bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exceptionally high cumulative percentage of NUMTs originating from linear mitochondrial DNA molecules in the Hydra magnipapillata genome
Authors: Song Shen , Jiang Feng , Yuan Jianbo , Guo Wei , Miao Yongwang 
Published: July 2013

AbstractBackgroundIn contrast to most animal genomes, mitochondrial genomes in species belonging to the phylum Cnidaria show distinct variations in genome structure, including the mtDNA structure (linear or circular) and the presence or absence of introns in protein-coding genes. Therefore, the analysis of nuclear insertions of mitochondrial sequences (NUMTs) in cnidarians allows us to compare the NUMT content in animals with different mitochondrial genome structures.ResultsNUMT identification in theHydra magnipapillata,Nematostella vectensisandAcropora digitiferagenomes showed that the NUMT density in theH. magnipapillatagenome clearly exceeds that in other two cnidarians with circular mitochondrial genomes. We found thatH. magnipapillatais an exceptional ancestral metazoan with a high NUMT cumulative percentage but a large genome, and its mitochondrial genome linearisation might be responsible for the NUMT enrichment. We also detected the co-transposition of exonic and intronic fragments within NUMTs inN. vectensisand provided direct evidence that mitochondrial sequences can be transposed into the nuclear genome through DNA-mediated fragment transfer. In addition, NUMT expression analyses showed that NUMTs are co-expressed with adjacent protein-coding genes, suggesting the relevance of their biological function.ConclusionsTaken together, our results provide valuable information for understanding the impact of mitochondrial genome structure on the interaction of mitochondrial molecules and nuclear genomes.
Compound heterozygosity of predicted loss-of-function DESvariants in a family with recessive desminopathy
Authors: McLaughlin Heather M , Kelly Melissa A , Hawley Pamela P , Darras Basil T , Funke Birgit , Picker Jonathan 
Published: July 2013

Abstract

Background
Variants in the desmin gene (DES) are associated with desminopathy; a myofibrillar myopathy mainly characterized by muscle weakness, conduction block, and dilated cardiomyopathy. To date, only ~50 disease-associated variants have been described, and the majority of these lead to dominant-negative effects. However, the complete genotypic spectrum of desminopathy is not well established.

Case presentation
Next-generation sequencing was performed on 51 cardiac disease genes in a proband with profound skeletal myopathy, dilated cardiomyopathy, and respiratory dysfunction. Our analyses revealed compound heterozygous DES variants, both of which are predicted to lead to a loss-of-function. Consistent with recessive inheritance, each variant was identified in an unaffected parent.

Conclusions
This case report serves to broaden the variant spectrum of desminopathies and provides insight into the molecular mechanisms of desminopathy, supporting distinct dominant-negative and loss-of-function etiologies.
Interrogating differences in expression of targeted gene sets to predict breast cancer outcome
Authors: Andres Sarah A , Brock Guy N , Wittliff James L 
Published: July 2013

AbstractBackgroundGenomics provides opportunities to develop precise tests for diagnostics, therapy selection and monitoring. From analyses of our studies and those of published results, 32 candidate genes were identified, whose expression appears related to clinical outcome of breast cancer. Expression of these genes was validated by qPCR and correlated with clinical follow-up to identify a gene subset for development of a prognostic test.MethodsRNA was isolated from 225 frozen invasive ductal carcinomas,and qRT-PCR was performed. Univariate hazard ratios and 95% confidence intervals for breast cancer mortality and recurrence were calculated for each of the 32 candidate genes. A multivariable gene expression model for predicting each outcome was determined using the LASSO, with 1000 splits of the data into training and testing sets to determine predictive accuracy based on the C-index. Models with gene expression data were compared to models with standard clinical covariates and models with both gene expression and clinical covariates.ResultsUnivariate analyses revealed over-expression of RABEP1, PGR, NAT1, PTP4A2, SLC39A6, ESR1, EVL, TBC1D9, FUT8, and SCUBE2 were all associated with reduced time to disease-related mortality (HR between 0.8 and 0.91, adjustedp < 0.05), while RABEP1, PGR, SLC39A6, and FUT8 were also associated with reduced recurrence times. Multivariable analyses using the LASSO revealed PGR, ESR1, NAT1, GABRP, TBC1D9, SLC39A6, and LRBA to be the most important predictors for both disease mortality and recurrence. Median C-indexes on test data sets for the gene expression, clinical, and combined models were 0.65, 0.63, and 0.65 for disease mortality and 0.64, 0.63, and 0.66 for disease recurrence, respectively.ConclusionsMolecular signatures consisting of five genes (PGR, GABRP, TBC1D9, SLC39A6 and LRBA) for disease mortality and of six genes (PGR, ESR1, GABRP, TBC1D9, SLC39A6 and LRBA) for disease recurrence were identified. These signatures were as effective as standard clinical parameters in predicting recurrence/mortality, and when combined, offered some improvement relative to clinical information alone for disease recurrence (median difference in C-values of 0.03, 95% CI of -0.08 to 0.13). Collectively, results suggest that these genes form the basis for a clinical laboratory test to predict clinical outcome of breast cancer.
Foxc2 regulates osteogenesis and angiogenesis of bone marrow mesenchymal stem cells
Authors: You Wulin , Gao Hongwei , Fan Lihong , Duan Dapeng , Wang Chunsheng , Wang Kunzheng 
Published: July 2013

