bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathological characteristics of familial SLE patients with lupus nephritis
Authors: Wang Z , Tang Z , Zhang HT , Hu WX , Liu ZH , Li LS 
Published: February 2009

This study aimed to analyze the clinicopathological characteristics of familial SLE patients with lupus nephritis (LN). A total of 136 Chinese patients with lupus nephritis diagnosed by renal biopsy, including 34 familial patients and 102 sporadic cases, were recruited. Their demographic information, age of onset, disease duration, clinical features, laboratory data and histological manifestations were compared. The first-degree relatives (17 sibling cases and eight parent–offspring cases) of familial SLE patients were primarily affected. The prevalence of fever, rash and arthritis in familial subjects was higher than that in sporadic subjects. Familial patients had lower platelet counts and higher low-density lipoprotein. In familial patients, class V lupus nephritis was less common. After adjusted with the Benjamini and Hochberg procedure, however, fever was the only feature occurring significantly and more frequently in familial patients (58.8% vs 26.5%, P = 0.001). Moreover, SLEDAI and other clinicopathological features did not differ significantly between the two groups. Multivariate analysis showed that a higher prevalence of fever was an independent predictor of familial SLE. Most clinicopathological features in familial SLE patients were not significantly different from those in sporadic patients; the severity of LN in familial SLE patients was similar to that of sporadic cases. Thus, familial SLE may not be a different clinical entity.
Co-existing sarcoidosis, systemic lupus erythematosus and the antiphospholipid antibody syndrome
Authors: Wesemann DR , Costenbader KH , Coblyn JS 
Published: February 2009

Sarcoidosis, systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APS) are chronic conditions of immune dysregulation whose aetiologies remain mysterious. Expression of sarcoidosis and SLE within individuals has been reported in a handful of cases in the last 60 years. In this study, we report two cases of sarcoidosis and SLE occurring together, and each case demonstrated complications associated with the presence of anticardiolipin antibodies. Clinical, serological and pathological findings confirmed the diagnoses in each case and both patients improved with therapy. The association of sarcoidosis, SLE and APS is unique and may present difficult therapeutic options, as well as to shed light on their immunopathogenesis.
Reaching the Unreachable
Authors: Bhatia Tej K. , Bhargava Mukesh 
Published: February 2009

Due to globalization and the need to seek out new markets (sometimes labelled as business to 4-billion [B2-4B]), rural marketing is gaining new importance in India as well as across the globe. This article examines three facets: the marketing, linguistic and advertising of these markets. Our study shows that global companies are engaged in devising new strategies to market their products. Indian media planners have pioneered new media forms (for example, Video Vans) combining conventional and non-conventional advertising to meet the challenge of reaching rural India. The result is that messages are customized effectively to meet their audiences’ regional sensibilities and tastes. The main focus of this study is on the analysis of the messages in the ‘unconventional’ media and wall advertising. We base our study on an empirical investigation of over 2,000 ads in rural settings. The ads include commercial, social and service advertisements. The findings indicate that the advertisers favour the ‘cooperative’ view as opposed to the ‘competitive’ view. They mix languages and scripts to optimize the strength and appeal of their messages. The strengths and limits of the ‘standardization’ versus ‘adaptation’ strategies are accounted for with special reference to the structural properties of wall ads. The directions for future research are outlined.
Results of high-dose imatinib mesylate in intermediate Sokal risk chronic myeloid leukemia patients in early chronic phase: a phase 2 trial of the GIMEMA CML Working Party
Authors: Castagnetti Fausto , Palandri Francesca , Amabile Marilina , Testoni Nicoletta , Luatti Simona , Soverini Simona , Iacobucci Ilaria , Breccia Massimo , Rege Cambrin Giovanna , Stagno Fabio , Specchia Giorgina , Galieni Piero , Iuliano Franco , Pane Fabrizio , Saglio Giuseppe , Alimena Giuliana , Martinelli Giovanni , Baccarani Michele , Rosti Gianantonio ,   for the GIMEMA CML Working Party
Published: February 2009

