bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional genomics of HMGN3a and SMARCAL1 in early mammalian embryogenesis
Authors: Uzun Alper , Rodriguez-Osorio Nelida , Kaya Abdullah , Wang Hongfeng , Parrish John J , Ilyin Valentin A , Memili Erdogan 
Published: April 2009

Abstract

Background
Embryonic genome activation (EGA) is a critical event for the preimplantation embryo, which is manifested by changes in chromatin structure, transcriptional machinery, expression of embryonic genes, and degradation of maternal transcripts. The objectives of this study were to determine transcript abundance of HMGN3a and SMARCAL1 in mature bovine oocytes and early bovine embryos, to perform comparative functional genomics analysis of these genes across mammals.

Results
New annotations of both HMGN3a and SMARCAL1 were submitted to the Bovine Genome Annotation Submission Database at BovineGenome.org. Careful analysis of the bovine SMARCAL1 consensus gene set for this protein (GLEAN_20241) showed that the NCBI protein contains sequencing errors, and that the actual bovine protein has a high degree of homology to the human protein. Our results showed that there was a high degree of structural conservation of HMGN3a and SMARCAL1 in the mammalian species studied. HMGN3a transcripts were present at similar levels in bovine matured oocytes and 2–4-cell embryos but at higher levels in 8–16-cell embryos, morulae and blastocysts. On the other hand, transcript levels of SMARCAL1 decreased throughout preimplantation development.

Conclusion
The high levels of structural conservation of these proteins highlight the importance of chromatin remodeling in the regulation of gene expression, particularly during early mammalian embryonic development. The greater similarities of human and bovine HMGN3a and SMARCAL1 proteins may suggest the cow as a valuable model to study chromatin remodeling at the onset of mammalian development. Understanding the roles of chromatin remodeling proteins during embryonic development emphasizes the importance of epigenetics and could shed light on the underlying mechanisms of early mammalian development.
Capecitabine plus Irinotecan (XELIRI regimen) compared to 5-FU/LV plus Irinotecan (FOLFIRI regimen) as neoadjuvant treatment for patients with unresectable liver-only metastases of metastatic colorectal cancer: a randomised prospective phase II trial
Authors: Skof Erik , Rebersek Martina , Hlebanja Zvezdana , Ocvirk Janja 
Published: April 2009

Abstract

Background
Phase II studies have shown that the combination of capecitabine and irinotecan (the XELIRI regimen) is active in metastatic colorectal cancer (MCRC). There are, however, no data about the use of the XELIRI regimen in the neoadjuvant treatment.

Methods
Patients with unresectable liver-only metastases of MCRC with ≤ 75 years of age were randomised to either the XELIRI (irinotecan 250 mg/m2 given on day one and capecitabine 1000 mg/m2 twice daily from day 2–15, every 21 days) or the FOLFIRI arm (irinotecan 180 mg/m2, 5-FU 400 mg/m2, LV 200 mg/m2, 5-FU 2400 mg/m2 (46-h infusion) – all given on day one, every 14 days). Primary end points were objective response rate (ORR) and rate of radical (R0) surgical resection. Secondary end points were progression-free survival (PFS), overall survival (OS) and safety.

Results
Altogether 87 patients were enrolled (41 pts in the XELIRI and 46 pts in the FOLFIRI arm). The median age was 63 years (63 years in the XELIRI and 62 years in the FOLFIRI arm) (p = 0.33). ORR was 49% in the XELIRI and 48% in the FOLFIRI arm (p = 0.76). The rate of radical R0 resection was 24% in both arms of patients. At the end of treatment, 37% of patients in the XELIRI and 26% of patients in the FOLFIRI arm were without evidence of the disease (CR+R0 resection) (p = 0.56). There were no statistical differences in grade 3 or 4 adverse events between both arms: diarrhoea 7% vs. 6%, neutropenia 5% vs. 13%, ischemic stroke 0 vs. 2%, acute coronary syndrome 2% vs. 4%, respectively. At the median follow up of 17 (range 1–39) months, the median PFS was 10.3 months in the XELIRI and 9.3 months in the FOLFIRI arm (p = 0.78), the median OS was 30.7 months in the XELIRI arm and 16.6 months in the FOLFIRI arm (p = 0.16).

