bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequencing of NOTCH1, GATA5, TGFBR1 and TGFBR2genes in familial cases of bicuspid aortic valve
Authors: Foffa Ilenia , Ait Alì Lamia , Panesi Paola , Mariani Massimiliano , Festa Pierluigi , Botto Nicoletta , Vecoli Cecilia , Andreassi Maria Grazia 
Published: April 2013

Abstract

Background
The purpose of our study was to investigate the potential contribution of germline mutations in NOTCH1, GATA5 and TGFBR1 and TGFBR2 genes in a cohort of Italian patients with familial Bicuspid Aortic Valve (BAV).

Methods
All the coding exons including adjacent intronic as well as 5′ and 3′ untranslated (UTR) sequences of NOTCH1, GATA5, TGFBR1 and TGFBR2 genes were screened by direct gene sequencing in 11 index patients (8 males; age = 42 ± 19 years) with familial BAV defined as two or more affected members.

Results
Two novel mutations, a missense and a nonsense mutation (Exon 5, p.P284L; Exon 26, p.Y1619X), were found in the NOTCH1 gene in two unrelated families. The mutations segregated with the disease in these families, and they were not found on 200 unrelated chromosomes from ethnically matched controls. No pathogenetic mutation was identified in GATA5, TGFBR1 and TGFBR2 genes.

Conclusions
Two novel NOTCH1 mutations were identified in two Italian families with BAV, highlighting the role of a NOTCH1 signaling pathway in BAV and its aortic complications. These findings are of relevance for genetic counseling and clinical care of families presenting with BAV. Future studies are needed in order to unravel the still largely unknown genetics of BAV.
Poor histological lesions in IgA nephropathy may be reflected in blood and urine peptide profiling
Authors: Graterol Fredzzia , Navarro-Muñoz Maribel , Ibernon Meritxell , López Dolores , Troya Maria-Isabel , Pérez Vanessa , Bonet Josep , Romero Ramón 
Published: April 2013

Abstract

Background
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, leading to renal failure in 15% to 40% of cases. IgAN is diagnosed by renal biopsy, an invasive method that is not risk-free. We used blood and urine peptide profiles as a noninvasive method of linking IgAN-associated changes with histological lesions by Oxford classification.

Methods
We prospectively studied 19 patients with biopsy-proven IgAN and 14 healthy subjects from 2006 to 2009, excluding subjects with crescentic glomerulonephritis and collecting clinical and biochemical data at the time of diagnosis and during follow-up (24 months). Histological lesions were evaluated by Oxford classification. Proteomic analysis was performed by combining magnetic bead (MB) technology and mass spectrometry (MALDI-TOF MS) to obtain peptide profiles. Doubling of serum creatinine was considered a variable of poor renal prognosis.

Results
We identified 55 peptides—13 in serum, 26 in plasma, and 16 in urine—that differentiated IgAN patients from healthy subjects. A significant association was noted between serum/plasma and urine peptides and histological findings—ie, tubulointerstitial damage, segmental glomerulosclerosis, and endocapillary injury.
We also identified 3 peptides—corresponding to bradykinin, uromodulin, and alpha-1-antitrypsin—that were associated with severity of lesions, such as tubulointerstitial damage and segmental glomerulosclerosis.
Moreover, blood peptides with m/z 2953, 5337, 9287, and 9289 and urine peptides with m/z 1769, 1898, 1913, 1945, 2491, 2756, 2977, 3004, 3389, and 4752 correlated significantly with poor renal function.

Conclusions
In patients with IgAN, the use of noninvasive approaches, such as blood and urine proteomics, can provide valuable information beyond that of standard diagnostic techniques, allowing us to identify blood and urine peptide profiles that are associated with poor histological lesions in IgAN patients.
Notch1 signaling is involved in regulating Foxp3 expression in T-ALL
Authors: Luo Xiaodan , Tan Huo , Zhou Yueqiao , Xiao Tiantian , Wang Chunyan , Li Yangqiu 
Published: April 2013

Abstract

Background
T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy. Immune tolerance induced by CD4+CD25+ regulatory T cells (Tregs) with high expression of Foxp3 is an important hypothesis for poor therapy response. Notch1 signaling is thought to be involved in the pathogenesis of this disease. Crosstalk between Notch and Foxp3+Tregs induced immune tolerance is unknown in T-ALL. We studied Foxp3 and Notch1 expression in vivo and in vitro, and analyzed the biological characteristics of T-ALL cell line systematically after Notch inhibition and explored the crosstalk between Notch signaling and Foxp3 expression.

