bluuebunny/crossref_metadata_2025 huggingface dataset:
Warm Conveyor Belts in Idealized Moist Baroclinic Wave Simulations
Authors: Schemm Sebastian , Wernli Heini , Papritz Lukas
Published: August 2012

This idealized modeling study of moist baroclinic waves addresses the formation of moist ascending airstreams, so-called warm conveyor belts (WCBs), their characteristics, and their significance for the downstream flow evolution. Baroclinic wave simulations are performed on the f plane, growing from a finite-amplitude upper-level potential vorticity (PV) perturbation on a zonally uniform jet stream. This nonmodal approach allows for dispersive upstream and downstream development and for studying WCBs in the primary cyclone and the downstream cyclone. A saturation adjustment scheme is used as the only difference between the dry and moist simulations, which are systematically compared using a cyclone-tracking algorithm, with an eddy kinetic energy budget analysis, and from a PV perspective. Using trajectories and a selection criterion of maximum ascent, forward- and rearward-sloping WCBs in the moist simulation are identified. No WCB is identified in the dry simulation. Forward-sloping WCBs originate in the warm sector, move into the frontal fracture region, and ascend over the bent-back front, where maximum latent heating occurs in this simulation. The outflow of these WCBs is located at altitudes with prevailing zonal winds; they hence flow anticyclonically (“forward”) into the downstream ridge. In case of a slightly weaker ascent, WCBs curve cyclonically (“rearward”) above the cyclone center. A detailed analysis of the PV evolution along the WCBs reveals PV production in the lower troposphere and destruction in the upper troposphere. Consequently, WCBs transport low-PV air into their outflow region, which contributes to the formation of distinct negative PV anomalies. They, in turn, affect the downstream flow and enhance downstream cyclogenesis.
Climatology and Meteorological Evolution of Major Wildfire Events over the Northeast United States
Authors: Pollina Joseph B. , Colle Brian A. , Charney Joseph J.
Published: August 2012

This study presents a spatial and temporal climatology of major wildfire events, defined as >100 acres burned (>40.47 ha, where 1 ha = 2.47 acre), in the northeast United States from 1999 to 2009 and the meteorological conditions associated with these events. The northeast United States is divided into two regions: region 1 is centered over the higher terrain of the northeast United States and region 2 is primarily over the coastal plain. About 59% of all wildfire events in these two regions occur in April and May, with ~76% in region 1 and ~53% in region 2. There is large interannual variability in wildfire frequency, with some years having 4–5 times more fire events than other years. The synoptic flow patterns associated with northeast United States wildfires are classified using the North American Regional Reanalysis. The most common synoptic pattern for region 1 is a surface high pressure system centered over the northern Appalachians, which occurred in approximately 46% of all events. For region 2, the prehigh anticyclone type extending from southeast Canada and the Great Lakes to the northeast United States is the most common pattern, occurring in about 46% of all events. A trajectory analysis highlights the influence of large-scale subsidence and decreasing relative humidity during the events, with the prehigh pattern showing the strongest subsidence and downslope drying in the lee of the Appalachians.
David and Jonathan: A Case of Unconditional Love?
Authors: Keren Orly
Published: August 2012

This article demonstrates that if there was love between Jonathan and David, it was primarily Jonathan's love for David; or at least, that it was a relationship based on both parties’ personal interests. Jonathan, under the guise of this love, seeks to obtain guarantees for private interests associated with his own future and that of his family and descendants. David, in turn, is concerned about his public image. He never expresses any sentiment for Jonathan; nowhere does the book of Samuel even hint that David returns Jonathan's love. Even when David, after Jonathan's death, pours out his soul in his lament and says: ‘I am distressed for you, my brother Jonathan; very pleasant have you been to me’ (2 Sam. 1.26), he is not expressing sincere grief. Instead, the purpose of the lament is to enhance Jonathan's image after his death, in keeping with custom ( de mortuus nil nisi bonum). It is also plausible that his mourning is a calculated pose, intended to impress the people and persuade them that he is deeply grieved by the death of the previous king's son, with all this implies.
1 Kings 19: A ‘Departure on a Journey’ Story
Authors: Roi Micha
Published: August 2012

This article deals with the story of the prophet Elijah's flight from the threats of Queen Jezebel in 1 Kings 19, which is classified as a story of a ‘departure on a journey’. The article identifies the features of this pattern which are reflected in this account, and adduces the distinctive characteristics of the example under discussion which deviate from the pattern and thereby help elucidate the significance of Elijah's experience and the evaluation of the figure of the prophet. The discussion distinguishes between two journeys described in this chapter: the flight to the desert (vv. 1–8a) and the journey to Horeb (vv. 8b–21).
The Exile of Kish: Syntax and History in Esther 2.5–6
Authors: Koller Aaron J.
Published: August 2012

Recent studies have relied on Esther 2.5–6 to establish the story as fiction or as farce, a way of reading the text that was also the case in ancient and medieval interpretations. This article proposes that that reading strategy ignores the syntactic ambiguity in these verses, an ambiguity that allows for an alternate reading in line with both Hebrew grammar and historical plausibility. As a result, it is argued that a reading which was acceptable to the pre-modern interpreters, without access to historical data regarding the Persian Empire, ought to be rejected today in light of current knowledge.
Attention to Student Needs Mediates the Relationship Between Teacher Emotional Intelligence and Student Misconduct in the Classroom
Authors: Nizielski Sophia , Hallum Suhair , Lopes Paulo N. , Schütz Astrid
Published: August 2012

