bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Nucleic Acid–Sensing TLRs in Diverse Autoantibody Specificities and Anti-Nuclear Antibody–Producing B Cells
Authors: Koh Yi Ting , Scatizzi John C. , Gahan Jennifer D. , Lawson Brian R. , Baccala Roberto , Pollard K. Michael , Beutler Bruce A. , Theofilopoulos Argyrios N. , Kono Dwight H. 
Published: April 2013

Abstract
Nucleic acid (NA)–sensing TLRs (NA-TLRs) promote the induction of anti-nuclear Abs in systemic lupus erythematosus. However, the extent to which other nonnuclear pathogenic autoantibody specificities that occur in lupus and independently in other autoimmune diseases depend on NA-TLRs, and which immune cells require NA-TLRs in systemic autoimmunity, remains to be determined. Using Unc93b13d lupus-prone mice that lack NA-TLR signaling, we found that all pathogenic nonnuclear autoantibody specificities examined, even anti-RBC, required NA-TLRs. Furthermore, we document that NA-TLRs in B cells were required for the development of antichromatin and rheumatoid factor. These findings support a unifying NA-TLR–mediated mechanism of autoantibody production that has both pathophysiological and therapeutic implications for systemic lupus erythematosus and several other humoral-mediated autoimmune diseases. In particular, our findings suggest that targeting of NA-TLR signaling in B cells alone would be sufficient to specifically block production of a broad diversity of autoantibodies.
The NADPH Oxidase Pathway Is Dysregulated by the P2X7 Receptor in the SOD1-G93A Microglia Model of Amyotrophic Lateral Sclerosis
Authors: Apolloni Savina , Parisi Chiara , Pesaresi Maria Grazia , Rossi Simona , Carrì Maria Teresa , Cozzolino Mauro , Volonté Cinzia , D’Ambrosi Nadia 
Published: April 2013

Abstract
Inflammation and oxidative stress are thought to play determinant roles in the pathogenesis of amyotrophic lateral sclerosis (ALS). Degenerating motor neurons produce signals that activate microglia to release reactive oxygen species (ROS) and proinflammatory cytokines, resulting in a vicious cycle of neurodegeneration. The ALS-causing mutant protein Cu+/Zn+ superoxide dismutase SOD1-G93A directly enhances the activity of the main ROS-producing enzyme in microglia, NADPH oxidase 2 (NOX2), a well-known player in the pathogenesis of ALS. Considering that extracellular ATP through P2X7 receptor constitutes a neuron-to-microglia alarm signal implicated in ALS pathology, we used primary microglial cells derived from transgenic SOD1-G93A mice and SOD1-G93A mice lacking the P2X7 receptor to investigate the effects of both pharmacological induction and genetic ablation of receptor activity on the NOX2 pathway. We observed that, in SOD1-G93A microglia, the stimulation of P2X7 receptor by 2′-3′-O-(benzoyl-benzoyl) ATP enhanced NOX2 activity in terms of translocation of p67phox to the membrane and ROS production; this effect was totally dependent on Rac1. We also found that, following P2X7 receptor stimulation, the phosphorylation of ERK1/2 was augmented in ALS microglia, and there was a mutual dependency between the NOX2 and ERK1/2 pathways. All of these microglia-mediated damaging mechanisms were prevented by knocking out P2X7 receptor and by the use of specific antagonists. These findings suggest a noxious mechanism by which P2X7 receptor leads to enhanced oxidative stress in ALS microglia and identify the P2X7 receptor as a promising target for the development of therapeutic strategies to slow down the progression of ALS.
The Survival of Memory CD8 T Cells That Is Mediated by IL-15 Correlates with Sustained Protection Against Malaria
Authors: Zarling Stasya , Berenzon Dmitriy , Dalai Sarat , Liepinsh Dmitry , Steers Nick , Krzych Urszula 
Published: April 2013