Methods
In vivo, we established T-ALL murine model by Jurkat cells transplantation to severe combined immunodeficiency (SCID) mice. Notch1 and Foxp3 expression was detected. In vitro, we used γ-secretase inhibitor N-S-phenyl-glycine-t-butyl ester (DAPT) to block Notch1 signaling in Jurkat cells. Notch1, Hes-1 and Foxp3 genes and protein expression were detected by PCR and western blotting, respectively. The proliferation pattern, cell cycle and viability of Jurkat cells after DAPT treatment were studied. Protein expression of Notch1 target genes including NF-κB, p-ERK1/2 and STAT1 were determined.

Results
We show that engraftment of Jurkat cells in SCID mice occurred in 8 of 10 samples (80%), producing disseminated human neoplastic lymphocytes in PB, bone marrow or infiltrated organs. Notch1 and Foxp3 expression were higher in T-ALL mice than normal mice. In vitro, Jurkat cells expressed Notch1 and more Foxp3 than normal peripheral blood mononuclear cells (PBMCs) in both mRNA and protein levels. Blocking Notch1 signal by DAPT inhibited the proliferation of Jurkat cells and induced G0/G1 phase cell cycle arrest and apoptosis. Foxp3 as well as p-ERK1/2, STAT1 and NF-κB expression was down regulated after DAPT treatment.

Conclusions
These findings indicate that regulation of Foxp3 expression does involve Notch signaling, and they may cooperatively regulate T cell proliferation in T-ALL.
Trends in US home food preparation and consumption: analysis of national nutrition surveys and time use studies from 1965–1966 to 2007–2008
Authors: Smith Lindsey P , Ng Shu Wen , Popkin Barry M 
Published: April 2013

Abstract

Background
It has been well-documented that Americans have shifted towards eating out more and cooking at home less. However, little is known about whether these trends have continued into the 21st century, and whether these trends are consistent amongst low-income individuals, who are increasingly the target of public health programs that promote home cooking. The objective of this study is to examine how patterns of home cooking and home food consumption have changed from 1965 to 2008 by socio-demographic groups.

Methods
This is a cross-sectional analysis of data from 6 nationally representative US dietary surveys and 6 US time-use studies conducted between 1965 and 2008. Subjects are adults aged 19 to 60 years (n= 38,565 for dietary surveys and n=55,424 for time-use surveys). Weighted means of daily energy intake by food source, proportion who cooked, and time spent cooking were analyzed for trends from 1965–1966 to 2007–2008 by gender and income. T-tests were conducted to determine statistical differences over time.

Results
The percentage of daily energy consumed from home food sources and time spent in food preparation decreased significantly for all socioeconomic groups between 1965–1966 and 2007–2008 (p ≤ 0.001), with the largest declines occurring between 1965 and 1992. In 2007–2008, foods from the home supply accounted for 65 to 72% of total daily energy, with 54 to 57% reporting cooking activities. The low income group showed the greatest decline in the proportion cooking, but consumed more daily energy from home sources and spent more time cooking than high income individuals in 2007–2008 (p ≤ 0.001).

Conclusions
US adults have decreased consumption of foods from the home supply and reduced time spent cooking since 1965, but this trend appears to have leveled off, with no substantial decrease occurring after the mid-1990’s. Across socioeconomic groups, people consume the majority of daily energy from the home food supply, yet only slightly more than half spend any time cooking on a given day. Efforts to boost the healthfulness of the US diet should focus on promoting the preparation of healthy foods at home while incorporating limits on time available for cooking.
Three-dimensional reconstruction of blood vessels in the rabbit eye by X-ray phase contrast imaging
Authors: Zhang Lu , Qian Xiuqing , Zhang Kunya , Cui Qianqian , Zhao Qiuyun , Liu Zhicheng 
Published: April 2013

Abstract

Background
A clear understanding of the blood vessels in the eye is helpful in the diagnosis and treatment of ophthalmic diseases, such as glaucoma. Conventional techniques such as micro-CT imaging and histology are not sufficiently accurate to identify the vessels in the eye, because their diameter is just a few microns. The newly developed medical imaging technology, X-ray phase-contrast imaging (XPCI), is able to distinguish the structure of the vessels in the eye. In this study, XPCI was used to identify the internal structure of the blood vessels in the eye.