Understanding the relationship between teacher Emotional intelligence (EI) and student misconduct was the goal of this research. We hypothesized that teachers high in EI tend to establish good working relationships with students by being attentive to their students’ needs. In a sample of 300 Syrian teachers, EI was assessed with the Wong and Law Emotional Intelligence scale (WLEIS; Wong & Law, 2002). Results showed that teachers’ perceived EI was negatively related to student misconduct and that this relationship was mediated by teachers’ attention to student needs. Our findings highlight the role of teachers’ EI in shaping social interactions in the classroom and lead to some practical implications for teacher selection and training.
Emotional Intelligence and Personality as Predictors of Psychological Well-Being
Authors: James Colin , Bore Miles , Zito Susanna
Published: August 2012

Research studies have reported elevated rates of psychological distress (e.g., depression) in practicing lawyers yet little research has examined predictors of such problems in law students. Specific personality traits have been shown to be predictors of a range of psychological problems. We administered a battery of tests to a cohort of 1st-year law students ( n = 150) and measured the Big Five personality traits and emotional intelligence (EI) to examine their relationships to psychological well-being as indicated by coping styles, satisfaction with life, performance-based self-esteem (PBSE), Global Severity Index (GSI) scores from the Brief Symptom Inventory (BSI), depression, and alcohol use. We found that whereas EI was significantly related to three of the five well-being variables, the Big Five personality factor of neuroticism was found to be a stronger predictor of well-being. The findings suggest that EI does not account for additional variance in well-being over personality.
The Heptadic Chronologies of Testament of Levi 16–17 and Their Sources
Authors: Berner Christoph
Published: August 2012

Chapters 16–17 of Testament of Levi ( T. Levi) preserve two examples for the creative reinterpretation of ancient Jewish chronologies in early Christianity. In T. Levi 16, the seventy weeks chronology from Dan. 9 is read as an announcement of Jesus' crucifixion and the destruction of the Second Temple. T. Levi 17, on the other hand, preserves an older Jewish source on the decline of the priesthood. This source was originally composed as a response to the deposition of Onias III (173 BCE) and later expanded through the addition of vv. 9-11 responding to the investment of Jonathan as high priest (152 BCE). For the Christian author of T. Levi 17, the original chronological implications of his source were no longer relevant. He incorporated it for purely theological reasons, namely, as a demonstration for the complete failure of the Jewish priesthood and its subsequent replacement by the eschatological high priest Jesus Christ ( T. Levi 18).
Josephus' Retelling of the Jonathan Narratives*
Authors: Avioz Michael
Published: August 2012

This article analyzes Josephus' rewriting of the biblical narratives about Jonathan, son of Saul (1 Sam. 13–14; 17–23; 31 // Ant. 6.95, 105–29, 205–12, 224–41, 252–53, 369). It compares the biblical narratives to Josephus' rewriting in an attempt to understand the nature of the changes he entered into the biblical text. These include omissions, additions, and changes of focus. Did these changes stem from a different Vorlage or from exegetical reasons? Can these changes be explained as deriving from Josephus' apologetic view?
Willingness to Pay for Nontraditional Attributes Among Participants of a Long-Distance Running Race
Authors: Söderberg Magnus
Published: August 2012

Adding value-driven attributes to sporting events has the potential to increase long-term financial growth for organizers of large sporting events. This study identifies which attributes are most valued by long-distance runners who have participated in Göteborgsvarvet, one of the world’s largest long-distance running races. Runners’ willingness to pay (WTP) for these attributes are calculated based on a choice experiment with data from 1,178 respondents. The primary findings are that (1) runners have the highest WTP for detailed stage time reporting and (2) there are significant variations in WTP among various segments.
Conserved cis-regulatory regions in a large genomic landscape control SHH and BMP-regulated Gremlin1expression in mouse limb buds
Authors: Zuniga Aimée , Laurent Frédéric , Lopez-Rios Javier , Klasen Christian , Matt Nicolas , Zeller Rolf
Published: August 2012

Background

Mouse limb bud is a prime model to study the regulatory interactions that control vertebrate organogenesis. Major aspects of limb bud development are controlled by feedback loops that define a self-regulatory signalling system. The SHH/GREM1/AER-FGF feedback loop forms the core of this signalling system that operates between the posterior mesenchymal organiser and the ectodermal signalling centre. The BMP antagonist Gremlin1 (GREM1) is a critical node in this system, whose dynamic expression is controlled by BMP, SHH, and FGF signalling and key to normal progression of limb bud development. Previous analysis identified a distant cis-regulatory landscape within the neighbouring Formin1 (Fmn1) locus that is required for Grem1 expression, reminiscent of the genomic landscapes controlling HoxD and Shh expression in limb buds.

