bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensitive detection of pathway perturbations in cancers
Authors: Rivera Corban G , Tyler Brett M , Murali TM 
Published: March 2012

AbstractBackgroundThe normal functioning of a living cell is characterized by complex interaction networks involving many different types of molecules. Associations detected between diseases and perturbations in well-defined pathways within such interaction networks have the potential to illuminate the molecular mechanisms underlying disease progression and response to treatment.ResultsIn this paper, we present a computational method that compares expression profiles of genes in cancer samples to samples from normal tissues in order to detect perturbations of pre-defined pathways in the cancer. In contrast to many previous methods, our scoring function approach explicitly takes into account the interactions between the gene products in a pathway. Moreover, we compute the sub-pathway that has the highest score, as opposed to merely computing the score for the entire pathway. We use a permutation test to assess the statistical significance of the most perturbed sub-pathway. We apply our method to 20 pathways in the Netpath database and to the Global Cancer Map of gene expression in 18 cancers. We demonstrate that our method yields more sensitive results than alternatives that do not consider interactions or measure the perturbation of a pathway as a whole. We perform a sensitivity analysis to show that our approach is robust to modest changes in the input data. Our method confirms numerous well-known connections between pathways and cancers.ConclusionsOur results indicate that integrating differential gene expression with the interaction structure in a pathway is a powerful approach for detecting links between a cancer and the pathways perturbed in it. Our results also suggest that even well-studied pathways may be perturbed only partially in any given cancer. Further analysis of cancer-specific sub-pathways may shed new light on the similarities and differences between cancers.
Quantitative genome re-sequencing defines multiple mutations conferring chloroquine resistance in rodent malaria
Authors: Kinga Modrzynska Katarzyna , Creasey Alison , Loewe Laurence , Cezard Timothee , Trindade Borges Sofia , Martinelli Axel , Rodrigues Louise , Cravo Pedro , Blaxter Mark , Carter Richard , Hunt Paul 
Published: March 2012

Abstract

Background
Drug resistance in the malaria parasite Plasmodium falciparum severely compromises the treatment and control of malaria. A knowledge of the critical mutations conferring resistance to particular drugs is important in understanding modes of drug action and mechanisms of resistances. They are required to design better therapies and limit drug resistance.
A mutation in the gene (pfcrt) encoding a membrane transporter has been identified as a principal determinant of chloroquine resistance in P. falciparum, but we lack a full account of higher level chloroquine resistance. Furthermore, the determinants of resistance in the other major human malaria parasite, P. vivax, are not known. To address these questions, we investigated the genetic basis of chloroquine resistance in an isogenic lineage of rodent malaria parasite P. chabaudi in which high level resistance to chloroquine has been progressively selected under laboratory conditions.

Results
Loci containing the critical genes were mapped by Linkage Group Selection, using a genetic cross between the high-level chloroquine-resistant mutant and a genetically distinct sensitive strain. A novel high-resolution quantitative whole-genome re-sequencing approach was used to reveal three regions of selection on chr11, chr03 and chr02 that appear progressively at increasing drug doses on three chromosomes. Whole-genome sequencing of the chloroquine-resistant parent identified just four point mutations in different genes on these chromosomes. Three mutations are located at the foci of the selection valleys and are therefore predicted to confer different levels of chloroquine resistance. The critical mutation conferring the first level of chloroquine resistance is found in aat1, a putative aminoacid transporter.