Abstract
Ag-specific memory T cell responses elicited by infections or vaccinations are inextricably linked to long-lasting protective immunity. Studies of protective immunity among residents of malaria endemic areas indicate that memory responses to Plasmodium Ags are not adequately developed or maintained, as people who survive episodes of childhood malaria are still vulnerable to either persistent or intermittent malaria infections. In contrast, multiple exposures to radiation-attenuated Plasmodium berghei sporozoites (Pb γ-spz) induce long-lasting protective immunity to experimental sporozoite challenge. We previously demonstrated that sterile protection induced by Pb γ-spz is MHC class I–dependent and CD8 T cells are the key effectors. IFN-γ+ CD8 T cells that arise in Pb γ-spz–immunized B6 mice are found predominantly in the liver and are sensitive to levels of liver-stage Ag depot and they express CD44hiCD62Llo markers indicative of effector/effector memory phenotype. The developmentally related central memory CD8 T (TCM) cells express elevated levels of CD122 (IL-15Rβ), which suggests that CD8 TCM cells depend on IL-15 for maintenance. Using IL-15–deficient mice, we demonstrate in this study that although protective immunity is inducible in these mice, protection is short-lived, mainly owing to the inability of CD8 TCM cells to survive in the IL-15–deficient milieu. We present a hypothesis consistent with a model whereby intrahepatic CD8 TCM cells, being maintained by IL-15–mediated survival and basal proliferation, are conscripted into the CD8 effector/effector memory T cell pool during subsequent infections.
Evaluation of Surface Conditioning of Zirconia and Its Effect on Bonding to Resin-Luting Agent
Authors: Gargava Sonu , Ram Sabita M 
Published: April 2013

ABSTRACTZirconia, a recently introduced ceramic exhibits excellent esthetic qualities and demonstrates outstanding flexural strength but its extensive use, requires a reliable bond of Zirconia with resinluting agent. Resin Zirconia bonding cannot be achieved as the material is resistant to common etching procedures used for other glass containing ceramics. With surface conditioning increased adhesion between Zirconia and resin-luting agent can be successfully achieved.AimAim of this study was to evaluate surface conditioning of Zirconia and its effect on bonding to resin-luting agent.Materials and MethodsFifteen blocks of Zirconia (VITA Zirconia) were fabricated in the laboratory according to manufacturer's instructions and embedded in acrylic resin to get 15 Zirconia samples. Fifteen composite resin cylinders were prepared one for each Zirconia sample. All the 15 Zirconia samples were divided into three groups of five samples each. Group A: Was kept as control with no surface conditioning done. Group B: Surface conditioning was done with 30 µ silicon dioxide. Group C: Surface conditioning was done with 110 µ aluminum oxide. Composite resin cylinders were cemented on the Zirconia samples using a resin-luting agent (Panavia F). The samples were subjected to universal testing machine to evaluate shear bond strength and the data was statistically analyzed by oneway ANOVA.ResultsGroup A showed least shear bond strength. Shear bond strength of group C was greater than group A while group B showed highest shear bond strength.ConclusionSurface conditioning results in significant increase bond strength between Zirconia and resin-luting agent. Among the two methods surface conditioning with 30 µ silicon dioxide is much better and efficient method.How to cite this articleGargava S, Ram SM. Evaluation of Surface Conditioning of Zirconia and Its Effect on Bonding to Resin-Luting Agent. J Contemp Dent 2013;3(1):7-10.
Prevalence and Severity of Periodontal Disease in Type II Diabetes Mellitus (Noninsulin-dependent Diabetes Mellitus) Patients in Gulbarga, Karnataka, India: An Epidemiological Study
Authors: Patil Veena Ashok , Shivaraya Roopashree , Desai Manthan Hemant 
Published: April 2013