AbstractImatinib mesylate has become the treatment of choice for chronic myeloid leukemia (CML): the standard dose for chronic- phase (CP) CML is 400 mg daily. Response rates are different according to Sokal score, being significantly lower in intermediate and high Sokal risk patients. Phase 1 and 2 trials have shown a dose-response effect and high-dose imatinib trials in early CP CML showed better results compared with standard dose. Our study is the first prospective trial planned to evaluate the efficacy and tolerability of high-dose imatinib in previously untreated intermediate Sokal risk CML patients. Seventy-eight patients were treated with 400 mg imatinib twice daily: complete cytogenetic response (CCgR) rates at 12 and 24 months were 88% and 91%; moreover, at 12 and 24 months 56% and 73% of CCgR patients achieved a major molecular response. The incidence of adverse events was slightly higher than reported by the most important standard-dose trials. With a median follow-up of 24 months, 3 patients progressed to advanced phase. In intermediate Sokal risk newly diagnosed CML patients, high-dose imatinib induced rapid and high response rates, apparently faster than those documented in the International Randomized Study of IFN and Imatinib for the same risk category. These clinical trials are registered at www.clinicaltrials.gov as no. NCT00510926.
The F12-Vif derivative Chim3 inhibits HIV-1 replication in CD4+ T lymphocytes and CD34+-derived macrophages by blocking HIV-1 DNA integration
Authors: Porcellini Simona , Alberici Luca , Gubinelli Francesco , Lupo Rossella , Olgiati Clelia , Rizzardi Gian-Paolo , Bovolenta Chiara 
Published: February 2009

AbstractThe viral infectivity factor (Vif) is essential for HIV-1 infectivity and hence is an ideal target for promising anti–HIV-1/AIDS gene therapy. We previously demonstrated that F12-Vif mutant inhibits HIV-1 replication in CD4+ T lymphocytes. Despite macrophage relevance to HIV-1 pathogenesis, most gene therapy studies do not investigate macrophages because of their natural resistance to genetic manipulation. Here, we confirm the F12-Vif antiviral activity also in macrophages differentiated in vitro from transduced CD34+ human stem cells (HSCs). Moreover, we identified the 126- to 170-amino-acid region in the C-terminal half of F12-Vif as responsible for its antiviral function. Indeed, Chim3 protein, containing this 45-amino-acid region embedded in a WT-Vif backbone, is as lethal as F12-Vif against HIV-1. Of major relevance, we demonstrated a dual mechanism of action for Chim3. First, Chim3 functions as a transdominant factor that preserves the antiviral function of the natural restriction factor APOBEC3G (hA3G). Second, Chim3 blocks the early HIV-1 retrotranscript accumulation and thereby HIV-1 DNA integration regardless of the presence of WT-Vif and hA3G. In conclusion, by impairing the early steps of HIV-1 life cycle, Chim3 conceivably endows engineered cells with survival advantage, which is required for the efficient immune reconstitution of patients living with HIV/AIDS.
Healthcare workers' attitudes to working during pandemic influenza: a qualitative study
Authors: Ives Jonathan , Greenfield Sheila , Parry Jayne M , Draper Heather , Gratus Christine , Petts Judith I , Sorell Tom , Wilson Sue 
Published: February 2009

