bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic infection during placental malaria is associated with up-regulation of cycloxygenase-2
Authors: Sarr Demba , Aldebert Delphine , Marrama Laurence , Frealle Emilie , Gaye Alioune , Brahim Hamoud O , Niang Makhtar , Dangou Jean Marie , Mercereau-Puijalon Odile , Lehesran Jean Yves , Jambou Ronan 
Published: March 2010

AbstractBackgroundPlacental malaria (PM) is associated with poor foetal development, but the pathophysiological processes involved are poorly understood. Cyclooxygenase (COX) and lipoxygenase (LOX) which convert fatty acids to prostaglandins and leukotrienes, play important roles in pregnancy and foetal development. COX-2, currently targeted by specific drugs, plays a dual role as it associates with both pre-eclampsia pathology and recovery during infection. The role of COX during PM was questioned by quantifying at delivery COX-1, COX-2, 15-LOX, and IL-10 expression in two groups of malaria infected and uninfected placenta.MethodsPlacental biopsies were collected at delivery for mRNA isolation and quantification, using real time PCR.ResultsCOX-2 and IL-10 mRNAs increased mainly during chronic infections (nine- and five-times, respectively), whereas COX-1 transcripts remained constant. COX-2 over-expression was associated with a higher birth weight of the baby, but with a lower rate of haemoglobin of the mother. It was associated with a macrophage infiltration of the placenta and with a low haemozoin infiltration. In the opposite way, placental infection was associated with lower expression of 15-LOX mRNA. A high degree of haemozoin deposition correlates with low birth weight and decreased expression of COX-2.ConclusionThese data provide evidence that COX-2 and IL-10 are highly induced during chronic infection of the placenta, but were not associated with preterm delivery or low birth weight. The data support the involvement of COX-2 in the recovery phase of the placental infection.
Markers of anti-malarial drug resistance in Plasmodium falciparum isolates from Swaziland: identification of pfmdr1-86F in natural parasite isolates
Authors: Dlamini Sabelo V , Beshir Khalid , Sutherland Colin J 
Published: March 2010

Abstract

Background
The development of Plasmodium falciparum resistance to chloroquine (CQ) has limited its use in many malaria endemic areas of the world. However, despite recent drug policy changes to adopt the more effective artemisinin-based combination (ACT) in Africa and in the Southern African region, in 2007 Swaziland still relied on CQ as first-line anti-malarial drug.

Methods
Parasite DNA was amplified from P. falciparum isolates from Swaziland collected in 1999 (thick smear blood slides) and 2007 (filter paper blood spots). Markers of CQ and sulphadoxine-pyrimethamine (SP) resistance were identified by probe-based qPCR and DNA sequencing.

Results
Retrospective microscopy, confirmed by PCR amplification, found that only six of 252 patients treated for uncomplicated malaria in 2007 carried detectable P. falciparum. The pfcrt haplotype 72C/73V/74I/75E/76T occurred at a prevalence of 70% (n = 64) in 1999 and 83% (n = 6) in 2007. Prevalence of the pfmdr1-86N allele was 24% in 1999 and 67% in 2007. A novel substitution of phenylalanine for asparagine at codon 86 of pfmdr1 (N86F) occurred in two of 51 isolates successfully amplified from 1999. The pfmdr1-1246Y allele was common in 1999, with a prevalence of 49%, but was absent among isolates collected in 2007. The 86N/184F/1246D pfmdr1 haplotype, associated with enhanced parasite survival in patients treated with artemether-lumefantrine, comprised 8% of 1999 isolates, and 67% among 2007 isolates. The pfdhfr triple-mutant 16C/51I/59R/108N/164I haplotype associated with pyrimethamine resistance was common in both 1999 (82%, n = 34) and 2007 (50%, n = 6), as was the wild-type 431I/436S/437A/540K/581A/613A haplotype of pfdhps (100% and 93% respectively in 1999 and 2007). The quintuple-mutant haplotype pfdhfr/pfdhps-CIRNI/ISGEAA, associated with high-level resistance to SP, was rare (9%) among 1999 isolates and absent among 2007 isolates.