ABSTRACTBackground/objectivesThe objective was to study the prevalence and severity of periodontal disease in type II DM patients in Gulbarga, Karnataka, India.Materials and MethodsA total of 100 type II DM patients and 100 nondiabetic patients with age group of 35 to 75 years were examined. The study group was divided into well, moderate and poorly controlled diabetes based on glycated hemoglobin (HbA1C) levels. Information regarding age, oral hygiene habits, personal habits, diabetic status and mode of diabetic therapy was obtained. Community periodontal index of treatment needs (CPITN) was used to assess the periodontal status. The results were statistically evaluated.ResultsThe mean CPITN score and the number of missing teeth was higher in diabetics compared to nondiabetics and was statistically significant (p = 0.05). The prevalence of periodontal disease was found to be more frequent and severe in diabetic patients as compared to nondiabetics. The risk factors like glycated hemoglobin HbA1C, duration of diabetes, personal habits and oral hygiene habits showed a positive correlation with periodontal destruction, whereas mode of diabetic therapy showed negative correlation with the periodontal status.ConclusionDiabetic patients showed higher prevalence and severity of periodontal disease compared to nondiabetics.How to cite this articlePatil VA, Shivaraya R, Desai MH. Prevalence and Severity of Periodontal Disease in Type II Diabetes Mellitus (Noninsulin-dependent Diabetes Mellitus) Patients in Gulbarga, Karnataka, India: An Epidemiological Study. J Contemp Dent 2013;3(1):32-35.
O sistema "UFSC sem papel” sob a perspectiva da inovação
Authors: Silva Naira , Jacobsen Alessandra de Linhares , Almeida Mário de Souza , De Olivo Luis Carlos Cancellier 
Published: April 2013

O presente artigo tem como objetivo analisar o sistema de informação “UFSC sem papel” sob a ótica da inovação. Para tanto, fez-se uso da pesquisa descritiva e do estudo de caso, com abordagem qualitativa. Apresenta uma perspectiva de estudo transversal, considerando-se o período compreendido entre outubro de 2011 a novembro de 2011. Trata-se, ainda, de uma pesquisa de campo, bibliográfica. O sujeito da pesquisa, escolhido por tipicidade, foi o superintendente da Superintendência de Governança Eletrônica e Tecnologia da Informação e Comunicação (SeTIC), da Universidade Federal de Santa Catarina. Para a coleta de dados, foi utilizada a entrevista semi-estruturada, a partir de um roteiro, sendo os dados analisados por meio da técnica pattern-matching. O sistema analisado é uma inovação técnica e radical, com efeitos sobre o âmbito administrativo, sendo dividido em módulos para a gestão dos processos administrativos (protocolo), de compras e licitações, de patrimônio e de materiais e almoxarifado. A sua finalidade é modernizar as atividades administrativas, reduzindo o uso de papel e gerando maior rapidez na tramitação dos documentos, mais transparência e maior eficiência na execução dos processos da organização. Em termos de desenvolvimento e aquisição da citada inovação, a UFSC fez opção pela compra de um pacote pronto, mas a implantação foi acompanhada pela equipe da SeTIC. Há certa preocupação com relação à falta de habilidade das pessoas em utilizá-lo. Conclui-se sobre a necessidade de conduzir uma apurada análise do sistema “UFSC sem Papel”, para que tal inovação possa ser bem sucedida.
« Qui sont les terroristes ? » Lutte de classement autour de la radicalité mapuche
Authors: Barbut Michael 
Published: April 2013

Dans le sud du Chili, depuis les années 1990 et l’enclenchement de la « transition à la démocratie », on a assisté à la multiplication d’actions de protestation mapuche, principal peuple indien du Chili, autour de la revendication de droits territoriaux et fonciers.
Ces actions défiant la propriété privée et la légalité ont vite été catégorisées comme l’expression d’un « nouveau radicalisme indigène » par la presse, et sanctionnées par la multiplication d’actions en justice contre leurs supposés auteurs, labéllisés comme « extrémistes », voire « terroristes ». Le présent article s’attache, à partir de l’évolution des mobilisations mapuche, à montrer que la radicalité n’est pas une essence et qu’elle doit avant tout être appréhendée comme une lutte de classement.
Evolution of Gene Expression in Human and Chimpanzee Brains
Authors: Osada Naoki , Sumio Sugano , Suzuki Yutaka 
Published: April 2013