AbstractBackgroundHealthcare workers (HCWs) will play a key role in any response to pandemic influenza, and the UK healthcare system's ability to cope during an influenza pandemic will depend, to a large extent, on the number of HCWs who are able and willing to work through the crisis. UK emergency planning will be improved if planners have a better understanding of the reasons UK HCWs may have for their absenteeism, and what might motivate them to work during an influenza pandemic.This paper reports the results of a qualitative study that explored UK HCWs' views (n = 64) about working during an influenza pandemic, in order to identify factors that might influence their willingness and ability to work and to identify potential sources of any perceived duty on HCWs to work.MethodsA qualitative study, using focus groups (n = 9) and interviews (n = 5).ResultsHCWs across a range of roles and grades tended to feel motivated by a sense of obligation to work through an influenza pandemic. A number of significant barriers that may prevent them from doing so were also identified. Perceived barriers to the ability to work included being ill oneself, transport difficulties, and childcare responsibilities. Perceived barriers to the willingness to work included: prioritising the wellbeing of family members; a lack of trust in, and goodwill towards, the NHS; a lack of information about the risks and what is expected of them during the crisis; fear of litigation; and the feeling that employers do not take the needs of staff seriously. Barriers to ability and barriers to willingness, however, are difficult to separate out.ConclusionAlthough our participants tended to feel a general obligation to work during an influenza pandemic, there are barriers to working, which, if generalisable, may significantly reduce the NHS workforce during a pandemic. The barriers identified are both barriers to willingness and to ability. This suggests that pandemic planning needs to take into account the possibility that staff may be absent for reasons beyond those currently anticipated in UK planning documents. In particular, staff who are physically able to attend work may nonetheless be unwilling to do so. Although there are some barriers that cannot be mitigated by employers (such as illness, transport infrastructure etc.), there are a number of remedial steps that can be taken to lesson the impact of others (providing accommodation, building reciprocity, provision of information and guidance etc). We suggest that barriers to working lie along an ability/willingness continuum, and that absenteeism may be reduced by taking steps to prevent barriers to willingness becoming perceived barriers to ability.
Chemical tools selectively target components of the PKA system
Authors: Bertinetti Daniela , Schweinsberg Sonja , Hanke Susanne E , Schwede Frank , Bertinetti Oliver , Drewianka Stephan , Genieser Hans-Gottfried , Herberg Friedrich W 
Published: February 2009

Abstract

Background
In the eukaryotic cell the cAMP-dependent protein kinase (PKA) is a key enzyme in signal transduction and represents the main target of the second messenger cAMP. Here we describe the design, synthesis and characterisation of specifically tailored cAMP analogs which can be utilised as a tool for affinity enrichment and purification as well as for proteomics based analyses of cAMP binding proteins.

Results
Two sets of chemical binders were developed based on the phosphorothioate derivatives of cAMP, Sp-cAMPS and Rp-cAMPS acting as cAMP-agonists and -antagonists, respectively. These compounds were tested via direct surface plasmon resonance (SPR) analyses for their binding properties to PKA R-subunits and holoenzyme. Furthermore, these analogs were used in an affinity purification approach to analyse their binding and elution properties for the enrichment and improvement of cAMP binding proteins exemplified by the PKA R-subunits. As determined by SPR, all tested Sp-analogs provide valuable tools for affinity chromatography. However, Sp-8-AEA-cAMPS displayed (i) superior enrichment properties while maintaining low unspecific binding to other proteins in crude cell lysates, (ii) allowing mild elution conditions and (iii) providing the capability to efficiently purify all four isoforms of active PKA R-subunit in milligram quantities within 8 h. In a chemical proteomics approach both sets of binders, Rp- and Sp-cAMPS derivatives, can be employed. Whereas Sp-8-AEA-cAMPS preferentially binds free R-subunit, Rp-AHDAA-cAMPS, displaying antagonist properties, not only binds to the free PKA R-subunits but also to the intact PKA holoenzyme both from recombinant and endogenous sources.

Conclusion
In summary, all tested cAMP analogs were useful for their respective application as an affinity reagent which can enhance purification of cAMP binding proteins. Sp-8-AEA-cAMPS was considered the most efficient analog since Sp-8-AHA-cAMPS and Sp-2-AHA-cAMPS, demonstrated incomplete elution from the matrix, as well as retaining notable amounts of bound protein contaminants. Furthermore it could be demonstrated that an affinity resin based on Rp-8-AHDAA-cAMPS provides a valuable tool for chemical proteomics approaches.
Anti-malarial activities of Andrographis paniculata and Hedyotis corymbosa extracts and their combination with curcumin
Authors: Mishra Kirti , Dash Aditya P , Swain Bijay K , Dey Nrisingha 
Published: February 2009

Abstract

Background
Herbal extracts of Andrographis paniculata (AP) and Hedyotis corymbosa (HC) are known as hepato-protective and fever-reducing drugs since ancient time and they have been used regularly by the people in the south Asian sub-continent. Methanolic extracts of these two plants were tested in vitro on choloroquine sensitive (MRC-pf-20) and resistant (MRC-pf-303) strains of Plasmodium falciparum for their anti-malarial activity.