Conclusion
The XELIRI regimen showed similar ORR as the FOLFIRI regimen in the neoadjuvant treatment of patients with MCRC. In addition, the XELIRI regimen showed similar PFS and OS with acceptable toxicity compared to the FOLFIRI regimen.

Trial Registration
Current Controlled Trials ISRCTN19912492
Resource heterogeneity and foraging behaviour of cattle across spatial scales
Authors: Utsumi Santiago A , Cangiano Carlos A , Galli Julio R , McEachern Mary B , Demment Montague W , Laca Emilio A 
Published: April 2009

Abstract

Background
Understanding the mechanisms that influence grazing selectivity in patchy environments is vital to promote sustainable production and conservation of cultivated and natural grasslands. To better understand how patch size and spatial dynamics influence selectivity in cattle, we examined grazing selectivity under 9 different treatments by offering alfalfa and fescue in patches of 3 sizes spaced with 1, 4, and 8 m between patches along an alley. We hypothesized that (1) selectivity is driven by preference for the forage species that maximizes forage intake over feeding scales ranging from single bites to patches along grazing paths, (2) that increasing patch size enhances selectivity for the preferred species, and that (3) increasing distances between patches restricts selectivity because of the aggregation of scale-specific behaviours across foraging scales.

Results
Cows preferred and selected alfalfa, the species that yielded greater short-term intake rates (P < 0.0001) and greater daily intake potential. Selectivity was not affected by patch arrangement, but it was scale dependent. Selectivity tended to emerge at the scale of feeding stations and became strongly significant at the bite scale, because of differences in bite mass between plant species. Greater distance between patches resulted in longer patch residence time and faster speed of travel but lower overall intake rate, consistent with maximization of intake rate. Larger patches resulted in greater residence time and higher intake rate.

Conclusion
We conclude that patch size and spacing affect components of intake rate and, to a lesser extent, the selectivity of livestock at lower hierarchies of the grazing process, particularly by enticing livestock to make more even use of the available species as patches are spaced further apart. Thus, modifications in the spatial pattern of plant patches along with reductions in the temporal and spatial allocation of grazing may offer opportunities to improve uniformity of grazing by livestock and help sustain biodiversity and stability of plant communities.
Assessing the molecular divergence between Anopheles (Kerteszia) cruzii populations from Brazil using the timeless gene: further evidence of a species complex
Authors: Rona Luísa DP , Carvalho-Pinto Carlos J , Gentile Carla , Grisard Edmundo C , Peixoto Alexandre A 
Published: April 2009

AbstractBackgroundAnopheles(Kerteszia) cruziiwas the most important vector of human malaria in southern Brazil between 1930–1960. Nowadays it is still considered an importantPlasmodiumspp. vector in southern and south-eastern Brazil, incriminated for oligosymptomatic malaria. Previous studies based on the analysis ofXchromosome banding patterns and inversion frequencies inAn. cruziipopulations from these areas have suggested the occurrence of three sibling species. In contrast, two genetically distinct groups amongAn. cruziipopulations from south/south-east and north-east Brazil have been revealed by isoenzyme analysis. Therefore,An. cruziiremains unclear.MethodsIn this study, a partial sequence of thetimelessgene (~400 bp), a locus involved in the control of circadian rhythms, was used as a molecular marker to assess the genetic differentiation betweenAn. cruziipopulations from six geographically distinct areas of Brazil.ResultsThetimelessgene revealed thatAn. cruziifrom Itaparica Island, Bahia State (north-east Brazil), constitutes a highly differentiated group compared with the other five populations from south and south-east Brazil. In addition, significant genetic differences were also observed among some of the latter populations.ConclusionAnalysis of the genetic differentiation in thetimelessgene amongAn. cruziipopulations from different areas of Brazil indicated that this malaria vector is a complex of at least two cryptic species. The data also suggest that further work might support the occurrence of other siblings within this complex in Brazil.
Age-specific effects of estrogen receptors' polymorphisms on the bone traits in healthy fertile women: the BONTURNO study
Authors: Massart Francesco , Marini Francesca , Bianchi Gerolamo , Minisola Salvatore , Luisetto Giovanni , Pirazzoli Antonella , Salvi Sara , Micheli Dino , Masi Laura , Brandi Maria Luisa 
Published: April 2009

Abstract

Background
Skeletal characteristics such as height (Ht), bone mineral density (BMD) or bone turnover markers are strongly inherited. Common variants in the genes encoding for estrogen receptor alpha (ESR1) and beta (ESR2) are proposed as candidates for influencing bone phenotypes at the population level.

