Progress of tissue culture and genetic transformation research in pigeon pea [Cajanus cajan (L.) Millsp.].

PubMed

Krishna, Gaurav; Reddy, P Sairam; Ramteke, P W; Bhattacharya, P S

2010-10-01

Pigeon pea [Cajanus cajan (L.) Millsp.] (Family: Fabaceae) is an important legume crop cultivated across 50 countries in Asia, Africa, and the Americas; and ranks fifth in area among pulses after soybean, common bean, peanut, and chickpea. It is consumed as a major source of protein (21%) to the human population in many developing countries. In India, it is the second important food legume contributing to 80% of the global production. Several biotic and abiotic stresses are posing a big threat to its production and productivity. Attempts to address these problems through conventional breeding methods have met with partial success. This paper reviews the chronological progress made in tissue culture through organogenesis and somatic embryogenesis, including the influence of factors such as genotypes, explant sources, and culture media including the supplementation of plant growth regulators. Comprehensive lists of morphogenetic pathways involved in in vitro regeneration through organogenesis and somatic embryogenesis using different explant tissues of diverse pigeon pea genotypes are presented. Similarly, the establishment of protocols for the production of transgenics via particle bombardment and Agrobacterium-mediated transformation using different explant tissues, Agrobacterium strains, Ti plasmids, and plant selectable markers, as well as their interactions on transformation efficiency have been discussed. Future research thrusts on the use of different promoters and stacking of genes for various biotic and abiotic stresses in pigeon pea are suggested.

Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

PubMed

Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

2015-02-01

During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

RGD-conjugated two-photon absorbing near-IR emitting fluorescent probes for tumor vascular imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Belfield, Kevin D.; Yue, Xiling; Morales, Alma R.; Githaiga, Grace W.; Woodward, Adam W.; Tang, Simon; Sawada, Junko; Komatsu, Masanobu; Liu, Xuan

2016-03-01

Observation of the activation and inhibition of angiogenesis processes is important in the progression of cancer. Application of targeting peptides, such as a small peptide that contains adjacent L-arginine (R), glycine (G) and L-aspartic acid (D) residues can afford high selectivity and deep penetration in vessel imaging. To facilitate deep tissue vasculature imaging, probes that can be excited via two-photon absorption (2PA) in the near-infrared (NIR) and subsequently emit in the NIR are essential. In this study, the enhancement of tissue image quality with RGD conjugates was investigated with new NIR-emitting pyranyl fluorophore derivatives in two-photon fluorescence microscopy. Linear and nonlinear photophysical properties of the new probes were comprehensively characterized; significantly the probes exhibited good 2PA over a broad spectral range from 700-1100 nm. Cell and tissue images were then acquired and examined, revealing deep penetration and high contrast with the new pyranyl RGD-conjugates up to 350 μm in tumor tissue.

The PAXgene® Tissue System Preserves Phosphoproteins in Human Tissue Specimens and Enables Comprehensive Protein Biomarker Research

PubMed Central

Gündisch, Sibylle; Schott, Christina; Wolff, Claudia; Tran, Kai; Beese, Christian; Viertler, Christian; Zatloukal, Kurt; Becker, Karl-Friedrich

2013-01-01

Precise quantitation of protein biomarkers in clinical tissue specimens is a prerequisite for accurate and effective diagnosis, prognosis, and personalized medicine. Although progress is being made, protein analysis from formalin-fixed and paraffin-embedded tissues is still challenging. In previous reports, we showed that the novel formalin-free tissue preservation technology, the PAXgene Tissue System, allows the extraction of intact and immunoreactive proteins from PAXgene-fixed and paraffin-embedded (PFPE) tissues. In the current study, we focused on the analysis of phosphoproteins and the applicability of two-dimensional gel electrophoresis (2D-PAGE) and enzyme-linked immunosorbent assay (ELISA) to the analysis of a variety of malignant and non-malignant human tissues. Using western blot analysis, we found that phosphoproteins are quantitatively preserved in PFPE tissues, and signal intensities are comparable to that in paired, frozen tissues. Furthermore, proteins extracted from PFPE samples are suitable for 2D-PAGE and can be quantified by ELISA specific for denatured proteins. In summary, the PAXgene Tissue System reliably preserves phosphoproteins in human tissue samples, even after prolonged fixation or stabilization times, and is compatible with methods for protein analysis such as 2D-PAGE and ELISA. We conclude that the PAXgene Tissue System has the potential to serve as a versatile tissue fixative for modern pathology. PMID:23555997

Current advances and future perspectives in extrusion-based bioprinting.

PubMed

Ozbolat, Ibrahim T; Hospodiuk, Monika

2016-01-01

Extrusion-based bioprinting (EBB) is a rapidly growing technology that has made substantial progress during the last decade. It has great versatility in printing various biologics, including cells, tissues, tissue constructs, organ modules and microfluidic devices, in applications from basic research and pharmaceutics to clinics. Despite the great benefits and flexibility in printing a wide range of bioinks, including tissue spheroids, tissue strands, cell pellets, decellularized matrix components, micro-carriers and cell-laden hydrogels, the technology currently faces several limitations and challenges. These include impediments to organ fabrication, the limited resolution of printed features, the need for advanced bioprinting solutions to transition the technology bench to bedside, the necessity of new bioink development for rapid, safe and sustainable delivery of cells in a biomimetically organized microenvironment, and regulatory concerns to transform the technology into a product. This paper, presenting a first-time comprehensive review of EBB, discusses the current advancements in EBB technology and highlights future directions to transform the technology to generate viable end products for tissue engineering and regenerative medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

A DNA methylation map of human cancer at single base-pair resolution

PubMed Central

Vidal, E; Sayols, S; Moran, S; Guillaumet-Adkins, A; Schroeder, M P; Royo, R; Orozco, M; Gut, M; Gut, I; Lopez-Bigas, N; Heyn, H; Esteller, M

2017-01-01

Although single base-pair resolution DNA methylation landscapes for embryonic and different somatic cell types provided important insights into epigenetic dynamics and cell-type specificity, such comprehensive profiling is incomplete across human cancer types. This prompted us to perform genome-wide DNA methylation profiling of 22 samples derived from normal tissues and associated neoplasms, including primary tumors and cancer cell lines. Unlike their invariant normal counterparts, cancer samples exhibited highly variable CpG methylation levels in a large proportion of the genome, involving progressive changes during tumor evolution. The whole-genome sequencing results from selected samples were replicated in a large cohort of 1112 primary tumors of various cancer types using genome-scale DNA methylation analysis. Specifically, we determined DNA hypermethylation of promoters and enhancers regulating tumor-suppressor genes, with potential cancer-driving effects. DNA hypermethylation events showed evidence of positive selection, mutual exclusivity and tissue specificity, suggesting their active participation in neoplastic transformation. Our data highlight the extensive changes in DNA methylation that occur in cancer onset, progression and dissemination. PMID:28581523

Grammatical Impairments in PPA

PubMed Central

Thompson, Cynthia K.; Mack, Jennifer E.

2015-01-01

Background Grammatical impairments are commonly observed in the agrammatic subtype of primary progressive aphasia (PPA-G), whereas grammatical processing is relatively preserved in logopenic (PPA-L) and semantic (PPA-S) subtypes. Aims We review research on grammatical deficits in PPA and associated neural mechanisms, with discussion focused on production and comprehension of four aspects of morphosyntactic structure: grammatical morphology, functional categories, verbs and verb argument structure, and complex syntactic structures. We also address assessment of grammatical deficits in PPA, with emphasis on behavioral tests of grammatical processing. Finally, we address research examining the effects of treatment for progressive grammatical impairments. Main Contribution PPA-G is associated with grammatical deficits that are evident across linguistic domains in both production and comprehension. PPA-G is associated with damage to regions including the left inferior frontal gyrus (IFG) and dorsal white matter tracts, which have been linked to impaired comprehension and production of complex sentences. Detailing grammatical deficits in PPA is important for estimating the trajectory of language decline and associated neuropathology. We, therefore, highlight several new assessment tools for examining different aspects of morphosyntactic processing in PPA. Conclusions Individuals with PPA-G present with agrammatic deficit patterns distinct from those associated with PPA-L and PPA-S, but similar to those seen in agrammatism resulting from stroke, and patterns of cortical atrophy and white matter changes associated with PPA-G have been identified. Methods for clinical evaluation of agrammatism, focusing on comprehension and production of grammatical morphology, functional categories, verbs and verb argument structure, and complex syntactic structures are recommended and tools for this are emerging in the literature. Further research is needed to investigate the real-time processes underlying grammatical impairments in PPA, as well as the structural and functional neural correlates of grammatical impairments across linguistic domains. Few studies have examined the effects of treatment for grammatical impairments in PPA; research in this area is needed to better understand how (or if) grammatical processing ability can be improved, the potential for spared neural tissue to be recruited to support this, and whether the neural connections within areas of dysfunctional tissue required for grammatical processing can be enhanced using cortical stimulation. PMID:25642014

Grammatical Impairments in PPA.

PubMed

Thompson, Cynthia K; Mack, Jennifer E

2014-09-01

Grammatical impairments are commonly observed in the agrammatic subtype of primary progressive aphasia (PPA-G), whereas grammatical processing is relatively preserved in logopenic (PPA-L) and semantic (PPA-S) subtypes. We review research on grammatical deficits in PPA and associated neural mechanisms, with discussion focused on production and comprehension of four aspects of morphosyntactic structure: grammatical morphology, functional categories, verbs and verb argument structure, and complex syntactic structures. We also address assessment of grammatical deficits in PPA, with emphasis on behavioral tests of grammatical processing. Finally, we address research examining the effects of treatment for progressive grammatical impairments. PPA-G is associated with grammatical deficits that are evident across linguistic domains in both production and comprehension. PPA-G is associated with damage to regions including the left inferior frontal gyrus (IFG) and dorsal white matter tracts, which have been linked to impaired comprehension and production of complex sentences. Detailing grammatical deficits in PPA is important for estimating the trajectory of language decline and associated neuropathology. We, therefore, highlight several new assessment tools for examining different aspects of morphosyntactic processing in PPA. Individuals with PPA-G present with agrammatic deficit patterns distinct from those associated with PPA-L and PPA-S, but similar to those seen in agrammatism resulting from stroke, and patterns of cortical atrophy and white matter changes associated with PPA-G have been identified. Methods for clinical evaluation of agrammatism, focusing on comprehension and production of grammatical morphology, functional categories, verbs and verb argument structure, and complex syntactic structures are recommended and tools for this are emerging in the literature. Further research is needed to investigate the real-time processes underlying grammatical impairments in PPA, as well as the structural and functional neural correlates of grammatical impairments across linguistic domains. Few studies have examined the effects of treatment for grammatical impairments in PPA; research in this area is needed to better understand how (or if) grammatical processing ability can be improved, the potential for spared neural tissue to be recruited to support this, and whether the neural connections within areas of dysfunctional tissue required for grammatical processing can be enhanced using cortical stimulation.

[Classical actions of vitamin D: insights from human genetics and from mouse models on calcium and phosphate homeostasis].

PubMed

Jehan, Frédéric; Voloc, Alexandru

2014-01-01

At the beginning of the 20th century, the discovery of vitamin D by Sir EV McCollum allowed a better comprehension of its origin and its role, and made it possible to cure rickets, a largely prevalent disease at that time. The main role of vitamin D3 is to maintain calcium and phosphate homeostasis through the action of 1,25-dihydroxyvitamin D3, its active form. This underlies physiological functions related to calcium and phosphate, such as bone mineralization or muscle function. Progress in basic research for the last 40 years led to the discovery of the main hydroxylation steps that produce and catabolize the active form of vitamin D. It also uncovered the molecular aspects of vitamin D action, from its nuclear receptor, VDR, to the various target genes of this hormone. Recent progress in human genetics pointed out mutations in genes involved in vitamin D metabolism and 1,25-dihydroxyvitamin D3 actions. It also helped to understand the role of the major actors that control vitamin D production and effects, through 1,25-dihydroxyvitamin D3 actions on phosphate and calcium homeostasis, and on bone biology. Genetical engineering targeting the whole animal or defined tissues or cell types have yielded many mouse models in the past decades. When targeted to tissues important for vitamin D metabolism and activity, these models allowed a more detailed comprehension of vitamin effects on calcium and phosphorus homeostasis. © Société de Biologie, 2014.

Contrasting breast cancer molecular subtypes across serial tumor progression stages: biological and prognostic implications

PubMed Central

Kimbung, Siker; Kovács, Anikó; Danielsson, Anna; Bendahl, Pär-Ola; Lövgren, Kristina; Stolt, Marianne Frostvik; Tobin, Nicholas P.; Lindström, Linda; Bergh, Jonas; Einbeigi, Zakaria; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

2015-01-01

The relevance of the intrinsic subtypes for clinical management of metastatic breast cancer is not comprehensively established. We aimed to evaluate the prevalence and prognostic significance of drifts in tumor molecular subtypes during breast cancer progression. A well-annotated cohort of 304 women with advanced breast cancer was studied. Tissue microarrays of primary tumors and synchronous lymph node metastases were constructed. Conventional biomarkers were centrally assessed and molecular subtypes were assigned following the 2013 St Gallen guidelines. Fine-needle aspirates of asynchronous metastases were transcriptionally profiled and subtyped using PAM50. Discordant expression of individual biomarkers and molecular subtypes was observed during tumor progression. Primary luminal-like tumors were relatively unstable, frequently adopting a more aggressive subtype in the metastases. Notably, loss of ER expression and a luminal to non-luminal subtype conversion was associated with an inferior post-recurrence survival. In addition, ER and molecular subtype assessed at all tumor progression stages were independent prognostic factors for post-recurrence breast cancer mortality in multivariable analyses. Our results demonstrate that drifts in tumor molecular subtypes may occur during tumor progression, conferring adverse consequences on outcome following breast cancer relapse. PMID:26375671

Multiparametric, Longitudinal Optical Coherence Tomography Imaging Reveals Acute Injury and Chronic Recovery in Experimental Ischemic Stroke

PubMed Central

Srinivasan, Vivek J.; Mandeville, Emiri T.; Can, Anil; Blasi, Francesco; Climov, Mihail; Daneshmand, Ali; Lee, Jeong Hyun; Yu, Esther; Radhakrishnan, Harsha; Lo, Eng H.; Sakadžić, Sava; Eikermann-Haerter, Katharina; Ayata, Cenk

2013-01-01

Progress in experimental stroke and translational medicine could be accelerated by high-resolution in vivo imaging of disease progression in the mouse cortex. Here, we introduce optical microscopic methods that monitor brain injury progression using intrinsic optical scattering properties of cortical tissue. A multi-parametric Optical Coherence Tomography (OCT) platform for longitudinal imaging of ischemic stroke in mice, through thinned-skull, reinforced cranial window surgical preparations, is described. In the acute stages, the spatiotemporal interplay between hemodynamics and cell viability, a key determinant of pathogenesis, was imaged. In acute stroke, microscopic biomarkers for eventual infarction, including capillary non-perfusion, cerebral blood flow deficiency, altered cellular scattering, and impaired autoregulation of cerebral blood flow, were quantified and correlated with histology. Additionally, longitudinal microscopy revealed remodeling and flow recovery after one week of chronic stroke. Intrinsic scattering properties serve as reporters of acute cellular and vascular injury and recovery in experimental stroke. Multi-parametric OCT represents a robust in vivo imaging platform to comprehensively investigate these properties. PMID:23940761

Current progress in bioactive ceramic scaffolds for bone repair and regeneration.

PubMed

Gao, Chengde; Deng, Youwen; Feng, Pei; Mao, Zhongzheng; Li, Pengjian; Yang, Bo; Deng, Junjie; Cao, Yiyuan; Shuai, Cijun; Peng, Shuping

2014-03-18

Bioactive ceramics have received great attention in the past decades owing to their success in stimulating cell proliferation, differentiation and bone tissue regeneration. They can react and form chemical bonds with cells and tissues in human body. This paper provides a comprehensive review of the application of bioactive ceramics for bone repair and regeneration. The review systematically summarizes the types and characters of bioactive ceramics, the fabrication methods for nanostructure and hierarchically porous structure, typical toughness methods for ceramic scaffold and corresponding mechanisms such as fiber toughness, whisker toughness and particle toughness. Moreover, greater insights into the mechanisms of interaction between ceramics and cells are provided, as well as the development of ceramic-based composite materials. The development and challenges of bioactive ceramics are also discussed from the perspective of bone repair and regeneration.

Current Progress in Bioactive Ceramic Scaffolds for Bone Repair and Regeneration

PubMed Central

Gao, Chengde; Deng, Youwen; Feng, Pei; Mao, Zhongzheng; Li, Pengjian; Yang, Bo; Deng, Junjie; Cao, Yiyuan; Shuai, Cijun; Peng, Shuping

2014-01-01

Bioactive ceramics have received great attention in the past decades owing to their success in stimulating cell proliferation, differentiation and bone tissue regeneration. They can react and form chemical bonds with cells and tissues in human body. This paper provides a comprehensive review of the application of bioactive ceramics for bone repair and regeneration. The review systematically summarizes the types and characters of bioactive ceramics, the fabrication methods for nanostructure and hierarchically porous structure, typical toughness methods for ceramic scaffold and corresponding mechanisms such as fiber toughness, whisker toughness and particle toughness. Moreover, greater insights into the mechanisms of interaction between ceramics and cells are provided, as well as the development of ceramic-based composite materials. The development and challenges of bioactive ceramics are also discussed from the perspective of bone repair and regeneration. PMID:24646912

Cell subpopulation deconvolution reveals breast cancer heterogeneity based on DNA methylation signature.

PubMed

Wen, Yanhua; Wei, Yanjun; Zhang, Shumei; Li, Song; Liu, Hongbo; Wang, Fang; Zhao, Yue; Zhang, Dongwei; Zhang, Yan

2017-05-01

Tumour heterogeneity describes the coexistence of divergent tumour cell clones within tumours, which is often caused by underlying epigenetic changes. DNA methylation is commonly regarded as a significant regulator that differs across cells and tissues. In this study, we comprehensively reviewed research progress on estimating of tumour heterogeneity. Bioinformatics-based analysis of DNA methylation has revealed the evolutionary relationships between breast cancer cell lines and tissues. Further analysis of the DNA methylation profiles in 33 breast cancer-related cell lines identified cell line-specific methylation patterns. Next, we reviewed the computational methods in inferring clonal evolution of tumours from different perspectives and then proposed a deconvolution strategy for modelling cell subclonal populations dynamics in breast cancer tissues based on DNA methylation. Further analysis of simulated cancer tissues and real cell lines revealed that this approach exhibits satisfactory performance and relative stability in estimating the composition and proportions of cellular subpopulations. The application of this strategy to breast cancer individuals of the Cancer Genome Atlas's identified different cellular subpopulations with distinct molecular phenotypes. Moreover, the current and potential future applications of this deconvolution strategy to clinical breast cancer research are discussed, and emphasis was placed on the DNA methylation-based recognition of intra-tumour heterogeneity. The wide use of these methods for estimating heterogeneity to further clinical cohorts will improve our understanding of neoplastic progression and the design of therapeutic interventions for treating breast cancer and other malignancies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Systems biology: A tool for charting the antiviral landscape.

PubMed

Bowen, James R; Ferris, Martin T; Suthar, Mehul S

2016-06-15

The host antiviral programs that are initiated following viral infection form a dynamic and complex web of responses that we have collectively termed as "the antiviral landscape". Conventional approaches to studying antiviral responses have primarily used reductionist systems to assess the function of a single or a limited subset of molecules. Systems biology is a holistic approach that considers the entire system as a whole, rather than individual components or molecules. Systems biology based approaches facilitate an unbiased and comprehensive analysis of the antiviral landscape, while allowing for the discovery of emergent properties that are missed by conventional approaches. The antiviral landscape can be viewed as a hierarchy of complexity, beginning at the whole organism level and progressing downward to isolated tissues, populations of cells, and single cells. In this review, we will discuss how systems biology has been applied to better understand the antiviral landscape at each of these layers. At the organismal level, the Collaborative Cross is an invaluable genetic resource for assessing how genetic diversity influences the antiviral response. Whole tissue and isolated bulk cell transcriptomics serves as a critical tool for the comprehensive analysis of antiviral responses at both the tissue and cellular levels of complexity. Finally, new techniques in single cell analysis are emerging tools that will revolutionize our understanding of how individual cells within a bulk infected cell population contribute to the overall antiviral landscape. Copyright © 2016 Elsevier B.V. All rights reserved.

In Vivo Biomarkers for Targeting Colorectal Neoplasms

PubMed Central

Hsiung, Pei-Lin; Wang, Thomas

2011-01-01

Summary Colorectal carcinoma continues to be a leading cause of cancer morbidity and mortality despite widespread adoption of screening methods. Targeted detection and therapy using recent advances in our knowledge of in vivo cancer biomarkers promise to significantly improve methods for early detection, risk stratification, and therapeutic intervention. The behavior of molecular targets in transformed tissues is being comprehensively assessed using new techniques of gene expression profiling and high throughput analyses. The identification of promising targets is stimulating the development of novel molecular probes, including significant progress in the field of activatable and peptide probes. These probes are being evaluated in small animal models of colorectal neoplasia and recently in the clinic. Furthermore, innovations in optical imaging instrumentation are resulting in the scaling down of size for endoscope compatibility. Advances in target identification, probe development, and novel instruments are progressing rapidly, and the integration of these technologies has a promising future in molecular medicine. PMID:19126961

Economic and care considerations of Marfan syndrome.

PubMed

Blankart, Carl Rudolf; Milstein, Ricarda; Rybczynski, Meike; Schüler, Helke; von Kodolitsch, Yskert

2016-10-01

Marfan syndrome is a rare multisystem disease of the connective tissue, which affects multiple organ systems. advances in healthcare have doubled the life-expectancy of patients over the past three decades. to date, there is no comprehensive review that consolidates economic considerations and care for marfan patients. Areas covered: Present research suggests that there may be a link between treatment pattern, disease progression and economic costs of Marfan syndrome. It indicates that an early detection of the disease and preventive interventions achieve a dual aim. From a patient perspective, it may reduce the amount of emergency surgery or intervention, and inpatient stays. In addition, it slows disease progression, lowers lifestyle restrictions, reduces psychological stress, and improves health-related quality of life. Expert commentary: Early detection and preventive measures are likely to achieve a dual aim by simultaneously containing costs and reducing the number and length of inpatient stays.

Bone tissue engineering using silica-based mesoporous nanobiomaterials:Recent progress.

PubMed

Shadjou, Nasrin; Hasanzadeh, Mohammad

2015-10-01

Bone disorders are of significant concern due to increase in the median age of our population. It is in this context that tissue engineering has been emerging as a valid approach to the current therapies for bone regeneration/substitution. Tissue-engineered bone constructs have the potential to alleviate the demand arising from the shortage of suitable autograft and allograft materials for augmenting bone healing. Silica based mesostructured nanomaterials possessing pore sizes in the range 2-50 nm and surface reactive functionalities have elicited immense interest due to their exciting prospects in bone tissue engineering. In this review we describe application of silica-based mesoporous nanomaterials for bone tissue engineering. We summarize the preparation methods, the effect of mesopore templates and composition on the mesopore-structure characteristics, and different forms of these materials, including particles, fibers, spheres, scaffolds and composites. Also, the effect of structural and textural properties of mesoporous materials on development of new biomaterials for production of bone implants and bone cements was discussed. Also, application of different mesoporous materials on construction of manufacture 3-dimensional scaffolds for bone tissue engineering was discussed. It begins by giving the reader a brief background on tissue engineering, followed by a comprehensive description of all the relevant components of silica-based mesoporous biomaterials on bone tissue engineering, going from materials to scaffolds and from cells to tissue engineering strategies that will lead to "engineered" bone. Copyright © 2015 Elsevier B.V. All rights reserved.

Analytical and Clinical Validation of a Digital Sequencing Panel for Quantitative, Highly Accurate Evaluation of Cell-Free Circulating Tumor DNA

PubMed Central

Zill, Oliver A.; Sebisanovic, Dragan; Lopez, Rene; Blau, Sibel; Collisson, Eric A.; Divers, Stephen G.; Hoon, Dave S. B.; Kopetz, E. Scott; Lee, Jeeyun; Nikolinakos, Petros G.; Baca, Arthur M.; Kermani, Bahram G.; Eltoukhy, Helmy; Talasaz, AmirAli

2015-01-01

Next-generation sequencing of cell-free circulating solid tumor DNA addresses two challenges in contemporary cancer care. First this method of massively parallel and deep sequencing enables assessment of a comprehensive panel of genomic targets from a single sample, and second, it obviates the need for repeat invasive tissue biopsies. Digital SequencingTM is a novel method for high-quality sequencing of circulating tumor DNA simultaneously across a comprehensive panel of over 50 cancer-related genes with a simple blood test. Here we report the analytic and clinical validation of the gene panel. Analytic sensitivity down to 0.1% mutant allele fraction is demonstrated via serial dilution studies of known samples. Near-perfect analytic specificity (> 99.9999%) enables complete coverage of many genes without the false positives typically seen with traditional sequencing assays at mutant allele frequencies or fractions below 5%. We compared digital sequencing of plasma-derived cell-free DNA to tissue-based sequencing on 165 consecutive matched samples from five outside centers in patients with stage III-IV solid tumor cancers. Clinical sensitivity of plasma-derived NGS was 85.0%, comparable to 80.7% sensitivity for tissue. The assay success rate on 1,000 consecutive samples in clinical practice was 99.8%. Digital sequencing of plasma-derived DNA is indicated in advanced cancer patients to prevent repeated invasive biopsies when the initial biopsy is inadequate, unobtainable for genomic testing, or uninformative, or when the patient’s cancer has progressed despite treatment. Its clinical utility is derived from reduction in the costs, complications and delays associated with invasive tissue biopsies for genomic testing. PMID:26474073

Progressive Achievement Tests in Reading: Comprehension & Vocabulary. Teacher's Handbook. Second Edition.

ERIC Educational Resources Information Center

Australian Council for Educational Research, Hawthorn.

The teacher handbook for Progressive Achievement Tests (PATs) in Reading presents an overall description of these survey tests in reading comprehension and vocabulary knowledge for school years 3 to 9. There are two alternative forms of each test: (1) the Reading Comprehension tests are designed to measure two major aspects of reading skills…

The changing face of dentistry: nanotechnology

PubMed Central

Kanaparthy, Rosaiah; Kanaparthy, Aruna

2011-01-01

The human body comprises molecules; hence, the availability of molecular nanotechnology will permit dramatic progress to address medical problems and will use molecular knowledge to maintain and improve human health at the molecular scale. Nanomedicine could develop devices that are able to work inside the human body in order to identify the early presence of a disease, and to identify and quantify toxic molecules and tumor cells, for example. Nanodentistry will make possible the maintenance of comprehensive oral health by employing nanomaterials, including tissue engineering and, ultimately, dental nanorobots. This review is an attempt to highlight the possible applications of nanotechnology and the use of nanomaterials in dentistry. PMID:22131826

Advancing the field of 3D biomaterial printing.

PubMed

Jakus, Adam E; Rutz, Alexandra L; Shah, Ramille N

2016-01-11

3D biomaterial printing has emerged as a potentially revolutionary technology, promising to transform both research and medical therapeutics. Although there has been recent progress in the field, on-demand fabrication of functional and transplantable tissues and organs is still a distant reality. To advance to this point, there are two major technical challenges that must be overcome. The first is expanding upon the limited variety of available 3D printable biomaterials (biomaterial inks), which currently do not adequately represent the physical, chemical, and biological complexity and diversity of tissues and organs within the human body. Newly developed biomaterial inks and the resulting 3D printed constructs must meet numerous interdependent requirements, including those that lead to optimal printing, structural, and biological outcomes. The second challenge is developing and implementing comprehensive biomaterial ink and printed structure characterization combined with in vitro and in vivo tissue- and organ-specific evaluation. This perspective outlines considerations for addressing these technical hurdles that, once overcome, will facilitate rapid advancement of 3D biomaterial printing as an indispensable tool for both investigating complex tissue and organ morphogenesis and for developing functional devices for a variety of diagnostic and regenerative medicine applications.

Tubular Tissues and Organs of Human Body--Challenges in Regenerative Medicine.