Methods
Growth inhibition was determined using different concentrations of these plant extracts on synchronized P. falciparum cultures at the ring stage. The interactions between these two plant extracts and individually with curcumin were studied in vitro. The performance of these two herbal extracts in isolation and combination were further evaluated in vivo on Balb/c mice infected with Plasmodium berghei ANKA and their efficacy was compared with that of curcumin. The in vivo toxicity of the plant derived compounds as well as their parasite stage-specificity was studied.

Results
The 50% inhibitory concentration (IC50) of AP (7.2 μg/ml) was found better than HC (10.8 μg/ml). Combination of these two herbal drugs showed substantial enhancement in their anti-malarial activity. Combinatorial effect of each of these with curcumin also revealed anti-malarial effect. Additive interaction between the plant extracts (AP + HC) and their individual synergism with curcumin (AP+CUR, HC+CUR) were evident from this study. Increased in vivo potency was also observed with the combination of plant extracts over the individual extracts and curcumin. Both the plant extracts were found to inhibit the ring stage of the parasite and did not show any in vivo toxicity, whether used in isolation or in combination.

Conclusion
Both these two plant extracts in combination with curcumin could be an effective, alternative source of herbal anti-malarial drugs.
Massively parallel pyrosequencing highlights minority variants in the HIV-1 env quasispecies deriving from lymphomonocyte sub-populations
Authors: Rozera Gabriella , Abbate Isabella , Bruselles Alessandro , Vlassi Crhysoula , D'Offizi Gianpiero , Narciso Pasquale , Chillemi Giovanni , Prosperi Mattia , Ippolito Giuseppe , Capobianchi Maria R 
Published: February 2009

Abstract

Background
Virus-associated cell membrane proteins acquired by HIV-1 during budding may give information on the cellular source of circulating virions. In the present study, by applying immunosorting of the virus and of the cells with antibodies targeting monocyte (CD36) and lymphocyte (CD26) markers, it was possible to directly compare HIV-1 quasispecies archived in circulating monocytes and T lymphocytes with that present in plasma virions originated from the same cell types. Five chronically HIV-1 infected patients who underwent therapy interruption after prolonged HAART were enrolled in the study. The analysis was performed by the powerful technology of ultra-deep pyrosequencing after PCR amplification of part of the env gene, coding for the viral glycoprotein (gp) 120, encompassing the tropism-related V3 loop region. V3 amino acid sequences were used to establish heterogeneity parameters, to build phylogenetic trees and to predict co-receptor usage.

Results
The heterogeneity of proviral and viral genomes derived from monocytes was higher than that of T-lymphocyte origin. Both monocytes and T lymphocytes might contribute to virus rebounding in the circulation after therapy interruptions, but other virus sources might also be involved. In addition, both proviral and circulating viral sequences from monocytes and T lymphocytes were predictive of a predominant R5 coreceptor usage. However, minor variants, segregating from the most frequent quasispecies variants, were present. In particular, in proviral genomes harboured by monocytes, minority variant clusters with a predicted X4 phenotype were found.

Conclusion
This study provided the first direct comparison between the HIV-1 quasispecies archived as provirus in circulating monocytes and T lymphocytes with that of plasma virions replicating in the same cell types. Ultra-deep pyrosequencing generated data with some order of magnitude higher than any previously obtained with conventional approaches. Next generation sequencing allowed the analysis of previously inaccessible aspects of HIV-1 quasispecies, such as co-receptor usage of minority variants present in archived proviral sequences and in actually replicating virions, which may have clinical and therapeutic relevance.
A simple model for the early events of quorum sensing in Pseudomonas aeruginosa: modeling bacterial swarming as the movement of an "activation zone"
Authors: Netotea Sergiu , Bertani Iris , Steindler Laura , Kerényi Ádám , Venturi Vittorio , Pongor Sándor 
Published: February 2009

Abstract

Background
Quorum sensing (QS) is a form of gene regulation based on cell-density that depends on inter-cellular communication. While there are a variety of models for bacterial colony morphology, there is little work linking QS genes to movement in an open system.