Results

Three highly conserved regions (HMCO1-3) were identified within the previously defined critical genomic region and tested for their ability to regulate Grem1 expression in mouse limb buds. Using a combination of BAC and conventional transgenic approaches, a 9 kb region located ~70 kb downstream of the Grem1 transcription unit was identified. This region, termed Grem1 Regulatory Sequence 1 (GRS1), is able to recapitulate major aspects of Grem1 expression, as it drives expression of a LacZ reporter into the posterior and, to a lesser extent, in the distal-anterior mesenchyme. Crossing the GRS1 transgene into embryos with alterations in the SHH and BMP pathways established that GRS1 depends on SHH and is modulated by BMP signalling, i.e. integrates inputs from these pathways. Chromatin immunoprecipitation revealed interaction of endogenous GLI3 proteins with the core cis-regulatory elements in the GRS1 region. As GLI3 is a mediator of SHH signal transduction, these results indicated that SHH directly controls Grem1 expression through the GRS1 region. Finally, all cis-regulatory regions within the Grem1 genomic landscape locate to the DNAse I hypersensitive sites identified in this genomic region by the ENCODE consortium.

Conclusions

This study establishes that distant cis-regulatory regions scattered through a larger genomic landscape control the highly dynamic expression of Grem1, which is key to normal progression of mouse limb bud development.
Genetic map of Triticum turgidumbased on a hexaploid wheat population without genetic recombination for D genome
Authors: Zhang Li , Luo Jiang-Tao , Hao Ming , Zhang Lian-Quan , Yuan Zhong-Wei , Yan Ze-Hong , Liu Ya-Xi , Zhang Bo , Liu Bao-Long , Liu Chun-Ji , Zhang Huai-Gang , Zheng You-Liang , Liu Deng-Cai
Published: August 2012

Background

A synthetic doubled-haploid hexaploid wheat population, SynDH1, derived from the spontaneous chromosome doubling of triploid F1 hybrid plants obtained from the cross of hybrids Triticum turgidum ssp. durum line Langdon (LDN) and ssp. turgidum line AS313, with Aegilops tauschii ssp. tauschii accession AS60, was previously constructed. SynDH1 is a tetraploidization-hexaploid doubled haploid (DH) population because it contains recombinant A and B chromosomes from two different T. turgidum genotypes, while all the D chromosomes from Ae. tauschii are homogenous across the whole population. This paper reports the construction of a genetic map using this population.

Results

Of the 606 markers used to assemble the genetic map, 588 (97%) were assigned to linkage groups. These included 513 Diversity Arrays Technology (DArT) markers, 72 simple sequence repeat (SSR), one insertion site-based polymorphism (ISBP), and two high-molecular-weight glutenin subunit (HMW-GS) markers. These markers were assigned to the 14 chromosomes, covering 2048.79 cM, with a mean distance of 3.48 cM between adjacent markers. This map showed good coverage of the A and B genome chromosomes, apart from 3A, 5A, 6A, and 4B. Compared with previously reported maps, most shared markers showed highly consistent orders. This map was successfully used to identify five quantitative trait loci (QTL), including two for spikelet number on chromosomes 7A and 5B, two for spike length on 7A and 3B, and one for 1000-grain weight on 4B. However, differences in crossability QTL between the two T. turgidum parents may explain the segregation distortion regions on chromosomes 1A, 3B, and 6B.

Conclusions

A genetic map of T. turgidum including 588 markers was constructed using a synthetic doubled haploid (SynDH) hexaploid wheat population. Five QTLs for three agronomic traits were identified from this population. However, more markers are needed to increase the density and resolution of this map in the future study.
Global transcriptome analysis of two wild relatives of peanut under drought and fungi infection
Authors: Guimarães Patricia M , Brasileiro Ana CM , Morgante Carolina V , Martins Andressa CQ , Pappas Georgios , Silva Orzenil B , Togawa Roberto , Leal-Bertioli Soraya CM , Araujo Ana CG , Moretzsohn Marcio C , Bertioli David J
Published: August 2012

Background

Cultivated peanut (Arachis hypogaea) is one of the most widely grown grain legumes in the world, being valued for its high protein and unsaturated oil contents. Worldwide, the major constraints to peanut production are drought and fungal diseases. Wild Arachis species, which are exclusively South American in origin, have high genetic diversity and have been selected during evolution in a range of environments and biotic stresses, constituting a rich source of allele diversity. Arachis stenosperma harbors resistances to a number of pests, including fungal diseases, whilst A. duranensis has shown improved tolerance to water limited stress. In this study, these species were used for the creation of an extensive databank of wild Arachis transcripts under stress which will constitute a rich source for gene discovery and molecular markers development.

Results

Transcriptome analysis of cDNA collections from A. stenosperma challenged with Cercosporidium personatum (Berk. and M.A. Curtis) Deighton
,
and A. duranensis submitted to gradual water limited stress was conducted using 454 GS FLX Titanium generating a total of 7.4 x 105 raw sequence reads covering 211 Mbp of both genomes. High quality reads were assembled to 7,723 contigs for A. stenosperma and 12,792 for A. duranensis and functional annotation indicated that 95% of the contigs in both species could be appointed to GO annotation categories. A number of transcription factors families and defense related genes were identified in both species. Additionally, the expression of five A. stenosperma Resistance Gene Analogs (RGAs) and four retrotransposon (FIDEL-related) sequences were analyzed by qRT-PCR. This data set was used to design a total of 2,325 EST-SSRs, of which a subset of 584 amplified in both species and 214 were shown to be polymorphic using ePCR.