PubMed

Góra, Aleksander; Pliszka, Damian; Mukherjee, Shayanti; Ramakrishna, Seeram

2016-01-01

Tissue engineering of tubular organs such as the blood vessel, trachea gastrointestinal tract, urinary tract are of the great interest due to the high amount of surgeries performed annually on those organs. Development in tissue engineering in recent years and promising results, showed need to investigate more complex constructs that need to be designed in special manner. Stent technology remain the most widely used procedure to restore functions of tubular tissues after cancer treatment, or after organ removal due to traumatic accidents. Tubular structures like blood vessels, intestines, and trachea have to work in specific environment at the boundary of the liquids, solids or air and surrounding tissues and ensure suitable separation between them. This brings additional challenges in tissue engineering science in order to construct complete organs by using combinations of various cells along with the support material systems. Here we give a comprehensive review of the tubular structures of the human body, in perspective of the current methods of treatment and progress in regenerative medicine that aims to develop fully functioning organs of tubular shape. Extensive analysis of the available literature has been done focusing on materials and methods of creations of such organs. This work describes the attempts to incorporate growth factors and drugs within the scaffolds to ensure localized drug release and enhance vascularization of the organ by attracting blood vessels to the site of implantation.

Are biomechanical changes necessary for tumor progression?

NASA Astrophysics Data System (ADS)

Kas, Josef A.

2014-03-01

Already the Roman Celsus recognized rigid tissue as characteristic for solid tumors. Conversely, changes towards a weaker cytoskeleton have been described as a feature of cancer cells since the early days of tumor biology. It remains unclear if a carcinoma's rigid signature stems from more inflexible cells or is caused by the stroma. Despite that the importance of cell biomechanics for tumor progression becomes more and more evident the chicken-and-egg problem to what extent cancer cells already change their mechanical properties within the solid tumor in order to transgress its boundary or mechanical changes are induced by the microenvironment when the cell has left the tumor has been discussed highly controversial. Comprehensive clinical biomechanical measurements only exist from tumor tissue without the possibility to identify individual cells or from individual cancer cells from pleural effusions. Since the biomechanical properties of cells in carcinomas remain unknown measurements on individual cells that directly stem out of primary tumor samples are required, which we have conducted. We found in cervix and mammary carcinomas a distinctive increase of softer cells as well as contractile cells. A soft and contractile cell is like a strong elastic rope. The cell can generate a strong tensile tension to pull its self along and is soft against compression to avoid jamming.

Deriving a Mutation Index of Carcinogenicity Using Protein Structure and Protein Interfaces

PubMed Central

Hakas, Jarle; Pearl, Frances; Zvelebil, Marketa

2014-01-01

With the advent of Next Generation Sequencing the identification of mutations in the genomes of healthy and diseased tissues has become commonplace. While much progress has been made to elucidate the aetiology of disease processes in cancer, the contributions to disease that many individual mutations make remain to be characterised and their downstream consequences on cancer phenotypes remain to be understood. Missense mutations commonly occur in cancers and their consequences remain challenging to predict. However, this knowledge is becoming more vital, for both assessing disease progression and for stratifying drug treatment regimes. Coupled with structural data, comprehensive genomic databases of mutations such as the 1000 Genomes project and COSMIC give an opportunity to investigate general principles of how cancer mutations disrupt proteins and their interactions at the molecular and network level. We describe a comprehensive comparison of cancer and neutral missense mutations; by combining features derived from structural and interface properties we have developed a carcinogenicity predictor, InCa (Index of Carcinogenicity). Upon comparison with other methods, we observe that InCa can predict mutations that might not be detected by other methods. We also discuss general limitations shared by all predictors that attempt to predict driver mutations and discuss how this could impact high-throughput predictions. A web interface to a server implementation is publicly available at http://inca.icr.ac.uk/. PMID:24454733

Genetic Testing and Tissue Banking for Personalized Oncology: Analytical and Institutional Factors

PubMed Central

Miles, George; Rae, James; Ramalingam, Suresh S.; Pfeifer, John

2016-01-01

Personalized oncology, or more aptly precision oncogenomics, refers to the identification and implementation of clinically actionable targets tailored to an individual patient’s cancer genomic information. Banking of human tissue and other biospecimens establishes a framework to extract and collect the data essential to our understanding of disease pathogenesis and treatment. Cancer cooperative groups in the United States have led the way in establishing robust biospecimen collection mechanisms to facilitate translational research, and combined with technological advances in molecular testing, tissue banking has expanded from its traditional base in academic research and is assuming an increasingly pivotal role in directing the clinical care of cancer patients. Comprehensive screening of tumors by DNA sequencing and the ability to mine and interpret these large data sets from well-organized tissue banks have defined molecular subtypes of cancer. Such stratification by genomic criteria has revolutionized our perspectives on cancer diagnosis and treatment, offering insight into prognosis, progression, and susceptibility or resistance to known therapeutic agents. In turn, this has enabled clinicians to offer treatments tailored to patients that can greatly improve their chances of survival. Unique challenges and opportunities accompany the rapidly evolving interplay between tissue banking and genomic sequencing, and are the driving forces underlying the revolution in precision medicine. Molecular testing and precision medicine clinical trials are now becoming the major thrust behind the cooperative groups’ clinical research efforts. PMID:26433552

Raman spectroscopy in biomedicine – non-invasive in vitro analysis of cells and extracellular matrix components in tissues

PubMed Central

Brauchle, Eva; Schenke-Layland, Katja

2013-01-01

Raman spectroscopy is an established laser-based technology for the quality assurance of pharmaceutical products. Over the past few years, Raman spectroscopy has become a powerful diagnostic tool in the life sciences. Raman spectra allow assessment of the overall molecular constitution of biological samples, based on specific signals from proteins, nucleic acids, lipids, carbohydrates, and inorganic crystals. Measurements are non-invasive and do not require sample processing, making Raman spectroscopy a reliable and robust method with numerous applications in biomedicine. Moreover, Raman spectroscopy allows the highly sensitive discrimination of bacteria. Rama spectra retain information on continuous metabolic processes and kinetics such as lipid storage and recombinant protein production. Raman spectra are specific for each cell type and provide additional information on cell viability, differentiation status, and tumorigenicity. In tissues, Raman spectroscopy can detect major extracellular matrix components and their secondary structures. Furthermore, the non-invasive characterization of healthy and pathological tissues as well as quality control and process monitoring of in vitro-engineered matrix is possible. This review provides comprehensive insight to the current progress in expanding the applicability of Raman spectroscopy for the characterization of living cells and tissues, and serves as a good reference point for those starting in the field. PMID:23161832

A Review on Automatic Mammographic Density and Parenchymal Segmentation

PubMed Central

He, Wenda; Juette, Arne; Denton, Erika R. E.; Oliver, Arnau

2015-01-01

Breast cancer is the most frequently diagnosed cancer in women. However, the exact cause(s) of breast cancer still remains unknown. Early detection, precise identification of women at risk, and application of appropriate disease prevention measures are by far the most effective way to tackle breast cancer. There are more than 70 common genetic susceptibility factors included in the current non-image-based risk prediction models (e.g., the Gail and the Tyrer-Cuzick models). Image-based risk factors, such as mammographic densities and parenchymal patterns, have been established as biomarkers but have not been fully incorporated in the risk prediction models used for risk stratification in screening and/or measuring responsiveness to preventive approaches. Within computer aided mammography, automatic mammographic tissue segmentation methods have been developed for estimation of breast tissue composition to facilitate mammographic risk assessment. This paper presents a comprehensive review of automatic mammographic tissue segmentation methodologies developed over the past two decades and the evidence for risk assessment/density classification using segmentation. The aim of this review is to analyse how engineering advances have progressed and the impact automatic mammographic tissue segmentation has in a clinical environment, as well as to understand the current research gaps with respect to the incorporation of image-based risk factors in non-image-based risk prediction models. PMID:26171249

Detailed Analysis of the African Green Monkey Model of Nipah Virus Disease

PubMed Central

Johnston, Sara C.; Briese, Thomas; Bell, Todd M.; Pratt, William D.; Shamblin, Joshua D.; Esham, Heather L.; Donnelly, Ginger C.; Johnson, Joshua C.; Hensley, Lisa E.; Lipkin, W. Ian; Honko, Anna N.

2015-01-01

Henipaviruses are implicated in severe and frequently fatal pneumonia and encephalitis in humans. There are no approved vaccines or treatments available for human use, and testing of candidates requires the use of well-characterized animal models that mimic human disease. We performed a comprehensive and statistically-powered evaluation of the African green monkey model to define parameters critical to disease progression and the extent to which they correlate with human disease. African green monkeys were inoculated by the intratracheal route with 2.5×104 plaque forming units of the Malaysia strain of Nipah virus. Physiological data captured using telemetry implants and assessed in conjunction with clinical pathology were consistent with shock, and histopathology confirmed widespread tissue involvement associated with systemic vasculitis in animals that succumbed to acute disease. In addition, relapse encephalitis was identified in 100% of animals that survived beyond the acute disease phase. Our data suggest that disease progression in the African green monkey is comparable to the variable outcome of Nipah virus infection in humans. PMID:25706617

Data-based Decision-making: Teachers' Comprehension of Curriculum-based Measurement Progress-monitoring Graphs

ERIC Educational Resources Information Center

van den Bosch, Roxette M.; Espin, Christine A.; Chung, Siuman; Saab, Nadira

2017-01-01

Teachers have difficulty using data from Curriculum-based Measurement (CBM) progress graphs of students with learning difficulties for instructional decision-making. As a first step in unraveling those difficulties, we studied teachers' comprehension of CBM graphs. Using think-aloud methodology, we examined 23 teachers' ability to…

The Yin and Yang of innate immunity in stroke.

PubMed

Xu, Xiaomeng; Jiang, Yongjun

2014-01-01

Immune system plays an elementary role in the pathophysiological progress of ischemic stroke. It consists of innate and adaptive immune system. Activated within minutes after ischemic onset, innate immunity is responsible for the elimination of necrotic cells and tissue repair, while it is critically involved in the initiation and amplification of poststroke inflammation that amplifies ischemic damage to the brain tissue. Innate immune response requires days to be fully developed, providing a considerable time window for therapeutic intervention, suggesting prospect of novel immunomodulatory therapies against poststroke inflammation-induced brain injury. However, obstacles still exist and a comprehensive understanding of ischemic stroke and innate immune reaction is essential. In this review, we highlighted the current experimental and clinical data depicting the innate immune response following ischemic stroke, mainly focusing on the recognition of damage-associated molecular patterns, activation and recruitment of innate immune cells, and involvement of various cytokines. In addition, clinical trials targeting innate immunity were also documented regardless of the outcome, stressing the requirements for further investigation.

[Progress of researches on the mechanism of cupping therapy].

PubMed

Cui, Shuai; Cui, Jin

2012-12-01

Cupping therapy of Chinese medicine is able to relieve a variety of diseases or clinical conditions, which results from the comprehensive effects of multiple types of stimulation exerted onto the regional acupoint areas. Among the stimuli, the negative pressure from cupping is one of the main factors inducing therapeutic effects. In the present paper, the authors review development of researches on the underlying mechanism of therapeutic effects of cupping-negative pressure from 1) the factor of intra-cup negative pressure; 2) influence of intra-cup negative pressure on cup-blackspot formation; 3) influence of cupping on regional blood vessels and blood flow; 4) effect of cupping on regional ultrastructure of the capillary in the raw-surface tissue; 5) effect of cupping-negative pressure on regional endothelial cells; and 6) biological effects of negative pressure drainage. Generally, cupping induced negative pressure can dilate local blood vessels to improve microcirculation, promote capillary endothelial cells repair, accelerate granulation and angiogenesis, etc., in the regional tissues, normalizing the patients' functional state at last.

Biomarker MicroRNAs for Diagnosis, Prognosis and Treatment of Hepatocellular Carcinoma: A Functional Survey and Comparison

PubMed Central

Shen, Sijia; Lin, Yuxin; Yuan, Xuye; Shen, Li; Chen, Jiajia; Chen, Luonan; Qin, Lei; Shen, Bairong

2016-01-01

Hepatocellular Carcinoma (HCC) is one of the most common malignant tumors with high incidence and mortality rate. Precision and effective biomarkers are therefore urgently needed for the early diagnosis and prognostic estimation. MicroRNAs (miRNAs) are important regulators which play functions in various cellular processes and biological activities. Accumulating evidence indicated that the abnormal expression of miRNAs are closely associated with HCC initiation and progression. Recently, many biomarker miRNAs for HCC have been identified from blood or tissues samples, however, the universality and specificity on clinicopathological features of them are less investigated. In this review, we comprehensively surveyed and compared the diagnostic, prognostic, and therapeutic roles of HCC biomarker miRNAs in blood and tissues based on the cancer hallmarks, etiological factors as well as ethnic groups, which will be helpful to the understanding of the pathogenesis of biomarker miRNAs in HCC development and further provide accurate clinical decisions for HCC diagnosis and treatment. PMID:27917899

Comparing Growth in Linguistic Comprehension and Reading Comprehension in School-Aged Children with Autism versus Typically Developing Children

ERIC Educational Resources Information Center

Grimm, Ryan P.; Solari, Emily J.; McIntyre, Nancy S.; Zajic, Matthew; Mundy, Peter C.

2017-01-01

Many children with autism spectrum disorders (ASD) struggle with reading comprehension. Linguistic comprehension is an important predictor of reading comprehension, especially as children progress through elementary school and later grades. Yet, there is a dearth of research examining longitudinal relations between linguistic comprehensions in…

Thinking Small: Progress on Microscale Neurostimulation Technology.

PubMed

Pancrazio, Joseph J; Deku, Felix; Ghazavi, Atefeh; Stiller, Allison M; Rihani, Rashed; Frewin, Christopher L; Varner, Victor D; Gardner, Timothy J; Cogan, Stuart F

2017-12-01

Neural stimulation is well-accepted as an effective therapy for a wide range of neurological disorders. While the scale of clinical devices is relatively large, translational, and pilot clinical applications are underway for microelectrode-based systems. Microelectrodes have the advantage of stimulating a relatively small tissue volume which may improve selectivity of therapeutic stimuli. Current microelectrode technology is associated with chronic tissue response which limits utility of these devices for neural recording and stimulation. One approach for addressing the tissue response problem may be to reduce physical dimensions of the device. "Thinking small" is a trend for the electronics industry, and for implantable neural interfaces, the result may be a device that can evade the foreign body response. This review paper surveys our current understanding pertaining to the relationship between implant size and tissue response and the state-of-the-art in ultrasmall microelectrodes. A comprehensive literature search was performed using PubMed, Web of Science (Clarivate Analytics), and Google Scholar. The literature review shows recent efforts to create microelectrodes that are extremely thin appear to reduce or even eliminate the chronic tissue response. With high charge capacity coatings, ultramicroelectrodes fabricated from emerging polymers, and amorphous silicon carbide appear promising for neurostimulation applications. We envision the emergence of robust and manufacturable ultramicroelectrodes that leverage advanced materials where the small cross-sectional geometry enables compliance within tissue. Nevertheless, future testing under in vivo conditions is particularly important for assessing the stability of thin film devices under chronic stimulation. © 2017 International Neuromodulation Society.

Explaining the Progressively Decreasing Scores on Comprehensive Tests of Basic Skills (CTBS) of the School Children of the District of Columbia Public Schools as They Progress from Elementary School into High School.

ERIC Educational Resources Information Center

Bell, Christopher C., Jr.

This report uses motivation theory, social and cognitive development theory, and a construct, Definition of Reality (DOR), to explain why the black students of the District of Columbia Public Schools (DCPS) do less well on the Comprehensive Tests of Basic Skills as they progress from elementary school into high school. The report is divided into 8…

MicroRNAs as growth regulators, their function and biomarker status in colorectal cancer

PubMed Central

Cekaite, Lina; Eide, Peter W.; Lind, Guro E.; Skotheim, Rolf I.; Lothe, Ragnhild A.

2016-01-01

Gene expression is in part regulated by microRNAs (miRNAs). This review summarizes the current knowledge of miRNAs in colorectal cancer (CRC); their role as growth regulators, the mechanisms that regulate the miRNAs themselves and the potential of miRNAs as biomarkers. Although thousands of tissue samples and bodily fluids from CRC patients have been investigated for biomarker potential of miRNAs (>160 papers presented in a comprehensive tables), none single miRNA nor miRNA expression signatures are in clinical use for this disease. More than 500 miRNA-target pairs have been identified in CRC and we discuss how these regulatory nodes interconnect and affect signaling pathways in CRC progression. PMID:26623728

Breakdown of Immune Tolerance in Systemic Lupus Erythematosus by Dendritic Cells

PubMed Central

Reihl, Alec M.

2016-01-01

Dendritic cells (DC) play an important role in the pathogenesis of systemic lupus erythematosus (SLE), an autoimmune disease with multiple tissue manifestations. In this review, we summarize recent studies on the roles of conventional DC and plasmacytoid DC in the development of both murine lupus and human SLE. In the past decade, studies using selective DC depletions have demonstrated critical roles of DC in lupus progression. Comprehensive in vitro and in vivo studies suggest activation of DC by self-antigens in lupus pathogenesis, followed by breakdown of immune tolerance to self. Potential treatment strategies targeting DC have been developed. However, many questions remain regarding the mechanisms by which DC modulate lupus pathogenesis that require further investigations. PMID:27034965

Single-cell sequencing in stem cell biology.

PubMed

Wen, Lu; Tang, Fuchou

2016-04-15

Cell-to-cell variation and heterogeneity are fundamental and intrinsic characteristics of stem cell populations, but these differences are masked when bulk cells are used for omic analysis. Single-cell sequencing technologies serve as powerful tools to dissect cellular heterogeneity comprehensively and to identify distinct phenotypic cell types, even within a 'homogeneous' stem cell population. These technologies, including single-cell genome, epigenome, and transcriptome sequencing technologies, have been developing rapidly in recent years. The application of these methods to different types of stem cells, including pluripotent stem cells and tissue-specific stem cells, has led to exciting new findings in the stem cell field. In this review, we discuss the recent progress as well as future perspectives in the methodologies and applications of single-cell omic sequencing technologies.

Current status and perspectives in atomic force microscopy-based identification of cellular transformation

PubMed Central

Dong, Chenbo; Hu, Xiao; Dinu, Cerasela Zoica

2016-01-01

Understanding the complex interplay between cells and their biomechanics and how the interplay is influenced by the extracellular microenvironment, as well as how the transforming potential of a tissue from a benign to a cancerous one is related to the dynamics of both the cell and its surroundings, holds promise for the development of targeted translational therapies. This review provides a comprehensive overview of atomic force microscopy-based technology and its applications for identification of cellular progression to a cancerous phenotype. The review also offers insights into the advancements that are required for the next user-controlled tool to allow for the identification of early cell transformation and thus potentially lead to improved therapeutic outcomes. PMID:27274238

Developing a universal reading comprehension intervention for mainstream primary schools within areas of social deprivation for children with and without language-learning impairment: a feasibility study.

PubMed

McCartney, Elspeth; Boyle, James; Ellis, Sue

2015-01-01

Some children in areas of social deprivation in Scotland have lower reading attainment than neighbouring children in less deprived areas, and some of these also have lower spoken language comprehension skills than expected by assessment norms. There is a need to develop effective reading comprehension interventions that fit easily into the school curriculum and can benefit all pupils. A feasibility study of reading comprehension strategies with existing evidence of efficacy was undertaken in three mainstream primary schools within an area of social deprivation in west central Scotland, to decide whether further investigation of this intervention was warranted. Aims were to measure comprehension of spoken language and reading via standardised assessments towards the beginning of the school year (T1) in mainstream primary school classrooms within an area of social deprivation; to have teachers introduce previously-validated text comprehension strategies, and to measure change in reading comprehension outcome measures towards the end of the year (T2). A pre- and post-intervention cohort design was used. Reading comprehension strategies were introduced to staff in participating schools and used throughout the school year as part of on-going reading instruction. Spoken language comprehension was measured by TROG-2 at T1, and reading progress by score changes from T1 to T2 on the WIAT-II(UK) -T reading comprehension scale. Forty-seven pupils in five classes in three primary schools took part: 38% had TROG-2 scores below the 10(th) centile. As a group, children made good reading comprehension progress, with a medium effect size of 0.46. Children with TROG-2 scores below the 10(th) centile had lower mean reading scores than others at T1 and T2, although with considerable overlap. However, TROG-2 did not make a unique contribution to reading progress: children below the 10(th) centile made as much progress as other children. The intervention was welcomed by schools, and the measure of reading comprehension proved responsive to change. The outcomes suggest the reading intervention may be effective for children with and without spoken language comprehension difficulties, and warrants further investigation in larger, controlled, studies. © 2014 Royal College of Speech and Language Therapists.

Progress and development of analytical methods for gibberellins.

PubMed

Pan, Chaozhi; Tan, Swee Ngin; Yong, Jean Wan Hong; Ge, Liya

2017-01-01

Gibberellins, as a group of phytohormones, exhibit a wide variety of bio-functions within plant growth and development, which have been used to increase crop yields. Many analytical procedures, therefore, have been developed for the determination of the types and levels of endogenous and exogenous gibberellins. As plant tissues contain gibberellins in trace amounts (usually at the level of nanogram per gram fresh weight or even lower), the sample pre-treatment steps (extraction, pre-concentration, and purification) for gibberellins are reviewed in details. The primary focus of this comprehensive review is on the various analytical methods designed to meet the requirements for gibberellins analyses in complex matrices with particular emphasis on high-throughput analytical methods, such as gas chromatography, liquid chromatography, and capillary electrophoresis, mostly combined with mass spectrometry. The advantages and drawbacks of the each described analytical method are discussed. The overall aim of this review is to provide a comprehensive and critical view on the different analytical methods nowadays employed to analyze gibberellins in complex sample matrices and their foreseeable trends. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analyzing Remodeling of Cardiac Tissue: A Comprehensive Approach Based on Confocal Microscopy and 3D Reconstructions

PubMed Central

Sachse, F. B.

2015-01-01

Microstructural characterization of cardiac tissue and its remodeling in disease is a crucial step in many basic research projects. We present a comprehensive approach for three-dimensional characterization of cardiac tissue at the submicrometer scale. We developed a compression-free mounting method as well as labeling and imaging protocols that facilitate acquisition of three-dimensional image stacks with scanning confocal microscopy. We evaluated the approach with normal and infarcted ventricular tissue. We used the acquired image stacks for segmentation, quantitative analysis and visualization of important tissue components. In contrast to conventional mounting, compression-free mounting preserved cell shapes, capillary lumens and extracellular laminas. Furthermore, the new approach and imaging protocols resulted in high signal-to-noise ratios at depths up to 60 μm. This allowed extensive analyses revealing major differences in volume fractions and distribution of cardiomyocytes, blood vessels, fibroblasts, myofibroblasts and extracellular space in control versus infarct border zone. Our results show that the developed approach yields comprehensive data on microstructure of cardiac tissue and its remodeling in disease. In contrast to other approaches, it allows quantitative assessment of all major tissue components. Furthermore, we suggest that the approach will provide important data for physiological models of cardiac tissue at the submicrometer scale. PMID:26399990

Thinking Small – Progress on Microscale Neurostimulation Technology

PubMed Central

Pancrazio, Joseph J.; Deku, Felix; Ghazavi, Atefeh; Stiller, Allison M.; Rihani, Rashed; Frewin, Christopher L.; Varner, Victor D.; Gardner, Timothy J.; Cogan, Stuart F.

2017-01-01

Objectives Neural stimulation is well-accepted as an effective therapy for a wide range of neurological disorders. While the scale of clinical devices is relatively large, translational and pilot clinical applications are underway for microelectrode-based systems. Microelectrodes have the advantage of stimulating a relatively small tissue volume which may improve selectivity of therapeutic stimuli. Current microelectrode technology is associated with chronic tissue response which limits utility of these devices for neural recording and stimulation. One approach for addressing the tissue response problem may be to reduce physical dimensions of the device. “Thinking small” is a trend for the electronics industry, and for implantable neural interfaces, the result may be a device that can evade the foreign body response. Materials and Methods This review paper surveys our current understanding pertaining to the relationship between implant size and tissue response and the state-of-the-art in ultra-small microelectrodes. A comprehensive literature search was performed using PubMed, Web of Science (Clarivate Analytics), and Google Scholar. Results The literature review shows recent efforts to create microelectrodes that are extremely thin appear to reduce or even eliminate the chronic tissue response. With high charge capacity coatings, ultra-microelectrodes fabricated from emerging polymers and amorphous silicon carbide appear promising for neurostimulation applications. Conclusion We envision the emergence of robust and manufacturable ultra-microelectrodes that leverage advanced materials where the small cross-sectional geometry enables compliance within tissue. Nevertheless, future testing under in vivo conditions is particularly important for assessing the stability of thin film devices under chronic stimulation. PMID:29076214

Differential expression of VEGF ligands and receptors in prostate cancer.

PubMed

Woollard, David J; Opeskin, Kenneth; Coso, Sanja; Wu, Di; Baldwin, Megan E; Williams, Elizabeth D

2013-05-01

Prostate cancer disseminates to regional lymph nodes, however the molecular mechanisms responsible for lymph node metastasis are poorly understood. The vascular endothelial growth factor (VEGF) ligand and receptor family have been implicated in the growth and spread of prostate cancer via activation of the blood vasculature and lymphatic systems. The purpose of this study was to comprehensively examine the expression pattern of VEGF ligands and receptors in the glandular epithelium, stroma, lymphatic vasculature and blood vessels in prostate cancer. The localization of VEGF-A, VEGF-C, VEGF-D, VEGF receptor (VEGFR)-1, VEGFR-2, and VEGFR-3 was examined in cancerous and adjacent benign prostate tissue from 52 subjects representing various grades of prostate cancer. Except for VEGFR-2, extensive staining was observed for all ligands and receptors in the prostate specimens. In epithelial cells, VEGF-A and VEGFR-1 expression was higher in tumor tissue compared to benign tissue. VEGF-D and VEGFR-3 expression was significantly higher in benign tissue compared to tumor in the stroma and the endothelium of lymphatic and blood vessels. In addition, the frequency of lymphatic vessels, but not blood vessels, was lower in tumor tissue compared with benign tissue. These results suggest that activation of VEGFR-1 by VEGF-A within the carcinoma, and activation of lymphatic endothelial cell VEGFR-3 by VEGF-D within the adjacent benign stroma may be important signaling mechanisms involved in the progression and subsequent metastatic spread of prostate cancer. Thus inhibition of these pathways may contribute to therapeutic strategies for the management of prostate cancer. Copyright © 2012 Wiley Periodicals, Inc.

Metabolite profiling of human colon carcinoma--deregulation of TCA cycle and amino acid turnover.

PubMed

Denkert, Carsten; Budczies, Jan; Weichert, Wilko; Wohlgemuth, Gert; Scholz, Martin; Kind, Tobias; Niesporek, Silvia; Noske, Aurelia; Buckendahl, Anna; Dietel, Manfred; Fiehn, Oliver

2008-09-18

Apart from genetic alterations, development and progression of colorectal cancer has been linked to influences from nutritional intake, hyperalimentation, and cellular metabolic changes that may be the basis for new diagnostic and therapeutic approaches. However, in contrast to genomics and proteomics, comprehensive metabolomic investigations of alterations in malignant tumors have rarely been conducted. In this study we investigated a set of paired samples of normal colon tissue and colorectal cancer tissue with gas-chromatography time-of-flight mass-spectrometry, which resulted in robust detection of a total of 206 metabolites. Metabolic phenotypes of colon cancer and normal tissues were different at a Bonferroni corrected significance level of p=0.00170 and p=0.00005 for the first two components of an unsupervised PCA analysis. Subsequent supervised analysis found 82 metabolites to be significantly different at p<0.01. Metabolites were connected to abnormalities in metabolic pathways by a new approach that calculates the distance of each pair of metabolites in the KEGG database interaction lattice. Intermediates of the TCA cycle and lipids were found down-regulated in cancer, whereas urea cycle metabolites, purines, pyrimidines and amino acids were generally found at higher levels compared to normal colon mucosa. This study demonstrates that metabolic profiling facilitates biochemical phenotyping of normal and neoplastic colon tissue at high significance levels and points to GC-TOF-based metabolomics as a new method for molecular pathology investigations.

Construction Strategy and Progress of Whole Intervertebral Disc Tissue Engineering.

