bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bios2mds: an R package for comparing orthologous protein families by metric multidimensional scaling
Authors: Pelé Julien , Bécu Jean-Michel , Abdi Hervé , Chabbert Marie 
Published: June 2012

Abstract

Background
The distance matrix computed from multiple alignments of homologous sequences is widely used by distance-based phylogenetic methods to provide information on the evolution of protein families. This matrix can also be visualized in a low dimensional space by metric multidimensional scaling (MDS). Applied to protein families, MDS provides information complementary to the information derived from tree-based methods. Moreover, MDS gives a unique opportunity to compare orthologous sequence sets because it can add supplementary elements to a reference space.

Results
The R package bios2mds (from BIOlogical Sequences to MultiDimensional Scaling) has been designed to analyze multiple sequence alignments by MDS. Bios2mds starts with a sequence alignment, builds a matrix of distances between the aligned sequences, and represents this matrix by MDS to visualize a sequence space. This package also offers the possibility of performing K-means clustering in the MDS derived sequence space. Most importantly, bios2mds includes a function that projects supplementary elements (a.k.a. “out of sample” elements) onto the space defined by reference or “active” elements. Orthologous sequence sets can thus be compared in a straightforward way. The data analysis and visualization tools have been specifically designed for an easy monitoring of the evolutionary drift of protein sub-families.

Conclusions
The bios2mds package provides the tools for a complete integrated pipeline aimed at the MDS analysis of multiple sets of orthologous sequences in the R statistical environment. In addition, as the analysis can be carried out from user provided matrices, the projection function can be widely used on any kind of data.
Variation of presence/absence genes among Arabidopsis populations
Authors: Tan Shengjun , Zhong Yan , Hou Huan , Yang Sihai , Tian Dacheng 
Published: June 2012

Abstract

Background
Gene presence/absence (P/A) polymorphisms are commonly observed in plants and are important in individual adaptation and species differentiation. Detecting their abundance, distribution and variation among individuals would help to understand the role played by these polymorphisms in a given species. The recently sequenced 80 Arabidopsis genomes provide an opportunity to address these questions.

Results
By systematically investigating these accessions, we identified 2,407 P/A genes (or 8.9%) absent in one or more genomes, averaging 444 absent genes per accession. 50.6% of P/A genes belonged to multi-copy gene families, or 31.0% to clustered genes. However, the highest proportion of P/A genes, outnumbered in singleton genes, was observed in the regions near centromeres. In addition, a significant correlation was observed between the P/A gene frequency among the 80 accessions and the diversity level at P/A loci. Furthermore, the proportion of P/A genes was different among functional gene categories. Finally, a P/A gene tree showed a diversified population structure in the worldwide Arabidopsis accessions.

Conclusions
An estimate of P/A genes and their frequency distribution in the worldwide Arabidopsis accessions was obtained. Our results suggest that there are diverse mechanisms to generate or maintain P/A genes, by which individuals and functionally different genes can selectively maintain P/A polymorphisms for a specific adaptation.
Divergent gene expression in the conserved dauer stage of the nematodes Pristionchus pacificus and Caenorhabditis elegans
Authors: Sinha Amit , Sommer Ralf J , Dieterich Christoph 
Published: June 2012

Abstract

Background
An organism can respond to changing environmental conditions by adjusting gene regulation and by forming alternative phenotypes. In nematodes, these mechanisms are coupled because many species will form dauer larvae, a stress-resistant and non-aging developmental stage, when exposed to unfavorable environmental conditions, and execute gene expression programs that have been selected for the survival of the animal in the wild. These dauer larvae represent an environmentally induced, homologous developmental stage across many nematode species, sharing conserved morphological and physiological properties. Hence it can be expected that some core components of the associated transcriptional program would be conserved across species, while others might diverge over the course of evolution. However, transcriptional and metabolic analysis of dauer development has been largely restricted to Caenorhabditis elegans. Here, we use a transcriptomic approach to compare the dauer stage in the evolutionary model system Pristionchus pacificus with the dauer stage in C. elegans.