Conclusions

This study comprises one of the largest unigene dataset for wild Arachis species and will help to elucidate genes involved in responses to biological processes such as fungal diseases and water limited stress. Moreover, it will also facilitate basic and applied research on the genetics of peanut through the development of new molecular markers and the study of adaptive variation across the genus.
Insights into the genome structure and copy-number variation of Eimeria tenella
Authors: Lim Lik-Sin , Tay Yea-Ling , Alias Halimah , Wan Kiew-Lian , Dear Paul H
Published: August 2012

Background

Eimeriais a genus of parasites in the same phylum (Apicomplexa) as human parasites such asToxoplasma,Cryptosporidiumand the malaria parasitePlasmodium.As an apicomplexan whose life-cycle involves a single host,Eimeriais a convenient model for understanding this group of organisms. Although the genomes of the Apicomplexa are diverse, that ofEimeriais unique in being composed of large alternating blocks of sequence with very different characteristics - an arrangement seen in no other organism. This arrangement has impeded efforts to fully sequence the genome ofEimeria, which remains the last of the major apicomplexans to be fully analyzed. In order to increase the value of the genome sequence data and aid in the effort to gain a better understanding of theEimeria tenellagenome, we constructed a whole genome map for the parasite.

Results

A total of 1245 contigs representing 70.0% of the whole genome assembly sequences (Wellcome Trust Sanger Institute) were selected and subjected to marker selection. Subsequently, 2482 HAPPY markers were developed and typed. Of these, 795 were considered as usable markers, and utilized in the construction of a HAPPY map. Markers developed from chromosomally-assigned genes were then integrated into the HAPPY map and this aided the assignment of a number of linkage groups to their respective chromosomes. BAC-end sequences and contigs from whole genome sequencing were also integrated to improve and validate the HAPPY map. This resulted in an integrated HAPPY map consisting of 60 linkage groups that covers approximately half of the estimated 60 Mb genome. Further analysis suggests that the segmental organization first seen in Chromosome 1 is present throughout the genome, with repeat-poor (P) regions alternating with repeat-rich (R) regions. Evidence of copy-number variation between strains was also uncovered.

Conclusions

This paper describes the application of a whole genome mapping method to improve the assembly of the genome ofE. tenellafrom shotgun data, and to help reveal its overall structure. A preliminary assessment of copy-number variation (extra or missing copies of genomic segments) between strains ofE. tenellawas also carried out. The emerging picture is of a very unusual genome architecture displaying inter-strain copy-number variation. We suggest that these features may be related to the known ability of this parasite to rapidly develop drug resistance.
Transcriptional profiling of gastric epithelial cells infected with wild type or arginase-deficient Helicobacter pylori
Authors: Kim Songhee H , Sierra Rosa A , McGee David J , Zabaleta Jovanny
Published: August 2012

Background

Helicobacter pylori causes acute and chronic gastric inflammation induced by proinflammatory cytokines and chemokines secreted by cells of the gastric mucosa, including gastric epithelial cells. Previous studies have demonstrated that the bacterial arginase, RocF, is involved in inhibiting T cell proliferation and CD3ζ expression, suggesting that arginase could be involved in a more general dampening of the immune response, perhaps by down-regulation of certain pro-inflammatory mediators.

Results

Global transcriptome analysis was performed on AGS gastric epithelial cells infected for 16 hours with a wild type Helicobacter pylori strain 26695, an arginase mutant (rocF-) or a rocF

+
complemented strain. H. pylori infection triggered altered host gene expression in genes involved in cell movement, death/growth/proliferation, and cellular function and maintenance. While the wild type strain stimulates host inflammatory pathways, the rocF- mutant induced significantly more expression of IL-8. The results of the microarray were verified using real-time PCR, and the differential levels of protein expression were confirmed by ELISA and Bioplex analysis. MIP-1B was also significantly secreted by AGS cells after H. pylori rocF- mutant infection, as determined by Bioplex. Even though not explored in this manuscript, the impact that the results presented here may have on the development of gastritis, warrant further research to understand the underlying mechanisms of the relationship between H. pylori RocF and IL-8 induction.

Conclusions

We conclude that H. pylori arginase modulates multiple host signaling and metabolic pathways of infected gastric epithelial cells. Arginase may play a critical role in anti-inflammatory host responses that could contribute to the ability of H. pylori to establish chronic infections.
Medication documentation in a primary care network serving North Carolina medicaid patients: results of a cross-sectional chart review
Authors: Olson Matthew D , Tong Gretchen L , Steiner Beat D , Viera Anthony J , Ashkin Evan , Newton Warren P
Published: August 2012

Background

Medical records that do not accurately reflect the patient’s current medication list are an open invitation to errors and may compromise patient safety.

Methods

This cross-sectional study compares primary care provider (PCP) medication lists and pharmacy claims for 100 patients seen in 8 primary care practices and examines the association of congruence with demographic, clinical, and practice characteristics. Medication list congruence was measured as agreement of pharmacy claims with the entire PCP chart, including current medication list, visit notes, and correspondence sections.

Results

Congruence between pharmacy claims and the PCP chart was 65%. Congruence was associated with large chronic disease burden, frequent PCP visits, group practice, and patient age ≥45 years.