Results
The onset of swarming in environmental P. aeruginosa PUPa3 was described with a simplified computational model in which cells in random motion communicate via a diffusible signal (representing N-acyl homoserine lactones, AHL) as well as diffusible, secreted factors (enzymes, biosurfactans, i.e. "public goods") that regulate the intensity of movement and metabolism in a threshold-dependent manner. As a result, an "activation zone" emerges in which nutrients and other public goods are present in sufficient quantities, and swarming is the spontaneous displacement of this high cell-density zone towards nutrients and/or exogenous signals. The model correctly predicts the behaviour of genomic knockout mutants in which the QS genes responsible either for the synthesis (lasI, rhlI) or the sensing (lasR, rhlR) of AHL signals were inactivated. For wild type cells the model predicts sustained colony growth that can however be collapsed by the overconsumption of nutrients.

Conclusion
While in more complex models include self-orienting abilities that allow cells to follow concentration gradients of nutrients and chemotactic agents, in this model, displacement towards nutrients or environmental signals is an emergent property of the community that results from the action of a few, well-defined QS genes and their products. Still the model qualitatively describes the salient properties of QS bacteria, i.e. the density-dependent onset of swarming as well as the response to exogenous signals or cues.

Reviewers
This paper was reviewed by Gáspár Jékely, L. Aravind, Eugene V. Koonin and Artem Novozhilov (nominated by Eugene V. Koonin).
Asymmetric relationships between proteins shape genome evolution
Authors: Notebaart Richard A , Kensche Philip R , Huynen Martijn A , Dutilh Bas E 
Published: February 2009

Abstract
Background
The relationships between proteins are often asymmetric: one protein (A) depends for its function on another protein (B), but the second protein does not depend on the first. In metabolic networks there are multiple pathways that converge into one central pathway. The enzymes in the converging pathways depend on the enzymes in the central pathway, but the enzymes in the latter do not depend on any specific enzyme in the converging pathways. Asymmetric relations are analogous to the “if->then” logical relation where A implies B, but B does not imply A (A->B).

Results
We show that the majority of relationships between enzymes in metabolic flux models of metabolism in Escherichia coli and Saccharomyces cerevisiae are asymmetric. We show furthermore that these asymmetric relationships are reflected in the expression of the genes encoding those enzymes, the effect of gene knockouts and the evolution of genomes. From the asymmetric relative dependency, one would expect that the gene that is relatively independent (B) can occur without the other dependent gene (A), but not the reverse. Indeed, when only one gene of an A->B pair is expressed, is essential, is present in a genome after an evolutionary gain or loss, it tends to be the independent gene (B). This bias is strongest for genes encoding proteins whose asymmetric relationship is evolutionarily conserved.

Conclusions
The asymmetric relations between proteins that arise from the system properties of metabolic networks affect gene expression, the relative effect of gene knockouts and genome evolution in a predictable manner.
PDGF/VEGF signaling controls cell size in Drosophila
Authors: Sims David , Duchek Peter , Baum Buzz 
Published: February 2009

Abstract
Background
In multicellular animals, cell size is controlled by a limited set of conserved intracellular signaling pathways, which when deregulated contribute to tumorigenesis by enabling cells to grow outside their usual niche. To delineate the pathways controlling this process, we screened a genome-scale, image-based Drosophila RNA interference dataset for double-stranded RNAs that reduce the average size of adherent S2R+ cells.

Results
Automated analysis of images from this RNA interference screen identified the receptor tyrosine kinase Pvr, Ras pathway components and several novel genes as regulators of cell size. Significantly, Pvr/Ras signaling also affected the size of other Drosophila cell lines and of larval hemocytes. A detailed genetic analysis of this growth signaling pathway revealed a role for redundant secreted ligands, Pvf2 and Pvf3, in the establishment of an autocrine growth signaling loop. Downstream of Ras1, growth signaling was found to depend on parallel mitogen-activated protein kinase (MAPK) and phospho-inositide-3-kinase (PI3K) signaling modules, as well as the Tor pathway.

Conclusions
This automated genome-wide screen identifies autocrine Pvf/Pvr signaling, upstream of Ras, MAPK and PI3K, as rate-limiting for the growth of immortalized fly cells in culture. Since, Pvf2/3 and Pvr show mutually exclusive in vivo patterns of gene expression, these data suggest that co-expression of this receptor-ligand pair plays a key role in driving cell autonomous growth during the establishment of Drosophila cell lines, as has been suggested to occur during tumor development.