Conclusions
Quantitative trait loci conferring selectable phenotypes, such as drug resistance, can be mapped directly using progressive genome-wide linkage group selection. Quantitative genome-wide short-read genome resequencing can be used to reveal these signatures of drug selection at high resolution. The identities of three genes (and mutations within them) conferring different levels of chloroquine resistance generate insights regarding the genetic architecture and mechanisms of resistance to chloroquine and other drugs. Importantly, their orthologues may now be evaluated for critical or accessory roles in chloroquine resistance in human malarias P. vivax and P. falciparum.
Potential T cell epitopes of Mycobacterium tuberculosis that can instigate molecular mimicry against host: implications in autoimmune pathogenesis
Authors: Babu Chodisetti Sathi , Rai Pradeep K , Gowthaman Uthaman , Pahari Susanta , Agrewala Javed N 
Published: March 2012

Abstract

Background
Molecular mimicry between microbial antigens and host-proteins is one of the etiological enigmas for the occurrence of autoimmune diseases. T cells that recognize cross-reactive epitopes may trigger autoimmune reactions. Intriguingly, autoimmune diseases have been reported to be prevalent in tuberculosis endemic populations. Further, association of Mycobacterium tuberculosis (M. tuberculosis) has been implicated in different autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. Although, in silico analyses have identified a number of M. tuberculosis specific vaccine candidates, the analysis on prospective cross-reactive epitopes, that may elicit autoimmune response, has not been yet attempted. Here, we have employed bioinformatics tools to determine T cell epitopes of homologous antigenic regions between M. tuberculosis and human proteomes.

Results
Employing bioinformatics tools, we have identified potentially cross-reactive T cell epitopes restricted to predominant class I and II alleles of human leukocyte antigens (HLA). These are similar to peptides of mycobacterial proteins and considerable numbers of them are promiscuous. Some of the identified antigens corroborated with established autoimmune diseases linked with mycobacterial infection.

Conclusions
The present study reveals many target proteins and their putative T cell epitopes that might have significant application in understanding the molecular basis of possible T cell autoimmune reactions during M. tuberculosis infections.
Multilocus microsatellite analysis of 'Candidatus Liberibacter asiaticus' associated with citrus Huanglongbing worldwide
Authors: Islam Md-Sajedul , Glynn Jonathan M , Bai Yang , Duan Yong-Ping , Coletta-Filho Helvecio D , Kuruba Gopal , Civerolo Edwin L , Lin Hong 
Published: March 2012

Abstract

Background
Huanglongbing (HLB) is one of the most destructive citrus diseases in the world. The disease is associated with the presence of a fastidious, phloem-limited α- proteobacterium, 'Candidatus Liberibacter asiaticus', 'Ca. Liberibacter africanus' or 'Ca. Liberibacter americanus'. HLB-associated Liberibacters have spread to North America and South America in recent years. While the causal agents of HLB have been putatively identified, information regarding the worldwide population structure and epidemiological relationships for 'Ca. L. asiaticus' is limited. The availability of the 'Ca. L. asiaticus' genome sequence has facilitated development of molecular markers from this bacterium. The objectives of this study were to develop microsatellite markers and conduct genetic analyses of 'Ca. L. asiaticus' from a worldwide collection. Two hundred eighty seven isolates from USA (Florida), Brazil, China, India, Cambodia, Vietnam, Taiwan, Thailand, and Japan were analyzed.

Results
A panel of seven polymorphic microsatellite markers was developed for 'Ca. L. asiaticus'. Microsatellite analyses across the samples showed that the genetic diversity of 'Ca. L. asiaticus' is higher in Asia than Americas. UPGMA and STRUCTURE analyses identified three major genetic groups worldwide. Isolates from India were genetically distinct. East-southeast Asian and Brazilian isolates were generally included in the same group; a few members of this group were found in Florida, but the majority of the isolates from Florida were clustered separately. eBURST analysis predicted three founder haplotypes, which may have given rise to three groups worldwide.