Methods
We studied 641 healthy premenopausal women aged 20–50 years (yrs) participating into the BONTURNO study. Exclusion criteria were irregular cyclic menses, low trauma fracture, metabolic bone or chronic diseases. Serum C-telopeptide of type I collagen (CTX), osteocalcin (OC), and N-terminal propeptide of type I procollagen (P1NP) were measured in all enrolled subjects, who underwent to lumbar spine (LS), total hip (TH) and femoral neck (FN) BMD evaluation by DXA. Five hundred seventy Caucasian women were genotyped for ESR1 rs2234693 and rs9340799 and ESR2 rs4986938 polymorphisms.

Results
Although no genotype differences were found in body parameters, subjects with combined ESR1 CCGG plus ESR2 AA-AG genotype were taller than those with opposite genotype (P = 0.044). Moreover, ESR1 rs2234693 genotypes correlated with family history of osteoporosis (FHO) and hip fracture (FHF) (P < 0.01), while ESR2 AA-AC genotypes were strongly associated with FHF (OR 2.387, 95% CI 1.432–3.977; P < 0.001).
When clustered by age, 20–30 yrs old subjects, having at least one ESR1 rs2234693 C allele presented lower LS- (P = 0.008) and TH-BMD (P = 0.047) than TT genotypes. In 41–50 yrs age, lower FN-BMD was associated with ESR2 AA (P = 0.0180) subjects than in those with the opposite genotype. ESR1 rs2234693 and rs9340799 and ESR2 rs4986938 polymorphisms did not correlate with age-adjusted values of OC, CTX and P1NP.

Conclusion
These findings support the presence of age-specific effects of ESR1 and ESR2 polymorphisms on various skeletal traits in healthy fertile women.
Scoring mechanisms of p16INK4a immunohistochemistry based on either independent nucleic stain or mixed cytoplasmic with nucleic expression can significantly signal to distinguish between endocervical and endometrial adenocarcinomas in a tissue microarray study
Authors: Koo Chiew-Loon , Kok Lai-Fong , Lee Ming-Yung , Wu Tina S , Cheng Ya-Wen , Hsu Jeng-Dong , Ruan Alexandra , Chao Kuan-Chong , Han Chih-Ping 
Published: April 2009

Abstract

Background
Endocervical adenocarcinomas (ECAs) and endometrial adenocarcinomas (EMAs) are malignancies that affect uterus; however, their biological behaviors are quite different. This distinction has clinical significance, because the appropriate therapy may depend on the site of tumor origin. The purpose of this study is to evaluate 3 different scoring mechanisms of p16INK4a immunohistochemical (IHC) staining in distinguishing between primary ECAs and EMAs.

Methods
A tissue microarray (TMA) was constructed using formalin-fixed, paraffin-embedded tissue from hysterectomy specimens, including 14 ECAs and 24 EMAs. Tissue array sections were immunostained with a commercially available antibody of p16INK4a. Avidin-biotin complex (ABC) method was used for antigens visualization. The staining intensity and area extent of the IHC reactions was evaluated using the semi-quantitative scoring system. The 3 scoring methods were defined on the bases of the following: (1) independent cytoplasmic staining alone (Method C), (2) independent nucleic staining alone (Method N), and (3) mean of the sum of cytoplasmic score plus nucleic score (Method Mean of C plus N).

Results
Of the 3 scoring mechanisms for p16INK4a expression, Method N and Method Mean of C plus N showed significant (p-values < 0.05), but Method C showed non-significant (p = 0.245) frequency differences between ECAs and EMAs. In addition, Method Mean of C plus N had the highest overall accuracy rate (81.6%) for diagnostic distinction among these 3 scoring methods.