Conclusion

Agreement of medication lists between the PCP chart and pharmacy records is low. Medication documentation was more accurate among patients who have more chronic conditions, those who have frequent PCP visits, those whose practice has multiple providers, and those at least 45 years of age. Improved congruence among patients with multiple chronic conditions and in group practices may reflect more frequent visits and reviews by providers.
Interferon regulatory factor 4 binding protein is a novel p53 target gene and suppresses cisplatin-induced apoptosis of breast cancer cells
Authors: Yang Mingzhen , Yuan Fang , Li Peng , Chen Zhongjiao , Chen An , Li Shuhui , Hu Chuanmin
Published: August 2012

Background

Our previous work demonstrated that ectopic expression of interferon regulatory factor 4 binding protein (IBP) was correlated with the malignant behaviour of human breast cancer cells. The mechanisms controlling differential expression of IBP in breast cancer still remain unknown.

Results

To investigate the mechanism of IBP dysregulation in breast cancer, we identified IBP was a novel p53 target gene. IBP expression was negatively regulated by wild-type p53 and was p53 dependently suppressed by DNA damage agent cisplatin. Furthermore, high levels of IBP were found to decrease cisplatin-induced growth suppression and apoptotic cell death, which was associated with decreased p53 activity and imbalanced Bcl-2 family member expression.

Conclusions

IBP is a novel p53 target gene which suppresses cisplatin-mediated apoptosis of breast cancer cells via negative feedback regulation of the p53 signalling pathway, suggesting IBP may serve as a target for pharmacologic intervention of breast cancer resistant to cisplatin therapy.
Genotype-phenotype associations in neurofibromatosis type 1 (NF1): an increased risk of tumor complications in patients with NF1splice-site mutations?
Authors: Alkindy Adila , Chuzhanova Nadia , Kini Usha , Cooper David N , Upadhyaya Meena
Published: August 2012

Neurofibromatosis type 1 (NF1) is a complex neurocutaneous disorder with an increased susceptibility to develop both benign and malignant tumors but with a wide spectrum of inter and intrafamilial clinical variability. The establishment of genotype-phenotype associations in NF1 is potentially useful for targeted therapeutic intervention but has generally been unsuccessful, apart from small subsets of molecularly defined patients. The objective of this study was to evaluate the clinical phenotype associated with the specific types ofNF1mutation in a retrospectively recorded clinical dataset comprising 149NF1mutation-known individuals from unrelated families. Each patient was assessed for ten NF1-related clinical features, including the number of café-au-lait spots, cutaneous and subcutaneous neurofibromas and the presence/absence of intertriginous skin freckling, Lisch nodules, plexiform and spinal neurofibromas, optic gliomas, other neoplasms (in particular CNS gliomas, malignant peripheral nerve sheath tumors (MPNSTs), juvenile myelomonocytic leukemia, rhabdomyosarcoma, phaechromocytoma, gastrointestinal stromal tumors, juvenile xanthogranuloma, and lipoma) and evidence of learning difficulties. Gender and age at examination were also recorded. Patients were subcategorized according to their associatedNF1germ line mutations: frame shift deletions (52), splice-site mutations (23), nonsense mutations (36), missense mutations (32) and other types of mutation (6). A significant association was apparent between possession of a splice-site mutation and the presence of brain gliomas and MPNSTs (p = 0.006). If confirmed, these findings are likely to be clinically important since up to a third of NF1 patients harbor splice-site mutations. A significant influence of gender was also observed on the number of subcutaneous neurofibromas (females,p = 0.009) and preschool learning difficulties (females,p = 0.022).
Virus-producing cells determine the host protein profiles of HIV-1 virion cores
Authors: Santos Steven , Obukhov Yuri , Nekhai Sergei , Bukrinsky Michael , Iordanskiy Sergey
Published: August 2012

Background

Upon HIV entry into target cells, viral cores are released and rearranged into reverse transcription complexes (RTCs), which support reverse transcription and also protect and transport viral cDNA to the site of integration. RTCs are composed of viral and cellular proteins that originate from both target and producer cells, the latter entering the target cell within the viral core. However, the proteome of HIV-1 viral cores in the context of the type of producer cells has not yet been characterized.

Results

We examined the proteomic profiles of the cores purified from HIV-1 NL4-3 virions assembled in Sup-T1 cells (T lymphocytes), PMA and vitamin D3activated THP1 (model of macrophages, mMΦ), and non-activated THP1 cells (model of monocytes, mMN) and assessed potential involvement of identified proteins in the early stages of infection using gene ontology information and data from genome-wide screens on proteins important for HIV-1 replication. We identified 202 cellular proteins incorporated in the viral cores (T cells: 125, mMΦ: 110, mMN: 90) with the overlap between these sets limited to 42 proteins. The groups of RNA binding (29), DNA binding (17), cytoskeleton (15), cytoskeleton regulation (21), chaperone (18), vesicular trafficking-associated (12) and ubiquitin-proteasome pathway-associated proteins (9) were most numerous. Cores of the virions from SupT1 cells contained twice as many RNA binding proteins as cores of THP1-derived virus, whereas cores of virions from mMΦ and mMN were enriched in components of cytoskeleton and vesicular transport machinery, most probably due to differences in virion assembly pathways between these cells. Spectra of chaperones, cytoskeletal proteins and ubiquitin-proteasome pathway components were similar between viral cores from different cell types, whereas DNA-binding and especially RNA-binding proteins were highly diverse. Western blot analysis showed that within the group of overlapping proteins, the level of incorporation of some RNA binding (RHA and HELIC2) and DNA binding proteins (MCM5 and Ku80) in the viral cores from T cells was higher than in the cores from both mMΦ and mMN and did not correlate with the abundance of these proteins in virus producing cells.