PubMed

Yang, Qiang; Xu, Hai-wei; Hurday, Sookesh; Xu, Bao-shan

2016-02-01

Degenerative disc disease (DDD) is the major cause of low back pain, which usually leads to work absenteeism, medical visits and hospitalization. Because the current conservative procedures and surgical approaches to treatment of DDD only aim to relieve the symptoms of disease but not to regenerate the diseased disc, their long-term efficiency is limited. With the rapid developments in medical science, tissue engineering techniques have progressed markedly in recent years, providing a novel regenerative strategy for managing intervertebral disc disease. However, there are as yet no ideal methods for constructing tissue-engineered intervertebral discs. This paper reviews published reports pertaining to intervertebral disc tissue engineering and summarizes data concerning the seed cells and scaffold materials for tissue-engineered intervertebral discs, construction of tissue-engineered whole intervertebral discs, relevant animal experiments and effects of mechanics on the construction of tissue-engineered intervertebral disc and outlines the existing problems and future directions. Although the perfect regenerative strategy for treating DDD has not yet been developed, great progress has been achieved in the construction of tissue-engineered intervertebral discs. It is believed that ongoing research on intervertebral disc tissue engineering will result in revolutionary progress in the treatment of DDD. © 2016 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

Tissue Engineering of Blood Vessels: Functional Requirements, Progress, and Future Challenges.

PubMed

Kumar, Vivek A; Brewster, Luke P; Caves, Jeffrey M; Chaikof, Elliot L

2011-09-01

Vascular disease results in the decreased utility and decreased availability of autologus vascular tissue for small diameter (< 6 mm) vessel replacements. While synthetic polymer alternatives to date have failed to meet the performance of autogenous conduits, tissue-engineered replacement vessels represent an ideal solution to this clinical problem. Ongoing progress requires combined approaches from biomaterials science, cell biology, and translational medicine to develop feasible solutions with the requisite mechanical support, a non-fouling surface for blood flow, and tissue regeneration. Over the past two decades interest in blood vessel tissue engineering has soared on a global scale, resulting in the first clinical implants of multiple technologies, steady progress with several other systems, and critical lessons-learned. This review will highlight the current inadequacies of autologus and synthetic grafts, the engineering requirements for implantation of tissue-engineered grafts, and the current status of tissue-engineered blood vessel research.

Theory of Mind and Reading Comprehension in Deaf and Hard-of-Hearing Signing Children

PubMed Central

Holmer, Emil; Heimann, Mikael; Rudner, Mary

2016-01-01

Theory of Mind (ToM) is related to reading comprehension in hearing children. In the present study, we investigated progression in ToM in Swedish deaf and hard-of-hearing (DHH) signing children who were learning to read, as well as the association of ToM with reading comprehension. Thirteen children at Swedish state primary schools for DHH children performed a Swedish Sign Language (SSL) version of the Wellman and Liu (2004) ToM scale, along with tests of reading comprehension, SSL comprehension, and working memory. Results indicated that ToM progression did not differ from that reported in previous studies, although ToM development was delayed despite age-appropriate sign language skills. Correlation analysis revealed that ToM was associated with reading comprehension and working memory, but not sign language comprehension. We propose that some factor not investigated in the present study, possibly represented by inference making constrained by working memory capacity, supports both ToM and reading comprehension and may thus explain the results observed in the present study. PMID:27375532

Theory of Mind and Reading Comprehension in Deaf and Hard-of-Hearing Signing Children.

PubMed

Holmer, Emil; Heimann, Mikael; Rudner, Mary

2016-01-01

Theory of Mind (ToM) is related to reading comprehension in hearing children. In the present study, we investigated progression in ToM in Swedish deaf and hard-of-hearing (DHH) signing children who were learning to read, as well as the association of ToM with reading comprehension. Thirteen children at Swedish state primary schools for DHH children performed a Swedish Sign Language (SSL) version of the Wellman and Liu (2004) ToM scale, along with tests of reading comprehension, SSL comprehension, and working memory. Results indicated that ToM progression did not differ from that reported in previous studies, although ToM development was delayed despite age-appropriate sign language skills. Correlation analysis revealed that ToM was associated with reading comprehension and working memory, but not sign language comprehension. We propose that some factor not investigated in the present study, possibly represented by inference making constrained by working memory capacity, supports both ToM and reading comprehension and may thus explain the results observed in the present study.

Use of the NBME Comprehensive Basic Science Examination as a Progress Test in the Preclerkship Curriculum of a New Medical School

ERIC Educational Resources Information Center

Johnson, Teresa R.; Khalil, Mohammed K.; Peppler, Richard D.; Davey, Diane D.; Kibble, Jonathan D.

2014-01-01

In the present study, we describe the innovative use of the National Board of Medical Examiners (NBME) Comprehensive Basic Science Examination (CBSE) as a progress test during the preclerkship medical curriculum. The main aim of this study was to provide external validation of internally developed multiple-choice assessments in a new medical…

The Development and Technical Adequacy of Seventh-Grade Reading Comprehension Measures in a Progress Monitoring Assessment System. Technical Report #1102

ERIC Educational Resources Information Center

Park, Bitnara Jasmine; Alonzo, Julie; Tindal, Gerald

2011-01-01

This technical report describes the process of development and piloting of reading comprehension measures that are appropriate for seventh-grade students as part of an online progress screening and monitoring assessment system, http://easycbm.com. Each measure consists of an original fictional story of approximately 1,600 to 1,900 words with 20…

Comprehensive progress report, July 1, 1974-September 30, 1977

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ames, B. N.

1977-05-01

Comprehensive research progress for the period July 1974 through September 1977 is reported. The objectives are to develop a set of bacterial strains that can be used to screen pesticides, herbicides, food additives, drugs, etc. for mutagens and to use these strains for investigating the mode of action of various mutagens and in particular for finding mutagens that make specific changes in DNA. (ACR)

In vivo Monitoring of Transcriptional Dynamics After Lower-Limb Muscle Injury Enables Quantitative Classification of Healing

PubMed Central

Aguilar, Carlos A.; Shcherbina, Anna; Ricke, Darrell O.; Pop, Ramona; Carrigan, Christopher T.; Gifford, Casey A.; Urso, Maria L.; Kottke, Melissa A.; Meissner, Alexander

2015-01-01

Traumatic lower-limb musculoskeletal injuries are pervasive amongst athletes and the military and typically an individual returns to activity prior to fully healing, increasing a predisposition for additional injuries and chronic pain. Monitoring healing progression after a musculoskeletal injury typically involves different types of imaging but these approaches suffer from several disadvantages. Isolating and profiling transcripts from the injured site would abrogate these shortcomings and provide enumerative insights into the regenerative potential of an individual’s muscle after injury. In this study, a traumatic injury was administered to a mouse model and healing progression was examined from 3 hours to 1 month using high-throughput RNA-Sequencing (RNA-Seq). Comprehensive dissection of the genome-wide datasets revealed the injured site to be a dynamic, heterogeneous environment composed of multiple cell types and thousands of genes undergoing significant expression changes in highly regulated networks. Four independent approaches were used to determine the set of genes, isoforms, and genetic pathways most characteristic of different time points post-injury and two novel approaches were developed to classify injured tissues at different time points. These results highlight the possibility to quantitatively track healing progression in situ via transcript profiling using high- throughput sequencing. PMID:26381351

Progress towards biocompatible intracortical microelectrodes for neural interfacing applications

NASA Astrophysics Data System (ADS)

Jorfi, Mehdi; Skousen, John L.; Weder, Christoph; Capadona, Jeffrey R.

2015-02-01

To ensure long-term consistent neural recordings, next-generation intracortical microelectrodes are being developed with an increased emphasis on reducing the neuro-inflammatory response. The increased emphasis stems from the improved understanding of the multifaceted role that inflammation may play in disrupting both biologic and abiologic components of the overall neural interface circuit. To combat neuro-inflammation and improve recording quality, the field is actively progressing from traditional inorganic materials towards approaches that either minimizes the microelectrode footprint or that incorporate compliant materials, bioactive molecules, conducting polymers or nanomaterials. However, the immune-privileged cortical tissue introduces an added complexity compared to other biomedical applications that remains to be fully understood. This review provides a comprehensive reflection on the current understanding of the key failure modes that may impact intracortical microelectrode performance. In addition, a detailed overview of the current status of various materials-based approaches that have gained interest for neural interfacing applications is presented, and key challenges that remain to be overcome are discussed. Finally, we present our vision on the future directions of materials-based treatments to improve intracortical microelectrodes for neural interfacing.

Progress Towards Biocompatible Intracortical Microelectrodes for Neural Interfacing Applications

PubMed Central

Jorfi, Mehdi; Skousen, John L.; Weder, Christoph; Capadona, Jeffrey R.

2015-01-01

To ensure long-term consistent neural recordings, next-generation intracortical microelectrodes are being developed with an increased emphasis on reducing the neuro-inflammatory response. The increased emphasis stems from the improved understanding of the multifaceted role that inflammation may play in disrupting both biologic and abiologic components of the overall neural interface circuit. To combat neuro-inflammation and improve recording quality, the field is actively progressing from traditional inorganic materials towards approaches that either minimizes the microelectrode footprint or that incorporate compliant materials, bioactive molecules, conducting polymers or nanomaterials. However, the immune-privileged cortical tissue introduces an added complexity compared to other biomedical applications that remains to be fully understood. This review provides a comprehensive reflection on the current understanding of the key failure modes that may impact intracortical microelectrode performance. In addition, a detailed overview of the current status of various materials-based approaches that have gained interest for neural interfacing applications is presented, and key challenges that remain to be overcome are discussed. Finally, we present our vision on the future directions of materials-based treatments to improve intracortical microelectrodes for neural interfacing. PMID:25460808

Advanced Imaging in Osteoarthritis

PubMed Central

Li, Qi; Amano, Keiko; Link, Thomas M.; Ma, C. Benjamin

2016-01-01

Context: Radiography is widely accepted as the gold standard for diagnosing osteoarthritis (OA), but it has limitations when assessing early stage OA and monitoring progression. While there are improvements in the treatment of OA, the challenge is early recognition. Evidence Acquisition: MEDLINE and PubMed as well as professional orthopaedic and imaging websites were reviewed from 2006 to 2016. Study Design: Clinical review. Level of Evidence: Level 4. Results: Magnetic resonance imaging (MRI) can provide the most comprehensive assessment of joint injury and OA with the advantages of being noninvasive and multiplanar with excellent soft tissue contrast. However, MRI is expensive, time consuming, and not widely used for monitoring OA clinically. Computed tomography (CT) and CT arthrography (CTA) can also be used to evaluate OA, but these are also invasive and require radiation exposure. Ultrasound is particularly useful for evaluation of synovitis but not for progression of OA. Conclusion: MRI, CT, and CTA are available for the diagnosis and monitoring of OA. Improvement in techniques and decrease in cost can allow some of these modalities to be effective methods of detecting early OA. PMID:27510507

Role of Antioxidants and Natural Products in Inflammation

PubMed Central

Fard, Masoumeh Tangestani; Tan, Woan Sean; Gothai, Sivapragasam; Kumar, S. Suresh

2016-01-01

Inflammation is a comprehensive array of physiological response to a foreign organism, including human pathogens, dust particles, and viruses. Inflammations are mainly divided into acute and chronic inflammation depending on various inflammatory processes and cellular mechanisms. Recent investigations have clarified that inflammation is a major factor for the progression of various chronic diseases/disorders, including diabetes, cancer, cardiovascular diseases, eye disorders, arthritis, obesity, autoimmune diseases, and inflammatory bowel disease. Free radical productions from different biological and environmental sources are due to an imbalance of natural antioxidants which further leads to various inflammatory associated diseases. In this review article, we have outlined the inflammatory process and its cellular mechanisms involved in the progression of various chronic modern human diseases. In addition, we have discussed the role of free radicals-induced tissue damage, antioxidant defence, and molecular mechanisms in chronic inflammatory diseases/disorders. The systematic knowledge regarding the role of inflammation and its associated adverse effects can provide a clear understanding in the development of innovative therapeutic targets from natural sources that are intended for suppression of various chronic inflammations associated diseases. PMID:27803762

Updated Lagrangian finite element formulations of various biological soft tissue non-linear material models: a comprehensive procedure and review.

PubMed

Townsend, Molly T; Sarigul-Klijn, Nesrin

2016-01-01

Simplified material models are commonly used in computational simulation of biological soft tissue as an approximation of the complicated material response and to minimize computational resources. However, the simulation of complex loadings, such as long-duration tissue swelling, necessitates complex models that are not easy to formulate. This paper strives to offer the updated Lagrangian formulation comprehensive procedure of various non-linear material models for the application of finite element analysis of biological soft tissues including a definition of the Cauchy stress and the spatial tangential stiffness. The relationships between water content, osmotic pressure, ionic concentration and the pore pressure stress of the tissue are discussed with the merits of these models and their applications.

Autoantibodies Associated With Connective Tissue Diseases: What Meaning for Clinicians?

PubMed Central

Didier, Kevin; Bolko, Loïs; Giusti, Delphine; Toquet, Segolene; Robbins, Ailsa; Antonicelli, Frank; Servettaz, Amelie

2018-01-01

Connective tissue diseases (CTDs) such as systemic lupus erythematosus, systemic sclerosis, myositis, Sjögren’s syndrome, and rheumatoid arthritis are systemic diseases which are often associated with a challenge in diagnosis. Autoantibodies (AAbs) can be detected in these diseases and help clinicians in their diagnosis. Actually, pathophysiology of these diseases is associated with the presence of antinuclear antibodies. In the last decades, many new antibodies were discovered, but their implication in pathogenesis of CTDs remains unclear. Furthermore, the classification of these AAbs is nowadays misused, as their targets can be localized outside of the nuclear compartment. Interestingly, in most cases, each antibody is associated with a specific phenotype in CTDs and therefore help in better defining either the disease subtypes or diseases activity and outcome. Because of recent progresses in their detection and in the comprehension of their pathogenesis implication in CTD-associated antibodies, clinicians should pay attention to the presence of these different AAbs to improve patient’s management. In this review, we propose to focus on the different phenotypes and features associated with each autoantibody used in clinical practice in those CTDs. PMID:29632529

Modeling Human Natural Killer Cell Development in the Era of Innate Lymphoid Cells

PubMed Central

Scoville, Steven D.; Freud, Aharon G.; Caligiuri, Michael A.

2017-01-01

Decades after the discovery of natural killer (NK) cells, their developmental pathways in mice and humans have not yet been completely deciphered. Accumulating evidence indicates that NK cells can develop in multiple tissues throughout the body. Moreover, detailed and comprehensive models of NK cell development were proposed soon after the turn of the century. However, with the recent identification and characterization of other subtypes of innate lymphoid cells (ILCs), which show some overlapping functional and phenotypic features with NK cell developmental intermediates, the distinct stages through which human NK cells develop from early hematopoietic progenitor cells remain unclear. Thus, there is a need to reassess and refine older models of NK cell development in the context of new data and in the era of ILCs. Our group has focused on elucidating the developmental pathway of human NK cells in secondary lymphoid tissues (SLTs), including tonsils and lymph nodes. Here, we provide an update of recent progress that has been made with regard to human NK cell development in SLTs, and we discuss these new findings in the context of contemporary models of ILC development. PMID:28396671

Modeling Human Natural Killer Cell Development in the Era of Innate Lymphoid Cells.

PubMed

Scoville, Steven D; Freud, Aharon G; Caligiuri, Michael A

2017-01-01

Decades after the discovery of natural killer (NK) cells, their developmental pathways in mice and humans have not yet been completely deciphered. Accumulating evidence indicates that NK cells can develop in multiple tissues throughout the body. Moreover, detailed and comprehensive models of NK cell development were proposed soon after the turn of the century. However, with the recent identification and characterization of other subtypes of innate lymphoid cells (ILCs), which show some overlapping functional and phenotypic features with NK cell developmental intermediates, the distinct stages through which human NK cells develop from early hematopoietic progenitor cells remain unclear. Thus, there is a need to reassess and refine older models of NK cell development in the context of new data and in the era of ILCs. Our group has focused on elucidating the developmental pathway of human NK cells in secondary lymphoid tissues (SLTs), including tonsils and lymph nodes. Here, we provide an update of recent progress that has been made with regard to human NK cell development in SLTs, and we discuss these new findings in the context of contemporary models of ILC development.

Mass spectrometry-based proteomics: from cancer biology to protein biomarkers, drug targets, and clinical applications.

PubMed

Jimenez, Connie R; Verheul, Henk M W

2014-01-01

Proteomics is optimally suited to bridge the gap between genomic information on the one hand and biologic functions and disease phenotypes at the other, since it studies the expression and/or post-translational modification (especially phosphorylation) of proteins--the major cellular players bringing about cellular functions--at a global level in biologic specimens. Mass spectrometry technology and (bio)informatic tools have matured to the extent that they can provide high-throughput, comprehensive, and quantitative protein inventories of cells, tissues, and biofluids in clinical samples at low level. In this article, we focus on next-generation proteomics employing nanoliquid chromatography coupled to high-resolution tandem mass spectrometry for in-depth (phospho)protein profiling of tumor tissues and (proximal) biofluids, with a focus on studies employing clinical material. In addition, we highlight emerging proteogenomic approaches for the identification of tumor-specific protein variants, and targeted multiplex mass spectrometry strategies for large-scale biomarker validation. Below we provide a discussion of recent progress, some research highlights, and challenges that remain for clinical translation of proteomic discoveries.

Molecular and epigenetic regulations and functions of the LAFL transcriptional regulators that control seed development.

PubMed

Lepiniec, L; Devic, M; Roscoe, T J; Bouyer, D; Zhou, D-X; Boulard, C; Baud, S; Dubreucq, B

2018-05-24

The LAFL (i.e. LEC1, ABI3, FUS3, and LEC2) master transcriptional regulators interact to form different complexes that induce embryo development and maturation, and inhibit seed germination and vegetative growth in Arabidopsis. Orthologous genes involved in similar regulatory processes have been described in various angiosperms including important crop species. Consistent with a prominent role of the LAFL regulators in triggering and maintaining embryonic cell fate, their expression appears finely tuned in different tissues during seed development and tightly repressed in vegetative tissues by a surprisingly high number of genetic and epigenetic factors. Partial functional redundancies and intricate feedback regulations of the LAFL have hampered the elucidation of the underpinning molecular mechanisms. Nevertheless, genetic, genomic, cellular, molecular, and biochemical analyses implemented during the last years have greatly improved our knowledge of the LALF network. Here we summarize and discuss recent progress, together with current issues required to gain a comprehensive insight into the network, including the emerging function of LEC1 and possibly LEC2 as pioneer transcription factors.

Development of polyurethanes for bone repair.

PubMed

Marzec, M; Kucińska-Lipka, J; Kalaszczyńska, I; Janik, H

2017-11-01

The purpose of this paper is to review recent developments on polyurethanes aimed at the design, synthesis, modifications, and biological properties in the field of bone tissue engineering. Different polyurethane systems are presented and discussed in terms of biodegradation, biocompatibility and bioactivity. A comprehensive discussion is provided of the influence of hard to soft segments ratio, catalysts, stiffness and hydrophilicity of polyurethanes. Interaction with various cells, behavior in vivo and current strategies in enhancing bioactivity of polyurethanes are described. The discussion on the incorporation of biomolecules and growth factors, surface modifications, and obtaining polyurethane-ceramics composites strategies is held. The main emphasis is placed on the progress of polyurethane applications in bone regeneration, including bone void fillers, shape memory scaffolds, and drug carrier. Copyright © 2017 Elsevier B.V. All rights reserved.

The novel KMO inhibitor CHDI-340246 leads to a restoration of electrophysiological alterations in mouse models of Huntington's disease.

PubMed

Beaumont, Vahri; Mrzljak, Ladislav; Dijkman, Ulrike; Freije, Robert; Heins, Mariette; Rassoulpour, Arash; Tombaugh, Geoffrey; Gelman, Simon; Bradaia, Amyaouch; Steidl, Esther; Gleyzes, Melanie; Heikkinen, Taneli; Lehtimäki, Kimmo; Puoliväli, Jukka; Kontkanen, Outi; Javier, Robyn M; Neagoe, Ioana; Deisemann, Heike; Winkler, Dirk; Ebneth, Andreas; Khetarpal, Vinod; Toledo-Sherman, Leticia; Dominguez, Celia; Park, Larry C; Munoz-Sanjuan, Ignacio

2016-08-01

Dysregulation of the kynurenine (Kyn) pathway has been associated with the progression of Huntington's disease (HD). In particular, elevated levels of the kynurenine metabolites 3-hydroxy kynurenine (3-OH-Kyn) and quinolinic acid (Quin), have been reported in the brains of HD patients as well as in rodent models of HD. The production of these metabolites is controlled by the activity of kynurenine mono-oxygenase (KMO), an enzyme which catalyzes the synthesis of 3-OH-Kyn from Kyn. In order to determine the role of KMO in the phenotype of mouse models of HD, we have developed a potent and selective KMO inhibitor termed CHDI-340246. We show that this compound, when administered orally to transgenic mouse models of HD, potently and dose-dependently modulates the Kyn pathway in peripheral tissues and in the central nervous system. The administration of CHDI-340246 leads to an inhibition of the formation of 3-OH-Kyn and Quin, and to an elevation of Kyn and Kynurenic acid (KynA) levels in brain tissues. We show that administration of CHDI-340246 or of Kyn and of KynA can restore several electrophysiological alterations in mouse models of HD, both acutely and after chronic administration. However, using a comprehensive panel of behavioral tests, we demonstrate that the chronic dosing of a selective KMO inhibitor does not significantly modify behavioral phenotypes or natural progression in mouse models of HD. Copyright © 2016. Published by Elsevier Inc.

A Learning Progression for Elementary Students' Functional Thinking

ERIC Educational Resources Information Center

Stephens, Ana C.; Fonger, Nicole; Strachota, Susanne; Isler, Isil; Blanton, Maria; Knuth, Eric; Murphy Gardiner, Angela

2017-01-01

In this article we advance characterizations of and supports for elementary students' progress in generalizing and representing functional relationships as part of a comprehensive approach to early algebra. Our learning progressions approach to early algebra research involves the coordination of a curricular framework and progression, an…

Effects of Coralliophila violacea on tissue loss in the scleractinian corals Porites spp. depend on host response

USGS Publications Warehouse

Raymundo, L.; Work, Thierry M.; Miller, R.L.; Lozada-Misa, P.L.

2016-01-01

We investigated interactions between the corallivorous gastropod Coralliophila violacea and its preferred hosts Porites spp. Our objectives were to experimentally determine whether tissue loss could progress in Porites during or after Coralliophila predation on corals with and without tissue loss and to histologically document snail predation. In 64% of feeding scars, tissue regenerated within 3 wk, leaving no trace of predation. However, in roughly 28% of scars, lesions progressed to subacute tissue loss resembling white syndrome. In feeding experiments, scars from snails previously fed diseased tissue developed progressive tissue loss twice as frequently as scars from snails previously fed healthy tissue. Scars from previously healthy-fed snails were 3 times as likely to heal as those from previously diseased-fed snails. Histology revealed marked differences in host responses to snails; P. cylindrica manifested a robust inflammatory response with fewer secondary colonizing organisms such as algae, sponges, and helminths, whereas P. rus showed no evident inflammation and more secondary colonization. We conclude that lesion progression associated with Coralliophila may be associated with secondary colonization of coral tissues damaged by predator-induced trauma and necrosis. Importantly, variation at the cellular level should be considered when explaining interspecific differences in host responses in corals impacted by phenomena such as predation.

Increased lipoprotein lipase activity in non-small cell lung cancer tissue predicts shorter patient survival.

PubMed

Trost, Zoran; Sok, Miha; Marc, Janja; Cerne, Darko

2009-07-01

Cumulative evidence suggests the involvement of lipoprotein lipase (LPL) in tumor progression. We tested the hypothesis that increased LPL activity in resectable non-small cell lung cancer (NSCLC) tissue and the increased LPL gene expression in the surrounding non-cancer lung tissue found in our previous study are predictors of patient survival. Forty two consecutive patients with resected NSCLC were enrolled in the study. Paired samples of lung cancer tissue and adjacent non-cancer lung tissue were collected from resected specimens for baseline LPL activity and gene expression estimation. During a 4-year follow-up, 21 patients died due to tumor progression. One patient died due to a non-cancer reason and was not included in Cox regression analysis. High LPL activity in cancer tissue (relative to the adjacent non-cancer lung tissue) predicted shorter survival, independently of standard prognostic factors (p=0.003). High gene expression in the non-cancer lung tissue surrounding the tumor had no predictive value. Our study further underlines the involvement of cancer tissue LPL activity in tumor progression.

Study Progress on Tissue Culture of Maize Mature Embryo

NASA Astrophysics Data System (ADS)

Wang, Hongzhen; Cheng, Jun; Cheng, Yanping; Zhou, Xioafu

It has been paid more and more attention on maize tissue culture as it is a basic work in maize genetic transformation, especially huge breakthrough has been made in maize tissue culture utilizing mature embryos as explants in the recent years. This paper reviewed the study progress on maize tissue culture and plant regeneration utilizing mature embryos as explants from callus induction, subculture, plant regeneration and browning reduction and so on.

Predicting Second Grade Listening Comprehension Using Prekindergarten Measures

ERIC Educational Resources Information Center

Alonzo, Crystle N.; Yeomans-Maldonado, Gloria; Murphy, Kimberly A.; Bevens, Beau

2016-01-01

Purpose: The purpose of this study was to determine prekindergarten predictors of listening comprehension in second grade. Methods: Within a large, 5-year longitudinal study, children progressing from prekindergarten to second grade were administered a comprehensive set of prekindergarten measures of foundational language skills (vocabulary and…

Spatial Systems Lipidomics Reveals Nonalcoholic Fatty Liver Disease Heterogeneity

PubMed Central

2018-01-01

Hepatocellular lipid accumulation characterizes nonalcoholic fatty liver disease (NAFLD). However, the types of lipids associated with disease progression are debated, as is the impact of their localization. Traditional lipidomics analysis using liver homogenates or plasma dilutes and averages lipid concentrations, and does not provide spatial information about lipid distribution. We aimed to characterize the distribution of specific lipid species related to NAFLD severity by performing label-free molecular analysis by mass spectrometry imaging (MSI). Fresh frozen liver biopsies from obese subjects undergoing bariatric surgery (n = 23) with various degrees of NAFLD were cryosectioned and analyzed by matrix-assisted laser desorption/ionization (MALDI)-MSI. Molecular identification was verified by tandem MS. Tissue sections were histopathologically stained, annotated according to the Kleiner classification, and coregistered with the MSI data set. Lipid pathway analysis was performed and linked to local proteome networks. Spatially resolved lipid profiles showed pronounced differences between nonsteatotic and steatotic tissues. Lipid identification and network analyses revealed phosphatidylinositols and arachidonic acid metabolism in nonsteatotic regions, whereas low–density lipoprotein (LDL) and very low–density lipoprotein (VLDL) metabolism was associated with steatotic tissue. Supervised and unsupervised discriminant analysis using lipid based classifiers outperformed simulated analysis of liver tissue homogenates in predicting steatosis severity. We conclude that lipid composition of steatotic and nonsteatotic tissue is highly distinct, implying that spatial context is important for understanding the mechanisms of lipid accumulation in NAFLD. MSI combined with principal component–linear discriminant analysis linking lipid and protein pathways represents a novel tool enabling detailed, comprehensive studies of the heterogeneity of NAFLD. PMID:29570976

Tissue engineering in urethral reconstruction—an update

PubMed Central

Mangera, Altaf; Chapple, Christopher R

2013-01-01

The field of tissue engineering is rapidly progressing. Much work has gone into developing a tissue engineered urethral graft. Current grafts, when long, can create initial donor site morbidity. In this article, we evaluate the progress made in finding a tissue engineered substitute for the human urethra. Researchers have investigated cell-free and cell-seeded grafts. We discuss different approaches to developing these grafts and review their reported successes in human studies. With further work, tissue engineered grafts may facilitate the management of lengthy urethral strictures requiring oral mucosa substitution urethroplasty. PMID:23042444

Evolving Relevance of Neuroproteomics in Alzheimer's Disease.