Results
We have employed Agilent microarrays, which represent 20,446 P. pacificus and 20,143 C. elegans genes to show an unexpected divergence in the expression profiles of these two nematodes in dauer and dauer exit samples. P. pacificus and C. elegans differ in the dynamics and function of genes that are differentially expressed. We find that only a small number of orthologous gene pairs show similar expression pattern in the dauers of the two species, while the non-orthologous fraction of genes is a major contributor to the active transcriptome in dauers. Interestingly, many of the genes acquired by horizontal gene transfer and orphan genes in P. pacificus, are differentially expressed suggesting that these genes are of evolutionary and functional importance.

Conclusion
Our data set provides a catalog for future functional investigations and indicates novel insight into evolutionary mechanisms. We discuss the limited conservation of core developmental and transcriptional programs as a common aspect of animal evolution.
Hypoglycemic and antioxidant effects of leaf essential oil of Pelargonium graveolens L’Hér. in alloxan induced diabetic rats
Authors: Boukhris Maher , Bouaziz Mohamed , Feki Ines , Jemai Hedya , El Feki Abdelfattah , Sayadi Sami 
Published: June 2012

Abstract

Background
Rose-scented geranium (Pelargonium graveolens L’Hér.), which is used in traditional Tunisian folk medicine for the treatment of hyperglycaemia, is widely known as one of the medicinal herbs with the highest antioxidant activity. The present paper is conducted to test the hypoglycemic and antioxidative activities of the leaf essential oil of P. graveolens.

Methods
The essential oil P. graveolens was administered daily and orally to the rats at two doses of 75 mg/kg and 150 mg/kg body weight (b.w.) for 30 days. The chemical composition of P. graveolens essential oil, body weight, serum glucose, hepatic glycogen, thiobarbituric acid-reactive substances (TBARS), the components of hepatic, and renal and serum antioxidant systems were evaluated. The hypoglycemic effect of rose-scented geranium was compared to that of the known anti-diabetic drug glibenclamide (600 μg/kg b.w.).

Results
After the administration of two doses of essential oil of Pelargonium graveolens L’Hér. together with glibenclamide which is known by its antidiabetic activities and used as reference (600 μg/kg b.w.), for four weeks, the serum glucose significantly decreased and antioxidant perturbations were restored. The hypoglycemic effect of P. graveolens at the dose of 150 mg/kg b.w. was significantly (p< 0.05) more effective than that of glibenclamide. It is through the histological findings in hepatic and renal tissues of diabetic rats that these beneficial effects of geranium oils were confirmed.

Conclusions
It suggests that administration of essential oil of P. graveolens may be helpful in the prevention of diabetic complications associated with oxidative stress. Our results, therefore, suggest that the rose-scented geranium could be used as a safe alternative antihyperglycemic drug for diabetic patients.
Adipose derived mesenchymal stem cells transplantation via portal vein improves microcirculation and ameliorates liver fibrosis induced by CCl4 in rats
Authors: Wang Yu , Lian Fan , Li Jiaping , Fan Wenzhe , Xu Hanshi , Yang Xiuyan , Liang Liuqin , Chen Wei , Yang Jianyong 
Published: June 2012

Abstract

Introduction
Adipose derived mesenchymal stem cells (ADMSCs), carrying the similar characteristics to bone marrow mesenchymal stem cells, only much more abundant and easier to obtain, may be a promising treatment for liver fibrosis. We aim to investigate the therapeutic potential of ADMSCs transplantation in liver fibrosis caused by carbon tetrachloride (CCl4) in rats as well as its underlying mechanism, and to further explore the appropriate infusion pathway.

Methods
ADMSCs were isolated, cultured and identified. Placebo and ADMSCs were transplanted via portal vein and tail vein respectively into carbon tetrachloride (CCl4)-induced liver fibrosis rats. Computed tomography (CT) perfusion scan and microvessel counts were performed to measure the alteration of liver microcirculation after therapy. Liver function tests and histological findings were estimated.