Abstract

It has long been proposed that for creating diverse phenotypes in closely related species, such as a striking difference between human and chimpanzee brain functions, evolutionary changes in gene expression are more important than the changes in protein structure. High‐throughput detection methods make it possible to gauge the differences in gene expression at the genome‐wide level. Initial studies using
deoxyribonucleic acid
microarrays have shown that gene expression evolution is more conserved in the brain than in other tissues. However, those studies have also shown that the divergence rate of gene expression in the brain is higher in humans than in the chimpanzee lineage. Subsequent studies have identified detailed differences in gene expression such as alterations in network connectivity and temporal order. In addition to the expression of protein‐coding genes, the expression of noncoding RNAs may also affect the divergence of gene expression and contribute to the phenotypic differences between humans and chimpanzees.

Key Concepts:

Differences in gene expression patterns rather than the changes in protein structures may have contributed to the functional differences between human and chimpanzee brains.

The set of genes that have different expression patterns in human and chimpanzee brains can be identified using high‐throughput methods such as DNA microarrays and RNA‐Seq.

Although we can detect functional gene expression changes specific to the human brain, it is not easy to elucidate the underlying evolutionary mechanisms.

Gene expression is a complex trait; understanding the molecular mechanisms of brain development is important to unveil the genetic basis of brain evolution.

Several studies revealed that the pattern of gene expression evolution in human brains was highly conservative in general, but showed acceleration after the split from the chimpanzee lineage.
Reconstruction of Ancestral Genomes
Authors: Stanyon Roscoe , Bigoni Francesca 
Published: April 2013

Abstract

Comparative genomics allow hypotheses about the content of the genome of ancestral species and for many major branching points on the tree of life, hypothetical ancestral genomes can be reconstructed. Cross‐species chromosome painting over the last two decades has led the way in the reconstruction of ancestral genomes. Chromosome painting techniques allow to rapidly track chromosome translocations in evolution. A cladistic analysis of syntenies and chromosome associations allows rearrangements to be placed on the evolutionary tree. More recently, assemblies of genome sequences have allowed more far ranging comparisons of vertebrate genome evolution. The

in‐situ

hybridisation of the
deoxyribonucleic acid (DNA)
cloned into bacterial artificial chromosome overcomes the limitations of chromosome painting permitting the reconstruction of ancestral marker order along the single chromosome and has revealed that centromeres can reposition during evolution. These reconstructions provide insight into the evolutionary forces that have sculpted the genomes of extant species.

Key Concepts:

All forms of life on this planet are connected by descent from common ancestors.

Hypothetical ancestral genomes can be reconstructed at various nodes on the tree of life.

FISH is the major technique of comparative molecular cytogenetics.

Chromosome painting can detect chromosomal homologies even between distantly related mammalian orders.

Chromosomal syntenies may often be fragmented but it is highly unlikely that the same syntenic group can be brought together independently in different lineages.

Chromosome associations are segments homologous to different human chromosomes that are found contiguously in genomes of other species.

Chromosome painting maps are now available for about 200 mammalian species from all eutherian orders.

Bioinformatics provided an alternative approach to reconstructing ancestral genomes from the comparison of complete genome assemblies.

Integration between molecular cytogenetics, sequencing and bioinformatics will allow even more refined hypotheses about genome evolution.
Dual‐Coding Regions in Alternatively Spliced Human Genes
Authors: Liang Han , Landweber Laura F 
Published: April 2013

Abstract

In eukaryotes, a coding
deoxyribonucleic acid (DNA)
sequence usually encodes amino acids in one reading frame only. However, by using different exon combinations, alternatively spliced genes may contain dual‐coding regions, where more than one reading frame encodes amino acid sequences. In recent years, quite a few studies have systematically identified such dual‐coding regions in the human genome. These special coding regions generate functionally related but distinct protein products, and they have evolved under unusual selective forces, with fewer synonymous sites. This article will first introduce the concept of dual‐coding regions in alternatively spliced genes through several well‐characterised examples, and then discusses the computational methods for detecting such regions and elucidating their evolutionary constraints and finally discusses the potential selective advantages.

Key Concepts:

The open reading frame in a DNA sequence defines the encoded amino acid sequences.