PubMed

Lista, Simone; Zetterberg, Henrik; O'Bryant, Sid E; Blennow, Kaj; Hampel, Harald

2017-01-01

Substantial progress in the understanding of the biology of Alzheimer's disease (AD) has been achieved over the past decades. The early detection and diagnosis of AD and other age-related neurodegenerative diseases, however, remain a challenging scientific frontier. Therefore, the comprehensive discovery (relating to all individual, converging or diverging biochemical disease mechanisms), development, validation, and qualification of standardized biological markers with diagnostic and prognostic functions with a precise performance profile regarding specificity, sensitivity, and positive and negative predictive value are warranted.Methodological innovations in the area of exploratory high-throughput technologies, such as sequencing, microarrays, and mass spectrometry-based analyses of proteins/peptides, have led to the generation of large global molecular datasets from a multiplicity of biological systems, such as biological fluids, cells, tissues, and organs. Such methodological progress has shifted the attention to the execution of hypothesis-independent comprehensive exploratory analyses (opposed to the classical hypothesis-driven candidate approach), with the aim of fully understanding the biological systems in physiology and disease as a whole. The systems biology paradigm integrates experimental biology with accurate and rigorous computational modelling to describe and foresee the dynamic features of biological systems. The use of dynamically evolving technological platforms, including mass spectrometry, in the area of proteomics has enabled to rush the process of biomarker discovery and validation for refining significantly the diagnosis of AD. Currently, proteomics-which is part of the systems biology paradigm-is designated as one of the dominant matured sciences needed for the effective exploratory discovery of prospective biomarker candidates expected to play an effective role in aiding the early detection, diagnosis, prognosis, and therapy development in AD.

Gynecologic Cancer Prevention and Control in the National Comprehensive Cancer Control Program: Progress, Current Activities, and Future Directions

PubMed Central

Lakhani, Naheed; Brown, Phaeydra M.; Larkin, O. Ann; Moore, Angela R.; Hayes, Nikki S.

2013-01-01

Abstract Gynecologic cancer confers a large burden among women in the United States. Several evidence-based interventions are available to reduce the incidence, morbidity, and mortality from these cancers. The National Comprehensive Cancer Control Program (NCCCP) is uniquely positioned to implement these interventions in the US population. This review discusses progress and future directions for the NCCCP in preventing and controlling gynecologic cancer. PMID:23865787

The Comprehensive, Powerful, Academic Database (CPAD): An Evaluative Study of a Predictive Tool Designed for Elementary School Personnel in Identifying At-Risk Students through Progress, Curriculum, and Performance Monitoring

ERIC Educational Resources Information Center

Chavez-Gibson, Sarah

2013-01-01

The purpose of this study is to exam in-depth, the Comprehensive, Powerful, Academic Database (CPAD), a data decision-making tool that determines and identifies students at-risk of dropping out of school, and how the CPAD assists administrators and teachers at an elementary campus to monitor progress, curriculum, and performance to improve student…

Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma.

PubMed

Rooprai, Harcharan K; Martin, Andrew J; King, Andrew; Appadu, Usha D; Jones, Huw; Selway, Richard P; Gullan, Richard W; Pilkington, Geoffrey J

2016-12-01

MMPs (matrix metalloproteinases), ADAMs (a disintegrin and metalloproteinase) and TIMPs (tissue inhibitors of metalloproteinases) are implicated in invasion and angiogenesis: both are tissue remodeling processes involving regulated proteolysis of the extracellular matrix, growth factors and their receptors. The expression of these three groups and their correlations with clinical behaviour has been reported in gliomas but a similar comprehensive study in meningiomas is lacking. In this study, we aimed to evaluate the patterns of expression of 23 MMPs, 4 TIMPs, 8 ADAMs, selective growth factors and their receptors in 17 benign meningiomas using a quantitative real-time polymerase chain reaction (qPCR). Results indicated very high gene expression of 13 proteases, inhibitors and growth factors studied: MMP2 and MMP14, TIMP-1, -2 and -3, ADAM9, 10, 12, 15 and 17, EGF-R, EMMPRIN and VEGF-A, in almost every meningioma. Expression pattern analysis showed several positive correlations between MMPs, ADAMs, TIMPs and growth factors. Furthermore, our findings suggest that expression of MMP14, ADAM9, 10, 12, 15 and 17, TIMP-2, EGF-R and EMMPRIN reflects histological subtype of meningioma such that fibroblastic subtype had the highest mRNA expression, transitional subtype was intermediate and meningothelial type had the lowest expression. In conclusion, this is the first comprehensive study characterizing gene expression of 8 ADAMs in meningiomas. These neoplasms, although by histological definition benign, have invasive potential. Taken together, the selected elevated gene expression pattern may serve to identify targets for therapeutic intervention or indicators of biological progression and recurrence.

The Spanish biology/disease initiative within the human proteome project: Application to rheumatic diseases.

PubMed

Ruiz-Romero, Cristina; Calamia, Valentina; Albar, Juan Pablo; Casal, José Ignacio; Corrales, Fernando J; Fernández-Puente, Patricia; Gil, Concha; Mateos, Jesús; Vivanco, Fernando; Blanco, Francisco J

2015-09-08

The Spanish Chromosome 16 consortium is integrated in the global initiative Human Proteome Project, which aims to develop an entire map of the proteins encoded following a gene-centric strategy (C-HPP) in order to make progress in the understanding of human biology in health and disease (B/D-HPP). Chromosome 16 contains many genes encoding proteins involved in the development of a broad range of diseases, which have a significant impact on the health care system. The Spanish HPP consortium has developed a B/D platform with five programs focused on selected medical areas: cancer, obesity, cardiovascular, infectious and rheumatic diseases. Each of these areas has a clinical leader associated to a proteomic investigator with the responsibility to get a comprehensive understanding of the proteins encoded by Chromosome 16 genes. Proteomics strategies have enabled great advances in the area of rheumatic diseases, particularly in osteoarthritis, with studies performed on joint cells, tissues and fluids. In this manuscript we describe how the Spanish HPP-16 consortium has developed a B/D platform with five programs focused on selected medical areas: cancer, obesity, cardiovascular, infectious and rheumatic diseases. Each of these areas has a clinical leader associated to a proteomic investigator with the responsibility to get a comprehensive understanding of the proteins encoded by Chromosome 16 genes. We show how the Proteomic strategy has enabled great advances in the area of rheumatic diseases, particularly in osteoarthritis, with studies performed on joint cells, tissues and fluids. This article is part of a Special Issue entitled: HUPO 2014. Copyright © 2015 Elsevier B.V. All rights reserved.

Single Case Design Elements in Text Comprehension Research for Students with Developmental Disabilities

ERIC Educational Resources Information Center

Snyder, Sara M.; Knight, Victoria F.; Ayres, Kevin M.; Mims, Pamela J.; Sartini, Emily C.

2017-01-01

Recently researchers have begun exploring the efficacy of interventions designed to improve text comprehension skills for students with developmental disabilities (DD). Text comprehension is essential for understanding academic content as students with disabilities make progress in the general education curriculum. This article focuses on single…

Motor Speech Phenotypes of Frontotemporal Dementia, Primary Progressive Aphasia, and Progressive Apraxia of Speech

ERIC Educational Resources Information Center

Poole, Matthew L.; Brodtmann, Amy; Darby, David; Vogel, Adam P.

2017-01-01

Purpose: Our purpose was to create a comprehensive review of speech impairment in frontotemporal dementia (FTD), primary progressive aphasia (PPA), and progressive apraxia of speech in order to identify the most effective measures for diagnosis and monitoring, and to elucidate associations between speech and neuroimaging. Method: Speech and…

State of the Art: MR Imaging after Knee Cartilage Repair Surgery.

PubMed

Guermazi, Ali; Roemer, Frank W; Alizai, Hamza; Winalski, Carl S; Welsch, Goetz; Brittberg, Mats; Trattnig, Siegfried

2015-10-01

Cartilage injuries are common, especially in athletes. Because these injuries frequently affect young patients, and they have the potential to progress to osteoarthritis, treatment to alleviate symptoms and delay joint degeneration is warranted. A number of surgical techniques are available to treat focal chondral defects, including marrow stimulation, osteochondral auto- and allografting, and autologous chondrocyte implantation. Although arthroscopy is considered the standard of reference for the evaluation of cartilage before and after repair, it is invasive with associated morbidity and cannot adequately depict the deep cartilage layer and underlying bone. Magnetic resonance (MR) imaging provides unparalleled noninvasive assessment of the repair site and all other joint tissues. MR observation of cartilage repair tissue is a well-established semiquantitative scoring system for repair tissue that has primarily been used in clinical research studies. The cartilage repair osteoarthritis knee score (CROAKS) optimizes comprehensive morphologic assessment of the knee joint after cartilage repair. Furthermore, quantitative, compositional MR imaging measurements (eg, T2, T2*, T1ρ), delayed gadolinium-enhanced MR imaging of cartilage (dGEMRIC), and sodium imaging are available for biochemical assessment. These quantitative MR imaging techniques help assess collagen content and orientation, water content, and glycosaminoglycan and/or proteoglycan content both in the repair tissue as it matures and in the "native" cartilage. In this review, the authors discuss the principles of state-of-the-art morphologic and compositional MR imaging techniques for imaging of cartilage repair and their application to longitudinal studies. (©) RSNA, 2015.

Deregulation of obesity-relevant genes is associated with progression in BMI and the amount of adipose tissue in pigs.

PubMed

Mentzel, Caroline M Junker; Cardoso, Tainã Figueiredo; Pipper, Christian Bressen; Jacobsen, Mette Juul; Jørgensen, Claus Bøttcher; Cirera, Susanna; Fredholm, Merete

2018-02-01

The aim of this study was to elucidate the relative impact of three phenotypes often used to characterize obesity on perturbation of molecular pathways involved in obesity. The three obesity-related phenotypes are (1) body mass index (BMI), (2) amount of subcutaneous adipose tissue (SATa), and (3) amount of retroperitoneal adipose tissue (RPATa). Although it is generally accepted that increasing amount of RPATa is 'unhealthy', a direct comparison of the relative impact of the three obesity-related phenotypes on gene expression has, to our knowledge, not been performed previously. We have used multiple linear models to analyze altered gene expression of selected obesity-related genes in tissues collected from 19 female pigs phenotypically characterized with respect to the obesity-related phenotypes. Gene expression was assessed by high-throughput qPCR in RNA from liver, skeletal muscle and abdominal adipose tissue. The stringent statistical approach used in the study has increased the power of the analysis compared to the classical approach of analysis in divergent groups of individuals. Our approach led to the identification of key components of cellular pathways that are modulated in the three tissues in association with changes in the three obesity-relevant phenotypes (BMI, SATa and RPATa). The deregulated pathways are involved in biosynthesis and transcript regulation in adipocytes, in lipid transport, lipolysis and metabolism, and in inflammatory responses. Deregulation seemed more comprehensive in liver (23 genes) compared to abdominal adipose tissue (10 genes) and muscle (3 genes). Notably, the study supports the notion that excess amount of intra-abdominal adipose tissue is associated with a greater metabolic disease risk. Our results provide molecular support for this notion by demonstrating that increasing amount of RPATa has a higher impact on perturbation of cellular pathways influencing obesity and obesity-related metabolic traits compared to increase in BMI and amount of SATa.

Towards a comprehensive understanding of emerging dynamics and function of pancreatic islets: A complex network approach. Comment on "Network science of biological systems at different scales: A review" by Gosak et al.

NASA Astrophysics Data System (ADS)

Loppini, Alessandro

2018-03-01

Complex network theory represents a comprehensive mathematical framework to investigate biological systems, ranging from sub-cellular and cellular scales up to large-scale networks describing species interactions and ecological systems. In their exhaustive and comprehensive work [1], Gosak et al. discuss several scenarios in which the network approach was able to uncover general properties and underlying mechanisms of cells organization and regulation, tissue functions and cell/tissue failure in pathology, by the study of chemical reaction networks, structural networks and functional connectivities.

The emergence and pitfalls of international tissue banking.

PubMed

Phillips, Glyn O

2018-05-23

The rapid growth of tissue banking and associated international organisations following the fall of the Berlin wall in 1991 is described. This surge in collaboration led to a world-wide constructive movement to use and to produce human tissues. As the years progressed industrialisation, led by the USA, improved the quality of tissue allografts but led higher costs and consolidation within the developing industry. The growth of litigation more than kept pace with the industrial progress. One landmark case is described, the outcome of which could revolutionise the current practices now applied to eliminate possible viral contamination of implanted tissue grafts.

Word Knowledge in a Theory of Reading Comprehension

ERIC Educational Resources Information Center

Perfetti, Charles; Stafura, Joseph

2014-01-01

We reintroduce a wide-angle view of reading comprehension, the Reading Systems Framework, which places word knowledge in the center of the picture, taking into account the progress made in comprehension research and theory. Within this framework, word-to-text integration processes can serve as a model for the study of local comprehension…

A Discrepancy in Comprehension and Production in Early Language Development in ASD: Is It Clinically Relevant?

ERIC Educational Resources Information Center

Davidson, Meghan M.; Ellis Weismer, Susan

2017-01-01

This study examined the extent to which a discrepant comprehension-production profile (i.e., relatively more delayed comprehension than production) is characteristic of the early language phenotype in autism spectrum disorders (ASD) and tracked the developmental progression of the profile. Our findings indicated that a discrepant…

[Tissue bank of the National Centre for Tumour Disease. An innovative platform for translational tumour].

PubMed

Herpel, E; Koleganova, N; Schirmacher, P

2008-11-01

The tissue bank of the National Centre for Tumour Diseases (NCT) in Heidelberg, Germany, was founded in 2005 by the University Hospital of Heidelberg and the German Cancer Research Centre as a section of the NCT. It is a nonprofit organization with a completely evaluated legal and ethical framework and supports the Comprehensive Cancer Centre concept. Its main aim is the acquisition and characterization of fresh-frozen and paraffin-embedded human tissues according to the standards of good scientific practice and the promotion of interdisciplinary tumour research of the comprehensive cancer centre and its cooperating partners. It also offers expert project assistance: a project leader can submit a short proposal, and the tissue collecting/preparing process will be performed in cooperation with a specialised pathologist and, if applicable, an experienced clinical researcher. The tissue bank is also a central platform for further developing of innovative technologies for tissue handling, e.g. multi-tissue-array and virtual microscopy, with links to digital image analysis and bioinformatics. Thus, the NCT tissue bank represents a model for innovative biobanking and for institutions with active interdisciplinary cancer research.

Microdialysis Sampling from Wound Fluids Enables Quantitative Assessment of Cytokines, Proteins, and Metabolites Reveals Bone Defect-Specific Molecular Profiles.

PubMed

Förster, Yvonne; Schmidt, Johannes R; Wissenbach, Dirk K; Pfeiffer, Susanne E M; Baumann, Sven; Hofbauer, Lorenz C; von Bergen, Martin; Kalkhof, Stefan; Rammelt, Stefan

2016-01-01

Bone healing involves a variety of different cell types and biological processes. Although certain key molecules have been identified, the molecular interactions of the healing progress are not completely understood. Moreover, a clinical routine for predicting the quality of bone healing after a fracture in an early phase is missing. This is mainly due to a lack of techniques to comprehensively screen for cytokines, growth factors and metabolites at their local site of action. Since all soluble molecules of interest are present in the fracture hematoma, its in-depth assessment could reveal potential markers for the monitoring of bone healing. Here, we describe an approach for sampling and quantification of cytokines and metabolites by using microdialysis, combined with solid phase extractions of proteins from wound fluids. By using a control group with an isolated soft tissue wound, we could reveal several bone defect-specific molecular features. In bone defect dialysates the neutrophil chemoattractants CXCL1, CXCL2 and CXCL3 were quantified with either a higher or earlier response compared to dialysate from soft tissue wound. Moreover, by analyzing downstream adaptions of the cells on protein level and focusing on early immune response, several proteins involved in the immune cell migration and activity could be identified to be specific for the bone defect group, e.g. immune modulators, proteases and their corresponding inhibitors. Additionally, the metabolite screening revealed different profiles between the bone defect group and the control group. In summary, we identified potential biomarkers to indicate imbalanced healing progress on all levels of analysis.

Microdialysis Sampling from Wound Fluids Enables Quantitative Assessment of Cytokines, Proteins, and Metabolites Reveals Bone Defect-Specific Molecular Profiles

PubMed Central

Wissenbach, Dirk K.; Pfeiffer, Susanne E. M.; Baumann, Sven; Hofbauer, Lorenz C.; von Bergen, Martin; Kalkhof, Stefan; Rammelt, Stefan

2016-01-01

Bone healing involves a variety of different cell types and biological processes. Although certain key molecules have been identified, the molecular interactions of the healing progress are not completely understood. Moreover, a clinical routine for predicting the quality of bone healing after a fracture in an early phase is missing. This is mainly due to a lack of techniques to comprehensively screen for cytokines, growth factors and metabolites at their local site of action. Since all soluble molecules of interest are present in the fracture hematoma, its in-depth assessment could reveal potential markers for the monitoring of bone healing. Here, we describe an approach for sampling and quantification of cytokines and metabolites by using microdialysis, combined with solid phase extractions of proteins from wound fluids. By using a control group with an isolated soft tissue wound, we could reveal several bone defect-specific molecular features. In bone defect dialysates the neutrophil chemoattractants CXCL1, CXCL2 and CXCL3 were quantified with either a higher or earlier response compared to dialysate from soft tissue wound. Moreover, by analyzing downstream adaptions of the cells on protein level and focusing on early immune response, several proteins involved in the immune cell migration and activity could be identified to be specific for the bone defect group, e.g. immune modulators, proteases and their corresponding inhibitors. Additionally, the metabolite screening revealed different profiles between the bone defect group and the control group. In summary, we identified potential biomarkers to indicate imbalanced healing progress on all levels of analysis. PMID:27441377

Nuclear medicine and imaging research. Quantitative studies in radiopharmaceutical science. Comprehensive progress report, January 1, 1983-June 30, 1985

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beck, R.N.; Cooper, M.D.

1985-09-01

This comprehensive report outlines the progress made during the past three years in the areas described below. In all instances, initial studies have been carried out and the technical feasibility of carrying through each study has been demonstrated. The studies described include development of cesium-130 and bromine-75 radioisotope generators, the feasibility of using rubidium-82 as a myocardial imaging agent, and radiochemical preparation of C-11 deoxyglucose. 28 refs. (DT)

Comparing the Performance of Older Low-Progress Readers on the York Assessment of Reading for Comprehension with Performance on the Neale Analysis of Reading Ability and Other Measures of Reading and Related Skills

ERIC Educational Resources Information Center

Wheldall, Kevin; Arakelian, Sarah

2016-01-01

The aim of this study was to compare the York Assessment of Reading for Comprehension (YARC) with the Neale Analysis of Reading Ability (NARA) and other measures of reading and related skills with a sample of older low-progress readers and to provide additional information regarding the validity of the YARC in Australia. The data from an…

Return to Throwing after Shoulder or Elbow Injury.

PubMed

Sgroi, Terrance A; Zajac, John M

2018-03-01

Throwing places high demands on the human body, and specific characteristics are developed over time unique to these athletes. When returning to throw after injury, it is important to follow a criterion-based progression that allows the body to be prepared appropriately for the stresses that throwing will require. There is currently a void in the literature for criteria-based progression that helps these athletes return to the highest level of play. As injury rates continue to rise in baseball, there is increased evidence showing contributions of the core and lower extremity to the baseball pitch. There is also additional data showing pitcher specific characteristics such as range of motion and scapular position in this unique population. The rehab professional should take into account every phase of the pitch starting from balance through ball release when designing a comprehensive return-to-throwing program. Returning an athlete back to a throwing sport can be an overwhelming task. The rehabilitation specialist must have a sound understanding of the throwing motion as well as any biomechanical implications on the body, contributions throughout the kinetic chain, range of motion, and strength characteristics specific to the thrower as well as proper tissue loading principles. It is important that these athletes are not progressed too quickly through their programs and that a criteria-based progression is followed. They should have normalized range of motion, strength, and scapular mechanics, followed by a sound plyometric progression. Once this is achieved, they are advanced to an interval throwing program with increasing distance, effort, and volume which should be tracked for workload, making sure they do not throw more than their body is prepared for.

Progress in the detection of neoplastic progress and cancer by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Bakker Schut, Tom C.; Stone, Nicholas; Kendall, Catherine A.; Barr, Hugh; Bruining, Hajo A.; Puppels, Gerwin J.

2000-05-01

Early detection of cancer is important because of the improved survival rates when the cancer is treated early. We study the application of NIR Raman spectroscopy for detection of dysplasia because this technique is sensitive to the small changes in molecular invasive in vivo detection using fiber-optic probes. The result of an in vitro study to detect neoplastic progress of esophageal Barrett's esophageal tissue will be presented. Using multivariate statistics, we developed three different linear discriminant analysis classification models to predict tissue type on the basis of the measured spectrum. Spectra of normal, metaplastic and dysplasia tissue could be discriminated with an accuracy of up to 88 percent. Therefore Raman spectroscopy seems to be a very suitable technique to detect dysplasia in Barrett's esophageal tissue.

Long non-coding RNA biomarker for human laryngeal squamous cell carcinoma prognosis.

PubMed

Chen, Jingjing; Shen, Zhisen; Deng, Hongxia; Zhou, Wei; Liao, Qi; Mu, Ying

2018-05-15

Long non-coding RNAs (lncRNA) were discovered in tumors. The regulation of lncRNA in human laryngeal squamous cell carcinoma (LSCC) remains incomplete. Uncovering the potential of lncRNA to stratify the prognosis of LSCC and streamline the vast amount of clinical information will affect medical interventions. The surgical resected LSCC tissues, adjacent non-cancerous tissues (ANCT) and lymph node metastatic tissue (LNM) were collected from 76 patients for lncRNA AC008440.10 expression assay. The stages of LSCC and LNM were classified accordingly. We integrated the epigenetic information with enhanced CT imaging and pathological evaluations to predict the patients' survival by comprehensive statistical algorithms using equal weighting. Significant downregulation of lncRNA AC008440.10 was detected in LSCC tumor and metastatic lymph node in advanced stage of patient samples compared with those in early stage. The pattern of differentially expressed AC008440.10 displayed a clear trend that significantly related to tumor progression. The downregulation of lncRNA AC008440.10 correlates with increasing risk of metastasis, poor prognosis and patient survival. The potential for lncRNA AC008440.10 to be developed as a novel biomarker for stratification of the prognosis was especially promising when clinic parameters were hybridized with equal weight, and using a panel of complementary parameters yielded a more powerful predictability of LSCC prognosis than any single parameter individually. Copyright © 2017. Published by Elsevier B.V.

Dendritic cells in Barrett's esophagus and esophageal adenocarcinoma.

PubMed

Bobryshev, Yuri V; Tran, Dinh; Killingsworth, Murray C; Buckland, Michael; Lord, Reginald V N

2009-01-01

Like other premalignant conditions that develop in the presence of chronic inflammation, the development and progression of Barrett's esophagus is associated with the development of an immune response, but how this immune response is regulated is poorly understood. A comprehensive literature search failed to find any report of the presence of dendritic cells in Barrett's intestinal metaplasia and esophageal adenocarcinoma and this prompted our study. We used immunohistochemical staining and electron microscopy to examine whether dendritic cells are present in Barrett's esophagus and esophageal adenocarcinoma. Immunohistochemical staining with CD83, a specific marker for dendritic cells, was performed on paraffin-embedded sections of Barrett's intestinal metaplasia (IM, n = 12), dysplasia (n = 11) and adenocarcinoma (n = 14). CD83+ cells were identified in the lamina propria surrounding intestinal type glands in Barrett's IM, dysplasia, and cancer tissues. Computerized quantitative analysis showed that the numbers of dendritic cells were significantly higher in cancer tissues. Double immunostaining with CD83, CD20, and CD3, and electron microscopy demonstrated that dendritic cells are present in Barrett's esophagus and form clusters with T cells and B cells directly within the lamina propria. These findings demonstrate that dendritic cells are present in Barrett's tissues, with a significant increase in density in adenocarcinoma compared to benign Barrett's esophagus. Dendritic cells may have a role in the pathogenesis and immunotherapy treatment of Barrett's esophagus and adenocarcinoma.

Pupil Progression Plan: Requirements and Procedures 1982-83.

ERIC Educational Resources Information Center

Duval County School Board, Jacksonville, FL.

The Pupil Progression Plan detailed in this document was developed in response to Florida's Educational Accountability Act, which requires each school district to establish a comprehensive program for pupil progression, and to fulfill the requirements of school board policy. The first section details general procedures for promotion, grades K-12.…

[Research progress of articular cartilage scaffold for tissue engineering].

PubMed

Liu, Qingyu; Wang, Fuyou; Yang, Liu

2012-10-01

To review the research progress of articular cartilage scaffold materials and look into the future development prospects. Recent literature about articular cartilage scaffold for tissue engineering was reviewed, and the results from experiments and clinical application about natural and synthetic scaffold materials were analyzed. The design of articular cartilage scaffold for tissue engineering is vital to articular cartilage defects repair. The ideal scaffold can promote the progress of the cartilage repair, but the scaffold materials still have their limitations. It is necessary to pay more attention to the research of the articular cartilage scaffold, which is significant to the repair of cartilage defects in the future.

Lower risk of progression from prediabetes to diabetes with health checkup with lifestyle education: Japan Ningen Dock study.

PubMed

Okada, R; Tsushita, K; Wakai, K; Ishizaka, Y; Kato, K; Wada, T; Watanabe, K

2017-08-01

To investigate whether the progression from prediabetes to diabetes is lower among those who undertake Ningen Dock (comprehensive health checkups with lifestyle education and doctor's consultation) than those who undertake basic mandatory occupational health checkups. Subjects aged 30-69 years with complete annual data from 2008 to 2012 for either Ningen Dock or basic health checkups were enrolled. Subjects with prediabetes (fasting plasma glucose 100-125 mg/dl or HbA1c 5.7-6.4%) at baseline were selected (14,928 in the comprehensive group and 10,433 in the basic group). The incidence of diabetes (fasting plasma glucose ≥ 126 mg/dl, HbA1c ≥ 6.5% or taking glucose-lowering drugs) and the reduction of risk factors were compared. After 4 years, 3226 cases of diabetes occurred among 25,361 subjects with prediabetes. The incidence of diabetes was lower in the comprehensive group than the basic group (2.9 vs. 3.8 cases/100 person-years, hazard ratio 0.75, 95% confidence interval 0.68-0.81 after adjustment). Moreover, more overweight subjects controlled their body mass index (16.2% vs. 13.2%) and more began a daily exercise habit (11.8% vs. 8.5%) in the comprehensive group than in the basic group. The incidence of diabetes was lower in subjects who could control their weight or start daily exercise at year 1 in the comprehensive group. Progression from prediabetes to diabetes was significantly lower in subjects undertaking a comprehensive health checkup with lifestyle education. Lifestyle education at health checkup for people with prediabetes might prevent progression to diabetes by reducing modifiable risk factors. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Progress and pitfalls in finding the 'missing proteins' from the human proteome map.

PubMed

Segura, Victor; Garin-Muga, Alba; Guruceaga, Elizabeth; Corrales, Fernando J

2017-01-01

The Human Proteome Project was launched with two main goals: the comprehensive and systematic definition of the human proteome map and the development of ready to use analytical tools to measure relevant proteins in their biological context in health and disease. Despite the great progress in this endeavour, there is still a group of reluctant proteins with no, or scarce, experimental evidence supporting their existence. These are called the 'missing proteins' and represent one of the biggest challenges to complete the human proteome map. Areas covered: This review focuses on the description of the missing proteome based on the HUPO standards, the analysis of the reasons explaining the difficulty of detecting missing proteins and the strategies currently used in the search for missing proteins. The present and future of the quest for the missing proteins is critically revised hereafter. Expert commentary: An overarching multidisciplinary effort is currently being done under the HUPO umbrella to allow completion of the human proteome map. It is expected that the detection of missing proteins will grow in the coming years since the methods and the best tissue/cell type sample for their search are already on the table.