Methods
After injection with barium sulfate via the ear border artery, an anesthetized rabbit was killed and its eye was fixed in vitro in 10% formalin solution. We acquired images using XPCI at the Shanghai Synchrotron Radiation Facility. The datasets were converted into slices by filtered back-projection (FBP). An angiographic score was obtained as a parameter to quantify the density of the blood vessels. A three-dimensional (3D) model of the blood vessels was then established using Amira 5.2 software.

Results
With XPCI, blood vessels in the rabbit eye as small as 18 μm in diameter and a sixth of the long posterior ciliary artery could be clearly distinguished. In the 3D model, we obtained the level 4 branch structure of vessels in the fundus. The diameters of the arteria centralis retinae and its branches are about 200 μm, 110 μm, 95 μm, 80 μm and 40 μm. The diameters of the circulus arteriosus iridis major and its branches are about 210 μm, 70 μm and 30 μm. Analysis of vessel density using the angiographic score showed that the blood vessels had maximum density in the fundus and minimum density in the area anterior to the equator (scores 0.27 ± 0.029 and 0.16 ± 0.032, respectively). We performed quantitative angiographic analysis of the blood vessels to further investigate the density of the vessels.

Conclusions
XPCI provided a feasible means to determine the structure of the blood vessels in the eye. We were able to determine the diameters and morphological characteristics of the vessels from both 2D images and the 3D model. By analyzing the images, we obtained measurements of the density distribution of the microvasculature, and this approach may provide valuable reference information prior to glaucoma filtration surgery.
L1R, A27L, A33R and B5R vaccinia virus genes expressed by fowlpox recombinants as putative novel orthopoxvirus vaccines
Authors: Pacchioni Sole Maria , Bissa Massimiliano , Zanotto Carlo , Morghen Carlo De Giuli , Illiano Elena , Radaelli Antonia 
Published: April 2013

Abstract

Background
The traditional smallpox vaccine, administered by scarification, was discontinued in the general population from 1980, because of the absence of new smallpox cases. However, the development of an effective prophylactic vaccine against smallpox is still necessary, to protect from the threat of deliberate release of the variola virus for bioterrorism and from new zoonotic infections, and to improve the safety of the traditional vaccine. Preventive vaccination still remains the most effective control and new vectors have been developed to generate recombinant vaccines against smallpox that induce the same immunogenicity as the traditional one. As protective antibodies are mainly directed against the surface proteins of the two infectious forms of vaccinia, the intracellular mature virions and the extracellular virions, combined proteins from these viral forms can be used to better elicit a complete and protective immunity.

Methods
Four novel viral recombinants were constructed based on the fowlpox genetic background, which independently express the vaccinia virus L1 and A27 proteins present on the mature virions, and the A33 and B5 proteins present on the extracellular virions. The correct expression of the transgenes was determined by RT-PCR, Western blotting, and immunofluorescence.

Results and conclusions
Using immunoprecipitation and Western blotting, the ability of the proteins expressed by the four novel FP
L1R
, FP
A27L
, FP
A33R
and FP
B5R
recombinants to be recognized by VV-specific hyperimmune mouse sera was demonstrated. By neutralisation assays, recombinant virus particles released by infected chick embryo fibroblasts were shown not be recognised by hyperimmune sera. This thus demonstrates that the L1R, A27L, A33R and B5R gene products are not inserted into the new viral progeny. Fowlpox virus replicates only in avian species, but it is permissive for entry and transgene expression in mammalian cells, while being immunologically non–cross-reactive with vaccinia virus. These recombinants might therefore represent safer and more promising immunogens that can circumvent neutralisation by vector-generated immunity in smallpox-vaccine-experienced humans.
‘Monster… -omics’: on segmentation, re-segmentation, and vertebrae formation in amphibians and other vertebrates
Authors: Buckley David , Molnár Viktor , Németh Gábor , Petneházy Örs , Vörös Judit 
Published: April 2013

Abstract

Background
The axial skeleton is one of the defining evolutionary landmarks of vertebrates. How this structure develops and how it has evolved in the different vertebrate lineages is, however, a matter of debate. Vertebrae and vertebral structures are derived from the embryonic somites, although the mechanisms of development are different between lineages.