Conclusions

Profiles of host proteins packaged in the cores of HIV-1 virions depend on the type of virus producing cell. The pool of proteins present in the cores of all virions is likely to contain factors important for viral functions. Incorporation ratio of certain RNA- and DNA-binding proteins suggests their more efficient, non-random packaging into virions in T cells than in mMΦ and mMN.
Single mutations in the transmembrane envelope protein abrogate the immunosuppressive property of HIV-1
Authors: Morozov Vladimir A , Morozov Alexey V , Semaan Marwan , Denner Joachim
Published: August 2012

Background

The mechanism by which HIV-1 induces AIDS is still unknown. Previously, synthetic peptides corresponding to the conserved immunosuppressive (isu) domain in gp41 of HIV-1 had been shown to inhibit proliferation and to modulate cytokine expression of immune cells. The question is, whether the viral gp41 can do the same.

Results

We show for the first time that two trimeric forms of glycosylated gp41 released from transfected human cells modulated expression of cytokines and other genes in human PBMCs in the same manner, but at least seven hundred-fold stronger compared to that induced by the isu peptide. Single amino acid substitutions in the isu domain of gp41 introduced by site-directed mutagenesis abrogated this property. Furthermore, replication-competent HIV-1 with a mutation in the isu domain of gp41 did not modulate the cytokine expression, while wild-type virus did. Interestingly, most of the abrogating mutations were not reported in viral sequences derived from infected individuals, suggesting that mutated non-immunosuppressive viruses were eliminated by immune responses. Finally, immunisation of rats with gp41 mutated in the isu domain resulted in increased antibody responses compared with the non-mutated gp41. These results show that non-mutated gp41 is immunosuppressive in immunisation experiments, i.e.in vivo, and this has implications for the vaccine development.

Conclusions

These findings indicate that the isu domain of gp41 modulates cytokine expressionin vitroand suppresses antibody responsein vivoand therefore may contribute to the virus induced immunodeficiency.
Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy
Authors: Betancor Gilberto , Garriga César , Puertas Maria C , Nevot María , Anta Lourdes , Blanco José L , Pérez-Elías M Jesús , de Mendoza Carmen , Martínez Miguel A , Martinez-Picado Javier , Menéndez-Arias Luis ,   for the Resistance Platform of the Spanish AIDS Research Network (ResRIS)
Published: August 2012

Background

Thymidine analogue resistance mutations (TAMs) selected under treatment with nucleoside analogues generate two distinct genotypic profiles in the HIV-1 reverse transcriptase (RT): (i) TAM1: M41L, L210W and T215Y, and (ii) TAM2: D67N, K70R and K219E/Q, and sometimes T215F. Secondary mutations, including thumb subdomain polymorphisms (e.g.R284K) have been identified in association with TAMs. We have identified mutational clusters associated with virological failure during salvage therapy with tenofovir/emtricitabine-based regimens. In this context, we have studied the role of R284K as a secondary mutation associated with mutations of the TAM1 complex.

Results

The cross-sectional study carried out with >200 HIV-1 genotypes showed that virological failure to tenofovir/emtricitabine was strongly associated with the presence of M184V (P <10-10) and TAMs (P <10-3), while K65R was relatively uncommon in previously-treated patients failing antiretroviral therapy. Clusters of mutations were identified, and among them, the TAM1 complex showed the highest correlation coefficients. Covariation of TAM1 mutations and V118I, V179I, M184V and R284K was observed. Virological studies showed that the combination of R284K with TAM1 mutations confers a fitness advantage in the presence of zidovudine or tenofovir. Studies with recombinant HIV-1 RTs showed that when associated with TAM1 mutations, R284K had a minimal impact on zidovudine or tenofovir inhibition, and in their ability to excise the inhibitors from blocked DNA primers. However, the mutant RT M41L/L210W/T215Y/R284K showed an increased catalytic rate for nucleotide incorporation and a higher RNase H activity in comparison with WT and mutant M41L/L210W/T215Y RTs. These effects were consistent with its enhanced chain-terminated primer rescue on DNA/DNA template-primers, but not on RNA/DNA complexes, and can explain the higher fitness of HIV-1 having TAM1/R284K mutations.

Conclusions

Our study shows the association of R284K and TAM1 mutations in individuals failing therapy with tenofovir/emtricitabine, and unveils a novel mechanism by which secondary mutations are selected in the context of drug-resistance mutations.
Increased cellular immune responses and CD4+ T-cell proliferation correlate with reduced plasma viral load in SIV challenged recombinant simian varicella virus - simian immunodeficiency virus (rSVV-SIV) vaccinated rhesus macaques
Authors: Pahar Bapi , Gray Wayne L , Phelps Kimberly , Didier Elizabeth S , deHaro Eileen , Marx Preston A , Traina-Dorge Vicki L
Published: August 2012

Background

An effective AIDS vaccine remains one of the highest priorities in HIV-research. Our recent study showed that vaccination of rhesus macaques with recombinant simian varicella virus (rSVV) vector – simian immunodeficiency virus (SIV) envelope and gag genes, induced neutralizing antibodies and cellular immune responses to SIV and also significantly reduced plasma viral loads following intravenous pathogenic challenge with SIVMAC251/CX1.