Metabolism dysregulation induces a specific lipid signature of nonalcoholic steatohepatitis in patients

PubMed Central

Chiappini, Franck; Coilly, Audrey; Kadar, Hanane; Gual, Philippe; Tran, Albert; Desterke, Christophe; Samuel, Didier; Duclos-Vallée, Jean-Charles; Touboul, David; Bertrand-Michel, Justine; Brunelle, Alain; Guettier, Catherine; Le Naour, François

2017-01-01

Nonalcoholic steatohepatitis (NASH) is a condition which can progress to cirrhosis and hepatocellular carcinoma. Markers for NASH diagnosis are still lacking. We performed a comprehensive lipidomic analysis on human liver biopsies including normal liver, nonalcoholic fatty liver and NASH. Random forests-based machine learning approach allowed characterizing a signature of 32 lipids discriminating NASH with 100% sensitivity and specificity. Furthermore, we validated this signature in an independent group of NASH patients. Then, metabolism dysregulations were investigated in both patients and murine models. Alterations of elongase and desaturase activities were observed along the fatty acid synthesis pathway. The decreased activity of the desaturase FADS1 appeared as a bottleneck, leading upstream to an accumulation of fatty acids and downstream to a deficiency of long-chain fatty acids resulting to impaired phospholipid synthesis. In NASH, mass spectrometry imaging on tissue section revealed the spreading into the hepatic parenchyma of selectively accumulated fatty acids. Such lipids constituted a highly toxic mixture to human hepatocytes. In conclusion, this study characterized a specific and sensitive lipid signature of NASH and positioned FADS1 as a significant player in accumulating toxic lipids during NASH progression. PMID:28436449

Epidermal growth factor receptor (EGFR) is overexpressed in high-grade dysplasia and adenocarcinoma of the esophagus and may represent a biomarker of histological progression in Barrett's esophagus (BE).

PubMed

Cronin, James; McAdam, Elizabeth; Danikas, Antonios; Tselepis, Chris; Griffiths, Paul; Baxter, John; Thomas, Linzi; Manson, James; Jenkins, Gareth

2011-01-01

The assessment of cancer risk in patients with Barrett's esophagus (BE) is currently fraught with difficulty. The current gold standard method of assessing cancer risk is histological assessment, with the appearance of high-grade dysplasia (HGD) as the key event monitored. Sampling error during endoscopy limits the usefulness of this approach, and there has been much recent interest in supplementing histological assessment with molecular markers, which may aid in patient stratification. No molecular marker has been yet validated to accurately correlate with esophageal histological progression. Here, we assessed the suitability of several membranous proteins as biomarkers by correlating their abundance with histological progression. In all, 107 patient samples, from 100 patients, were arranged on a tissue microarray (TMA) and represented the various stages of histological progression in BE. This TMA was probed with antibodies for eight receptor proteins (mostly membranous). Epidermal growth factor receptor (EGFR) staining was found to be the most promising biomarker identified with clear increases in staining accompanying histological progression. Further, immunohistochemistry was performed using the full-tissue sections from BE, HGD, and adenocarcinoma tissues, which confirmed the stepwise increase in EGFR abundance. Using a robust H-score analysis, EGFR abundance was shown to increase 13-fold in the adenocarcinoma tissues compared to the BE tissues. EGFR was "overexpressed" in 35% of HGD specimens and 80% of adenocarcinoma specimens when using the H-score of the BE patients (plus 3 s.d.) as the threshold to define overexpression. EGFR staining was also noted to be higher in BE tissues adjacent to HGD/adenocarcinoma. Western blotting, although showing more EGFR protein in the adenocarcinomas compared to the BE tissue, was highly variable. EGFR overexpression was accompanied by aneuploidy (gain) of chromosome 7, plus amplification of the EGFR locus. Finally, the bile acid deoxycholic acid (DCA) (at neutral and acidic pH) and acid alone was capable of upregulating EGFR mRNA in vitro, and in the case of neutral pH DCA, this was NF-κB dependent. EGFR is overexpressed during the histological progression in BE tissues and hence may be useful as a biomarker of histological progression. Furthermore, as EGFR is a membranous protein expressed on the luminal surface of the esophageal mucosa, it may also be a useful target for biopsy guidance during endoscopy.

Beyond Screening and Progress Monitoring: An Examination of the Reliability and Concurrent Validity of Maze Comprehension Assessments for Fourth-Grade Students

ERIC Educational Resources Information Center

Brasher, Casey F.

2017-01-01

Reading comprehension assessments often lack instructional utility because they do not accurately pinpoint why a student has difficulty. The varying formats, directions, and response requirements of comprehension assessments lead to differential measurement of underlying skills and contribute to noted amounts of unshared variance among tests. Maze…

Progress and Impact. A Report of Programs Funded for 1995-96 by the Comprehensive Health Education Act of 1990.

ERIC Educational Resources Information Center

Terrill, Jerry L.; Connell, Karen

During the 1995-96 school year, the Colorado Department of Education supported Comprehensive Health Education Programs as authorized by the Comprehensive Health Education Act of 1990. This report summarizes the projects funded under that grant along with additional observations and recommendations regarding the operation of such grants. Grant…

Towards Community Employment: A Comprehensive Data-Based Training System for Mentally Retarded Adults.

ERIC Educational Resources Information Center

Dardig, Jill C.; Jewett, Robert J.

1979-01-01

The article describes the efforts of Project PATH (Progressive Approach to Training and Habilitation) to design a comprehensive training program for moderately and severely retarded adults in a sheltered workshop setting. (SBH)

Comprehensive Plasma Metabolomic Analyses of Atherosclerotic Progression Reveal Alterations in Glycerophospholipid and Sphingolipid Metabolism in Apolipoprotein E-deficient Mice

PubMed Central

Dang, Vi T.; Huang, Aric; Zhong, Lexy H.; Shi, Yuanyuan; Werstuck, Geoff H.

2016-01-01

Atherosclerosis is the major underlying cause of most cardiovascular diseases. Despite recent advances, the molecular mechanisms underlying the pathophysiology of atherogenesis are not clear. In this study, comprehensive plasma metabolomics were used to investigate early-stage atherosclerotic development and progression in chow-fed apolipoprotein E-deficient mice at 5, 10 and 15 weeks of age. Comprehensive plasma metabolomic profiles, based on 4365 detected metabolite features, differentiate atherosclerosis-prone from atherosclerosis-resistant models. Metabolites in the sphingomyelin pathway were significantly altered prior to detectable lesion formation and at all subsequent time-points. The cytidine diphosphate-diacylglycerol pathway was up-regulated during stage I of atherosclerosis, while metabolites in the phosphatidylethanolamine and glycosphingolipid pathways were augmented in mice with stage II lesions. These pathways, involving glycerophospholipid and sphingolipid metabolism, were also significantly affected during the course of atherosclerotic progression. Our findings suggest that distinct plasma metabolomic profiles can differentiate the different stages of atherosclerotic progression. This study reveals that alteration of specific, previously unreported pathways of glycerophospholipid and sphingolipid metabolism are associated with atherosclerosis. The clear difference in the level of several metabolites supports the use of plasma lipid profiling as a diagnostic tool of atherogenesis. PMID:27721472

Experience of 14 years of emergency reconstruction of electrical injuries.

PubMed

Zhu, Zhi-Xiang; Xu, Xiao-Guang; Li, Wei-Ping; Wang, Dao-Xin; Zhang, Li-Yong; Chen, Li-Ying; Liu, Tian-yi

2003-02-01

Although there have been great advances in the treatment of electrical injuries in the last 20 years, the extremity loss ratio in electrical injuries remains at an unacceptably high level. The primary cause is due to the progressive tissue necrosis which results in the continuous extension of necrosis in the wound, leading to loss of the whole injured extremity. This study reports attempts to break the dangerous tissue necrosis circle and save the form and function of damaged extremities. After 14 years of systematic experimental and clinical studies a successful comprehensive urgent reconstruction alternative (CURA) for electrical injuries is proposed. CURA includes: debriding the wound as early as possible after injury; preserving the vital tissue structures as much as possible, such as nerves, vessels, joints, tendons, bone, even though they have undergone devitalization or local necrosis; repairing these vital tissues during the first surgery if functional reconstruction requires it; protecting the wound bed by covering with tissue flaps of rich blood supply; improving flap survival through moist dressings supported by continuous irrigation beneath the flaps for a 24-72h period after surgery with measures to control local infection; and last, giving general systemic treatment with vasoactive agents and antibiotics. Four hundred and fifty nine wounds in 155 patients suffering from electrical injuries have been successfully treated with this technique between 1986 and 2000 and are reported in this paper. Satisfactory results were obtained with the extremity loss proportion reduced to less than 9% compared with 41.5% during the 10 years before 1984 in the same hospital. The authors suggest that CURA is an effective and workable method for treatment of electrical injuries.

Pathophysiology and Japanese clinical characteristics in Marfan syndrome.

PubMed

Fujita, Daishi; Takeda, Norifumi; Imai, Yasushi; Inuzuka, Ryo; Komuro, Issei; Hirata, Yasunobu

2014-08-01

Marfan syndrome is an autosomal dominant heritable disorder of the connective tissue, caused by mutations of the gene FBN1, which encodes fibrillin-1, a major component of the microfibrils of the extracellular matrix. Fibrillin-1 interacts with transforming growth factor-β (TGF-β), and dysregulated TGF-β signaling plays a major role in the development of connective tissue disease and familial aortic aneurysm and dissection, including Marfan syndrome. Losartan, an angiotensin II blocker, has the potential to reduce TGF-β signaling and is expected to be an additional therapeutic option. Clinical diagnosis is made using the Ghent nosology, which requires comprehensive patient assessment and has been proven to work well, but evaluation of some of the diagnostic criteria by a single physician is difficult and time-consuming. A Marfan clinic was established at the University of Tokyo Hospital in 2005, together with cardiologists, cardiac surgeons, pediatricians, orthopedists, and ophthalmologists in one place, for the purpose of speedy and accurate evaluation and diagnosis of Marfan syndrome. In this review, we discuss the recent progress in diagnosis and treatment of Marfan syndrome, and the characteristics of Japanese patients with Marfan syndrome. © 2014 Japan Pediatric Society.

Protein C receptor stimulates multiple signaling pathways in breast cancer cells.

PubMed

Wang, Daisong; Liu, Chunye; Wang, Jingqiang; Jia, Yingying; Hu, Xin; Jiang, Hai; Shao, Zhi-Ming; Zeng, Yi Arial

2018-01-26

The protein C receptor (PROCR) has emerged as a stem cell marker in several normal tissues and has also been implicated in tumor progression. However, the functional role of PROCR and the signaling mechanisms downstream of PROCR remain poorly understood. Here, we dissected the PROCR signaling pathways in breast cancer cells. Combining protein array, knockdown, and overexpression methods, we found that PROCR concomitantly activates multiple pathways. We also noted that PROCR-dependent ERK and PI3k-Akt-mTOR signaling pathways proceed through Src kinase and transactivation of insulin-like growth factor 1 receptor (IGF-1R). These pathway activities led to the accumulation of c-Myc and cyclin D1. On the other hand, PROCR-dependent RhoA-ROCK-p38 signaling relied on coagulation factor II thrombin receptor (F2R). We confirmed these findings in primary cells isolated from triple-negative breast cancer-derived xenografts (PDX) that have high expression of PROCR. To the best our knowledge, this is the first comprehensive study of PROCR signaling in breast cancer cells, and its findings also shed light on the molecular mechanisms of PROCR in stem cells in normal tissue. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Endothelial necrosis at 1h post-burn predicts progression of tissue injury

PubMed Central

Hirth, Douglas; McClain, Steve A.; Singer, Adam J.; Clark, Richard A.F.

2013-01-01

Burn injury progression has not been well characterized at the cellular level. To define burn injury progression in terms of cell death, histopathologic spatiotemporal relationships of cellular necrosis and apoptosis were investigated in a validated porcine model of vertical burn injury progression. Cell necrosis was identified by High Mobility Group Box 1 protein and apoptosis by Caspase 3a staining of tissue samples taken 1h, 24h and 7 days post-burn. Level of endothelial cell necrosis at 1h was predictive of level of apoptosis at 24h (Pearson's r=0.87) and of level of tissue necrosis at 7 days (Pearson's r=0.87). Furthermore, endothelial cell necrosis was deeper than interstitial cell necrosis at 1h (p<0.001). Endothelial cell necrosis at 1h divided the zone of injury progression (Jackson's zone of stasis) into an upper subzone with necrotic endothelial cells and initially viable adnexal and interstitial cells at 1h that progressed to necrosis by 24h, and a lower zone with initially viable endothelial cells at 1h, but necrosis and apoptosis of all cell types by 24h. Importantly, this spatiotemporal series of events and rapid progression resembles myocardial infarction and stroke, and implicates mechanisms of these injuries, ischemia, ischemia reperfusion, and programmed cell death, in burn progression. PMID:23627744

Beneficial and detrimental role of adenosine signaling in diseases and therapy

PubMed Central

Liu, Hong

2015-01-01

Adenosine is a major signaling nucleoside that orchestrates cellular and tissue adaptation under energy depletion and ischemic/hypoxic conditions by activation of four G protein-coupled receptors (GPCR). The regulation and generation of extracellular adenosine in response to stress are critical in tissue protection. Both mouse and human studies reported that extracellular adenosine signaling plays a beneficial role during acute states. However, prolonged excess extracellular adenosine is detrimental and contributes to the development and progression of various chronic diseases. In recent years, substantial progress has been made to understand the role of adenosine signaling in different conditions and to clarify its significance during the course of disease progression in various organs. These efforts have and will identify potential therapeutic possibilities for protection of tissue injury at acute stage by upregulation of adenosine signaling or attenuation of chronic disease progression by downregulation of adenosine signaling. This review is to summarize current progress and the importance of adenosine signaling in different disease stages and its potential therapeutic effects. PMID:26316513

Introgression of physiological traits for a comprehensive improvement of drought adaptation in crop plants

NASA Astrophysics Data System (ADS)

Sreeman, Sheshshayee M.; Vijayaraghavareddy, Preethi; Sreevathsa, Rohini; Rajendrareddy, Sowmya; Arakesh, Smitharani; Bharti, Pooja; Dharmappa, Prathibha; Soolanayakanahally, Raju

2018-04-01

Burgeoning population growth, industrial demand and the predicted global climate change resulting in erratic monsoon rains are expected to severely limit fresh water availability for agriculture both in irrigated and rainfed ecosystems. In order to remain food and nutrient secure, agriculture research needs to focus on devising strategies to save water in irrigated conditions and to develop superior cultivars with improved water productivity to sustain yield under rainfed conditions. Recent opinions accruing in the scientific literature strongly favour the adoption of a “trait based” approach for increasing water productivity especially the traits associated with maintenance of positive tissue turgor and maintenance of increased carbon assimilation as the most relevant traits to improve crop growth rates under water limiting conditions and to enhance water productivity. The advent of several water saving agronomic practices notwithstanding, a genetic enhancement strategy of introgressing distinct physiological, morphological and cellular mechanisms on to a single elite genetic background is essential for achieving a comprehensive improvement in drought adaptation in crop plants. The significant progress made in genomics, though would provide the necessary impetus, a clear understanding of the “traits” to be introgressed is the most essential need of the hour. Water uptake by a better root architecture, water conservation by preventing unproductive transpiration is crucial for maintaining positive tissue water relations. Improved carbon assimilation associated with carboxylation capacity and mesophyll conductance is equally important in sustaining crop growth rates under water limited conditions. Besides these major traits, we summarized the available information in literature on classifying various drought adaptive traits. We provide evidences that water-use efficiency when introgressed with moderately higher transpiration, would significantly enhance growth rates and water productivity in rice through an improved photosynthetic capacity.

From the WPA to Workfare: It's Time for a Truly Progressive Government Work Program.

ERIC Educational Resources Information Center

Rose, Nancy E.

1990-01-01

Examines two government voluntary job creation programs: the Works Progress Administration in the 1930s and the Comprehensive Employment and Training Act in the 1970s, that have created conflicts with the logic of capitalist production for profit. Suggests principles and policies for a progressive government work program. (JOW)

Grammatical comprehension deficits in non-fluent/agrammatic primary progressive aphasia.

PubMed

Charles, Dorothy; Olm, Christopher; Powers, John; Ash, Sharon; Irwin, David J; McMillan, Corey T; Rascovsky, Katya; Grossman, Murray

2014-03-01

Grammatical comprehension difficulty is an essential supporting feature of the non-fluent/agrammatic variant of primary progressive aphasia (naPPA), but well-controlled clinical measures of grammatical comprehension are unavailable. To develop a measure of grammatical comprehension and examine this comparatively in PPA variants and behavioural-variant frontotemporal degeneration (bvFTD) and to assess the neuroanatomic basis for these deficits with volumetric grey matter atrophy and whole-brain fractional anisotropy (FA) in white matter tracts. Case-control study. Academic medical centre. 39 patients with variants of PPA (naPPA=12, lvPPA=15 and svPPA=12), 27 bvFTD patients without aphasia and 12 healthy controls. Grammatical comprehension accuracy. Patients with naPPA had selective difficulty understanding cleft sentence structures, while all PPA variants and patients with bvFTD were impaired with sentences containing a centre-embedded subordinate clause. Patients with bvFTD were also impaired understanding sentences involving short-term memory. Linear regressions related grammatical comprehension difficulty in naPPA to left anterior-superior temporal atrophy and reduced FA in corpus callosum and inferior frontal-occipital fasciculus. Difficulty with centre-embedded sentences in other PPA variants was related to other brain regions. These findings emphasise a distinct grammatical comprehension deficit in naPPA and associate this with interruption of a frontal-temporal neural network.

Field defects in progression to gastrointestinal tract cancers

PubMed Central

Bernstein, Carol; Bernstein, Harris; Payne, Claire M.; Dvorak, Katerina; Garewal, Harinder

2009-01-01

A field of defective tissue may represent a pre-malignant stage in progression to many cancers. However, field defects are often overlooked in studies of cancer progression through assuming tissue at some distance from the cancer is normal. We indicate, however, the generality of field defects in gastrointestinal cancers, including cancers of the oropharynx, esophagus, stomach, bile duct, pancreas, small intestine and colon/rectum. Common features of these field defects are reduced apoptosis competence, aberrant proliferation and genomic instability. These features are often associated with high bile acid exposure and may explain the association of dietary-related factors with cancer progression. PMID:18164807

H3.1 K36M mutation in a congenital-onset soft tissue neoplasm.

PubMed

Kernohan, Kristin D; Grynspan, David; Ramphal, Raveena; Bareke, Eric; Wang, You Chang; Nizalik, Elizabeth; Ragoussis, Jiannis; Jabado, Nada; Boycott, Kym M; Majewski, Jacek; Sawyer, Sarah L

2017-12-01

We describe a patient who presented with a congenital soft tissue lesion initially diagnosed as infantile fibromatosis at 15 days of age. Unusually, the mass demonstrated malignant progression leading to death at 20 months of age. Biological progression to malignancy is not known to occur in fibromatosis, and fibrosarcoma is not known to progress from a benign lesion. Whole-exome sequencing of the tumor identified a driver mutation in histone H3.1 at lysine (K)36. Our findings support the link between oncohistones and infantile soft tissue tumors and provide additional evidence for the oncogenic effects of p.K36M in H3 variants. © 2017 Wiley Periodicals, Inc.

Modern Soft Tissue Pathology | Center for Cancer Research

Cancer.gov

This book comprehensively covers modern soft tissue pathology and includes both tumors and non-neoplastic entities. Soft tissues make up a large bulk of the human body, and they are susceptible to a wide range of diseases. Many soft-tissue tumors are biologically very aggressive, and the chance of them metastasizing to vital organs is quite high. In recent years, the outlook

Comprehensive approach to systemic sclerosis patients during pregnancy.

PubMed

Rueda de León Aguirre, Alexandra; Ramírez Calvo, José Antonio; Rodríguez Reyna, Tatiana Sofía

2015-01-01

Systemic sclerosis (SSc) is a connective tissue disease that usually affects women, with a male:female ratio of 1:4-10. It was thought that there was a prohibitive risk of fatal complications in the pregnancies of patients with SSc. It is now known that the majority of these women undergo a normal progression of pregnancy if the right time is chosen and a close obstetric care is delivered. The obstetric risk will depend on the subtype and clinical stage of the disease, and the presence and severity of the internal organ involvement during the pregnancy. The management of these pregnancies should be provided in a specialized center, with a multidisciplinary team capable of identifying and promptly treating complications. Treatment should be limited to drugs with no teratogenic potential, except when renal crises or severe cardiovascular complications develop. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Proteomics Improves the New Understanding of Honeybee Biology.

PubMed

Hora, Zewdu Ararso; Altaye, Solomon Zewdu; Wubie, Abebe Jemberie; Li, Jianke

2018-04-11

The honeybee is one of the most valuable insect pollinators, playing a key role in pollinating wild vegetation and agricultural crops, with significant contribution to the world's food production. Although honeybees have long been studied as model for social evolution, honeybee biology at the molecular level remained poorly understood until the year 2006. With the availability of the honeybee genome sequence and technological advancements in protein separation, mass spectrometry, and bioinformatics, aspects of honeybee biology such as developmental biology, physiology, behavior, neurobiology, and immunology have been explored to new depths at molecular and biochemical levels. This Review comprehensively summarizes the recent progress in honeybee biology using proteomics to study developmental physiology, task transition, and physiological changes in some of the organs, tissues, and cells based on achievements from the authors' laboratory in this field. The research advances of honeybee proteomics provide new insights for understanding of honeybee biology and future research directions.

Computational approaches to substrate-based cell motility

DOE PAGES

Ziebert, Falko; Aranson, Igor S.

2016-07-15

Substrate-based crawling motility of eukaryotic cells is essential for many biological functions, both in developing and mature organisms. Motility dysfunctions are involved in several life-threatening pathologies such as cancer and metastasis. Motile cells are also a natural realization of active, self-propelled ‘particles’, a popular research topic in nonequilibrium physics. Finally, from the materials perspective, assemblies of motile cells and evolving tissues constitute a class of adaptive self-healing materials that respond to the topography, elasticity, and surface chemistry of the environment and react to external stimuli. Although a comprehensive understanding of substrate-based cell motility remains elusive, progress has been achieved recentlymore » in its modeling on the whole cell level. Furthermore we survey the most recent advances in computational approaches to cell movement and demonstrate how these models improve our understanding of complex self-organized systems such as living cells.« less

Ted Hall and the science of biological microprobe X-ray analysis: a historical perspective of methodology and biological dividends.

PubMed

Gupta, B L

1991-06-01

This review surveys the emergence of electron probe X-ray microanalysis as a quantitative method for measuring the chemical elements in situ. The extension of the method to the biological sciences under the influence of Ted Hall is reviewed. Some classical experiments by Hall and his colleagues in Cambridge, UK, previously unpublished, are described; as are some of the earliest quantitative results from the cryo-sections obtained in Cambridge and elsewhere. The progress of the methodology is critically evaluated from the earliest starts to the present state of the art. Particular attention has been focused on the application of the method in providing fresh insights into the role of ions in cell and tissue physiology and pathology. A comprehensive list of references is included for a further pursuit of the topics by the interested reader.

[Progress of treatments in non-small cell lung cancer with brain metastases].

PubMed

Ma, Chunhua; Jiang, Rong

2012-05-01

Brain metastases is one of the most common complications of non-small cell lung cancer, whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), surgery and chemotherapy are standard methods in the treatment of brain metastases. But the effect of those treatments are still sad. Comprehensive treatment can prolong the survival and improve the quality of life. Recently, the improvement of technology, targeted therapy, survival time and the quality of life are in increasingly concerned. The paper make a summary of current situation and progress for comprehensive therapy of brain metastases.

Engineering Lubrication in Articular Cartilage

PubMed Central

McNary, Sean M.; Athanasiou, Kyriacos A.

2012-01-01

Despite continuous progress toward tissue engineering of functional articular cartilage, significant challenges still remain. Advances in morphogens, stem cells, and scaffolds have resulted in enhancement of the bulk mechanical properties of engineered constructs, but little attention has been paid to the surface mechanical properties. In the near future, engineered tissues will be able to withstand and support the physiological compressive and tensile forces in weight-bearing synovial joints such as the knee. However, there is an increasing realization that these tissue-engineered cartilage constructs will fail without the optimal frictional and wear properties present in native articular cartilage. These characteristics are critical to smooth, pain-free joint articulation and a long-lasting, durable cartilage surface. To achieve optimal tribological properties, engineered cartilage therapies will need to incorporate approaches and methods for functional lubrication. Steady progress in cartilage lubrication in native tissues has pushed the pendulum and warranted a shift in the articular cartilage tissue-engineering paradigm. Engineered tissues should be designed and developed to possess both tribological and mechanical properties mirroring natural cartilage. In this article, an overview of the biology and engineering of articular cartilage structure and cartilage lubrication will be presented. Salient progress in lubrication treatments such as tribosupplementation, pharmacological, and cell-based therapies will be covered. Finally, frictional assays such as the pin-on-disk tribometer will be addressed. Knowledge related to the elements of cartilage lubrication has progressed and, thus, an opportune moment is provided to leverage these advances at a critical step in the development of mechanically and tribologically robust, biomimetic tissue-engineered cartilage. This article is intended to serve as the first stepping stone toward future studies in functional tissue engineering of articular cartilage that begins to explore and incorporate methods of lubrication. PMID:21955119

Improving comprehension in adolescents with severe receptive language impairments: a randomized control trial of intervention for coordinating conjunctions.

PubMed

Ebbels, Susan H; Marić, Nataša; Murphy, Aoife; Turner, Gail

2014-01-01

Little evidence exists for the effectiveness of therapy for children with receptive language difficulties, particularly those whose difficulties are severe and persistent. To establish the effectiveness of explicit speech and language therapy with visual support for secondary school-aged children with language impairments focusing on comprehension of coordinating conjunctions in a randomized control trial with an assessor blind to group status. Fourteen participants (aged 11;3-16;1) with severe RELI (mean standard scores: CELF4 ELS = 48, CELF4 RLS = 53 and TROG-2 = 57), but higher non-verbal (Matrices = 83) and visual perceptual skills (Test of Visual Perceptual Skills (TVPS) = 86) were randomly assigned to two groups: therapy versus waiting controls. In Phase 1, the therapy group received eight 30-min individual sessions of explicit teaching with visual support (Shape Coding) with their usual SLT. In Phase 2, the waiting controls received the same therapy. The participants' comprehension was tested pre-, post-Phase 1 and post-Phase 2 therapy on (1) a specific test of the targeted conjunctions, (2) the TROG-2 and (3) a test of passives. After Phase 1, the therapy group showed significantly more progress than the waiting controls on the targeted conjunctions (d = 1.6) and overall TROG-2 standard score (d = 1.4). The two groups did not differ on the passives test. After Phase 2, the waiting controls made similar progress to those in the original therapy group, who maintained their previous progress. Neither group showed progress on passives. When the two groups were combined, significant progress was found on the specific conjunctions (d = 1.3) and TROG-2 raw (d = 1.1) and standard scores (d = 0.9). Correlations showed no measures taken (including Matrices and TVPS) correlated significantly with progress on the targeted conjunctions or the TROG-2. Four hours of Shape Coding therapy led to significant gains on comprehension of coordinating conjunctions which were maintained after 4 months. Given the significant progress at a group level and the lack of reliable predictors of progress, this approach could be offered to other children with similar difficulties to the participants. However, the intervention was delivered one-to-one by speech and language therapists, thus the effectiveness of this therapy method with other methods of delivery remains to be evaluated. © 2013 Royal College of Speech and Language Therapists.

Glyoxalase 1 copy number variation in patients with well differentiated gastro-entero-pancreatic neuroendocrine tumours (GEP-NET)

PubMed Central

Xue, Mingzhan; Shafie, Alaa; Qaiser, Talha; Rajpoot, Nasir M.; Kaltsas, Gregory; James, Sean; Gopalakrishnan, Kishore; Fisk, Adrian; Dimitriadis, Georgios K.; Grammatopoulos, Dimitris K.; Rabbani, Naila; Thornalley, Paul J.; Weickert, Martin O.