Results
CT perfusion scan shown significant decrease of hepatic arterial perfusion index, significant increased portal vein perfusion, total liver perfusion in rats receiving ADMSCs from portal vein, and Factor VIII (FVIII) immunohistochemical staining shown significant decrease of microvessels in rats receiving ADMSCs from portal vein, indicating microcirculation improvement in portal vein group. Vascular endothelial growth Factor (VEGF) was significantly up-regulated in fibrosis models, and decreased after ADMSCs intraportal transplantation. A significant improvement of liver functional test and histological findings in portal vein group were observed. No significance was found in rats receiving ADMSCs from tail vein.

Conclusions
ADMSCs have a therapeutic effect against CCl4-mediated liver fibrosis. ADMSCs may benefit the fibrotic liver through alteration of microcirculation, evidenced by CT perfusion scan and down-regulation of VEGF. Intraportal transplantation is a better pathway than tail vein transplantation.
Synthesis of size-controlled monodisperse Pd nanoparticles via a non-aqueous seed-mediated growth
Authors: Zhang Lei , Wang Lin , Jiang Zhiyuan , Xie Zhaoxiong 
Published: June 2012

Abstract
We demonstrated that stepwise seed-mediated growth could be extended in non-aqueous solution (solvothermal synthesis) and improved as an effective method for controlling the uniform size of palladium nanoparticles (Pd NPs) in a wide range. The monodisperse Pd NPs with the size of about 5 nm were synthesized by simply reducing Pd(acac)2 with formaldehyde in different organic amine solvents. By an improved stepwise seed-mediated synthesis, the size of the monodisperse Pd NPs can be precisely controlled from approximately 5 to 10 nm. The as-prepared Pd NPs could self assemble to well-shaped superlattice crystal without size selection process.
Metabolic profiling detects early effects of environmental and lifestyle exposure to cadmium in a human population
Authors: Ellis James K , Athersuch Toby J , Thomas Laura DK , Teichert Friederike , Pérez-Trujillo Miriam , Svendsen Claus , Spurgeon David J , Singh Rajinder , Järup Lars , Bundy Jacob G , Keun Hector C 
Published: June 2012

Abstract

Background
The 'exposome' represents the accumulation of all environmental exposures across a lifetime. Top-down strategies are required to assess something this comprehensive, and could transform our understanding of how environmental factors affect human health. Metabolic profiling (metabonomics/metabolomics) defines an individual's metabolic phenotype, which is influenced by genotype, diet, lifestyle, health and xenobiotic exposure, and could also reveal intermediate biomarkers for disease risk that reflect adaptive response to exposure. We investigated changes in metabolism in volunteers living near a point source of environmental pollution: a closed zinc smelter with associated elevated levels of environmental cadmium.

Methods
High-resolution 1H NMR spectroscopy (metabonomics) was used to acquire urinary metabolic profiles from 178 human volunteers. The spectral data were subjected to multivariate and univariate analysis to identify metabolites that were correlated with lifestyle or biological factors. Urinary levels of 8-oxo-deoxyguanosine were also measured, using mass spectrometry, as a marker of systemic oxidative stress.

Results
Six urinary metabolites, either associated with mitochondrial metabolism (citrate, 3-hydroxyisovalerate, 4-deoxy-erythronic acid) or one-carbon metabolism (dimethylglycine, creatinine, creatine), were associated with cadmium exposure. In particular, citrate levels retained a significant correlation to urinary cadmium and smoking status after controlling for age and sex. Oxidative stress (as determined by urinary 8-oxo-deoxyguanosine levels) was elevated in individuals with high cadmium exposure, supporting the hypothesis that heavy metal accumulation was causing mitochondrial dysfunction.