Conclusion
According to the data characteristics and test effectiveness in this study, Method N and Method Mean of C plus N can significantly signal to distinguish between ECAs and EMAs; while Method C cannot do. Method Mean of C plus N is the most promising and favorable means among the three scoring mechanisms.
Birth weight and characteristics of endothelial and smooth muscle cell cultures from human umbilical cord vessels
Authors: Martín de Llano José Javier , Fuertes Graciela , Torró Isabel , García Vicent Consuelo , Fayos José Luis , Lurbe Empar 
Published: April 2009

Abstract

Background
Low birth weight has been related to an increased risk for developing high blood pressure in adult life. The molecular and cellular analysis of umbilical cord artery and vein may provide information about the early vascular characteristics of an individual. We have assessed several phenotype characteristics of the four vascular cell types derived from human umbilical cords of newborns with different birth weight. Further follow-up studies could show the association of those vascular properties with infancy and adulthood blood pressure.

Methods
Endothelial and smooth muscle cell cultures were obtained from umbilical cords from two groups of newborns of birth weight less than 2.8 kg or higher than 3.5 kg. The expression of specific endothelial cell markers (von Willebrand factor, CD31, and the binding and internalization of acetylated low-density lipoprotein) and the smooth muscle cell specific α-actin have been evaluated. Cell culture viability, proliferation kinetic, growth fraction (expression of Ki67) and percentage of senescent cells (detection of β-galactosidase activity at pH 6.0) have been determined. Endothelial cell projection area was determined by morphometric analysis of cell cultures after CD31 immunodetection.

Results
The highest variation was found in cell density at the confluence of endothelial cell cultures derived from umbilical cord arteries (66,789 ± 5,093 cells/cm2 vs. 45,630 ± 11,927 cells/cm2, p < 0.05). Morphometric analysis indicated that the projection area of the artery endothelial cells (1,161 ± 198 and 1,544 ± 472 μm2, p < 0.05), but not those derived from the vein from individuals with a birth weight lower than 2.8 kg was lower than that of cells from individuals with a birth weight higher than 3.5 kg.

Conclusion
The analysis of umbilical cord artery endothelial cells, which demonstrated differences in cell size related to birth weight, can provide hints about the cellular and molecular links between lower birth weight and increased adult high blood pressure risk.
Immunomodulatory parasites and toll-like receptor-mediated tumour necrosis factor alpha responsiveness in wild mammals
Authors: Jackson Joseph A , Friberg Ida M , Bolch Luke , Lowe Ann , Ralli Catriona , Harris Philip D , Behnke Jerzy M , Bradley Janette E 
Published: April 2009

AbstractBackgroundImmunological analyses of wild populations can increase our understanding of how vertebrate immune systems respond to 'natural' levels of exposure to diverse infections. A major recent advance in immunology has been the recognition of the central role of phylogenetically conserved toll-like receptors in triggering innate immunity and the subsequent recruitment of adaptive response programmes. We studied the cross-sectional associations between individual levels of systemic toll-like receptor-mediated tumour necrosis factor alpha responsiveness and macro- and microparasite infections in a natural wood mouse (Apodemus sylvaticus) population.ResultsAmongst a diverse group of macroparasites, only levels of the nematodeHeligmosomoides polygyrusand the lousePolyplax serratawere correlated (negatively) with innate immune responsiveness (measured by splenocyte tumour necrosis factor alpha responses to a panel of toll-like receptor agonists).Polyplax serratainfection explained a strikingly high proportion of the total variation in innate responses. Contrastingly, faecal oocyst count in microparasiticEimeriaspp. was positively associated with innate immune responsiveness, most significantly for the endosomal receptors TLR7 and TLR9.ConclusionAnalogy with relevant laboratory models suggests the underlying causality for the observed patterns may be parasite-driven immunomodulatory effects on the host. A subset of immunomodulatory parasite species could thus have a key role in structuring other infections in natural vertebrate populations by affecting the 'upstream' innate mediators, like toll-like receptors, that are important in initiating immunity. Furthermore, the magnitude of the present result suggests that populations free from immunosuppressive parasites may exist at 'unnaturally' elevated levels of innate immune activation, perhaps leading to an increased risk of immunopathology.
Amplitude-modulated electromagnetic fields for the treatment of cancer: Discovery of tumor-specific frequencies and assessment of a novel therapeutic approach
Authors: Barbault Alexandre , Costa Frederico P , Bottger Brad , Munden Reginald F , Bomholt Fin , Kuster Niels , Pasche Boris 
Published: April 2009

Abstract

Purpose
Because in vitro studies suggest that low levels of electromagnetic fields may modify cancer cell growth, we hypothesized that systemic delivery of a combination of tumor-specific frequencies may have a therapeutic effect. We undertook this study to identify tumor-specific frequencies and test the feasibility of administering such frequencies to patients with advanced cancer.