2017-01-01

Background The glyoxalase-1 gene (GLO1) is a hotspot for copy-number variation (CNV) in human genomes. Increased GLO1 copy-number is associated with multidrug resistance in tumour chemotherapy, but prevalence of GLO1 CNV in gastro-entero-pancreatic neuroendocrine tumours (GEP-NET) is unknown. Methods GLO1 copy-number variation was measured in 39 patients with GEP-NET (midgut NET, n = 25; pancreatic NET, n = 14) after curative or debulking surgical treatment. Primary tumour tissue, surrounding healthy tissue and, where applicable, additional metastatic tumour tissue were analysed, using real time qPCR. Progression and survival following surgical treatment were monitored over 4.2 ± 0.5 years. Results In the pooled GEP-NET cohort, GLO1 copy-number in healthy tissue was 2.0 in all samples but significantly increased in primary tumour tissue in 43% of patients with pancreatic NET and in 72% of patients with midgut NET, mainly driven by significantly higher GLO1 copy-number in midgut NET. In tissue from additional metastases resection (18 midgut NET and one pancreatic NET), GLO1 copy number was also increased, compared with healthy tissue; but was not significantly different compared with primary tumour tissue. During mean 3 - 5 years follow-up, 8 patients died and 16 patients showed radiological progression. In midgut NET, a high GLO1 copy-number was associated with earlier progression. In NETs with increased GLO1 copy number, there was increased Glo1 protein expression compared to non-malignant tissue. Conclusions GLO1 copy-number was increased in a large percentage of patients with GEP-NET and correlated positively with increased Glo1 protein in tumour tissue. Analysis of GLO1 copy-number variation particularly in patients with midgut NET could be a novel prognostic marker for tumour progression. PMID:29100361

seq-ImmuCC: Cell-Centric View of Tissue Transcriptome Measuring Cellular Compositions of Immune Microenvironment From Mouse RNA-Seq Data.

PubMed

Chen, Ziyi; Quan, Lijun; Huang, Anfei; Zhao, Qiang; Yuan, Yao; Yuan, Xuye; Shen, Qin; Shang, Jingzhe; Ben, Yinyin; Qin, F Xiao-Feng; Wu, Aiping

2018-01-01

The RNA sequencing approach has been broadly used to provide gene-, pathway-, and network-centric analyses for various cell and tissue samples. However, thus far, rich cellular information carried in tissue samples has not been thoroughly characterized from RNA-Seq data. Therefore, it would expand our horizons to better understand the biological processes of the body by incorporating a cell-centric view of tissue transcriptome. Here, a computational model named seq-ImmuCC was developed to infer the relative proportions of 10 major immune cells in mouse tissues from RNA-Seq data. The performance of seq-ImmuCC was evaluated among multiple computational algorithms, transcriptional platforms, and simulated and experimental datasets. The test results showed its stable performance and superb consistency with experimental observations under different conditions. With seq-ImmuCC, we generated the comprehensive landscape of immune cell compositions in 27 normal mouse tissues and extracted the distinct signatures of immune cell proportion among various tissue types. Furthermore, we quantitatively characterized and compared 18 different types of mouse tumor tissues of distinct cell origins with their immune cell compositions, which provided a comprehensive and informative measurement for the immune microenvironment inside tumor tissues. The online server of seq-ImmuCC are freely available at http://wap-lab.org:3200/immune/.

Toxicogenomics and Cancer Susceptibility: Advances with Next-Generation Sequencing

PubMed Central

Ning, Baitang; Su, Zhenqiang; Mei, Nan; Hong, Huixiao; Deng, Helen; Shi, Leming; Fuscoe, James C.; Tolleson, William H.

2017-01-01

The aim of this review is to comprehensively summarize the recent achievements in the field of toxicogenomics and cancer research regarding genetic-environmental interactions in carcinogenesis and detection of genetic aberrations in cancer genomes by next-generation sequencing technology. Cancer is primarily a genetic disease in which genetic factors and environmental stimuli interact to cause genetic and epigenetic aberrations in human cells. Mutations in the germline act as either high-penetrance alleles that strongly increase the risk of cancer development, or as low-penetrance alleles that mildly change an individual’s susceptibility to cancer. Somatic mutations, resulting from either DNA damage induced by exposure to environmental mutagens or from spontaneous errors in DNA replication or repair are involved in the development or progression of the cancer. Induced or spontaneous changes in the epigenome may also drive carcinogenesis. Advances in next-generation sequencing technology provide us opportunities to accurately, economically, and rapidly identify genetic variants, somatic mutations, gene expression profiles, and epigenetic alterations with single-base resolution. Whole genome sequencing, whole exome sequencing, and RNA sequencing of paired cancer and adjacent normal tissue present a comprehensive picture of the cancer genome. These new findings should benefit public health by providing insights in understanding cancer biology, and in improving cancer diagnosis and therapy. PMID:24875441

Degradable Adhesives for Surgery and Tissue Engineering.

PubMed

Bhagat, Vrushali; Becker, Matthew L

2017-10-09

This review highlights the research on degradable polymeric tissue adhesives for surgery and tissue engineering. Included are a comprehensive listing of specific uses, advantages, and disadvantages of different adhesive groups. A critical evaluation of challenges affecting the development of next generation materials is also discussed, and insights into the outlook of the field are explored.

Molecular profiling of tumor progression in head and neck cancer.

PubMed

Belbin, Thomas J; Singh, Bhuvanesh; Smith, Richard V; Socci, Nicholas D; Wreesmann, Volkert B; Sanchez-Carbayo, Marta; Masterson, Jessica; Patel, Snehal; Cordon-Cardo, Carlos; Prystowsky, Michael B; Childs, Geoffrey

2005-01-01

To assess gene expression changes associated with tumor progression in patients with squamous cell carcinoma of the oral cavity. A microarray containing 17 840 complementary DNA clones was used to measure gene expression changes associated with tumor progression in 9 patients with squamous cell carcinoma of the oral cavity. Samples were taken for analysis from the primary tumor, nodal metastasis, and "normal" mucosa from the patients' oral cavity. Tertiary care facility. Patients Nine patients with stage III or stage IV untreated oral cavity squamous cell carcinoma. Our analysis to categorize genes based on their expression patterns has identified 140 genes that consistently increased in expression during progression from normal tissue to invasive tumor and subsequently to metastatic node (in at least 4 of the 9 cases studied). A similar list of 94 genes has been identified that decreased in expression during tumor progression and metastasis. We validated this gene discovery approach by selecting moesin (a member of the ezrin/radixin/moesin [ERM] family of cytoskeletal proteins) and one of the genes that consistently increased in expression during tumor progression for subsequent immunohistochemical analysis using a head and neck squamous cell carcinoma tissue array. A distinct pattern of gene expression, with progressive up- or down-regulation of expression, is found during the progression from histologically normal tissue to primary carcinoma and to nodal metastasis.

Comprehension of concrete and abstract words in semantic variant primary progressive aphasia and Alzheimer's disease: A behavioral and neuroimaging study.

PubMed

Joubert, Sven; Vallet, Guillaume T; Montembeault, Maxime; Boukadi, Mariem; Wilson, Maximiliano A; Laforce, Robert Jr; Rouleau, Isabelle; Brambati, Simona M

2017-07-01

The aim of this study was to investigate the comprehension of concrete, abstract and abstract emotional words in semantic variant primary progressive aphasia (svPPA), Alzheimer's disease (AD), and healthy elderly adults (HE) Three groups of participants (9 svPPA, 12 AD, 11 HE) underwent a general neuropsychological assessment, a similarity judgment task, and structural brain MRI. The three types of words were processed similarly in the group of AD participants. In contrast, patients in the svPPA group were significantly more impaired at processing concrete words than abstract words, while comprehension of abstract emotional words was in between. VBM analyses showed that comprehension of concrete words relative to abstract words was significantly correlated with atrophy in the left anterior temporal lobe. These results support the view that concrete words are disproportionately impaired in svPPA, and that concrete and abstract words may rely upon partly dissociable brain regions. Copyright © 2017 Elsevier Inc. All rights reserved.

Examining Predictive Validity of Oral Reading Fluency Slope in Upper Elementary Grades Using Quantile Regression.

PubMed

Cho, Eunsoo; Capin, Philip; Roberts, Greg; Vaughn, Sharon

2017-07-01

Within multitiered instructional delivery models, progress monitoring is a key mechanism for determining whether a child demonstrates an adequate response to instruction. One measure commonly used to monitor the reading progress of students is oral reading fluency (ORF). This study examined the extent to which ORF slope predicts reading comprehension outcomes for fifth-grade struggling readers ( n = 102) participating in an intensive reading intervention. Quantile regression models showed that ORF slope significantly predicted performance on a sentence-level fluency and comprehension assessment, regardless of the students' reading skills, controlling for initial ORF performance. However, ORF slope was differentially predictive of a passage-level comprehension assessment based on students' reading skills when controlling for initial ORF status. Results showed that ORF explained unique variance for struggling readers whose posttest performance was at the upper quantiles at the end of the reading intervention, but slope was not a significant predictor of passage-level comprehension for students whose reading problems were the most difficult to remediate.

PM2.5 exposure-induced autophagy is mediated by lncRNA loc146880 which also promotes the migration and invasion of lung cancer cells.

PubMed

Deng, Xiaobei; Feng, Nannan; Zheng, Min; Ye, Xiaofei; Lin, Hongyan; Yu, Xiao; Gan, Zhihua; Fang, Zheng; Zhang, Huan; Gao, Ming; Zheng, Zhi-Jie; Yu, Herbert; Ding, Wenjun; Qian, Biyun

2017-02-01

Evidence shows that individuals who are under long-term exposure to environmental PM 2.5 are at increased risk of lung cancer. Various laboratory experiments also suggest several mechanistic links between PM 2.5 exposure and lung carcinogenesis. However, a long non-coding RNA (lncRNA) mediated pathogenic change after PM 2.5 exposure and its potential roles in tumorigenesis and disease progression have not been reported. Cytotoxicity induced by PM 2.5 was assessed by using scanning electron microscopy and transmission electron microscopy. ROS generation, autophagy, and metastasis induced by PM 2.5 were detected by using comprehensive approaches. Expression of lncRNA-loc146880 and lc3b (autophagy marker) in A549 cells, lung tissue and serum were determined by RT-PCR and Western blotting. PM 2.5 could be internalized into lung cancer cells, resulting in marked increases in ROS levels and autophagy. ROS may be responsible for increased expression of loc146880 which further up-regulates autophagy. Both loc146880 and autophagy could promote lung tumor cell migration, invasion and EMT. In addition, a positive correlation was observed between loc146880 expression and lc3b levels in tumor tissues and serum of lung cancer patients. Taken together, our data suggest that PM 2.5 exposure induces ROS, which activates loc146880 expression. The lncRNA, in turn, up-regulates autophagy and promotes the malignant behaviors of lung cancer cells. The results show the toxicological effects of PM 2.5 in lung tumor progression and metastasis. Copyright © 2016 Elsevier B.V. All rights reserved.

Horse species symposium: a novel approach to monitoring pathogen progression during uterine and placental infection in the mare using bioluminescence imaging technology and lux-modified bacteria.

PubMed

Ryan, P L; Christiansen, D L; Hopper, R M; Walters, F K; Moulton, K; Curbelo, J; Greene, J M; Willard, S T

2011-05-01

Uterine and placental infections are the leading cause of abortion, stillbirth, and preterm delivery in the mare. Whereas uterine and placental infections in women have been studied extensively, a comprehensive examination of the pathogenic processes leading to this unsatisfactory pregnancy outcome in the mare has yet to be completed. Most information in the literature relating to late-term pregnancy loss in mares is based on retrospective studies of clinical cases submitted for necropsy. Here we report the development and application of a novel approach, whereby transgenically modified bacteria transformed with lux genes of Xenorhabdus luminescens or Photorhabdus luminescens origin and biophotonic imaging are utilized to better understand pathogen-induced preterm birth in late-term pregnant mares. This technology uses highly sensitive bioluminescence imaging camera systems to localize and monitor pathogen progression during tissue invasion by measuring the bioluminescent signatures emitted by the lux-modified pathogens. This method has an important advantage in that it allows for the potential tracking of pathogens in vivo in real time and over time, which was hitherto impossible. Although the application of this technology in domestic animals is in its infancy, investigators were successful in identifying the fetal lungs, sinuses, nares, urinary, and gastrointestinal systems as primary tissues for pathogen invasion after experimental infection of pregnant mares with lux-modified Escherichia coli. It is important that pathogens were not detected in other vital organs, such as the liver, brain, and cardiac system. Such precision in localizing sites of pathogen invasion provides potential application for this novel approach in the development of more targeted therapeutic interventions for pathogen-related diseases in the equine and other domestic species.

Quantitative pre-clinical screening of therapeutics for joint diseases using contrast enhanced micro-computed tomography.

PubMed

Willett, N J; Thote, T; Hart, M; Moran, S; Guldberg, R E; Kamath, R V

2016-09-01

The development of effective therapies for cartilage protection has been limited by a lack of efficient quantitative cartilage imaging modalities in pre-clinical in vivo models. Our objectives were two-fold: first, to validate a new contrast-enhanced 3D imaging analysis technique, equilibrium partitioning of an ionic contrast agent-micro computed tomography (EPIC-μCT), in a rat medial meniscal transection (MMT) osteoarthritis (OA) model; and second, to quantitatively assess the sensitivity of EPIC-μCT to detect the effects of matrix metalloproteinase inhibitor (MMPi) therapy on cartilage degeneration. Rats underwent MMT surgery and tissues were harvested at 1, 2, and 3 weeks post-surgery or rats received an MMPi or vehicle treatment and tissues harvested 3 weeks post-surgery. Parameters of disease progression were evaluated using histopathology and EPIC-μCT. Correlations and power analyses were performed to compare the techniques. EPIC-μCT was shown to provide simultaneous 3D quantification of multiple parameters, including cartilage degeneration and osteophyte formation. In MMT animals treated with MMPi, OA progression was attenuated, as measured by 3D parameters such as lesion volume and osteophyte size. A post-hoc power analysis showed that 3D parameters for EPIC-μCT were more sensitive than 2D parameters requiring fewer animals to detect a therapeutic effect of MMPi. 2D parameters were comparable between EPIC-μCT and histopathology. This study demonstrated that EPIC-μCT has high sensitivity to provide 3D structural and compositional measurements of cartilage and bone in the joint. EPIC-μCT can be used in combination with histology to provide a comprehensive analysis to screen new potential therapies. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Estrogen receptors in gastric cancer: Advances and perspectives.

PubMed

Ur Rahman, Muhammad Saif; Cao, Jiang

2016-02-28

Worldwide, gastric cancer is one of the most common malignancies with high mortality. Various aspects of the development and progression of gastric cancer continue to be extensively investigated in order to further our understanding and provide more effective means for the prevention, diagnosis, and treatment of the disease. Estrogen receptors (ERs) are steroid hormone receptors that regulate cellular activities in many physiological and pathological processes in different tissues. There are two distinct forms of ERs, namely ERα and ERβ, with several alternative-splicing isoforms for each. They show distinct tissue distribution patterns and exert different biological functions. Dysregulation of ERs has been found to be associated closely with many diseases, including cancer. A number of studies have been conducted to investigate the role of ERs in gastric cancer, the possible mechanisms underlying these roles, and the clinical relevance of deregulated ERs in gastric cancer patients. To date, inconsistent associations of different ERs with gastric cancer have been reported. These inconsistencies may be caused by variations in in vitro cell models and clinical samples, including assay conditions and protocols with regard to different forms of ERs. Given the potential of the deregulated ERs as diagnostic/prognostic markers or therapeutic targets for gastric cancer, it will be important to identify/confirm the association of each ER isoform with gastric cancer, to determine the specific roles and interactions that these individual ER isoforms play under specific conditions in the development and/or progression of gastric cancer, and to elucidate precisely these mechanisms. In this review, we summarize the achievements from early ER studies in gastric cancer to the most up-to-date discoveries, with an effort to provide a comprehensive understanding of the role of ERs roles in gastric cancer and its possible mechanisms. Furthermore, we propose directions for future investigations.

An epigenetic signature of adhesion molecules predicts poor prognosis of ovarian cancer patients

PubMed Central

Chang, Ping-Ying; Liao, Yu-Ping; Wang, Hui-Chen; Chen, Yu-Chih; Huang, Rui-Lan; Wang, Yu-Chi; Yuan, Chiou-Chung; Lai, Hung-Cheng

2017-01-01

DNA methylation is a promising biomarker for cancer. The epigenetic effects of cell adhesion molecules may affect the therapeutic outcome and the present study examined their effects on survival in ovarian cancer. We integrated methylomics and genomics datasets in The Cancer Genome Atlas (n = 391) and identified 106 highly methylated adhesion-related genes in ovarian cancer tissues. Univariate analysis revealed the methylation status of eight genes related to progression-free survival. In multivariate Cox regression analysis, four highly methylated genes (CD97, CTNNA1, DLC1, HAPLN2) and three genes (LAMA4, LPP, MFAP4) with low methylation were significantly associated with poor progression-free survival. Low methylation of VTN was an independent poor prognostic factor for overall survival after adjustment for age and stage. Patients who carried any two of CTNNA1, DLC1 or MFAP4 were significantly associated with poor progression-free survival (hazard ratio: 1.59; 95% confidence interval: 1.23, 2.05). This prognostic methylation signature was validated in a methylomics dataset generated in our lab (n = 37, hazard ratio: 16.64; 95% confidence interval: 2.68, 103.14) and in another from the Australian Ovarian Cancer Study (n = 91, hazard ratio: 2.43; 95% confidence interval: 1.11, 5.36). Epigenetics of cell adhesion molecules is related to ovarian cancer prognosis. A more comprehensive methylomics of cell adhesion molecules is needed and may advance personalized treatment with adhesion molecule-related drugs. PMID:28881822

Multiplex, quantitative cellular analysis in large tissue volumes with clearing-enhanced 3D microscopy (Ce3D)

PubMed Central

Li, Weizhe; Germain, Ronald N.

2017-01-01

Organ homeostasis, cellular differentiation, signal relay, and in situ function all depend on the spatial organization of cells in complex tissues. For this reason, comprehensive, high-resolution mapping of cell positioning, phenotypic identity, and functional state in the context of macroscale tissue structure is critical to a deeper understanding of diverse biological processes. Here we report an easy to use method, clearing-enhanced 3D (Ce3D), which generates excellent tissue transparency for most organs, preserves cellular morphology and protein fluorescence, and is robustly compatible with antibody-based immunolabeling. This enhanced signal quality and capacity for extensive probe multiplexing permits quantitative analysis of distinct, highly intermixed cell populations in intact Ce3D-treated tissues via 3D histo-cytometry. We use this technology to demonstrate large-volume, high-resolution microscopy of diverse cell types in lymphoid and nonlymphoid organs, as well as to perform quantitative analysis of the composition and tissue distribution of multiple cell populations in lymphoid tissues. Combined with histo-cytometry, Ce3D provides a comprehensive strategy for volumetric quantitative imaging and analysis that bridges the gap between conventional section imaging and disassociation-based techniques. PMID:28808033

Current progress in 3D printing for cardiovascular tissue engineering.

PubMed

Mosadegh, Bobak; Xiong, Guanglei; Dunham, Simon; Min, James K

2015-03-16

3D printing is a technology that allows the fabrication of structures with arbitrary geometries and heterogeneous material properties. The application of this technology to biological structures that match the complexity of native tissue is of great interest to researchers. This mini-review highlights the current progress of 3D printing for fabricating artificial tissues of the cardiovascular system, specifically the myocardium, heart valves, and coronary arteries. In addition, how 3D printed sensors and actuators can play a role in tissue engineering is discussed. To date, all the work with building 3D cardiac tissues have been proof-of-principle demonstrations, and in most cases, yielded products less effective than other traditional tissue engineering strategies. However, this technology is in its infancy and therefore there is much promise that through collaboration between biologists, engineers and material scientists, 3D bioprinting can make a significant impact on the field of cardiovascular tissue engineering.

Polytene Chromosomes - A Portrait of Functional Organization of the Drosophila Genome.

PubMed

Zykova, Tatyana Yu; Levitsky, Victor G; Belyaeva, Elena S; Zhimulev, Igor F

2018-04-01

This mini-review is devoted to the problem genetic meaning of main polytene chromosome structures - bands and interbands. Generally, densely packed chromatin forms black bands, moderately condensed regions form grey loose bands, whereas decondensed regions of the genome appear as interbands. Recent progress in the annotation of the Drosophila genome and epigenome has made it possible to compare the banding pattern and the structural organization of genes, as well as their activity. This was greatly aided by our ability to establish the borders of bands and interbands on the physical map, which allowed to perform comprehensive side-by-side comparisons of cytology, genetic and epigenetic maps and to uncover the association between the morphological structures and the functional domains of the genome. These studies largely conclude that interbands 5'-ends of housekeeping genes that are active across all cell types. Interbands are enriched with proteins involved in transcription and nucleosome remodeling, as well as with active histone modifications. Notably, most of the replication origins map to interband regions. As for grey loose bands adjacent to interbands, they typically host the bodies of house-keeping genes. Thus, the bipartite structure composed of an interband and an adjacent grey band functions as a standalone genetic unit. Finally, black bands harbor tissue-specific genes with narrow temporal and tissue expression profiles. Thus, the uniform and permanent activity of interbands combined with the inactivity of genes in bands forms the basis of the universal banding pattern observed in various Drosophila tissues.

Programmed cell death progressively models the development of anther sporophytic tissues from the tapetum and is triggered in pollen grains during maturation.

PubMed

Varnier, Anne-Lise; Mazeyrat-Gourbeyre, Florence; Sangwan, Rajbir S; Clément, Christophe

2005-11-01

To characterize the spatial and temporal occurrence of programmed cell death (PCD) in Lilium anther tissues, we used both microscopical and molecular markers of apoptosis for developmental stages from meiosis to pollen release. The first hallmarks of PCD include cell condensation and shrinkage of the cytoplasm, separation of chromatin into delineated masses, and DNA fragmentation in the tapetum as early as the premeiosis stage. PCD then extended to other anther sporophytic tissues, leading to anther dehiscence. Although the PCD clearly affected the endothecium and the epidermis, these two cell layers remained alive until anther dehiscence. In pollen, no sign of PCD was found until pollen mitosis I, after what apoptotic features developed progressively in the vegetative cell. In addition, DNA ladders were detected in all sporophytic tissues and cell types throughout pollen development, whereas in the male gametophyte DNA ladders were only detected during pollen maturation. Our data suggest that PCD is a progressive and active process affecting all the anther tissues, first being triggered in the tapetum.

Breast reconstruction with tissue expanders: implementation of a standardized best-practices protocol to reduce infection rates.

PubMed

Khansa, Ibrahim; Hendrick, Russell G; Shore, Alison; Meyerson, Joseph; Yang, Maelee; Boehmler, James H

2014-07-01

Periprosthetic infection remains a frustrating and costly complication of breast reconstruction with tissue expanders. Although some specific steps have been previously shown to reduce periprosthetic infections, no comprehensive protocol addressing all aspects of preoperative, intraoperative, and postoperative patient management has been evaluated in the literature. The authors' goal was to evaluate the effectiveness of their protocol at reducing periprosthetic infections. A comprehensive, best-practices protocol was introduced and implemented in November of 2010. All patients undergoing breast reconstruction using tissue expanders at the authors' institution in the 5 years before the protocol, and in the 2 years after, were analyzed. Three hundred five patients underwent 456 tissue expander reconstructions in the 5 years before the protocol, and 198 patients underwent 313 reconstructions in the 2 years after. Significantly fewer patients developed periprosthetic infection after protocol (11.6 percent versus 18.4 percent; p=0.042), and the number of infected tissue expanders trended toward a decrease (9.3 percent versus 13.2 percent; p=0.097). On multivariate analysis, the protocol significantly reduced the odds of periprosthetic infection (OR, 0.45; p=0.022). Predictors of infection included obesity (OR, 2.01; p=0.045) and preoperative breast size larger than C cup (OR, 2.83; p=0.006). The authors' comprehensive, best-practices protocol allowed them to reduce the odds of tissue expander infections by 55 percent (OR, 0.45; p=0.022). The authors were able to identify several potential areas of improvement that may help them lower the rate of infection further in the future. Therapeutic, III.

Le Facteur d'Adaptation dans la Comprehension de l'Anglais Oral (The Adaptation Factor in the Understanding of Spoken English). Melanges Pedagogiques, 1972.

ERIC Educational Resources Information Center

Roussel, F.

Progress in the teaching of oral comprehension depends partly on the isolation of factors which block comprehension. Research in conjunction with an experimental course in English as a second language led to the definition of errors due to: (1) insufficient knowledge of the language and the cultural context of its use, and (2) a failure to…

Losartan Attenuates Degradation of Aorta and Lung Tissue Micromechanics in a Mouse Model of Severe Marfan Syndrome

PubMed Central

Lee, Jia-Jye; Galatioto, Josephine; Rao, Satish; Ramirez, Francesco; Costa, Kevin D.

2018-01-01

Marfan syndrome (MFS) is an autosomal dominant disease of the connective tissue due to mutations in the fibrillin-1 gene (FBN1). This study aimed at characterizing microelastic properties of the ascending aorta wall and lung parenchyma tissues from wild type (WT) and age-matched Fbn1 hypomorphic mice (Fbn1mgR/mgR mice) to identify tissue-specific biomechanical effects of aging and disease in MFS. Atomic force microscopy (AFM) was used to indent lung parenchyma and aortic wall tissues, using Hybrid Eshelby Decomposition analysis to extract layer-specific properties of the intima and media. The intima stiffened with age and was not different between WT and Fbn1mgR/mgR tissues, whereas the media layer of mutant aortas showed progressive structural and mechanical degradation with a modulus that was 50% softer than WT by 3.5 months of age. Similarly, mutant mice displayed progressive structural and mechanical deterioration of lung tissue, which was over 85% softer than WT by 3.5 months of age. Chronic treatment with the angiotensin type I receptor antagonist, losartan, attenuated the aorta and lung tissue degradation, resulting in structural and mechanical properties not significantly different from age-matched WT controls. By revealing micromechanical softening of elastin-rich aorta and lung tissues with disease progression in fibrillin-1 deficient mice, our findings support the use of losartan as a prophylactic treatment that may abrogate the life-threatening symptoms of MFS. PMID:27090893

Losartan Attenuates Degradation of Aorta and Lung Tissue Micromechanics in a Mouse Model of Severe Marfan Syndrome.

PubMed

Lee, Jia-Jye; Galatioto, Josephine; Rao, Satish; Ramirez, Francesco; Costa, Kevin D

2016-10-01

Marfan syndrome (MFS) is an autosomal dominant disease of the connective tissue due to mutations in the fibrillin-1 gene (FBN1). This study aimed at characterizing microelastic properties of the ascending aortic wall and lung parenchyma tissues from wild type (WT) and age-matched Fbn1 hypomorphic mice (Fbn1(mgR/mgR) mice) to identify tissue-specific biomechanical effects of aging and disease in MFS. Atomic force microscopy was used to indent lung parenchyma and aortic wall tissues, using Hybrid Eshelby Decomposition analysis to extract layer-specific properties of the intima and media. The intima stiffened with age and was not different between WT and Fbn1(mgR/mgR) tissues, whereas the media layer of MFS aortas showed progressive structural and mechanical degradation with a modulus that was 50% softer than WT by 3.5 months of age. Similarly, MFS mice displayed progressive structural and mechanical deterioration of lung tissue, which was over 85% softer than WT by 3.5 months of age. Chronic treatment with the angiotensin type I receptor antagonist, losartan, attenuated the aorta and lung tissue degradation, resulting in structural and mechanical properties not significantly different from age-matched WT controls. By revealing micromechanical softening of elastin-rich aorta and lung tissues with disease progression in fibrillin-1 deficient mice, our findings support the use of losartan as a prophylactic treatment that may abrogate the life-threatening symptoms of MFS.

Foreign Language Analysis and Recognition (FLARe) Initial Progress

DTIC Science & Technology

2012-11-29

University Language Modeling ToolKit CoMMA Count Mediated Morphological Analysis CRUD Create, Read , Update & Delete CPAN Comprehensive Perl Archive...DATES COVERED (From - To) 1 October 2010 – 30 September 2012 4. TITLE AND SUBTITLE Foreign Language Analysis and Recognition (FLARe) Initial Progress...AFRL-RH-WP-TR-2012-0165 FOREIGN LANGUAGE ANALYSIS AND RECOGNITION (FLARE) INITIAL PROGRESS Brian M. Ore

Testing the Importance of Individual Growth Curves in Predicting Performance on a High-Stakes Reading Comprehension Test in Florida. REL 2014-006

ERIC Educational Resources Information Center

Petscher, Yaacov; Kershaw, Sarah; Koon, Sharon; Foorman, Barbara R.

