders
in England, 1998–2010
Authors: Ilyas Stephen , Moncrieff Joanna 
Published: March 2012

BackgroundIncreasing rates of prescriptions for antidepressants, antipsychotics and
stimulants have been reported from various countries.AimsTo examine trends in prescriptions and the costs of all classes of
psychiatric medication in England.MethodData from the Prescription Cost Analysis 1998–2010 was examined, using
linear regression analysis to examine trends.ResultsPrescriptions of drugs used for mental disorders increased by 6.8% (95%
CI 6.3–7.4) per year on average, in line with other drugs, but made up an
increasing proportion of all prescription drug costs (P
= 0.001). There were rising trends in prescriptions of all classes of
psychiatric drugs, except anxiolytics and hypnotics (which did not
change). Antidepressant prescriptions increased by 10% (95% CI 9.0–11)
per year on average, and antipsychotics by 5.1% (95% CI 4.3–5.9).
Antipsychotics overtook antidepressants as the most costly class of
psychiatric medication, with costs rising 22% (95% CI 17–27) per
year.ConclusionsRising prescriptions may be partly explained by longer-term treatment and
increasing population. Nevertheless, it appears that psychiatric drugs
make an increasing contribution to total prescription drug costs, with
antipsychotics becoming the most costly. Low-dose prescribing of some
antipsychotics is consistent with other evidence that their use may not
be restricted to those with severe mental illness.
Physical properties and culture-specific factors as principles of semantic categorisation of the Gújjolaay Eegimaa noun class system
Authors: Sagna, Serge 
Published: March 2012

Abstract
This paper investigates the semantic bases of class membership in the noun class system of Gújjolaay Eegimaa (Eegimaa henceforth), a Niger-Congo and Atlantic language of the BAK group spoken in Southern Senegal. The question of whether semantic principles underlie the overt classification of nouns in Niger-Congo languages is a controversial one. There is a common perception of Niger-Congo noun class systems as being mainly semantically arbitrary. The goal of the present paper is to show that physical properties and culture-specific factors are central principles of semantic categorisation in the Eegimaa noun class system. I argue that the Eegimaa overt grammatical classification of nouns into classes is a semantic categorisation system whereby categories are structured according to prototypicality, family resemblance, metaphorical and metonymic extensions and chaining processes, as argued within the framework of Cognitive Linguistics. I show that the categorisation of entities in the Eegimaa nominal classification system productively makes use of physical properties such as shape as well as using culture-specific, less productive parameters for the semantic categorisation of entities denoted by nouns. The analysis proposed here also shows that the cases of multiple morphosyntactic classifications of nouns reflect multiple conceptual categorisation strategies. A detailed examination of the formal and semantic instances of multiple classification reveals the existence of conceptual correlations between the physical properties and the culture-specific semantic parameters of categorisation used in the Eegimaa noun class system.
Weitzenböck derivations of nilpotency 3
Authors: Wehlau David L. 
Published: March 2012

Abstract
We consider a Weitzenböck derivation Δ acting on a polynomial ring

R
=
K
[

ξ
1

,

ξ
2

,
...
,

ξ
m

]

$
R=K[\xi _1,\xi _2,\ldots ,\xi _m]
$

over a field K of characteristic 0. The K-algebra

R
Δ

=

{
h
∈
R
∣
Δ

(
h
)

=
0
}

${R^\Delta = \lbrace h \in R \mid \Delta (h) = 0\rbrace }$

is called the algebra of constants. Nowicki considered the case where the Jordan matrix for Δ acting on R
1, the degree 1 component of
R, has only Jordan blocks of size 2. He conjectured that a certain set generates

R
Δ

$R^{\Delta }$

in that case. Recently Khoury,
Drensky and Makar-Limanov
and Kuroda
have given proofs of Nowicki's conjecture. Here we consider the case where the Jordan matrix for Δ acting on R
1 has only Jordan blocks of size at most
3. We use combinatorial methods to give a minimal set of generators 𝒢 for the algebra of constants

R
Δ

$R^{\Delta }$

.
Moreover, we show how our proof yields an algorithm to express any

h
∈

R
Δ

$h \in R^\Delta $

as a polynomial
in the elements of 𝒢. In particular, our solution shows how the classical techniques of polarization and restitution may be used to augment the techniques of SAGBI bases to construct generating sets for subalgebras.