Patients and methods
We examined patients with various types of cancer using a noninvasive biofeedback method to identify tumor-specific frequencies. We offered compassionate treatment to some patients with advanced cancer and limited therapeutic options.

Results
We examined a total of 163 patients with a diagnosis of cancer and identified a total of 1524 frequencies ranging from 0.1 Hz to 114 kHz. Most frequencies (57–92%) were specific for a single tumor type. Compassionate treatment with tumor-specific frequencies was offered to 28 patients. Three patients experienced grade 1 fatigue during or immediately after treatment. There were no NCI grade 2, 3 or 4 toxicities. Thirteen patients were evaluable for response. One patient with hormone-refractory breast cancer metastatic to the adrenal gland and bones had a complete response lasting 11 months. One patient with hormone-refractory breast cancer metastatic to liver and bones had a partial response lasting 13.5 months. Four patients had stable disease lasting for +34.1 months (thyroid cancer metastatic to lung), 5.1 months (non-small cell lung cancer), 4.1 months (pancreatic cancer metastatic to liver) and 4.0 months (leiomyosarcoma metastatic to liver).

Conclusion
Cancer-related frequencies appear to be tumor-specific and treatment with tumor-specific frequencies is feasible, well tolerated and may have biological efficacy in patients with advanced cancer.

Trial registration
clinicaltrials.gov identifier NCT00805337
Pregnancy in the mature adult mouse does not alter the proportion of mammary epithelial stem/progenitor cells
Authors: Britt Kara L , Kendrick Howard , Regan Joseph L , Molyneux Gemma , Magnay Fiona-Ann , Ashworth Alan , Smalley Matthew J 
Published: April 2009

Abstract
Introduction
In humans, an early full-term pregnancy reduces lifetime breast cancer risk by up to 50% whereas a later pregnancy (>35 years old) can increase lifetime risk. Several mechanisms have been suggested, including changes in levels of circulating hormones, changes in the way the breast responds to these hormones, changes in gene expression programmes which may alter susceptibility to transformation and changes to mammary stem cell numbers or behaviour. Previous studies have shown that the mammary tissue isolated from both virgin and parous mice has the ability to repopulate a cleared mammary fat pad in transplant experiments. Limited dilution transplant assays have demonstrated that early pregnancy (at 5 weeks of age) reduces stem/progenitor cell numbers in the mouse mammary epithelium by twofold. However, the effects on stem/progenitor cell numbers in the mammary epithelium of a pregnancy in older animals have not yet been tested.

Methods
Mice were put through a full-term pregnancy at 9 weeks of age, when the mammary epithelium is mature. The total mammary epithelium was purified from parous 7-week post-lactation and age-matched virgin mice and analysed by flow cytometry and limiting dilution cleared fat pad transplants.

Results
There were no significant differences in the proportions of different mammary epithelial cell populations or numbers of CD24+/Low Sca-1- CD49fHigh cells (stem cell enriched basal mammary epithelial compartment). There was no significant difference in stem/progenitor cell frequency based on limiting dilution transplants between the parous and age-matched virgin epithelium.

Conclusions
Although differences between parous and virgin mammary epithelium at later time points post lactation or following multiple pregnancies cannot be ruled out, there are no differences in stem/progenitor cell numbers between mammary epithelium isolated from parous animals which were mated at 9 weeks old and virgin animals. However, a recent report has suggested that animals that were mated at 5 weeks old have a twofold reduction in stem/progenitor cell numbers. This is of interest given the association between early, but not late, pregnancy and breast cancer risk reduction in humans. However, a mechanistic connection between stem cell numbers and breast cancer risk remains to be established.