2014-01-01

Districts and schools use progress monitoring to assess student progress, to identify students who fail to respond to intervention, and to further adapt instruction to student needs. Researchers and practitioners often use progress monitoring data to estimate student achievement growth (slope) and evaluate changes in performance over time for…

Comprehensive Trail Making Test

ERIC Educational Resources Information Center

Gray, Rebecca

2006-01-01

The Comprehensive Trail Making Test (CTMT) is designed to be used in neuropsychological assessment for the purposes of detecting effects of brain defects and deficits and in tracking progress in rehabilitation. More specific purposes include the detection of frontal lobe deficits, problems with psychomotor speed, visual search and sequencing,…

Adult Soft Tissue Sarcoma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Adult soft tissue sarcoma (STS) treatment is determined by the tumor grade and may include surgery, radiation therapy, and/or chemotherapy. Get comprehensive information for newly diagnosed and recurrent STS and treatment in this summary for clinicians.

The nanomechanical signature of liver cancer tissues and its molecular origin

NASA Astrophysics Data System (ADS)

Tian, Mengxin; Li, Yiran; Liu, Weiren; Jin, Lei; Jiang, Xifei; Wang, Xinyan; Ding, Zhenbin; Peng, Yuanfei; Zhou, Jian; Fan, Jia; Cao, Yi; Wang, Wei; Shi, Yinghong

2015-07-01

Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the ``gold standard'' in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus distribution of surgically removed liver cancer tissues can serve as a mechanical fingerprint to evaluate the malignancy of liver cancer. Cirrhotic tissues shared the same LEP as normal tissues. However, a noticeable downward shift in the LEP was detected when the cirrhotic tissues progressed to a malignant state, making the tumor tissues more prone to microvascular invasion. Cell-level mechanistic studies revealed that the expression level of a Rho-family effector (mDia1) was consistent with the mechanical trend exhibited by the tissue. Our findings indicate that the mechanical profiles of liver cancer tissues directly varied with tumor progression, providing an additional platform for the future diagnosis of HCC.Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma (HCC), the second most frequent cause of cancer-related deaths. Although HCC diagnosis based on conventional morphological characteristics serves as the ``gold standard'' in the clinic, there is a high demand for more convenient and effective diagnostic methods that employ new biophysical perspectives. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC. Using indentation-type atomic force microscopy (IT-AFM), we demonstrate that the lowest elasticity peak (LEP) in the Young's modulus distribution of surgically removed liver cancer tissues can serve as a mechanical fingerprint to evaluate the malignancy of liver cancer. Cirrhotic tissues shared the same LEP as normal tissues. However, a noticeable downward shift in the LEP was detected when the cirrhotic tissues progressed to a malignant state, making the tumor tissues more prone to microvascular invasion. Cell-level mechanistic studies revealed that the expression level of a Rho-family effector (mDia1) was consistent with the mechanical trend exhibited by the tissue. Our findings indicate that the mechanical profiles of liver cancer tissues directly varied with tumor progression, providing an additional platform for the future diagnosis of HCC. Electronic supplementary information (ESI) available: Detailed experimental procedures and supplementary figures. See DOI: 10.1039/c5nr02192h

Tissue redox activity as a hallmark of carcinogenesis: from early to terminal stages of cancer.

PubMed

Bakalova, Rumiana; Zhelev, Zhivko; Aoki, Ichio; Saga, Tsuneo

2013-05-01

The study aimed to clarify the dynamics of tissue redox activity (TRA) in cancer progression and assess the importance of this parameter for therapeutic strategies. The experiments were carried out on brain tissues of neuroblastoma-bearing, glioma-bearing, and healthy mice. TRA was visualized in vivo by nitroxide-enhanced MRI on anesthetized animals or in vitro by electron paramagnetic resonance spectroscopy on isolated tissue specimens. Two biochemical parameters were analyzed in parallel: tissue total antioxidant capacity (TTAC) and plasma levels of matrix metalloproteinases (MMP). In the early stage of cancer, the brain tissues were characterized by a shorter-lived MRI signal than that from healthy brains (indicating a higher reducing activity for the nitroxide radical), which was accompanied by an enhancement of TTAC and MMP9 plasma levels. In the terminal stage of cancer, tissues in both hemispheres were characterized by a longer-lived MRI signal than in healthy brains (indicating a high-oxidative activity) that was accompanied by a decrease in TTAC and an increase in the MMP2/MMP9 plasma levels. Cancer progression also affected the redox potential of tissues distant from the primary tumor locus (liver and lung). Their oxidative status increased in both stages of cancer. The study shows that tissue redox balance is very sensitive to the progression of cancer and can be used as a diagnostic marker of carcinogenesis. The study also suggests that the noncancerous tissues of a cancer-bearing organism are susceptible to oxidative damage and should be considered a therapeutic target. ©2013 AACR.

Expression of spermidine/spermine N(1) -acetyl transferase (SSAT) in human prostate tissues is related to prostate cancer progression and metastasis.

PubMed

Huang, Wei; Eickhoff, Jens C; Mehraein-Ghomi, Farideh; Church, Dawn R; Wilding, George; Basu, Hirak S

2015-08-01

Prostate cancer (PCa) in many patients remains indolent for the rest of their lives, but in some patients, it progresses to lethal metastatic disease. Gleason score is the current clinical method for PCa prognosis. It cannot reliably identify aggressive PCa, when GS is ≤ 7. It is shown that oxidative stress plays a key role in PCa progression. We have shown that in cultured human PCa cells, an activation of spermidine/spermine N(1) -acetyl transferase (SSAT; EC 2.3.1.57) enzyme initiates a polyamine oxidation pathway and generates copious amounts of reactive oxygen species in polyamine-rich PCa cells. We used RNA in situ hybridization and immunohistochemistry methods to detect SSAT mRNA and protein expression in two tissue microarrays (TMA) created from patient's prostate tissues. We analyzed 423 patient's prostate tissues in the two TMAs. Our data show that there is a significant increase in both SSAT mRNA and the enzyme protein in the PCa cells as compared to their benign counterpart. This increase is even more pronounced in metastatic PCa tissues as compared to the PCa localized in the prostate. In the prostatectomy tissues from early-stage patients, the SSAT protein level is also high in the tissues obtained from the patients who ultimately progress to advanced metastatic disease. Based on these results combined with published data from our and other laboratories, we propose an activation of an autocrine feed-forward loop of PCa cell proliferation in the absence of androgen as a possible mechanism of castrate-resistant prostate cancer growth. © 2015 Wiley Periodicals, Inc.

Translational models of tumor angiogenesis: A nexus of in silico and in vitro models.

PubMed

Soleimani, Shirin; Shamsi, Milad; Ghazani, Mehran Akbarpour; Modarres, Hassan Pezeshgi; Valente, Karolina Papera; Saghafian, Mohsen; Ashani, Mehdi Mohammadi; Akbari, Mohsen; Sanati-Nezhad, Amir

2018-03-05

Emerging evidence shows that endothelial cells are not only the building blocks of vascular networks that enable oxygen and nutrient delivery throughout a tissue but also serve as a rich resource of angiocrine factors. Endothelial cells play key roles in determining cancer progression and response to anti-cancer drugs. Furthermore, the endothelium-specific deposition of extracellular matrix is a key modulator of the availability of angiocrine factors to both stromal and cancer cells. Considering tumor vascular network as a decisive factor in cancer pathogenesis and treatment response, these networks need to be an inseparable component of cancer models. Both computational and in vitro experimental models have been extensively developed to model tumor-endothelium interactions. While informative, they have been developed in different communities and do not yet represent a comprehensive platform. In this review, we overview the necessity of incorporating vascular networks for both in vitro and in silico cancer models and discuss recent progresses and challenges of in vitro experimental microfluidic cancer vasculature-on-chip systems and their in silico counterparts. We further highlight how these two approaches can merge together with the aim of presenting a predictive combinatorial platform for studying cancer pathogenesis and testing the efficacy of single or multi-drug therapeutics for cancer treatment. Copyright © 2018. Published by Elsevier Inc.

Halfway between 2D and Animal Models: Are 3D Cultures the Ideal Tool to Study Cancer-Microenvironment Interactions?

PubMed

Hoarau-Véchot, Jessica; Rafii, Arash; Touboul, Cyril; Pasquier, Jennifer

2018-01-18

An area that has come to be of tremendous interest in tumor research in the last decade is the role of the microenvironment in the biology of neoplastic diseases. The tumor microenvironment (TME) comprises various cells that are collectively important for normal tissue homeostasis as well as tumor progression or regression. Seminal studies have demonstrated the role of the dialogue between cancer cells (at many sites) and the cellular component of the microenvironment in tumor progression, metastasis, and resistance to treatment. Using an appropriate system of microenvironment and tumor culture is the first step towards a better understanding of the complex interaction between cancer cells and their surroundings. Three-dimensional (3D) models have been widely described recently. However, while it is claimed that they can bridge the gap between in vitro and in vivo, it is sometimes hard to decipher their advantage or limitation compared to classical two-dimensional (2D) cultures, especially given the broad number of techniques used. We present here a comprehensive review of the different 3D methods developed recently, and, secondly, we discuss the pros and cons of 3D culture compared to 2D when studying interactions between cancer cells and their microenvironment.

Role of adipose tissue in methionine-choline-deficient model of non-alcoholic steatohepatitis (NASH).

PubMed

Jha, Pooja; Knopf, Astrid; Koefeler, Harald; Mueller, Michaela; Lackner, Carolin; Hoefler, Gerald; Claudel, Thierry; Trauner, Michael

2014-07-01

Methionine-choline-deficient (MCD) diet is a widely used dietary model of non-alcoholic steatohepatitis (NASH) in rodents. However, the contribution of adipose tissue to MCD-induced steatosis, and inflammation as features of NASH are not fully understood. The goal of this study was to elucidate the role of adipose tissue fatty acid (FA) metabolism, adipogenesis, lipolysis, inflammation and subsequent changes in FA profiles in serum and liver in the pathogenesis of steatohepatitis. We therefore fed ob/ob mice with control or MCD diet for 5 weeks. MCD-feeding increased adipose triglyceride lipase and hormone sensitive lipase activities in all adipose depots which may be attributed to increased systemic FGF21 levels. The highest lipase enzyme activity was exhibited by visceral WAT. Non-esterified fatty acid (NEFA)-18:2n6 was the predominantly elevated FA species in serum and liver of MCD-fed ob/ob mice, while overall serum total fatty acid (TFA) composition was reduced. In contrast, an overall increase of all FA species from TFA pool was found in liver, reflecting the combined effects of increased FA flux to liver, decreased FA oxidation and decrease in lipase activity in liver. NAFLD activity score was increased in liver, while WAT showed no changes and BAT showed even reduced inflammation. This study demonstrates a key role for adipose tissue lipases in the pathogenesis of NASH and provides a comprehensive lipidomic profiling of NEFA and TFA homeostasis in serum and liver. Our findings provide novel mechanistic insights for the role of WAT in progression of MCD-induced liver injury. Copyright © 2014. Published by Elsevier B.V.

Mechanical Model Analysis for Quantitative Evaluation of Liver Fibrosis Based on Ultrasound Tissue Elasticity Imaging

NASA Astrophysics Data System (ADS)

Shiina, Tsuyoshi; Maki, Tomonori; Yamakawa, Makoto; Mitake, Tsuyoshi; Kudo, Masatoshi; Fujimoto, Kenji

2012-07-01

Precise evaluation of the stage of chronic hepatitis C with respect to fibrosis has become an important issue to prevent the occurrence of cirrhosis and to initiate appropriate therapeutic intervention such as viral eradication using interferon. Ultrasound tissue elasticity imaging, i.e., elastography can visualize tissue hardness/softness, and its clinical usefulness has been studied to detect and evaluate tumors. We have recently reported that the texture of elasticity image changes as fibrosis progresses. To evaluate fibrosis progression quantitatively on the basis of ultrasound tissue elasticity imaging, we introduced a mechanical model of fibrosis progression and simulated the process by which hepatic fibrosis affects elasticity images and compared the results with those clinical data analysis. As a result, it was confirmed that even in diffuse diseases like chronic hepatitis, the patterns of elasticity images are related to fibrous structural changes caused by hepatic disease and can be used to derive features for quantitative evaluation of fibrosis stage.

Bioinformatics approach reveals systematic mechanism underlying lung adenocarcinoma.

PubMed

Wu, Xiya; Zhang, Wei; Hu, Yunhua; Yi, Xianghua

2015-01-01

The purpose of this work was to explore the systematic molecular mechanism of lung adenocarcinoma and gain a deeper insight into it. Comprehensive bioinformatics methods were applied. Initially, significant differentially expressed genes (DEGs) were analyzed from the Affymetrix microarray data (GSE27262) deposited in the Gene Expression Omnibus (GEO). Subsequently, gene ontology (GO) analysis was performed using online Database for Annotation, Visualization and Integration Discovery (DAVID) software. Finally, significant pathway crosstalk was investigated based on the information derived from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. According to our results, the N-terminal globular domain of the type X collagen (COL10A1) gene and transmembrane protein 100 (TMEM100) gene were identified to be the most significant DEGs in tumor tissue compared with the adjacent normal tissues. The main GO categories were biological process, cellular component and molecular function. In addition, the crosstalk was significantly different between non-small cell lung cancer pathways and inositol phosphate metabolism pathway, focal adhesion signal pathway, vascular smooth muscle contraction signal pathway, peroxisome proliferator-activated receptor (PPAR) signaling pathway and calcium signaling pathway in tumor. Dysfunctional genes and pathways may play key roles in the progression and development of lung adenocarcinoma. Our data provide a systematic perspective for understanding this mechanism and may be helpful in discovering an effective treatment for lung adenocarcinoma.

Sarcopenia and cachexia in the era of obesity: clinical and nutritional impact.

PubMed

Prado, C M; Cushen, S J; Orsso, C E; Ryan, A M

2016-05-01

Our understanding of body composition (BC) variability in contemporary populations has significantly increased with the use of imaging techniques. Abnormal BC such as sarcopenia (low muscle mass) and obesity (excess adipose tissue) are predictors of poorer prognosis in a variety of conditions or clinical situations. As a catabolic illness, a defining feature of cancer is muscle loss. Although the conceptual model of wasting in cancer is typically conceived as involuntary weight loss leading to low body weight, recent studies have shown that both sarcopenia and cachexia can be present with obesity. The combination of low muscle and high adipose tissue (sarcopenic obesity) is an emerging abnormal BC phenotype prevalent across the body weight, and hence BMI spectra. Sarcopenia and sarcopenic obesity in cancer are in most instances occult conditions, which have been independently associated with higher incidence of chemotherapy toxicity, shorter time to tumour progression, poorer outcomes of surgery, physical impairment and shorter survival. Although the mechanisms are yet to be fully understood, the associations with poorer clinical outcomes emphasise the value of nutritional assessment as well as the need to develop appropriate interventions to countermeasure abnormal BC. Sarcopenia and sarcopenic obesity create diverse nutritional requirements, highlighting the compelling need for a more comprehensive and differentiated understanding of energy and protein requirements in this heterogeneous population.

Developmental biology of the pancreas: a comprehensive review.

PubMed

Gittes, George K

2009-02-01

Pancreatic development represents a fascinating process in which two morphologically distinct tissue types must derive from one simple epithelium. These two tissue types, exocrine (including acinar cells, centro-acinar cells, and ducts) and endocrine cells serve disparate functions, and have entirely different morphology. In addition, the endocrine tissue must become disconnected from the epithelial lining during its development. The pancreatic development field has exploded in recent years, and numerous published reviews have dealt specifically with only recent findings, or specifically with certain aspects of pancreatic development. Here I wish to present a more comprehensive review of all aspects of pancreatic development, though still there is not a room for discussion of stem cell differentiation to pancreas, nor for discussion of post-natal regeneration phenomena, two important fields closely related to pancreatic development.

Blends and Nanocomposite Biomaterials for Articular Cartilage Tissue Engineering

PubMed Central

Doulabi, Azadehsadat Hashemi; Mequanint, Kibret; Mohammadi, Hadi

2014-01-01

This review provides a comprehensive assessment on polymer blends and nanocomposite systems for articular cartilage tissue engineering applications. Classification of various types of blends including natural/natural, synthetic/synthetic systems, their combination and nanocomposite biomaterials are studied. Additionally, an inclusive study on their characteristics, cell responses ability to mimic tissue and regenerate damaged articular cartilage with respect to have functionality and composition needed for native tissue, are also provided. PMID:28788131

Is the Autism Treatment Evaluation Checklist a Useful Tool for Monitoring Progress in Children with Autism Spectrum Disorders?

ERIC Educational Resources Information Center

Magiati, I.; Moss, J.; Yates, R.; Charman, T.; Howlin, P.

2011-01-01

Background: There are few well validated brief measures that can be used to assess the general progress of young children with autism spectrum disorders (ASD) over time. In the present study, the Autism Treatment Evaluation Checklist (ATEC) was used as part of a comprehensive assessment battery to monitor the progress of 22 school-aged children…

Testing the Importance of Individual Growth Curves in Predicting Performance on a High-Stakes Reading Comprehension Test in Florida. Summary. REL 2014-006

ERIC Educational Resources Information Center

Petscher, Yaacov; Kershaw, Sarah; Koon, Sharon; Foorman, Barbara R.

2014-01-01

Districts and schools use progress monitoring to assess student progress, to identify students who fail to respond to intervention, and to further adapt instruction to student needs. Researchers and practitioners often use progress monitoring data to estimate student achievement growth (slope) and evaluate changes in performance over time for…

NEIBank: Genomics and bioinformatics resources for vision research

PubMed Central

Peterson, Katherine; Gao, James; Buchoff, Patee; Jaworski, Cynthia; Bowes-Rickman, Catherine; Ebright, Jessica N.; Hauser, Michael A.; Hoover, David

2008-01-01

NEIBank is an integrated resource for genomics and bioinformatics in vision research. It includes expressed sequence tag (EST) data and sequence-verified cDNA clones for multiple eye tissues of several species, web-based access to human eye-specific SAGE data through EyeSAGE, and comprehensive, annotated databases of known human eye disease genes and candidate disease gene loci. All expression- and disease-related data are integrated in EyeBrowse, an eye-centric genome browser. NEIBank provides a comprehensive overview of current knowledge of the transcriptional repertoires of eye tissues and their relation to pathology. PMID:18648525

Complicated acute appendicitis presenting as a rapidly progressive soft tissue infection of the abdominal wall: a case report.

PubMed

Beerle, Corinne; Gelpke, Hans; Breitenstein, Stefan; Staerkle, Ralph F

2016-12-01

We report a case of a rare complication of acute appendicitis with perforation through the abdominal wall. The case points out that an intraabdominal origin should be considered in patients presenting with rapidly spreading soft tissue infections of the trunk. A 58-year-old European woman presented to our hospital with a 1-week history of severe abdominal pain accompanied by rapidly spreading erythema and emphysema of the lower abdomen. On admission, the patient was in septic shock with leukocytosis and elevation of C-reactive protein. Among other diagnoses, necrotizing fasciitis was suspected. Computed tomography showed a large soft tissue infection with air-fluid levels spreading through the lower abdominal wall. During the operation, we found a perforated appendicitis breaking through the fascia and causing a rapidly progressive soft tissue infection of the abdominal wall. Appendicitis was the origin of the soft tissue infection. The abdominal wall was only secondarily involved. Even though perforated appendicitis as an etiology of a rapidly progressive soft tissue infection of the abdominal wall is very rare, it should be considered in the differential diagnosis of abdominal wall cellulitis. The distinction between rapidly spreading subcutaneous infection with abscess formation and early onset of necrotizing fasciitis is often difficult and can be confirmed only by surgical intervention.

Mass Transportation in Massachusetts : demonstration project progress report no. 5 - tentative conclusions

DOT National Transportation Integrated Search

1963-11-22

This fifth progress report is submitted twelve months after the initiation of the first MTC-HHFA experiment, and ten months after the start of the large Boston and Maine Railroad. Because of the urgent need to present comprehensive analyses in some d...

Variable disruption of a syntactic processing network in primary progressive aphasia.

PubMed

Wilson, Stephen M; DeMarco, Andrew T; Henry, Maya L; Gesierich, Benno; Babiak, Miranda; Miller, Bruce L; Gorno-Tempini, Maria Luisa

2016-11-01

Syntactic processing deficits are highly variable in individuals with primary progressive aphasia. Damage to left inferior frontal cortex has been associated with syntactic deficits in primary progressive aphasia in a number of structural and functional neuroimaging studies. However, a contrasting picture of a broader syntactic network has emerged from neuropsychological studies in other aphasic cohorts, and functional imaging studies in healthy controls. To reconcile these findings, we used functional magnetic resonance imaging to investigate the functional neuroanatomy of syntactic comprehension in 51 individuals with primary progressive aphasia, composed of all clinical variants and a range of degrees of syntactic processing impairment. We used trial-by-trial reaction time as a proxy for syntactic processing load, to determine which regions were modulated by syntactic processing in each patient, and how the set of regions recruited was related to whether syntactic processing was ultimately successful or unsuccessful. Relationships between functional abnormalities and patterns of cortical atrophy were also investigated. We found that the individual degree of syntactic comprehension impairment was predicted by left frontal atrophy, but also by functional disruption of a broader syntactic processing network, comprising left posterior frontal cortex, left posterior temporal cortex, and the left intraparietal sulcus and adjacent regions. These regions were modulated by syntactic processing in healthy controls and in patients with primary progressive aphasia with relatively spared syntax, but they were modulated to a lesser extent or not at all in primary progressive aphasia patients whose syntax was relatively impaired. Our findings suggest that syntactic comprehension deficits in primary progressive aphasia reflect not only structural and functional changes in left frontal cortex, but also disruption of a wider syntactic processing network. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Comprehensive Monte-Carlo simulator for optimization of imaging parameters for high sensitivity detection of skin cancer at the THz

NASA Astrophysics Data System (ADS)

Ney, Michael; Abdulhalim, Ibrahim

2016-03-01

Skin cancer detection at its early stages has been the focus of a large number of experimental and theoretical studies during the past decades. Among these studies two prominent approaches presenting high potential are reflectometric sensing at the THz wavelengths region and polarimetric imaging techniques in the visible wavelengths. While THz radiation contrast agent and source of sensitivity to cancer related tissue alterations was considered to be mainly the elevated water content in the cancerous tissue, the polarimetric approach has been verified to enable cancerous tissue differentiation based on cancer induced structural alterations to the tissue. Combining THz with the polarimetric approach, which is considered in this study, is examined in order to enable higher detection sensitivity than previously pure reflectometric THz measurements. For this, a comprehensive MC simulation of radiative transfer in a complex skin tissue model fitted for the THz domain that considers the skin`s stratified structure, tissue material optical dispersion modeling, surface roughness, scatterers, and substructure organelles has been developed. Additionally, a narrow beam Mueller matrix differential analysis technique is suggested for assessing skin cancer induced changes in the polarimetric image, enabling the tissue model and MC simulation to be utilized for determining the imaging parameters resulting in maximal detection sensitivity.

3D Bioprinting for Tissue and Organ Fabrication

PubMed Central

Zhang, Yu Shrike; Yang, Jingzhou; Jia, Weitao; Dell’Erba, Valeria; Assawes, Pribpandao; Shin, Su Ryon; Dokmeci, Mehmet Remzi; Oklu, Rahmi; Khademhosseini, Ali

2016-01-01

The field of regenerative medicine has progressed tremendously over the past few decades in its ability to fabricate functional tissue substitutes. Conventional approaches based on scaffolding and microengineering are limited in their capacity of producing tissue constructs with precise biomimetic properties. Three-dimensional (3D) bioprinting technology, on the other hand, promises to bridge the divergence between artificially engineered tissue constructs and native tissues. In a sense, 3D bioprinting offers unprecedented versatility to co-deliver cells and biomaterials with precise control over their compositions, spatial distributions, and architectural accuracy, therefore achieving detailed or even personalized recapitulation of the fine shape, structure, and architecture of target tissues and organs. Here we briefly describe recent progresses of 3D bioprinting technology and associated bioinks suitable for the printing process. We then focus on the applications of this technology in fabrication of biomimetic constructs of several representative tissues and organs, including blood vessel, heart, liver, and cartilage. We finally conclude with future challenges in 3D bioprinting as well as potential solutions for further development. PMID:27126775

3D Bioprinting for Tissue and Organ Fabrication.

PubMed

Zhang, Yu Shrike; Yue, Kan; Aleman, Julio; Moghaddam, Kamyar Mollazadeh; Bakht, Syeda Mahwish; Yang, Jingzhou; Jia, Weitao; Dell'Erba, Valeria; Assawes, Pribpandao; Shin, Su Ryon; Dokmeci, Mehmet Remzi; Oklu, Rahmi; Khademhosseini, Ali

2017-01-01

The field of regenerative medicine has progressed tremendously over the past few decades in its ability to fabricate functional tissue substitutes. Conventional approaches based on scaffolding and microengineering are limited in their capacity of producing tissue constructs with precise biomimetic properties. Three-dimensional (3D) bioprinting technology, on the other hand, promises to bridge the divergence between artificially engineered tissue constructs and native tissues. In a sense, 3D bioprinting offers unprecedented versatility to co-deliver cells and biomaterials with precise control over their compositions, spatial distributions, and architectural accuracy, therefore achieving detailed or even personalized recapitulation of the fine shape, structure, and architecture of target tissues and organs. Here we briefly describe recent progresses of 3D bioprinting technology and associated bioinks suitable for the printing process. We then focus on the applications of this technology in fabrication of biomimetic constructs of several representative tissues and organs, including blood vessel, heart, liver, and cartilage. We finally conclude with future challenges in 3D bioprinting as well as potential solutions for further development.

Intravital imaging reveals new ancillary mechanisms co-opted by cancer cells to drive tumor progression

PubMed Central

Lucas, Morghan C.; Timpson, Paul

2016-01-01

Intravital imaging is providing new insights into the dynamics of tumor progression in native tissues and has started to reveal the layers of complexity found in cancer. Recent advances in intravital imaging have allowed us to look deeper into cancer behavior and to dissect the interactions between tumor cells and the ancillary host niche that promote cancer development. In this review, we provide an insight into the latest advances in cancer biology achieved by intravital imaging, focusing on recently discovered mechanisms by which tumor cells manipulate normal tissue to facilitate disease progression. PMID:27239290

Story Retell: A Fluency-Based Indicator of Reading Comprehension

ERIC Educational Resources Information Center

Roberts, Greg; Good, Roland; Corcoran, Stephanie

2005-01-01

This article presents a fluency-based measure of reading comprehension. A part of the Vitals Indicators of Progress (VIP) system, the measure outlined here represents an alternate form to the retell-fluency measure in the Dynamic Indicators of Basic Early Literacy System (DIBELS). Measures of retell fluency provide an efficient, fluency-based tool…

Relationships between Visual and Auditory Perceptual Skills and Comprehension in Students with Learning Disabilities.

ERIC Educational Resources Information Center

Weaver, Phyllis A.; Rosner, Jerome

1979-01-01

Scores of 25 learning disabled students (aged 9 to 13) were compared on five tests: a visual-perceptual test (Coloured Progressive Matrices); an auditory-perceptual test (Auditory Motor Placement); a listening and reading comprehension test (Durrell Listening-Reading Series); and a word recognition test (Word Recognition subtest, Diagnostic…

Race to the Top. Ohio. State-Reported APR: Year One

ERIC Educational Resources Information Center

US Department of Education, 2012

2012-01-01

This paper describes Ohio's progress in implementing a comprehensive and coherent approach to education reform from the time of application through June 30, 2011. The sections presented in this report highlight key accomplishments made by Ohio to implement a comprehensive and coherent approach to education reform over the reporting period in the…

Most Comprehension Tests Do Measure Reading Comprehension: A Response to McLean and Goldstein.

ERIC Educational Resources Information Center

Stenner, A. Jackson; And Others

1988-01-01

Rebuffs Leslie Maclean and Harvey Goldstein's claims that the National Assessment of Educational Progress (NAEP) Reading Proficiency Scale is unidimensional. Critics' confusion may stem from failing to separate what a test measures from a score's usefulness. The Lexile Reading Scale should be integrated with the NAEP scale. Includes eight…

U. S. Fourth Graders' Informational Text Comprehension: Indicators from NAEP

ERIC Educational Resources Information Center

Schugar, Heather R.; Dreher, Miriam Jean

2017-01-01

This study is a secondary analysis of reading data collected from over 165,000 fourth graders as part of the U.S. National Assessment of Educational Progress. Using hierarchical linear modelling, the authors investigated factors associated with students' informational text comprehension, including out-of-school reading engagement, and in-school…

[Research progress of in vivo bioreactor as vascularization strategies in bone tissue engineering].