Findings

The purpose of this study was to define cellular immunological correlates of protection in rSVV-SIV vaccinated and SIV challenged animals. Immunofluorescent staining and multifunctional assessment of SIV-specific T-cell responses were evaluated in both Experimental and Control vaccinated animal groups. Significant increases in the proliferating CD4+ T-cell population and polyfunctional T-cell responses were observed in all Experimental-vaccinated animals compared with the Control-vaccinated animals.

Conclusions

Increased CD4+ T-cell proliferation was significantly and inversely correlated with plasma viral load. Increased SIV-specific polyfunctional cytokine responses and increased proliferation of CD4+ T-cell may be crucial to control plasma viral loads in vaccinated and SIVMAC251/CX1 challenged macaques.
Deficits in retrospective and prospective components underlying prospective memory tasks in amnestic mild cognitive impairment
Authors: Zhou Ting , Broster Lucas S , Jiang Yang , Bao Feng , Wang Huali , Li Juan
Published: August 2012

Objectives

By use of purer indices of PM and RM components than previous studies and adoption of three PM task types, the present study aimed to investigate the deficits of these two components underlying global impairment at a PM task in individuals with amnestic mild cognitive impairment (aMCI).

Methods

Nineteen aMCI patients and 22 normal controls were examined on event-, time- and activity-based PM tasks. Separate scores were obtained for initiation of intentions (i.e. PM component) and for the content of the intentions (i.e. RM component).

Results

Individuals with aMCI achieved lower PM component (but not RM component) scores than NCs across all three PM tasks. Furthermore, there was a trend for greater impairment on activity-based than time-based and event-based PM tasks, but which did not reach significance. In addition, a significant association between PM component and an executive function test was observed in aMCI group. PM task performance, especially activity-based PM task performance and PM component performance, successfully discriminated between aMCI and NC and was able to do so above and beyond the executive function tests.

Conclusions

Our finding suggested that the deficits in PM component, related to a disrupted executive control processes, were responsible for the impaired ability of individuals with aMCI to realize delayed intentions.
Gamma Knife® radiosurgery for recurrent intracranial olfactory neuroblastoma (esthesioneuroblastoma): a case report
Authors: Dinca Eduard B , Radatz Matthias W , Rowe Jeremy , Kemeny Andras A
Published: August 2012

Background

We report the use of salvage radiosurgery to manage an aggressive olfactory neuroblastoma (esthesioneuroblastoma) with multiple recurrences and intracranial extension.

Case presentation

A 43-year-old Caucasian woman presented 11 years ago with progressive nasal blockage and headaches. A necrotic polyp originating in her left middle meatus and extending to the ethmoid air cells and cribriform plate (Kadish stage C) was radically resected via a craniofacial approach. Four years later, a local recurrence extending into her left cavernous sinus was identified and deemed inoperable. She received vincristine, ifosfamide, doxorubicin and etoposide chemotherapy (with minimal benefit) and external beam radiotherapy (60Gy in 30 fractions) to her skull base. Two years later, tumour extension in her left neck was treated with radical radiotherapy. She developed visual disturbances in her left eye, which progressed to blindness in the next two years. Having exhausted chemoradiotherapy, the left cavernous sinus esthesioneuroblastoma was treated with Gamma Knife® radiosurgery 2 years ago (20Gy at 50% isodose, tumour volume 7.5cm3). At one year, there was dramatic reduction in the tumour and no new symptoms; however, there were new tumour foci (in her left frontal lobe and above her right orbital apex). These were again treated with radiosurgery (20Gy at 50% isodose, total tumour volume 0.67cm3). Repeat imaging at six months showed no further disease progression.

Conclusion

Whilst rare, olfactory neuroblastoma (esthesioneuroblastoma) can present management challenges and Gamma Knife® radiosurgery may prove a useful strategy in controlling intracranial spread.
Calcified gallstone in a 3 year-old boy: a case report
Authors: Barthel Erik R , Pierce James R , Zmora Osnat , Harlan Susan R , Russell Sudha , Shin Cathy
Published: August 2012

Background

Gallstones are relatively rare in children. At-risk populations include patients suffering from hemolysis syndromes. Regardless of etiology, these patients usually will present with postprandial abdominal pain, and ultrasonography is the mainstay of diagnosis. However, some gallstones are radiopaque and can be visualized on plain abdominal radiography.

Case presentation

We present the uncommon but classic plain x-ray finding of a calcified gallstone in a 3 year-old Hispanic boy. He was treated with elective laparoscopic cholecystectomy.

Conclusions

Cholelithiasis is rare in children, and calcified stones that will appear on plain abdominal x-rays are even rarer. If symptomatic, cholecystectomy by a pediatric surgeon is the treatment of choice. We discuss some of the recent developments in treatment of this condition in this patient population.
Molecular characterization of thyroid hormone receptor beta from Schistosoma japonicum and assessment of its potential as a vaccine candidate antigen against schistosomiasis in BALB/c mice
Authors: Qiu Chunhui , Liu Shengfa , Hong Yang , Fu Zhiqiang , Wei Meimei , Ai Dezhou , Lin Jiaojiao
Published: August 2012

Background

Thyroid hormones (TH) modulate growth, development and differentiation and metabolic processes by interacting with thyroid hormone receptors (THRs). The purpose of this study was to identify a novel thyroid hormone receptor beta encoding gene of Schistosoma japonicum (SjTHRβ) and to investigate its potential as a vaccine candidate antigen against schistosomiasis in BALB/c mice.