Conclusions
This study shows evidence that an NMR-based metabolic profiling study in an uncontrolled human population is capable of identifying intermediate biomarkers of response to toxicants at true environmental concentrations, paving the way for exposome research.
Long-term impact of systemic bacterial infection on the cerebral vasculature and microglia
Authors: Püntener Ursula , Booth Steven G , Perry V Hugh , Teeling Jessica L 
Published: June 2012

AbstractBackgroundSystemic infection leads to generation of inflammatory mediators that result in metabolic and behavioural changes. Repeated or chronic systemic inflammation leads to a state of innate immune tolerance: a protective mechanism against overactivity of the immune system. In this study, we investigated the immune adaptation of microglia and brain vascular endothelial cells in response to systemic inflammation or bacterial infection.MethodsMice were given repeated doses of lipopolysaccharide (LPS) or a single injection of liveSalmonella typhimurium. Inflammatory cytokines were measured in serum, spleen and brain, and microglial phenotype studied by immunohistochemistry. To assess priming of the innate immune response in the brain, mice were infected withSalmonella typhimuriumand subsequently challenged with a focal unilateral intracerebral injection of LPS.ResultsRepeated systemic LPS challenges resulted in increased brain IL-1β, TNF-α and IL-12 levels, despite attenuated systemic cytokine production. Each LPS challenge induced significant changes in burrowing behaviour. In contrast, brain IL-1β and IL-12 levels inSalmonella typhimurium-infected mice increased over three weeks, with high interferon-γ levels in the circulation. Behavioural changes were only observed during the acute phase of the infection. Microglia and cerebral vasculature display an activated phenotype, and focal intracerebral injection of LPS four weeks after infection results in an exaggerated local inflammatory response when compared to non-infected mice.ConclusionsThese studies reveal that the innate immune cells in the brain do not become tolerant to systemic infection, but are primed instead. This may lead to prolonged and damaging cytokine production that may have a profound effect on the onset and/or progression of pre-existing neurodegenerative disease.
Live sequence charts to model medical information
Authors: Aslakson Eric , Szekely Smadar , Vernon Suzanne D , Bateman Lucinda , Baumbach Jan , Setty Yaki 
Published: June 2012

Abstract

Background
Medical records accumulate data concerning patient health and the natural history of disease progression. However, methods to mine information systematically in a form other than an electronic health record are not yet available. The purpose of this study was to develop an object modeling technique as a first step towards a formal database of medical records.

Method
Live Sequence Charts (LSC) were used to formalize the narrative text obtained during a patient interview. LSCs utilize a visual scenario-based programming language to build object models. LSC extends the classical language of UML message sequence charts (MSC), predominantly through addition of modalities and providing executable semantics. Inter-object scenarios were defined to specify natural history event interactions and different scenarios in the narrative text.

Result
A simulated medical record was specified into LSC formalism by translating the text into an object model that comprised a set of entities and events. The entities described the participating components (i.e., doctor, patient and record) and the events described the interactions between elements. A conceptual model is presented to illustrate the approach. An object model was generated from data extracted from an actual new patient interview, where the individual was eventually diagnosed as suffering from Chronic Fatigue Syndrome (CFS). This yielded a preliminary formal designated vocabulary for CFS development that provided a basis for future formalism of these records.

Conclusions
Translation of medical records into object models created the basis for a formal database of the patient narrative that temporally depicts the events preceding disease, the diagnosis and treatment approach. The LSCs object model of the medical narrative provided an intuitive, visual representation of the natural history of the patient’s disease.
Patterns of failure after multimodal treatments for high-grade glioma: effectiveness of MIB-1 labeling index
Authors: Uehara Kazuyuki , Sasayama Takashi , Miyawaki Daisuke , Nishimura Hideki , Yoshida Kenji , Okamoto Yoshiaki , Mukumoto Naritoshi , Akasaka Hiroaki , Nishihara Masamitsu , Fujii Osamu , Soejima Toshinori , Sugimura Kazuro , Kohmura Eiji , Sasaki Ryohei 
Published: June 2012

Abstract

Background
The purpose of the present study was to analyze the recurrence pattern of high-grade glioma treated with a multimodal treatment approach and to evaluate whether the MIB-1 labeling index (LI) could be a useful marker for predicting the pattern of failure in glioblastoma (GB).