Conclusions
The prevalence of pfcrt and pfmdr1 alleles reported in this study is consistent with a parasite population under sustained CQ drug pressure. The low prevalence of dhps-437G and dhps-540E mutations (ISGEAA) and the rarity of quintuple-mutant haplotype pfdhfr/pfdhps-CIRNI/ISGEAA suggest that SP retains some efficacy in Swaziland. Anti-malarial policy changes in neighbouring countries may have had an impact on the prevalence of molecular markers of anti-malarial resistance in Swaziland, and it is hoped that this new information will add to understanding of the regional anti-malarial resistance map.
Identification and characterization of Dlc1 isoforms in the mouse and study of the biological function of a single gene trapped isoform
Authors: Sabbir Mohammad G , Wigle Nichola , Loewen Shauna , Gu Yuan , Buse Cordula , Hicks Geoffrey G , Mowat Michael RA 
Published: March 2010

Abstract

Background
The Dlc1 (deleted in liver cancer 1) tumour suppressor gene codes for a RhoGTPase activating protein that is found inactivated in many tumour types. Several transcriptional isoforms have been described but the functional significance and tissue distribution of each form is presently poorly understood. Also, differences in the number of isoforms and splice variants reported still exist between different mammalian species. In order to better understand the number and function of the different variants of the Dlc1 gene in the mouse, we have carried out a detailed analysis. Extensive 3' RACE experiments were carried out in order to identify all possible Dlc1 isoforms and splice variants in the mouse. In addition, we have generated a gene trapped mouse that targets one of these isoforms in order to study its biological function. The effect of this gene trap insertion on the splicing of other isoforms has also been studied.

Results
In addition to the known 6.1 and 6.2 Kb transcripts of Dlc1, our study revealed the existence of a novel 7.6 Kb transcriptional isoform in the mouse, which corresponds to the human 7.4 Kb (KIAA1723) cDNA transcript. A gene trapped embryonic cell line, with an insertion between Exon 1 and 2 of the 6.1 Kb transcriptional isoform, was used to generate a transgenic mouse. This line showed a significant reduction in the expression of the trapped isoform. However, reduced expression of the other isoforms was not seen. Mice heterozygous for the gene trapped allele were phenotypically normal, but homozygous mutant embryos did not survive beyond 10.5 days post coitum. Dlc1gt/gt embryos showed defects in the brain, heart, and placental blood vessels. Cultured serum-free mouse embryo cells from Dlc1 deficient embryos had elevated RhoA activity and displayed alterations in the organization of actin filaments and focal adhesions. The Dlc1 deficient cells also exhibited increased wound closure in an in vitro scratch assay.

Conclusions
The mouse has three major transcriptional isoforms of the Dlc1 gene that are differentially expressed in various tissues. A mouse with exon 1 of the 6.1 Kb transcript gt resulted in hypomorphic expression of Dlc1 protein and an embryonic lethal phenotype in the homozygous condition, which indicates that this isoform plays a major role in mouse development. The Dlc1 deficient cells showed altered cytoskeleton structure, increased RhoA activity and cellular migration.
Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging
Authors: Bhaskar Sonu , Tian Furong , Stoeger Tobias , Kreyling Wolfgang , de la Fuente Jesús M , Grazú Valeria , Borm Paul , Estrada Giovani , Ntziachristos Vasilis , Razansky Daniel 
Published: March 2010

AbstractNanotechnology has brought a variety of new possibilities into biological discovery and clinical practice. In particular, nano-scaled carriers have revolutionalized drug delivery, allowing for therapeutic agents to be selectively targeted on an organ, tissue and cell specific level, also minimizing exposure of healthy tissue to drugs. In this review we discuss and analyze three issues, which are considered to be at the core of nano-scaled drug delivery systems, namely functionalization of nanocarriers, delivery to target organs andin vivoimaging. The latest developments on highly specific conjugation strategies that are used to attach biomolecules to the surface of nanoparticles (NP) are first reviewed. Besides drug carrying capabilities, the functionalization of nanocarriers also facilitate their transport to primary target organs. We highlight the leading advantage of nanocarriers, i.e. their ability to cross the blood-brain barrier (BBB), a tightly packed layer of endothelial cells surrounding the brain that prevents high-molecular weight molecules from entering the brain. The BBB has several transport molecules such as growth factors, insulin and transferrin that can potentially increase the efficiency and kinetics of brain-targeting nanocarriers. Potential treatments for common neurological disorders, such as stroke, tumours and Alzheimer's, are therefore a much sought-after application of nanomedicine. Likewise any other drug delivery system, a number of parameters need to be registered once functionalized NPs are administered, for instance their efficiency in organ-selective targeting, bioaccumulation and excretion. Finally, directin vivoimaging of nanomaterials is an exciting recent field that can provide real-time tracking of those nanocarriers. We review a range of systems suitable forin vivoimaging and monitoring of drug delivery, with an emphasis on most recently introduced molecular imaging modalities based on optical and hybrid contrast, such as fluorescent protein tomography and multispectral optoacoustic tomography. Overall, great potential is foreseen for nanocarriers in medical diagnostics, therapeutics and molecular targeting. A proposed roadmap for ongoing and future research directions is therefore discussed in detail with emphasis on the development of novel approaches for functionalization, targeting and imaging of nano-based drug delivery systems, a cutting-edge technology poised to change the ways medicine is administered.
Construction of an Yucatec Maya soil classification and comparison with the WRB framework
Authors: Bautista Francisco , Zinck J Alfred 
Published: March 2010