Conclusions
Our results identified three major genetic groups of 'Ca. L. asiaticus' worldwide. Isolates from Brazil showed similar genetic makeup with east-southeast Asian dominant group, suggesting the possibility of a common origin. However, most of the isolates recovered from Florida were clustered in a separate group. While the sources of the dominant 'Ca. L. asiaticus' in Florida were not clearly understood, the less-pervasive groups may have been introduced directly from Asia or via Brazil. Notably, the recent outbreak of HLB in Florida probably occurred through multiple introductions. Microsatellite markers developed in this study provide adequate discriminatory power for the identification and differentiation of closely-related isolates, as well as for genetic studies of 'Ca. L. asiaticus'.
The mediating role of psychological capital on the association between occupational stress and depressive symptoms among Chinese physicians: a cross-sectional study
Authors: Liu Li , Chang Ying , Fu Jialiang , Wang Jiana , Wang Lie 
Published: March 2012

AbstractBackgroundAlthough occupational stress is an identified predictor of depressive symptoms, the mechanism behind the association is not well understood. The purpose of this study was to examine how psychological capital (PsyCap), a positive psychological state, mediates the association between occupational stress and depressive symptoms among Chinese physicians.MethodsA cross-sectional survey was conducted in Liaoning Province, China, during September–October 2010. Self-administered questionnaires including items on depressive symptoms assessed by the Center for Epidemiologic Studies Depression Scale, occupational stress assessed by the effort–reward imbalance scale and PsyCap estimated by a 24-item Psychological Capital Questionnaire, together with age, gender, marital status and education were distributed to 1300 physicians employed in large general hospitals. The final sample consisted of 998 participants. Asymptotic and resampling strategies were used to examine how PsyCap mediates the association between occupational stress and depressive symptoms.ResultsBoth the effort/reward ratio (ERR) and overcommitment were significantly associated with depressive symptoms among male and female physicians. There was a gender difference in the mediating role of PsyCap on the occupational stress–depressive symptoms association. For male physicians, PsyCap did not mediate the association between occupational stress and depressive symptoms. For female physicians, ERR and overcommitment were negatively associated with PsyCap, and PsyCap was negatively associated with depressive symptoms. As a result, PsyCap significantly mediated the associations of ERR and overcommitment with depressive symptoms. The proportion of PsyCap mediation was 19.07% for ERR, and 24.29% for overcommitment.ConclusionsPsyCap could be a positive resource for combating depressive symptoms in Chinese physicians. In addition to reducing occupational stress, PsyCap development should be included in depression prevention and treatment strategies, especially for female physicians.
Pro-oxidant status and matrix metalloproteinases in apical lesions and gingival crevicular fluid as potential biomarkers for asymptomatic apical periodontitis and endodontic treatment response
Authors: Dezerega Andrea , Madrid Sonia , Mundi Verónica , Valenzuela María A , Garrido Mauricio , Paredes Rodolfo , García-Sesnich Jocelyn , Ortega Ana V , Gamonal Jorge , Hernández Marcela 
Published: March 2012

Abstract

Background
Oxidative stress and matrix metalloproteinases -9 and -2 are involved in periodontal breakdown, whereas gingival crevicular fluid has been reported to reflect apical status. The aim of this study was to characterize oxidant balance and activity levels of MMP -2 and -9 in apical lesions and healthy periodontal ligament; and second, to determine whether potential changes in oxidant balance were reflected in gingival crevicular fluid from asymptomatic apical periodontitis (AAP)-affected teeth at baseline and after endodontic treatment.

Methods
Patients with clinical diagnosis of AAP and healthy volunteers having indication of tooth extraction were recruited. Apical lesions and healthy periodontal ligaments, respectively, were homogenized or processed to obtain histological tissue sections. Matrix metalloproteinase -9 and -2 levels and/or activity were analyzed by Immunowestern blot, zymography and consecutive densitometric analysis, and their tissue localization was confirmed by immunohistochemistry. A second group of patients with AAP and indication of endodontic treatment was recruited. Gingival crevicular fluid was extracted from AAP-affected teeth at baseline, after endodontic treatment and healthy contralateral teeth. Total oxidant and antioxidant status were determined in homogenized tissue and GCF samples. Statistical analysis was performed using STATA v10 software with unpaired t test, Mann-Whitney test and Spearman's correlation.