Methods

The full-length cDNA sequence of SjTHRβ, its gene organization, and its transcript levels were characterized, and the phylogenetic relationship between THR, RAR and RXR from other organisms were analysis, the ability of this protein binding to a conserved DNA core motif, and its potential as a vaccine candidate antigen against schistosomiasis in BALB/c mice were evaluated.

Results

The SjTHRβ cDNA was cloned, verified by 5’ and 3’ Rapid Amplification of cDNA Ends and shown to be polyadenylated at the 3’end, suggesting the transcript is full-length. SjTHRβ is homologous to THRs from other species and has a predicted conservative DNA binding domain and ligand binding domain that normally characterizes these receptors. A comparative quantitative PCR analysis showed that SjTHRβ was the highest expressed in 21d worms and the lowest in 7 d and 13 d schistosomula. The cDNA corresponding to DNA binding domain (SjTHRβ-DBD) and ligand binding domain (SjTHRβ-LBD) were cloned and subsequently expressed in E coli. The expressed proteins were used to immunize mice and generate specific serum against recombinant SjTHRβ (rSjTHRβ). Western blotting revealed that anti-rSjTHRβ-LBD serum recognized two protein bands in extracts from 21 d worm with molecular sizes of approximately 95 kDa and 72 kDa. Electrophoretic mobility shift assay (EMSA) analysis showed that rSjTHRβ-DBD could bind to a conserved DNA core motif. Immunization of BALB/c mice with rSjTHRβ-LBD could induce partial protective efficacy(27.52% worm reduction and 29.50% liver eggs reduction)against schistosome infection. Enzyme-linked immunosorbent assay showed that mice vaccinated with recombinant SjTHRβ-LBD (rSjTHRβ-LBD) generated increased levels of specific IgG, IgG1 and IgG2a antibody. Bio-plex analysis demonstrated that rSjTHRβ-LBD induced considerably higher levels of T helper 1 cytokines (IL-2, IL-12 and TNF-α) than T helper 2 cytokines (IL-10, IL-4), suggesting that rSjTHRβ-LBD vaccination could stimulate mixed Th1/Th2 types with Th1 dominant immune responses.

Conclusions

Our study presented here identified SjTHRβ as a new schistosome THR that might play an important role in host-parasite interaction and be a vaccine candidate for schistosomiasis.
Acute graft versus host disease after orthotopic liver transplantation
Authors: Rogulj Inga Mandac , Deeg Joachim , Lee Stephanie J
Published: August 2012

Graft versus host disease (GVHD) is an uncommon complication after orthotopic liver transplantation (OLT) with an incidence of 0.1–2%, but an 80–100% mortality rate. Patients can present with skin rashes, diarrhea, and bone marrow aplasia between two to eight weeks after OLT. Diagnosis of GVHD is made based on clinical and histologic evidence, supported by chimerism studies showing donor HLA alleles in the recipient bone marrow or blood. Several therapeutic approaches have been used for the management of GVHD after OLT including increased immunosuppression, decreased immunosuppression, and cellular therapies. However, success rates have been low, and new approaches are needed.
Reliability of the TekScan MatScan® system for the measurement of postural stability in older people with rheumatoid arthritis
Authors: Brenton‐Rule Angela , Mattock Joshua , Carroll Matthew , Dalbeth Nicola , Bassett Sandra , Menz Hylton B , Rome Keith
Published: August 2012

Background

Postural stability can be measured in clinical and research settings using portable plantar pressure systems. People with rheumatoid arthritis (RA) have decreased postural stability compared to non‐RA populations and impaired postural stability is associated with falls in people with RA. The purpose of this study was therefore to investigate the reliability of the TekScan MatScan® system in assessing postural stability in people with RA.

Methods

Twenty three participants with RA, mean (SD) age 69.74 (10.1) years, were assessed in barefoot double‐limb quiet standing, with eyes open and eyes closed, for antero‐posterior and medio‐lateral postural sway values. Three repetitions, at a sampling frequency of 40 Hz, were recorded for each test condition to obtain a mean value. Measurements were repeated one hour later. Intraclass correlation coefficients (ICC) with 95% confidence intervals (CI) were calculated to determine between‐session reliability. Measurement error was assessed through the calculation of the standard error of the measurement (SEM) and the smallest real difference (SRD).

Results

The system displayed good to excellent reliability for antero‐posterior and medio‐lateral sway, with eyes open and closed, as indicated by ICC values ranging from 0.84 to 0.92. Measurement error, as evidenced by the SEM, ranged from 1.27 to 2.35 mm. The degree of change required to exceed the expected trial to trial variability was relatively high, compared to mean values, with SRD ranging from 3.08 to 5.71 mm.

Conclusions

The portability and ease of use of the TekScan MatScan® makes it a useful tool for the measurement of postural stability in clinical and research settings. The TekScan MatScan® system can reliably measure double‐limb quiet standing in older people, aged 60 to 80 years, with RA.