Discussion
Using the anecdotal description of a teratological newt (Triturus dobrogicus) with an unusual malformation in its axial skeleton, we review, compare, and discuss the development of vertebral structures and, in particular, the development of centra from somitic cellular domains in different vertebrate groups. Vertebrae development through re-segmentation of the somitic sclerotomal cells is considered the general mechanism among vertebrates, which has been generalized from studies in amniotic model organisms. The prevalence of this mechanism among anamniotes is, however, controversial. We propose alternative developmental mechanisms for vertebrae formation that should be experimentally tested.

Summary
Research in model organisms, especially amniotes, is laying the foundations for a thorough understanding of the mechanisms of development of the axial skeleton in vertebrates, foundations that should expand the extent of future comparative studies. Although immersed in the ‘-omics’ era, we emphasize the need for an integrative and organismal approach in evolutionary developmental biology for a better understanding of the causal role of development in the evolution of morphological diversity in nature.
Serum paraoxonase-1 as biomarker for improved diagnosis of fatty liver in dairy cows
Authors: Farid Ayman Samir , Honkawa Kazuyuki , Fath Eman Mohamed , Nonaka Nariaki , Horii Yoichiro 
Published: April 2013

Abstract

Background
Fatty liver is a major metabolic disorder in dairy cows and is believed to result in major economic losses in dairy farming due to decreased health status, reproductive performance and fertility. Currently, the definitive means for diagnosing fatty liver is determining the fat content of hepatic tissue by liver biopsy, which is an invasive and costly procedure, making it poorly suited to dairy farms. Therefore, the key aim of this study was to investigate the measurement of serum paraoxonase-1 (PON1), an enzyme exclusively synthesized by the liver, as a sensitive noninvasive biomarker for diagnosis of fatty liver in dairy cows.

Results
A comparative cohort study using serum specimens from Holstein–Friesian dairy cows (46 healthy and 46 fatty liver cases) was conducted. Serum PON1 (paraoxonase, lactonase and arylesterase) activity and other biochemical and hematological parameters were measured. We found that serum PON1 activity was lower (P<0.001) in cows suffering from fatty liver. The area under the receiver operating characteristic curve (AUC-ROC) of PON1 activity for diagnosis of fatty liver was 0.973–0.989 [95% confidence interval (CI) 0.941, 1.000] which was higher than the AUC-ROC of aspartate aminotransferase (AST), lecithin-cholesterol acyltransferase (LCAT), alkaline phosphatase (ALP), non-esterified fatty acids (NEFA), beta-hydroxybutyrate (BHBA), total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL). We found that adding serum PON1 measurement to different batteries of serum diagnostic panels showed a combination of high sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+LR), negative likelihood ratio (−LR), diagnostic odd ratio (DOR) and overall diagnostic accuracy in diagnosing fatty liver.

Conclusions
The present results indicate that addition of serum PON1 activity measurement to the biochemical profile could improve the diagnosis of fatty liver in dairy cows, which would have a considerable clinical impact and lead to greater profitability in the dairy industry.
The novel BTB-kelch protein, KBTBD8, is located in the Golgi apparatus and translocates to the spindle apparatus during mitosis
Authors: Lührig Sandra , Kolb Susanne , Mellies Nadine , Nolte Jessica 
Published: April 2013

Abstract
Proteins of the BTB-kelch family are known to be involved in multiple biological processes such as migration, cytoskeleton arrangement, regulation of cell morphology, protein ubiquitination and gene expression. KBTBD8 is a new member of this family. The gene was found in a comparative transcriptome analysis of pluripotent stem cells and was therefore suggested to play a role in the regulation of pluripotency. Comparative analysis of the gene and protein sequences revealed a high conservation throughout evolution especially in the characteristic domains of BTB, BACK and kelch. We identified the Golgi apparatus as the subcellular localization of the KBTBD8 protein in non-dividing cells and could show that KBTBD8 co-localizes with α-tubulin on the spindle apparatus of mitotic cells suggesting a role in cell proliferation. In conclusion, KBTBD8 is a new member of the BTB-kelch superfamily that is located in the Golgi apparatus and translocates to the spindle apparatus during mitosis.
Correlation between nasopharyngeal carcinoma tumor volume and the 2002 International Union Against Cancer tumor classification system
Authors: Wu Zheng , Gu Mo-Fa , Zeng Rui-Fang , Su Yong , Huang Shao-Min 
Published: April 2013

Abstract

Background
The correlation between primary tumor volume and nasopharyngeal carcinoma (NPC) UICC 2002 T classification, N classification and distant metastasis after radiation therapy was discussed to provide further evidence for the inclusion of tumor volume into the TNM classification staging system.