Abstract

Background
The Forkhead/Fox transcription factor Foxc2 is a critical regulator of osteogenesis and angiogenesis of cells. Bone marrow mesenchymal stem cells (BMSCs) have the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, myocytes and fibroblasts. The present study investigates the role of Foxc2 overexpression in osteogenesis and angiogenesis of BMSCs in vitro.

Methods
BMSCs were isolated from SD rat femurs and tibias, and characterized by cell surface antigen identification and osteoblasts and adipocytes differentiation. The cells were transfected with lentiviral Foxc2 (Lv-Foxc2) or green fluorescent protein (Lv-GFP). Seventy hours later, Foxc2 expression was observed using real time-PCR and Western blot. The transfected cells were stained with Alizarin red S or alkaline phosphatase (ALP) after osteogenic induction. Meanwhile, the expression levels of osteocalcin (OCN), Runt-related transcription factor 2 (Runx2), vascular endothelial growth factor (VEGF) and platelet-derived growth factor-β (PDGF-β) were measured by real time-PCR, Western blot and immunostaining.

Results
Results of cell characterization showed that the cells were positive to CD44 (99.56%) and negative to CD34 (0.44%), and could differentiate into osteoblasts and adipocytes. Foxc2 overexpression not only increased the numbers of mineralized nodes and ALP activity, but also enhanced the expressions of Runx2, OCN, VEGF and PDGF-β in transfected BMSCs after osteogenic induction. The effects of Foxc2 on osteogenesis and angiogenesis were significantly different between Lv-Foxc2 transfected BMSCs and Lv-GFP transfected BMSCs (P<0.05). In addition, the MAPK-specific inhibitors, PD98059 and LY294002, blocked the Foxc2-induced regulation of BMSC differentiation.

Conclusions
Foxc2 gene is successfully transfected into BMSCs with stable and high expression. The overexpression of Foxc2 acts on BMSCs to stimulate osteogenesis and angiogenesis. The effect of Foxc2 on angiogenesis of the cells is mediated via activating PI3K and ERK.
Dioxin-like compounds and bone quality in Cree women of Eastern James Bay (Canada): a cross-sectional study
Authors: Paunescu Alexandra-Cristina , Dewailly Éric , Dodin Sylvie , Nieboer Evert , Ayotte Pierre 
Published: July 2013

Abstract

Background
Aboriginal populations living in Canada’s northern regions are exposed to a number of persistent organic pollutants through their traditional diet which includes substantial amounts of predator fish species. Exposure to dioxin-like compounds (DLCs) can cause a variety of toxic effects including adverse effects on bone tissue. This descriptive cross-sectional study was conducted to investigate the relationship between plasma concentrations of DLCs and bone quality parameters in Cree women of Eastern James Bay (Canada).

Methods
Two hundred and forty-nine Cree women from seven communities in Eastern James Bay (Canada), aged 35 to 74 years old, participated in the study. In order to determine the total DLC concentration in plasma samples of participants, we measured the aryl hydrocarbon receptor-mediated transcriptional activity elicited by plasma sample extracts using a luciferase reporter gene assay. Plasma concentrations of mono-ortho-substituted dioxin-like polychlorinated biphenyls (DL-PCBs) 105, 118 and 156 were measured by gas chromatography–mass spectrometry. Bone quality parameters (speed of sound, m/s; broadband ultrasound attenuation, dB/MHz; stiffness index, %) were assessed by quantitative ultrasound at the right calcaneus with the Achilles InSight system. Several factors known to be associated with osteoporosis were documented by questionnaire. Multiple linear regression models were constructed for the three ultrasound parameters.