Results
Activity of MMP-2 and MMP-9 along with oxidant status were higher in apical lesions (p < 0.05). Total oxidant status correlated positively with matrix metalloproteinase-2 and lesion size (p < 0.05). Gingival crevicular fluid showed significantly lower levels of total antioxidant status in diseased teeth at baseline compared to controls and endodontically-treated groups.

Conclusions
Apical lesions display an oxidant imbalance along with increased activity of matrix metalloproteinase-2 and -9 and might contribute to AAP progression. Oxidant imbalance can also be reflected in GCF from AAP-affected teeth and was restored to normal levels after conservative endodontic treatment. These mediators might be useful as potential biomarkers for chair-side complementary diagnostic of apical status in GCF.
Single dose testosterone increases total cholesterol levels and induces the expression of HMG CoA Reductase
Authors: Gårevik Nina , Skogastierna Cristine , Rane Anders , Ekström Lena 
Published: March 2012

Abstract

Background
Cholesterol is mainly synthesised in liver and the rate-limiting step is the reduction of 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) to mevalonate, a reaction catalysed by HMG-CoA reductase (HMGCR). There is a comprehensive body of evidence documenting that anabolic-androgenic steroids are associated with deleterious alterations of lipid profile. In this study we investigated whether a single dose of testosterone enanthate affects the cholesterol biosynthesis and the expression of HMGCR.

Methods
39 healthy male volunteers were given 500 mg testosterone enanthate as single intramuscular dose of Testoviron®--Depot. The total cholesterol levels prior to and two days after testosterone administration were analysed. Protein expression of HMGCR in whole blood was investigated by Western blotting. In order to study whether testosterone regulates the mRNA expression of HMGCR, in vitro studies were performed in a human liver cell-line (HepG2).

Results
The total cholesterol level was significantly increased 15% two days after the testosterone injection (p = 0.007). This is the first time a perturbation in the lipoprotein profile is observed after only a single dose of testosterone. Moreover, the HMGCR mRNA and protein expression was induced by testosterone in vitro and in vivo, respectively.

Conclusion
Here we provide a molecular explanation how anabolic androgenic steroids may impact on the cholesterol homeostasis, i.e. via an increase of the HMGCR expression. Increasing knowledge and understanding of AAS induced side-effects is important in order to find measures for treatment and care of these abusers.
Notes on the blood-feeding behavior of Aedes albopictus (Diptera: Culicidae) in Cameroon
Authors: Kamgang Basile , Nchoutpouen Elysée , Simard Frédéric , Paupy Christophe 
Published: March 2012

AbstractBackgroundThe invasive mosquitoAedes albopictusis often considered a poor vector of human pathogens, owing to its catholic feeding behavior. However, it was recently incriminated as a major vector in several Chikungunya epidemics, outside of its native range. Here we assessed two key elements of feeding behavior byAe. albopictusfemales in Yaoundé, Cameroon, Central Africa. Host preference was explored and the human-biting activity of females was monitored over 24 h to determine periods of maximum bite exposure.FindingsAnalysis of ingested blood in outdoor-resting females showed thatAe. albopictuspreferentially fed on humans rather than on available domestic animals (95% of the blood meals contained human blood). Our results further showed thatAe. albopictusis a day-biting species in Yaoundé, with a main peak of activity in the late afternoon.ConclusionThis is the first report on the feeding behavior ofAe. albopictusin Central Africa. The species is highly aggressive to humans and might therefore be involved in human-human virus transmission in this setting.
Open science versus commercialization: a modern research conflict?
Authors: Caulfield Timothy , Harmon Shawn HE , Joly Yann 
Published: March 2012

Abstract
Background
Efforts to improve research outcomes have resulted in genomic researchers being confronted with complex and seemingly contradictory instructions about how to perform their tasks. Over the past decade, there has been increasing pressure on university researchers to commercialize their work. Concurrently, they are encouraged to collaborate, share data and disseminate new knowledge quickly (that is, to adopt an open science model) in order to foster scientific progress, meet humanitarian goals, and to maximize the impact of their research.