Methods and materials
We evaluated histologically confirmed 131 patients with either anaplastic astrocytoma (AA) or GB. A median dose was 60 Gy. Concomitant and adjuvant chemotherapy were administered to 111 patients. MIB-1 LI was assessed by immunohistochemistry. Recurrence patterns were categorized according to the areas of recurrence as follows: central failure (recurrence in the 95% of 60 Gy); in-field (recurrence in the high-dose volume of 50 Gy; marginal (recurrence outside the high-dose volume) and distant (recurrence outside the RT field).

Results
The median follow-up durations were 13 months for all patients and 19 months for those remaining alive. Among AA patients, the 2-year progression-free and overall survival rates were 23.1% and 39.2%, respectively, while in GB patients, the rates were 13.3% and 27.6%, respectively. The median survival time was 20 months for AA patients and 15 months for GB patients. Among AA patients, recurrences were central in 68.7% of patients; in-field, 18.8%; and distant, 12.5%, while among GB patients, 69.0% of recurrences were central, 15.5% were in-field, 12.1% were marginal, and 3.4% were distant. The MIB-1 LI medians were 18.2% in AA and 29.8% in GB. Interestingly, in patients with GB, the MIB-1 LI had a strong effect on the pattern of failure (P = 0.014), while the extent of surgical removal (P = 0.47) and regimens of chemotherapy (P = 0.57) did not.

Conclusions
MIB-1 LI predominantly affected the pattern of failure in GB patients treated with a multimodal approach, and it might be a useful tool for the management of the disease.
Rediscovering the chick embryo as a model to study retinal development
Authors: Vergara M Natalia , Canto-Soler M Valeria 
Published: June 2012

Abstract
The embryonic chick occupies a privileged place among animal models used in developmental studies. Its rapid development and accessibility for visualization and experimental manipulation are just some of the characteristics that have made it a vertebrate model of choice for more than two millennia. Until a few years ago, the inability to perform genetic manipulations constituted a major drawback of this system. However, the completion of the chicken genome project and the development of techniques to manipulate gene expression have allowed this classic animal model to enter the molecular age. Such techniques, combined with the embryological manipulations that this system is well known for, provide a unique toolkit to study the genetic basis of neural development. A major advantage of these approaches is that they permit targeted gene misexpression with extremely high spatiotemporal resolution and over a large range of developmental stages, allowing functional analysis at a level, speed and ease that is difficult to achieve in other systems. This article provides a general overview of the chick as a developmental model focusing more specifically on its application to the study of eye development. Special emphasis is given to the state of the art of the techniques that have made gene gain- and loss-of-function studies in this model a reality. In addition, we discuss some methodological considerations derived from our own experience that we believe will be beneficial to researchers working with this system.
A generalizable pre-clinical research approach for orphan disease therapy
Authors: Beaulieu Chandree L , Samuels Mark E , Ekins Sean , McMaster Christopher R , Edwards Aled M , Krainer Adrian R , Hicks Geoffrey G , Frey Brendan J , Boycott Kym M , MacKenzie Alex E 
Published: June 2012

Abstract
With the advent of next-generation DNA sequencing, the pace of inherited orphan disease gene identification has increased dramatically, a situation that will continue for at least the next several years. At present, the numbers of such identified disease genes significantly outstrips the number of laboratories available to investigate a given disorder, an asymmetry that will only increase over time. The hope for any genetic disorder is, where possible and in addition to accurate diagnostic test formulation, the development of therapeutic approaches. To this end, we propose here the development of a strategic toolbox and preclinical research pathway for inherited orphan disease. Taking much of what has been learned from rare genetic disease research over the past two decades, we propose generalizable methods utilizing transcriptomic, system-wide chemical biology datasets combined with chemical informatics and, where possible, repurposing of FDA approved drugs for pre-clinical orphan disease therapies. It is hoped that this approach may be of utility for the broader orphan disease research community and provide funding organizations and patient advocacy groups with suggestions for the optimal path forward. In addition to enabling academic pre-clinical research, strategies such as this may also aid in seeding startup companies, as well as further engaging the pharmaceutical industry in the treatment of rare genetic disease.