Results
DL-PCBs 105 and 118 concentrations, but not the global DLC concentration, were inversely associated with the stiffness index, even after adjusting for several confounding factors. The stiffness index (log) decreased by −0.22% (p=0.0414) and −0.04% (p=0.0483) with an increase of one μg/L in plasma concentrations of DL-PCB 105 and DL-PCB 118, respectively. Other factors, including age, height, smoking status, menopausal status and the percentage of omega-6 polyunsaturated fatty acids (PUFAs) in erythrocyte membranes were negatively associated with one of the ultrasound parameters, while the percentage of omega-3 PUFAs in these membranes and levels of physical activity and education were positively associated with them.

Conclusions
Our results show that an increase in plasma concentrations of DL-PCBs 105 and 118 was negatively associated with stiffness index, a measure of bone quality/strength, in women of this population. In addition to environmental contaminants, future studies should also consider PUFA intake as a factor influencing bone quality.
Serum Procalcitonin is a sensitive and specific marker in the diagnosis of septic arthritis and acute osteomyelitis
Authors: Maharajan Karthikeyan , Patro Dilip Kumar , Menon Jagdish , Hariharan Ananthanarayanan Palghat , Parija Sabhash Chandra , Poduval Murali , Thimmaiah Sreenivas 
Published: July 2013

AbstractBackgroundEarly diagnosis of Acute Osteomyelitis (OM) and Septic Arthritis (SA) is of vital importance to avoid devastating complications. There is no single laboratory marker which is sensitive and specific in diagnosing these infections accurately. Total Count, ESR and CRP are not specific as they can also be elevated in non pyogenic causes of inflammation. Pus Culture and sensitivity is not a true gold standard due to its varied positivity rates (40 – 70%). Serum Procalcitonin (PCT), at0.5 ng/mlis found to be an accurate marker for pyogenic infections. The objectives of this study were to show that PCT is an accurate marker in differentiating Acute Osteomyelitis and Septic Arthritis from viral and non infective inflammatory bone and joint conditions.MethodsPatients of all age groups (n = 82) with suspected Acute Osteomyelitis and Septic Arthritis were prospectively included in this study. All patients were subjected to TC, CRP, PCT, IgM Dengue, IgM Chikungunya, pus and blood culture and sensitivity. At the end of the study, patients were classified into 3 groups: Group 1 = Confirmed Pyogenic (n = 27); Group 2 = Presumed Pyogenic (n = 21); Group 3 = Non – infective inflammatory (n = 34).ResultsGroup 1 has higher mean PCT levels than Group 2 and 3 (p < 0.05). PCT, at0.4 ng/ml, was 85.2% sensitive and 87.3% specific in diagnosing Septic Arthritis and Acute Osteomyelitis. In comparison, PCT at conventional cut – off of0.5 ng/mlis 66.7% sensitive and 91% specific.ConclusionSerum Procalcitonin, at a cut – off of0.4 ng/ml, is a sensitive and specific marker in the diagnosis of Septic Arthritis and Acute Osteomyelitis.
Report of the Post Kala-Azar Dermal Leishmaniasis (PKDL) consortium meeting, New Delhi, India, 27–29 June 2012
Authors: Desjeux Philippe , Ghosh Raj Shankar , Dhalaria Pritu , Strub-Wourgaft Nathalie , Zijlstra Ed E 
Published: July 2013

Abstract
Post kala-azar dermal leishmaniasis (PKDL) is a neglected complication of visceral leishmaniasis (VL)―a deadly, infectious disease that claims approximately 20,000 to 40,000 lives every year. PKDL is thought to be a reservoir for transmission of VL, thus, adequate control of PKDL plays a key role in the ongoing effort to eliminate VL. Over the past few years, several expert meetings have recommended that a greater focus on PKDL was needed, especially in South Asia. This report summarizes the Post Kala-Azar Dermal Leishmaniasis Consortium Meeting held in New Delhi, India, 27–29 June 2012. The PKDL Consortium is committed to promote and facilitate activities that lead to better understanding of all aspects of PKDL that are needed for improved clinical management and to achieve control of PKDL and VL. Fifty clinicians, scientists, policy makers, and advocates came together to discuss issues relating to PKDL epidemiology, diagnosis, pathogenesis, clinical presentation, treatment, and control. Colleagues who were unable to attend participated during drafting of the consortium meeting report.
Memantine-induced speech problems in two patients with autistic disorder
Authors: Alaghband-Rad Javad , Nikvarz Naemeh , Tehrani-Doost Mehdi , Ghaeli Padideh 
Published: July 2013