Particularly low synonymous substitution rate suggests the presence of overlapping reading frames.

During translation, ribosomes move along an mRNA not by one nucleotide, but by one codon at a time.

The presence of in‐frame stop codons indicates that the ORF no longer encodes a functional protein product.

Two reading frames of a dual‐coding region resulting from alternative splicing are in the same strand whereas those resulting from other mechanisms may be in different strands.
Human‐specific Accelerated Evolution of Noncoding Sequences
Authors: Webster Matthew T 
Published: April 2013

Abstract

Mutations in functional noncoding elements are likely to be responsible for a large fraction of phenotypic evolution. There is considerable interest in identifying genes and genomic regions under positive selection on the human lineage, as they may govern the traits that make us unique. Several studies have attempted to identify functional noncoding elements under positive selection in the human lineage by identifying those with evidence of accelerated evolutionary rates since the common ancestor of humans and chimpanzees. These studies have identified a catalogue of human‐accelerated regions (HARs). Two of the most extremely accelerated HARs are implicated in controlling human‐specific morphology and cognition. However, detailed analyses of the forces governing the evolution of HARs suggest that a number of different processes distinct from positive selection may be involved in their accelerated rates. These include relaxation of constraint, variation in mutation rate and GC‐biased gene conversion.

Key Concepts:

Noncoding genomic regions under evolutionary constraint are likely to be functional elements such as the transcription binding sites.

Evolutionarily constrained elements that have undergone accelerated evolution on the human lineage are candidates for governing human‐specific traits.

Positive selection represents a bias towards fixation of alleles conferring an increased fitness.

GC‐biased gene conversion (gBGC) is a recombination‐associated process that increases the probabilty of fixation of G and C nucleotides independent of their fitness.

Multiple processes, including positive selection and gBGC are implicated in governing the evolution of human‐accelerated regions.
Genetics of Disordered Gambling
Authors: Slutske Wendy S 
Published: April 2013

Abstract

There is evidence from twin studies that genetic variation contributes to individual differences in the risk for disordered gambling (DG), and that some of this genetic variation overlaps with the genetic risk for other comorbid disorders such as alcohol dependence, antisocial behaviour disorders and major depression. It is likely that the specific genes that contribute to DG risk will be of small effect; there are no established susceptibility genes for DG. The most promising candidates based on theory and cumulative evidence are dopamine system genes. Other interesting leads come from the norepinephrine system, including the
ADRAC2
and
MAO‐A
genes, and several novel variants identified in a recent genome‐wide association study. Genetic research on DG is in its infancy, with most of the interesting findings based on single unreplicated studies. There is much uncharted territory in research on the genetics of DG.

Key Concepts:

Disordered gambling affects approximately 1–2% of the population in the United States, and many individuals who do not qualify for a clinical diagnosis may also experience substantial harms from their gambling involvement.

There are cross‐national and cross‐temporal differences in the prevalence of disordered gambling, highlighting the importance of nongenetic factors.

Twin studies suggest that the variation in risk for disordered gambling among adults is due to genetic and unique environmental influences, with no evidence for an important role of the shared family environment.

The contribution of genes and environment to disordered gambling risk appears to be similar among men and women.

Genetic variation in disordered gambling risk overlaps with the genetic risk for other comorbid disorders such as alcohol dependence, antisocial behaviour disorders and major depression.

Genetic susceptibility for DG will also include those genes related to individual differences in the earlier stages of gambling involvement.

Like other complex polygenic disorders, genetic variation in disordered gambling risk appears to be due to many genes of small effect.

There are no known susceptibility genes for disordered gambling; the most promising candidates are the dopamine system genes, with other interesting leads from the norepinephrine system.

The much‐needed research on disordered gambling endophenotypes will improve the understanding of the pathways from genes to disordered gambling and may facilitate efforts to identify susceptibility genes.

There is little research evaluating the potential disordered gambling endophenotypes, but the broader disordered gambling literature suggests that neural systems, cognitive distortions and decision making, personality traits such as impulsivity and negative emotionality, and loss‐chasing are viable candidates.