Methods
Between February 2001 and December 2008, 666 patients with NPC treated with intensity-modulated radiation therapy (IMRT) were analyzed retrospectively. Primary gross tumor volume was calculated from treatment planning computed tomography scans. The Kruskal-Wallis and Mann–Whitney tests were used for comparison of continuous variables and the chi-square test was used for categorical variables. A logistic regression model was used for multivariate analysis.

Results
Median primary tumor volume of the 666 patients was 20.35 ml (range, 0.44 − 192.63 ml), and it gradually increased with T classification. Statistically significant differences in tumor volume were observed between patients with different T classifications (p < 0.001). The cervical lymph node metastasis rate was 64.7% (430/666); the differences in primary tumor volume between patients with or without lymph node metastasis were statistically significant (p < 0.001). Posttreatment distant metastasis occurred in 100 NPC patients, and the five-year distant metastasis-free survival was 84.2%. Univariate and multivariate analyses showed that N classification (p < 0.001) and tumor volume (p = 0.007) were the main factors influencing distant metastasis.

Conclusion
Tumor volume was correlated with T classification, cervical lymph node mestastasis and distant metastasis after radiation therapy in nasopharyngeal carcinoma, suggesting that tumor volume should be included into the TNM staging system.
Neurosurgery and prognosis in patients with radiation-induced brain injury after nasopharyngeal carcinoma radiotherapy: a follow-up study
Authors: Li Yi , Shi Xiaolei , Rong Xiaoming , Peng Ying , Tang Yamei 
Published: April 2013

Abstract

Background
Radiotherapy is the standard radical treatment for nasopharyngeal carcinoma (NPC) and may cause radiation-induced brain injury (RI). Treatment for RI remains a challenge. We conducted this study to investigate the indications of neurosurgery, operation time and prognosis of patients with RI after NPC radiotherapy who underwent neurosurgical management.

Methods
This was a follow-up study between January 2005 and July 2011. Fifteen NPC cases of RI who underwent neurosurgery were collected. Brain Magnetic resonance imaging (MRI), surgery and histology were studied. The outcome was assessed by LENT/SOMA scales and modified Rankin scale.

Results
Brain lesion resection (86.7%) was more common than decompressive craniotomy (13.3%). According to LENT/SOMA scale before and six months after surgery, 13 of 15, 12 of 15, 14 of 15, and 14 of 15 cases showed improvement at subjective, objective, management and analytic domains, respectively. 12 of 15 patients showed improvement of modified Rankin scale after surgery. Three patients who underwent emergency surgery showed significant improvement (average score increment of 2, 2.7, 2.7, 3 and 2 at LENT/SOMA scale subjective, objective, management, analytic, and modified Rankin scale, respectively), as compared with 12 cases underwent elective surgery (average score increment of 1, 1, 1.4, 1.8 and 1 at LENT SOMA scale subjective, objective, management, analytic, and modified Rankin scale, respectively).

Conclusions
Neurosurgery, including brain necrotic tissue resection and decompressive craniotomy, improves the prognosis for RI patients, especially for those with indications of emergency surgery.
Inhibition of attachment of oral bacteria to immortalized human gingival fibroblasts (HGF-1) by tea extracts and tea components
Authors: Wang Yi , Chung Felicia FL , Lee Sui M , Dykes Gary A 
Published: April 2013

Abstract

Background
Tea has been suggested to promote oral health by inhibiting bacterial attachment to the oral cavity. Most studies have focused on prevention of bacterial attachment to hard surfaces such as enamel.

Findings
This study investigated the effect of five commercial tea (green, oolong, black, pu-erh and chrysanthemum) extracts and tea components (epigallocatechin gallate and gallic acid) on the attachment of five oral pathogens (Streptococcus mutans ATCC 25175, Streptococcus mutans ATCC 35668, Streptococcus mitis ATCC 49456, Streptococcus salivarius ATCC 13419 and Actinomyces naeslundii ATCC 51655) to the HGF-1 gingival cell line. Extracts of two of the teas (pu-erh and chrysanthemum) significantly (p < 0.05) reduced attachment of all the Streptococcus strains by up to 4 log CFU/well but effects of other teas and components were small.

Conclusions
Pu-erh and chrysanthemum tea may have the potential to reduce attachment of oral pathogens to gingival tissue and improve the health of oral soft tissues.