Abstract
Background
Mayas living in southeast Mexico have used soils for millennia and provide thus a good example for understanding soil-culture relationships and for exploring the ways indigenous people name and classify the soils of their territory. This paper shows an attempt to organize the Maya soil knowledge into a soil classification scheme and compares the latter with the World Reference Base for Soil Resources (WRB).

Methods
Several participative soil surveys were carried out in the period 2000-2009 with the help of bilingual Maya-Spanish-speaking farmers. A multilingual soil database was built with 315 soil profile descriptions.

Results
On the basis of the diagnostic soil properties and the soil nomenclature used by Maya farmers, a soil classification scheme with a hierarchic, dichotomous and open structure was constructed, organized in groups and qualifiers in a fashion similar to that of the WRB system. Maya soil properties were used at the same categorical levels as similar diagnostic properties are used in the WRB system.

Conclusions
The Maya soil classification (MSC) is a natural system based on key properties, such as relief position, rock types, size and quantity of stones, color of topsoil and subsoil, depth, water dynamics, and plant-supporting processes. The MSC addresses the soil properties of surficial and subsurficial horizons, and uses plant communities as qualifier in some cases. The MSC is more accurate than the WRB for classifying Leptosols.
The value of SPECT in the detection of stress injury to the pars interarticularis in patients with low back pain
Authors: Zukotynski Katherine , Curtis Christine , Grant Frederick D , Micheli Lyle , Treves S Ted 
Published: March 2010

Abstract
The medical cost associated with back pain in the United States is considerable and growing. Although the differential diagnosis of back pain is broad, epidemiological studies suggest a correlation between adult and adolescent complaints. Injury of the pars interarticularis is one of the most common identifiable causes of ongoing low back pain in adolescent athletes. It constitutes a spectrum of disease ranging from bone stress to spondylolysis and spondylolisthesis. Bone stress may be the earliest sign of disease. Repetitive bone stress causes bone remodeling and may result in spondylolysis, a non-displaced fracture of the pars interarticularis. A fracture of the pars interarticularis may ultimately become unstable leading to spondylolisthesis. Results in the literature support the use of bone scintigraphy to diagnose bone stress in patients with suspected spondylolysis. Single photon emission computed tomography (SPECT) provides more contrast than planar bone scintigraphy, increases the sensitivity and improves anatomic localization of skeletal lesions without exposing the patient to additional radiation. It also provides an opportunity for better correlation with other imaging modalities, when necessary. As such, the addition of SPECT to standard planar bone scintigraphy can result in a more accurate diagnosis and a better chance for efficient patient care. It is our expectation that by improving our ability to correctly diagnose bone stress in patients with suspected injury of the posterior elements, the long-term cost of managing this condition will be lowered.
Detection of siRNA induced mRNA silencing by RT-qPCR: considerations for experimental design
Authors: Holmes Katherine , Williams Catrin M , Chapman Elinor A , Cross Michael J 
Published: March 2010

Abstract

Background
RNA interference (RNAi) has been one of the most rapidly expanding areas of biological research in the past decade, revolutionizing the ability to analyze gene function. Thorough validation of siRNA duplexes is required prior to use in experimental systems, ideally by western blotting to show a reduction in protein levels. However, in many cases good antibodies are not available, and researchers must rely on RT-qPCR to detect knockdown of the mRNA species.