Abstract
Stuttering is a complex speech disorder. There are two forms of stuttering: developmental stuttering and acquired stuttering. Developmental stuttering is a disorder of early childhood but acquired stuttering can develop at any age. Some medications can induce or deteriorate stuttering as an adverse effect. There are several reports of stuttering due to psychotropic drugs. Memantine, a glutamate antagonist used in the treatment of Alzheimer’s disease, has also been studied for the treatment of autism spectrum disorders. This report presents deterioration of stuttering and speech problem in two children with autistic disorder who were receiving memantine. Based on our knowledge, this is the first time these adverse drug reactions have been attributed to memantine. In conclusion clinicians should consider that speech problems including stuttering may be due to the consumption of memantine, especially, in children may be a side effect of memantine especially in children.
Developmental coupling of larval and adult stages in a complex life cycle: insights from limb regeneration in the flour beetle, Tribolium castaneum
Authors: Lee Alison K , Sze Christie C , Kim Elaine R , Suzuki Yuichiro 
Published: July 2013

Abstract

Background
A complex life cycle, such as complete metamorphosis, is a key innovation that can promote diversification of species. The evolution of a morphologically distinct larval stage is thought to have enabled insects to occupy broader ecological niches and become the most diverse metazoan taxon, yet the extent to which larval and adult morphologies can evolve independently remains unknown. Perturbation of larval limb regeneration allows us to generate larval legs and antennae with altered limb morphologies, which may be used to explore the developmental continuity that might exist between larval and adult appendages. In this study, we determined the roles of several appendage patterning transcription factors, abrupt (ab), dachshund (dac), Distal-less (Dll), and spineless (ss), in the red flour beetle, Tribolium castaneum, during larval appendage regeneration. The functions of these genes in regenerating and non-regenerating limbs were compared using RNA interference.

Results
During limb regeneration, dac and ss were necessary to re-pattern the same larval structures as those patterned during embryogenesis. Removal of these two genes led to larval appendage patterning defects that were carried over to the adult legs. Surprisingly, even though maternal knockdown of ab had minimal effects on limb allocation and patterning in the embryo, it was necessary for blastema growth, an earlier phase of regeneration. Finally, knockdown of Dll prevented the blastema-like bumps from re-differentiating into appendages.

Conclusions
Our results suggest that, similar to vertebrates, the re-patterning phase of Tribolium larval limb regeneration relies on the same genes that are used during embryonic limb patterning. Thus, the re-patterning phase of regeneration is likely to be regulated by taxon-specific patterning mechanisms. Furthermore, Ab and Dll appear to play important roles during blastema proliferation and re-differentiation, respectively. Finally, our results show that continuity exists between larval and adult limb patterning, and that larval and adult leg morphologies may be developmentally coupled. Thus, the evolution of imaginal discs may have been a key step towards completely removing any developmental constraints that existed between larval and adult phenotypes.
Cytometric profiling in various clinical forms of multiple sclerosis with respect to CD21+, CD32+, and CD35+ B and T cells
Authors: Zandieh Ali , Izad Maryam , Fakhri Mohammad , Amirifard Hamed , Khazaeipour Zahra , Harirchian Mohammad Hosein 
Published: July 2013

AbstractBackgroundWe aimed to evaluate the frequency of various types of B and T cells expressing CD21, CD32, and CD35 in multiple sclerosis (MS) clinical courses.MethodsPeripheral blood mononuclear cell from 30 MS patients (17 relapsing remitting [RRMS], six secondary progressive [SPMS], and seven primary progressive MS [PPMS]) and 18 healthy subjects were analyzed. All patients were in acute attack. Healthy controls were matched for age and gender ratio. The frequencies of various subsets of B and T cells were determined using flow cytometry.ResultsThe frequency of CD4+T cells was lower in MS patients compared to control subjects (41.14 ± 9.45% vs. 46.88 ± 6.98%, respectively,P < 0.05). The CD32+fraction of CD4+T cells and the CD21+fraction of CD8+T cells were higher in MS patients (2.85 ± 3.72% vs. 1.06 ± 0.62% for CD32+CD4+T cells, 2.71 ± 1.86% vs. 1.16 ± 0.99% for CD21+CD8+T cells in MS patients and control subjects, respectively,P < 0.05). After dividing subjects by type of MS course, higher values of these two T cell subsets were found in SPMS patients compared to control subjects (P < 0.05). Further, RRMS patients had lower levels of CD32+CD4+T cells than SPMS patients and also they had lower levels of CD32+CD8+T cells than PPMS patients (P < 0.05). However, neither the expression of CD35 on T cells nor the various B cell subsets were statistically different between the compared groups.ConclusionsOur findings demonstrate that T cell subsets expressing CD21 and CD32 may differ with respect to the presence or clinical forms of MS disease. By contrast, CD35+T cells and different subsets of B cells are not altered in various MS clinical courses.
Notch activation stimulates migration of breast cancer cells and promotes tumor growth
Authors: Bolós Victoria , Mira Emilia , Martínez-Poveda Beatriz , Luxán Guillermo , Cañamero Marta , Martínez-A Carlos , Mañes Santos , de la Pompa José Luis 
Published: July 2013