Discussion
We present selected guidelines from three countries (Canada, United States, and United Kingdom) situated at the forefront of genomics to illustrate this potential policy conflict. Examining the innovation ecosystem and the messages conveyed by the different policies surveyed, we further investigate the inconsistencies between open science and commercialization policies.

Summary
Commercialization and open science are not necessarily irreconcilable and could instead be envisioned as complementary elements of a more holistic innovation framework. Given the exploratory nature of our study, we wish to point out the need to gather additional evidence on the coexistence of open science and commercialization policies and on its impact, both positive and negative, on genomics academic research.
Autotrophic carbon budget in coral tissue: a new 13C-based model of photosynthate translocation
Authors: Tremblay Pascale , Grover Renaud , Maguer Jean François , Legendre Louis , Ferrier-Pagès Christine 
Published: March 2012

SUMMARYCorals live in symbiosis with dinoflagellates of the genus Symbiodinum. These dinoflagellates translocate a large part of the photosynthetically fixed carbon to the host, which in turn uses it for its own needs. Assessing the carbon budget in coral tissue is a central question in reef studies that still vexes ecophysiologists. The amount of carbon fixed by the symbiotic association can be determined by measuring the rate of photosynthesis, but the amount of carbon translocated by the symbionts to the host and the fate of this carbon are more difficult to assess. In the present study, we propose a novel approach to calculate the budget of autotrophic carbon in the tissue of scleractinian corals, based on a new model and measurements made with the stable isotope 13C. Colonies of the scleractinian coral Stylophora pistillata were incubated in H13CO –3-enriched seawater, after which the fate of 13C was followed in the symbionts, the coral tissue and the released particulate organic carbon (i.e. mucus). Results obtained showed that after 15 min, ca. 60% of the carbon fixed was already translocated to the host, and after 48 h, this value reached 78%. However, ca. 48% of the photosynthetically fixed carbon was respired by the symbiotic association, and 28% was released as dissolved organic carbon. This is different from other coral species, where &lt;1% of the total organic carbon released is from newly fixed carbon. Only 23% of the initially fixed carbon was retained in the symbionts and coral tissue after 48 h. Results show that our 13C-based model could successfully trace the carbon flow from the symbionts to the host, and the photosynthetically acquired carbon lost from the symbiotic association.
Evaporation dynamics of tarsal liquid footprints in flies (Calliphora vicina)and beetles (Coccinella septempunctata)
Authors: Peisker Henrik , Gorb Stanislav N. 
Published: March 2012

SUMMARYInsect tarsal adhesive structures secrete a thin layer of fluid into the contact area. It was previously reported that the presence of this fluid significantly increases adhesion on various substrata. Previous data obtained from representatives of different insect groups suggest a difference not only in the chemical composition of the fluid, but also in its physical properties. In the present study, we have measured for the first time changes in the droplet geometry over time and the evaporation rate of the fluid in flies (Calliphora vicina) and beetles (Coccinella septempunctata) by the use of atomic force microscopy. Flattened droplets of the beetle had lower evaporation rates than hemispherical footprints of the fly. Within 1 h, the droplet volume reduced to 21% of the initial volume for the fly, and to 65% for the beetle, suggesting a larger fraction of volatile compounds in the fly fluid. It was revealed that drop geometry changes significantly during evaporation and shows pinning effects for the fly footprints due to an assumed self-organizing oil layer on top of the water fraction of the micro-emulsion. The data obtained suggest that the adhesion strength in capillarity-based switchable adhesive systems must be time-dependent because of the specific evaporation rate of the adhesive fluid. These results are important for our understanding of the functional mechanism of insect adhesive systems and also for biomimetics of artificial capillarity-based adhesive systems.