Findings
We have observed a phenomenon that gives a disparity between analyzing small interfering RNA (siRNA) efficacy by western blotting of the protein levels and real-time quantitative PCR (RT-qPCR) measurement of mRNA levels. Detection of this phenomenon was dependent upon the location of the target amplicon for PCR primers within the mRNA.

Conclusions
Our data suggests that for certain mRNAs, degradation of the 3' mRNA fragment resulting from siRNA mediated cleavage is blocked, leaving an mRNA fragment that can act as a template for cDNA synthesis, giving rise to false negative results and the rejection of a valid siRNA duplex. We show that this phenomenon may be avoided by the careful design of RT-qPCR primers for each individual siRNA experiment.
Summary of 615 patients of chronic myeloid leukemia in Shanghai from 2001 to 2006
Authors: Wang Ai-Hua , Wang Yan-Yan , Yao Yu , Xu Zi-Zhen , Zhou Li , Wang Li , Zhang Li , Chen Yu , Shen Zhi-Xiang , Hu Jiong , Li Jun-Min 
Published: March 2010

Abstract

Background
To retrospectively review the incidence, treatment efficacy, we followed up newly diagnosed chronic myelogenous leukemia (CML) patients residing in Shanghai during 2001-2006.

Methods
All eligible cases were reviewed with the data of efficacy responses as well as overall survival (OS) and progression-free survival (PFS) time.

Results
A total of 615 cases entered the study. CML mainly afflicted those aged 40-60 years old and was slightly more frequent in males than females. More than 85% of the patients were in chronic phase (CP) when diagnosed. All patients were divided into four groups based on the main regimens - hydroxyurea, interferon alpha (IFN-α), imatinib, and hemopoietic stem cell transplantation (HSCT). With the median follow-up of 18 months, imatinib treatment induced 92.2% complete hematologic responses, and 64.3% complete cytogenetic responses among CML-CP patients. Overall the therapeutic efficacy in the imatinib group was higher than that in the hydroxyurea or IFN-α group. Meanwhile, in the imatinib group, all response rates of patients in CP were significantly greater than that in accelerated or blastic crisis phase. The patients treated with imatinib also showed the most promising results regarding OS and PFS. Patients receiving HSCT decreased markedly in number with the introduction of imatinib.

Conclusions
The number of new patients arising in Shanghai increased from 2001 to 2006. There were still patients receiving hydroxyurea and IFN-α. As the first-line regime for CML, imatinib was less administered in Shanghai before, but has received considerable development and great responses since 2003.
Short-term nutritional counseling reduces body mass index, waist circumference, triceps skinfold and triglycerides in women with metabolic syndrome
Authors: Pimentel Gustavo D , Arimura Silvia T , de Moura Bruno M , Silva Maria ER , de Sousa Maysa V 
Published: March 2010

Abstract

Background
It is recognized that the growing epidemic of metabolic syndrome is related to dietary and lifestyle changes.

Objective
The purpose of this study was to evaluate short-term application of nutritional counseling in women with metabolic syndrome.

Methods
This follow-up study was conducted from September to November 2008 with thirty three women ≥35 years old screened clinically for nutritional counseling. Dietary intake was reported, and biochemical and body composition measures were taken at baseline and after three months of follow-up.

Results
Of the 33 women evaluated, 29 patients completed the study. The prevalence of type 2 diabetes mellitus, hypertension, dyslipidemia, and obesity was high at 38%, 72.4%, 55.2%, and 75.8%, respectively. At the end of three-months of follow-up, a significant decline in body mass index, waist circumference, triceps skinfold, and triglycerides was observed, as was an increase in calcium and vitamin D intake. The multiple regression analysis showed that changes in body mass index, triceps skinfold, waist circumference and triglyceride levels after nutritional intervention were positively associated with changes in anthropometric (loss of body weight) and biochemical (decrease of TG/HDL-c ratio) parameters. Moreover, waist circumference changes were negatively associated with changes in calcium and vitamin D intake.