Abstract
Introduction
Dysregulated NOTCH receptor activity has been implicated in breast cancer but the mechanisms by which NOTCH contributes to transformation are not yet clear, as it has context-dependent effects on the properties of transformed cells.

Methods
We have used various in vitro and in vivo carcinogenic models to analyze the impact of Notch signaling in the onset and progression of breast tumors.

Results
We found that ectopic expression of the Notch1 intracellular domain (N1ICD) in MCF-7 breast adenocarcinoma cell line caused reduction and delocalization of E-CADHERIN levels and increased migratory and invasive abilities. Notch inhibition in the invasive breast cancer cell line MDA-MB-231 resulted in increased E-CADHERIN expression and a parallel reduction in their invasive capacity. The growth of subcutaneous xenografts produced with MCF-7 cells was boosted after N1ICD induction, in a cell autonomous manner. In vivo Notch1 activation in the mammary gland using the MMTV-Cre driver caused the formation of papillary tumors that showed increased Hes1 and Hey1 expression and delocalized E-cadherin staining.

Conclusions
These results confirm NOTCH1 as a signal triggering epithelial-mesenchymal transition in epithelial cancer cells, which may have implications in tumor dissemination, metastasis and proliferation in vivo. The identification of specific factors interacting with NOTCH signaling could thus be relevant to fully understanding the role of NOTCH in breast neoplasia.
Human umbilical cord mesenchymal stem cell-derived neuron-like cells rescue memory deficits and reduce amyloid-beta deposition in an AβPP/PS1 transgenic mouse model
Authors: Yang Hui , Xie Zhao Hong , Wei Li Fei , Yang Hong Na , Yang Shao Nan , Zhu Zheng Yu , Wang Ping , Zhao Cui Ping , Bi Jian Zhong 
Published: July 2013

Abstract
Introduction
Cell therapy is a potential therapeutic approach for neurodegenerative disorders, such as Alzheimer disease (AD). Neuronal differentiation of stem cells before transplantation is a promising procedure for cell therapy. However, the therapeutic impact and mechanisms of action of neuron-like cells differentiated from human umbilical cord mesenchymal stem cells in AD have not been determined.

Methods
In this study, we used tricyclodecan-9-yl-xanthogenate (D609) to induce human mesenchymal stem cells isolated from Wharton jelly of the umbilical cord (HUMSCs) to differentiate into neuron-like cells (HUMSC-NCs), and transplanted the HUMSC-NCs into an AβPP/PS1 transgenic AD mouse model. The effects of HUMSC-NC transplantation on the cognitive function, synapsin I level, amyloid β-peptides (Aβ) deposition, and microglial function of the mice were investigated.

Results
We found that transplantation of HUMSC-NCs into AβPP/PS1 mice improved the cognitive function, increased synapsin I level, and significantly reduced Aβ deposition in the mice. The beneficial effects were associated with “alternatively activated” microglia (M2-like microglia). In the mice transplanted with HUMSC-NCs, M2-like microglial activation was significantly increased, and the expression of antiinflammatory cytokine associated with M2-like microglia, interleukin-4 (IL-4), was also increased, whereas the expression of proinflammatory cytokines associated with classic microglia (M1-like microglia), including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), was significantly reduced. Moreover, the expression of Aβ-degrading factors, insulin-degrading enzyme (IDE) and neprilysin (NEP), was increased substantially in the mice treated with HUMSC-NCs.

Conclusions
HUMSC-NC transplantation decreased Aβ deposition and improved memory in AβPP/PS1 mice by a mechanism associated with activating M2-like microglia and modulating neuroinflammation. Transplantation of neuron-like cells differentiated from mesenchymal stem cells might be a promising cell therapy for Alzheimer disease.