Conclusion
Short-term nutritional counseling improved some factors of metabolic syndrome. Moreover, the increases in calcium and vitamin D consumption can be associated with the improvement in markers of metabolic syndrome.
Urokinase-type plasminogen activator and arthritis progression: role in systemic disease with immune complex involvement
Authors: Cook Andrew D , De Nardo Christine M , Braine Emma L , Turner Amanda L , Vlahos Ross , Way Kerrie J , Beckman S Kaye , Lenzo Jason C , Hamilton John A 
Published: March 2010

Abstract
Introduction
Urokinase-type plasminogen activator (u-PA) has been implicated in fibrinolysis, cell migration, latent cytokine activation, cell activation, T-cell activation, and tissue remodeling, all of which are involved in the development of rheumatoid arthritis. Previously, u-PA has been reported to play a protective role in monoarticular arthritis models involving mBSA as the antigen, but a deleterious role in the systemic polyarticular collagen-induced arthritis (CIA) model. The aim of the current study is to determine how u-PA might be acting in systemic arthritis models.

Methods
The CIA model and bone marrow chimeras were used to determine the cellular source of u-PA required for the arthritis development. Gene expression of inflammatory and destructive mediators was measured in joint tissue by quantitiative PCR and protein levels by ELISA. The requirement for u-PA in the type II collagen mAb-induced arthritis (CAIA) and K/BxN serum transfer arthritis models was determined using u-PA-/- mice. Neutrophilia was induced in the peritoneal cavity using either ovalbumin/anti-ovalbumin or the complement component C5a.

Results
u-PA from a bone marrow-derived cell was required for the full development of CIA. The disease in u-PA-/- mice reconstituted with bone marrrow from C57BL/6 mice was indistinguishable from that in C57BL/6 mice, in terms of clincal score, histologic features, and protein and gene expression of key mediators. u-PA-/- mice were resistant to both CAIA and K/BxN serum transfer arthritis development. u-PA-/- mice developed a reduced neutrophilia and chemokine production in the peritoneal cavity following ovalbumin/anti-ovalbumin injection; in contrast, the peritoneal neutrophilia in response to C5a was u-PA independent.

Conclusions
u-PA is required for the full development of systemic arthritis models involving immune complex formation and deposition. The cellular source of u-PA required for CIA is bone marrow derived and likely to be of myeloid origin. For immune complex-mediated peritonitis, and perhaps some other inflammatory responses, it is suggested that the u-PA involvement may be upstream of C5a signaling.
Adrenocortical Zonation in Humans under Normal and Pathological Conditions
Authors: Nishimoto Koshiro , Nakagawa Ken , Li Dan , Kosaka Takeo , Oya Mototsugu , Mikami Shuji , Shibata Hirotaka , Itoh Hiroshi , Mitani Fumiko , Yamazaki Takeshi , Ogishima Tadashi , Suematsu Makoto , Mukai Kuniaki 
Published: March 2010

AbstractContext: Aldosterone synthase (CYP11B2) and steroid 11β-hydroxylase (CYP11B1) catalyze the terminal steps for aldosterone and cortisol syntheses, respectively, thereby determining the functional differentiation of human adrenocortical cells. Little is known, however, about how the cells expressing the enzymes are actually distributed in the adrenals under normal and pathological conditions.Objective: The objective of the study was to determine the localization of CYP11B2 and -B1 in human adrenal specimens by using developed antibodies capable of distinguishing the two enzymes from each other.Results: Under normal conditions, CYP11B2 was sporadically detected in the zona glomerulosa, whereas CYP11B1 was entirely detected in the zonae fasciculata-reticularis. Adrenocortical cells lacking both enzymes were observed in the outer cortical regions. In addition to conventional zonation, we found a variegated zonation consisting of a subcapsular cell cluster expressing CYP11B2, which we termed aldosterone-producing cell cluster, and a CYP11B1-expressing area. Aldosterone-producing adenomas differed in cell populations expressing CYP11B2 from one another, whereas CYP11B1-expressing and double-negative cells were also intermingled. Adenomas from patients with Cushing’s syndrome expressed CYP11B1 entirely but not CYP11B2, resulting in atrophic nontumor glands. The nontumor portions of both types of adenomas bore frequently one or more aldosterone-producing cell clusters, which sustained CYP11B2 expression markedly under the conditions of the suppressed renin-angiotensin system.Conclusion: Immunohistochemistry of the human normal adrenal cortex for CYP11B2 and CYP11B1 revealed a variegated zonation with cell clusters constitutively expressing CYP11B2. This technique may provide a pathological confirmatory diagnosis of adrenocortical adenomas.