PubMed

Zhang, Haifeng; Han, Dong

2014-09-01

To review the application and research progress of in vivo bioreactor as vascularization strategies in bone tissue engineering. The original articles about in vivo bioreactor that can enhance vascularization of tissue engineered bone were extensively reviewed and analyzed. The in vivo bioreactor can be created by periosteum, muscle, muscularis membrane, and fascia flap as well as biomaterials. Using in vivo bioreactor can effectively promote the establishment of a microcirculation in the tissue engineered bones, especially for large bone defects. However, main correlative researches, currently, are focused on animal experiments, more clinical trials will be carried out in the future. With the rapid development of related technologies of bone tissue engineering, the use of in vivo bioreactor will to a large extent solve the bottleneck limitations and has the potential values for clinical application.

Adult Soft Tissue Sarcoma Treatment (PDQ®)—Health Professional Version

Cancer.gov

Soft tissue sarcomas (STS) arise in any of the extremities, trunk, retroperitoneum, or head and neck. Treatment is determined by the tumor grade and options include surgery, radiation therapy, and chemotherapy. Get comprehensive information for STS and treatment in this clinician summary.

Mathematics Framework for the 2013 National Assessment of Educational Progress

ERIC Educational Resources Information Center

National Assessment Governing Board, 2012

2012-01-01

Since 1973, the National Assessment of Educational Progress (NAEP) has gathered information about student achievement in mathematics. Results of these periodic assessments, produced in print and web-based formats, provide valuable information to a wide variety of audiences. They inform citizens about the nature of students' comprehension of the…

Progress Testing: Critical Analysis and Suggested Practices

ERIC Educational Resources Information Center

Albanese, Mark; Case, Susan M.

2016-01-01

Educators have long lamented the tendency of students to engage in rote memorization in preparation for tests rather than engaging in deep learning where they attempt to gain meaning from their studies. Rote memorization driven by objective exams has been termed a steering effect. Progress testing (PT), in which a comprehensive examination…

Expression of autophagy-related protein LC3B, p62, and cytoplasmic p53 in human retinoblastoma tissues.

PubMed

Zhang, M; Zhou, Y-F; Gong, J-Y; Gao, C-B; Li, S-L

2016-07-01

Dysfunction of autophagy has been implicated in development and progression of diverse human cancers. However, the exact role and mechanism of autophagy have not been fully understood in human cancers, especially in retinoblastoma (Rb). We determined the autophagy activity in human Rb tissues by assessing the autophagy markers microtubule-associated protein light chain 3B (LC3) and p62 (SQSTM1) in formalin fixed and paraffin embedded human tissue by immunohistochemistry and then associated their expression with patient clinicopathological features. We further explored the correlation between the expression of LC3B and p62 and the expression of cytoplasmic p53, a newly identified autophagy suppressor, in Rb tissues. Our data revealed that the expression of LC3B and p62, was significantly associated with disease progression and tumor invasion of Rb. Furthermore, we also revealed that cytoplasmic expression of p53 was inversely associated with the behavior of tumor invasion. Finally, Spearman correlation analysis demonstrated that cytoplasmic expression of p53 was significantly and inversely correlated to the expression of both LC3B and p62. Autophagy might play an important role in human Rb progression, and LC3B and p62 may be useful predictors of disease progression in patients with Rb.

The Wernicke conundrum and the anatomy of language comprehension in primary progressive aphasia

PubMed Central

Thompson, Cynthia K.; Weintraub, Sandra; Rogalski, Emily J.

2015-01-01

Wernicke’s aphasia is characterized by severe word and sentence comprehension impairments. The location of the underlying lesion site, known as Wernicke’s area, remains controversial. Questions related to this controversy were addressed in 72 patients with primary progressive aphasia who collectively displayed a wide spectrum of cortical atrophy sites and language impairment patterns. Clinico-anatomical correlations were explored at the individual and group levels. These analyses showed that neuronal loss in temporoparietal areas, traditionally included within Wernicke’s area, leave single word comprehension intact and cause inconsistent impairments of sentence comprehension. The most severe sentence comprehension impairments were associated with a heterogeneous set of cortical atrophy sites variably encompassing temporoparietal components of Wernicke’s area, Broca’s area, and dorsal premotor cortex. Severe comprehension impairments for single words, on the other hand, were invariably associated with peak atrophy sites in the left temporal pole and adjacent anterior temporal cortex, a pattern of atrophy that left sentence comprehension intact. These results show that the neural substrates of word and sentence comprehension are dissociable and that a circumscribed cortical area equally critical for word and sentence comprehension is unlikely to exist anywhere in the cerebral cortex. Reports of combined word and sentence comprehension impairments in Wernicke’s aphasia come almost exclusively from patients with cerebrovascular accidents where brain damage extends into subcortical white matter. The syndrome of Wernicke’s aphasia is thus likely to reflect damage not only to the cerebral cortex but also to underlying axonal pathways, leading to strategic cortico-cortical disconnections within the language network. The results of this investigation further reinforce the conclusion that the left anterior temporal lobe, a region ignored by classic aphasiology, needs to be inserted into the language network with a critical role in the multisynaptic hierarchy underlying word comprehension and object naming. PMID:26112340

The Wernicke conundrum and the anatomy of language comprehension in primary progressive aphasia.

PubMed

Mesulam, M-Marsel; Thompson, Cynthia K; Weintraub, Sandra; Rogalski, Emily J

2015-08-01

Wernicke's aphasia is characterized by severe word and sentence comprehension impairments. The location of the underlying lesion site, known as Wernicke's area, remains controversial. Questions related to this controversy were addressed in 72 patients with primary progressive aphasia who collectively displayed a wide spectrum of cortical atrophy sites and language impairment patterns. Clinico-anatomical correlations were explored at the individual and group levels. These analyses showed that neuronal loss in temporoparietal areas, traditionally included within Wernicke's area, leave single word comprehension intact and cause inconsistent impairments of sentence comprehension. The most severe sentence comprehension impairments were associated with a heterogeneous set of cortical atrophy sites variably encompassing temporoparietal components of Wernicke's area, Broca's area, and dorsal premotor cortex. Severe comprehension impairments for single words, on the other hand, were invariably associated with peak atrophy sites in the left temporal pole and adjacent anterior temporal cortex, a pattern of atrophy that left sentence comprehension intact. These results show that the neural substrates of word and sentence comprehension are dissociable and that a circumscribed cortical area equally critical for word and sentence comprehension is unlikely to exist anywhere in the cerebral cortex. Reports of combined word and sentence comprehension impairments in Wernicke's aphasia come almost exclusively from patients with cerebrovascular accidents where brain damage extends into subcortical white matter. The syndrome of Wernicke's aphasia is thus likely to reflect damage not only to the cerebral cortex but also to underlying axonal pathways, leading to strategic cortico-cortical disconnections within the language network. The results of this investigation further reinforce the conclusion that the left anterior temporal lobe, a region ignored by classic aphasiology, needs to be inserted into the language network with a critical role in the multisynaptic hierarchy underlying word comprehension and object naming. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Herbal medicine, radical scavenger and metal detoxification: bioinorganic, complexity and nano science perspectives

NASA Astrophysics Data System (ADS)

Sumitro, Sutiman B.; Alit, Sukmaningsih

2018-03-01

Developing Complexity Science and Nano Biological perspective giving the ideas of interfacing between modern physical and biological sciences for more comprehensive understanding of life. The study of bioinorganic is a trans-disciplinary, and will initiate the way to more comprehensive and better understanding life. We can talk about energy generation, motive forces and energy transfer at the level of macromolecules. We can then develop understanding biological behavior on nano size biological materials and its higher order using modern physics as well as thermodynamic law. This is a necessity to ovoid partial understanding of life that are not match with holism. In animal tissues, the accumulation or overwhelmed production of free radicals can damage cells and are believed to accelerate the progression of cancer, cardiovascular disease, and age-related diseases. Thus a guarded balance of radical species is imperative. Edward Kosower [1] proposed an idea of biradical in an aromatic organic compounds. Each of which having unpaired electrons. The magnetic force of this compound used for making agregation based on their magnetic characters. Bioinorganic low molecular weight complex compounds composing herbal medicine can bind toxic metals. This low molecular weight complex molecules then easily excerted the metals from the body, removing them from their either intracellular or extracellular existences. This bioinorganic chelation potential is now inspiring a new therapeutic strategies.

RNA sequencing-based cell proliferation analysis across 19 cancers identifies a subset of proliferation-informative cancers with a common survival signature.

PubMed

Ramaker, Ryne C; Lasseigne, Brittany N; Hardigan, Andrew A; Palacio, Laura; Gunther, David S; Myers, Richard M; Cooper, Sara J

2017-06-13

Despite advances in cancer diagnosis and treatment strategies, robust prognostic signatures remain elusive in most cancers. Cell proliferation has long been recognized as a prognostic marker in cancer, but the generation of comprehensive, publicly available datasets allows examination of the links between cell proliferation and cancer characteristics such as mutation rate, stage, and patient outcomes. Here we explore the role of cell proliferation across 19 cancers (n = 6,581 patients) by using tissue-based RNA sequencing data from The Cancer Genome Atlas Project and calculating a 'proliferative index' derived from gene expression associated with Proliferating Cell Nuclear Antigen (PCNA) levels. This proliferative index is significantly associated with patient survival (Cox, p-value < 0.05) in 7 of 19 cancers, which we have defined as "proliferation-informative cancers" (PICs). In PICs, the proliferative index is strongly correlated with tumor stage and nodal invasion. PICs demonstrate reduced baseline expression of proliferation machinery relative to non-PICs. Additionally, we find the proliferative index is significantly associated with gross somatic mutation burden (Spearman, p = 1.76 x 10-23) as well as with mutations in individual driver genes. This analysis provides a comprehensive characterization of tumor proliferation indices and their association with disease progression and prognosis in multiple cancer types and highlights specific cancers that may be particularly susceptible to improved targeting of this classic cancer hallmark.

Recovery in treated aphasia in the first year post-stroke.

PubMed

Sarno, M T; Levita, E

1979-01-01

During a one year post-stroke period of observation, the recovery trend in treated aphasic patients was characterized by general progression in communication skill. The most notable improvement occurred on a measure of everyday function with changes worthy of note on tasks of auditory comprehension and spontaneous word production. In the first 6 months post-stroke, the greatest gain occurred in aphasic patients classified as Fluent, and the least gain in Global aphasics. On the auditory comprehension task, however, improvement was noted in all aphasics regardless of type. In contrast, during the latter half of the first year post-stroke, Fluent aphasics showed least and Global aphasics the greatest improvement. In spite of their progress, Global aphasic patients remained considerably more impaired than the other groups. That the Global aphasics remained so impaired was expected, but the extent and temporal characteristics of their progress in communicating was unexpected.

Assessing the role of prevention partnerships in STD prevention: a review of comprehensive STD prevention systems progress reports.

PubMed

Hogben, Matthew; Hood, Julia; Collins, Dayne; McFarlane, Mary

2013-11-01

Systematic analysis of STD programme data contributes to a national portrait of sexually transmitted disease (STD) prevention activities, including research and evaluation specifically designed to optimise programme efficiency and impact. We analysed the narrative of the 2009 annual progress reports of the US Comprehensive STD Prevention Systems cooperative agreement for 58 STD programmes, concentrating on programme characteristics and partnerships. Programmes described 516 unique partnerships with a median of seven organisations cited per STD programme. Non-profit organisations (including service providers) were most frequently cited. Higher gonorrhoea morbidity was associated with reporting more partnerships; budget problems were associated with reporting fewer. Challenges to engaging in partnerships included budget constraints, staff turnover and low interest. Data provide a source of information for judging progress in programme collaboration and for informing a sustained programme-focused research and evaluation agenda.

Evaluating core technology capacity based on an improved catastrophe progression method: the case of automotive industry

NASA Astrophysics Data System (ADS)

Zhao, Shijia; Liu, Zongwei; Wang, Yue; Zhao, Fuquan

2017-01-01

Subjectivity usually causes large fluctuations in evaluation results. Many scholars attempt to establish new mathematical methods to make evaluation results consistent with actual objective situations. An improved catastrophe progression method (ICPM) is constructed to overcome the defects of the original method. The improved method combines the merits of the principal component analysis' information coherence and the catastrophe progression method's none index weight and has the advantage of highly objective comprehensive evaluation. Through the systematic analysis of the influencing factors of the automotive industry's core technology capacity, the comprehensive evaluation model is established according to the different roles that different indices play in evaluating the overall goal with a hierarchical structure. Moreover, ICPM is developed for evaluating the automotive industry's core technology capacity for the typical seven countries in the world, which demonstrates the effectiveness of the method.

Role of adipose tissue-derived stem cells in the progression of renal disease.

PubMed

Donizetti-Oliveira, Cassiano; Semedo, Patricia; Burgos-Silva, Marina; Cenedeze, Marco Antonio; Malheiros, Denise Maria Avancini Costa; Reis, Marlene Antônia Dos; Pacheco-Silva, Alvaro; Câmara, Niels Olsen Saraiva

2011-03-01

To analyze the role of adipose tissue-derived stem cells in reducing the progression of renal fibrosis. adipose tissue-derived stem cells were isolated from C57Bl/6 mice and characterized by cytometry and differentiation. Renal fibrosis was established after unilateral clamping of the renal pedicle for 1 hour. Four hours after reperfusion, 2.105 adipose tissue-derived stem cells were administered intraperitoneally and the animals were followed for 24 hours during 6 weeks. In another experimental group, 2.105adipose tissue-derived stem cells were administered only after 6 weeks of reperfusion, and they were euthanized and studied 4 weeks later. Twenty-four hours after reperfusion, the animals treated with adipose tissue-derived stem cells displayed reduced renal and tubular dysfunction and an increase of the regenerative process. Renal expression of IL-6 and TNF mRNA were decreased in the animals treated with adipose tissue-derived stem cells, while the levels of IL-4, IL-10, and HO-1 were increased, despite the fact that adipose tissue-derived stem cells were not observed in the kidneys via SRY analysis. In 6 weeks, the kidneys of non-treated animals decreased in size, and the kidneys of the animals treated with adipose tissue-derived stem cells remained at normal size and display less deposition of type 1 collagen and FSP-1. The renal protection observed in animals treated with adipose tissue-derived stem cells was followed by a drop in serum levels of TNF-α, KC, RANTES, and IL-1a. Treatment with adipose tissue-derived stem cells after 6 weeks, when the animals already displayed established fibrosis, demonstrated an improvement in functional parameters and less fibrosis analyzed by Picrosirius stain, as well as a reduction of the expression of type 1 collagen and vimentin mRNA. Treatment with adipose tissue-derived stem cells may deter the progression of renal fibrosis by modulation of the early inflammatory response, likely via reduction of the epithelial-mesenchymal transition.

Does rat granulation tissue maturation involve gap junction communications?

PubMed

Au, Katherine; Ehrlich, H Paul

2007-07-01

Wound healing, a coordinated process, proceeds by sequential changes in cell differentiation and terminates with the deposition of a new connective tissue matrix, a scar. Initially, there is the migratory fibroblast, followed by the proliferative fibroblast, then the synthetic fibroblast, which transforms into the myofibroblast, and finally the apoptotic fibroblast. Gap junction intercellular communications are proposed to coordinate the stringent control of fibroblast phenotypic changes. Does added oleamide, a natural fatty acid that blocks gap junction intercellular communications, alter the phenotypic progression of wound fibroblasts? Pairs of polyvinyl alcohol sponges attached to Alzet pumps, which constantly pumped either oleamide or vehicle solvent, were implanted subcutaneously into three rats. On day 8, implants were harvested and evaluated histologically and biochemically. The capsule of oleamide-treated sponge contained closely packed fibroblasts with little connective tissue between them. The birefringence intensity of that connective tissue was reduced, indicating a reduced density of collagen fiber bundles. Myofibroblasts, identified immunohistologically by alpha-smooth muscle actin-stained stress fibers, were reduced in oleamide-treated implants. Western blot analysis showing less alpha-smooth muscle actin confirmed the reduced density of myofibroblasts. It appears that oleamide retards the progression of wound repair, where less connective tissue is deposited, the collagen is less organized, and the appearance of myofibroblasts is impaired. These findings support the hypothesis that gap junction intercellular communications between wound fibroblasts in granulation tissue play a role in the progression of repair and the maturation of granulation tissue into scar.

Use of GDNF-Releasing Nanofiber Nerve Guide Conduits for the Repair of Conus Medullaris/Cauda Equina Injury in the Non-Human Primate

DTIC Science & Technology

2012-10-01

peripheral nerve graft to bridge the tissue gap. A comprehensive set of electrodiagnostic, imaging , behavioral and anatomical studies will provide...spinal cord and avulsed ventral roots. All 20 surgeries have been completed and collections of comprehensive functional and imaging data are in...gap. A comprehensive set of electrodiagnostic, imaging , behavioral and anatomical studies will provide detailed information about the outcome of the

Evaluation of Quality of Life at Progression in Patients with Soft Tissue Sarcoma.

PubMed

Hudgens, Stacie; Forsythe, Anna; Kontoudis, Ilias; D'Adamo, David; Bird, Ashley; Gelderblom, Hans

2017-01-01

Introduction . Soft Tissue Sarcoma (STS) is a rare malignancy of mesodermal tissue, with international incidence estimates between 1.8 and 5 per 100,000 per year. Understanding quality of life (QoL) and the detrimental impact of disease progression is critical for long-term care and survival. Objectives . The primary objective was to explore the relationship between disease progression and health-related quality of life (HRQoL) using data from Eisai's study (E7389-G000-309). Methods . This was a 1 : 1 randomized, open-label, multicenter, Phase 3 study comparing the efficacy and safety of eribulin versus dacarbazine in patients with advanced STS. The QoL analysis was conducted for the baseline and progression populations using the European Organization for Research and Treatment of Cancer 30-item core QoL questionnaire (EORTC QLQ-C30). Results . There were no statistical differences between the two treatment arms at baseline for any domain ( p > 0.05; n = 452). Of the 399 patients who experienced disease progression (unadjusted and adjusting for histology), dacarbazine patients had significantly lower Global Health Status, Physical Functioning scores, and significantly worse Nausea and Vomiting, Insomnia, and Appetite Loss ( p < 0.05). Conclusions . These results indicate differences in HRQoL overall and at progression between dacarbazine and eribulin patients, with increases in symptom severity observed among dacarbazine patients.

Summaries of press automation conference presented

NASA Astrophysics Data System (ADS)

Makhlin, A. Y.; Pokrovskaya, G. M.

1985-01-01

The automation and mechanization of cold and hot stamping were discussed. Problems in the comprehensive mechanization and automatio of stamping in machine building development were examined. Automation becomes effective when it is implemented in progressive manufacturing processes and a comprehensive approach to the solution of all problems, beginning with the delivery of initial materials and ending with the transportation of finished products to the warehouse. Production intensification and improvments of effectiveness of produced output through the comprehensive mechanization and automation of stamping operations are reported.

New candidate markers of head and neck squamous cell carcinoma progression

NASA Astrophysics Data System (ADS)

Kakurina, G. V.; Kolegova, E. S.; Cheremisina, O. V.; Kulbakin, D. E.; Choinzonov, E. L.

2017-09-01

The tumor progression in head and neck squamous cell carcinoma (HNSCC) is one of the main causes of high mortality of the patients with HNSCC. The tumor progression, particularly the metastasis, is characterized by the changes in the composition, functions and structure of different proteins. We have previously shown that serum of HNSCC patients contains the proteins which regulate various cellular processes—adenylyl cyclase associated protein 1 (CAP1), protein phosphatase 1 B (PPM1B), etc. The levels of CAP1 and PPM1B were determined using the enzyme immunoassay. The results of this study show that CAP1 and PPM1B take a part in the progression of HNSCC. The levels of CAP1 and PPM1B in the tumor and in morphologically normal tissue depended on the prevalence of the tumor process. The CAP1 and PPM1B levels were significantly higher in tumor tissue of the patients with regional metastasis. Our data allow assuming the potential possibility for predicting the outcome of the HNSCC measuring the level of tissue CAP1.

Chondroitin Sulfate (CS) Lyases: Structure, Function and Application in Therapeutics.

PubMed

Rani, Aruna; Patel, Seema; Goyal, Arun

2018-01-01

Glycosaminoglycans (GAGs) such as chondroitin sulfate (CS) are the chief natural polysaccharides which reside in biological tissues mainly in extracellular matrix. These CS along with adhesion molecules and growth factors are involved in central nervous system (CNS) development, cell progression and pathogenesis. The chondroitin lyases are the enzyme that degrade and alter the CS chains and hence modify various signalling pathways involving CS chains. These CS lyases are substrate specific, can precisely manipulate the CS polysaccharides and have various biotechnological, medical and therapeutic applications. These enzymes can be used to produce the unsaturated oligosaccharides, which have immune-modulatory, anti-inflammatory and neuroprotective properties. This review focuses on the major breakthrough of the chondroitin sulfate degrading enzymes, their structures and functioning mechanism. This also provides comprehensive information regarding production, purification, characterization of CS lyases and their major applications, both established as well as emerging ones such as neural development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Preclinical imaging methods for assessing the safety and efficacy of regenerative medicine therapies

NASA Astrophysics Data System (ADS)

Scarfe, Lauren; Brillant, Nathalie; Kumar, J. Dinesh; Ali, Noura; Alrumayh, Ahmed; Amali, Mohammed; Barbellion, Stephane; Jones, Vendula; Niemeijer, Marije; Potdevin, Sophie; Roussignol, Gautier; Vaganov, Anatoly; Barbaric, Ivana; Barrow, Michael; Burton, Neal C.; Connell, John; Dazzi, Francesco; Edsbagge, Josefina; French, Neil S.; Holder, Julie; Hutchinson, Claire; Jones, David R.; Kalber, Tammy; Lovatt, Cerys; Lythgoe, Mark F.; Patel, Sara; Patrick, P. Stephen; Piner, Jacqueline; Reinhardt, Jens; Ricci, Emanuelle; Sidaway, James; Stacey, Glyn N.; Starkey Lewis, Philip J.; Sullivan, Gareth; Taylor, Arthur; Wilm, Bettina; Poptani, Harish; Murray, Patricia; Goldring, Chris E. P.; Park, B. Kevin

2017-10-01

Regenerative medicine therapies hold enormous potential for a variety of currently incurable conditions with high unmet clinical need. Most progress in this field to date has been achieved with cell-based regenerative medicine therapies, with over a thousand clinical trials performed up to 2015. However, lack of adequate safety and efficacy data is currently limiting wider uptake of these therapies. To facilitate clinical translation, non-invasive in vivo imaging technologies that enable careful evaluation and characterisation of the administered cells and their effects on host tissues are critically required to evaluate their safety and efficacy in relevant preclinical models. This article reviews the most common imaging technologies available and how they can be applied to regenerative medicine research. We cover details of how each technology works, which cell labels are most appropriate for different applications, and the value of multi-modal imaging approaches to gain a comprehensive understanding of the responses to cell therapy in vivo.

Radiofrequency heating of nanomaterials for cancer treatment: Progress, controversies, and future development

NASA Astrophysics Data System (ADS)

Liu, Xiaoming; Chen, Hui-jiuan; Chen, Xiaodong; Alfadhl, Yasir; Yu, Junsheng; Wen, Dongsheng

2015-03-01

In recent years, the application of nanomaterials to biological and biomedicine areas has attracted intensive interest. One of the hot topics is the nanomaterial mediated radiofrequency (RF) hyperthermia or ablation, i.e., using RF fields/waves to heat tumor tissues treated with nanomaterials to destroy cancerous cells while minimizing the side-heating effect. However, there are currently many contradictive results reported concerning the heating effect of nanomaterials under a RF field. This paper provided a comprehensive review to nanomaterial mediated RF ablation from both experimental and theoretical aspects. Three heating mechanisms were discussed, i.e., laser heating, magnetic field heating, and electric field heating in RF spectrum, with the focus on the last one. The results showed that while diluted pure metallic nanoparticles could be heated significantly by a laser through the surface plasmon resonance, they cannot be easily heated by a RF electric field. Further studies are proposed focusing on nanoparticle structure and morphology, electromagnetic frequency and localized heating effect to pave the way for future development.

Magnesium based degradable biomaterials: A review

NASA Astrophysics Data System (ADS)

Gu, Xue-Nan; Li, Shuang-Shuang; Li, Xiao-Ming; Fan, Yu-Bo

2014-09-01

Magnesium has been suggested as a revolutionary biodegradable metal for biomedical applications. The corrosion of magnesium, however, is too rapid to match the rates of tissue healing and, additionally, exhibits the localized corrosion mechanism. Thus it is necessary to control the corrosion behaviors of magnesium for their practical use. This paper comprehensively reviews the research progress on the development of representative magnesium based alloys, including Mg-Ca, Mg-Sr, Mg-Zn and Mg-REE alloy systems as well as the bulk metallic glass. The influence of alloying element on their microstructures, mechanical properties and corrosion behaviors is summarized. The mechanical and corrosion properties of wrought magnesium alloys are also discussed in comparison with those of cast alloys. Furthermore, this review also covers research carried out in the field of the degradable coatings on magnesium alloys for biomedical applications. Calcium phosphate and biodegradable polymer coatings are discussed based on different preparation techniques used. We also compare the effect of different coatings on the corrosion behaviors of magnesium alloys substrate.

The developmental proteome of Drosophila melanogaster

PubMed Central

Casas-Vila, Nuria; Bluhm, Alina; Sayols, Sergi; Dinges, Nadja; Dejung, Mario; Altenhein, Tina; Kappei, Dennis; Altenhein, Benjamin; Roignant, Jean-Yves; Butter, Falk

2017-01-01

Drosophila melanogaster is a widely used genetic model organism in developmental biology. While this model organism has been intensively studied at the RNA level, a comprehensive proteomic study covering the complete life cycle is still missing. Here, we apply label-free quantitative proteomics to explore proteome remodeling across Drosophila’s life cycle, resulting in 7952 proteins, and provide a high temporal-resolved embryogenesis proteome of 5458 proteins. Our proteome data enabled us to monitor isoform-specific expression of 34 genes during development, to identify the pseudogene Cyp9f3Ψ as a protein-coding gene, and to obtain evidence of 268 small proteins. Moreover, the comparison with available transcriptomic data uncovered examples of poor correlation between mRNA and protein, underscoring the importance of proteomics to study developmental progression. Data integration of our embryogenesis proteome with tissue-specific data revealed spatial and temporal information for further functional studies of yet uncharacterized proteins. Overall, our high resolution proteomes provide a powerful resource and can be explored in detail in our interactive web interface. PMID:28381612

Top-Down Quantitative Proteomics Identified Phosphorylation of Cardiac Troponin I as a Candidate Biomarker for Chronic Heart Failure

PubMed Central

Zhang, Jiang; Guy, Moltu J.; Norman, Holly S.; Chen, Yi-Chen; Xu, Qingge; Dong, Xintong; Guner, Huseyin; Wang, Sijian; Kohmoto, Takushi; Young, Ken H.; Moss, Richard L.; Ge, Ying

2011-01-01

The rapid increase in the prevalence of chronic heart failure (CHF) worldwide underscores an urgent need to identify biomarkers for the early detection of CHF. Post-translational modifications (PTMs) are associated with many critical signaling events during disease progression and thus offer a plethora of candidate biomarkers. We have employed top-down quantitative proteomics methodology for comprehensive assessment of PTMs in whole proteins extracted from normal and diseased tissues. We have systematically analyzed thirty-six clinical human heart tissue samples and identified phosphorylation of cardiac troponin I (cTnI) as a candidate biomarker for CHF. The relative percentages of the total phosphorylated cTnI forms over the entire cTnI populations (%Ptotal) were 56.4±3.5%, 36.9±1.6%, 6.1±2.4%, and 1.0±0.6% for postmortem hearts with normal cardiac function (n=7), early-stage of mild hypertrophy (n=5), severe hypertrophy/dilation (n=4), and end-stage CHF (n=6), respectively. In fresh transplant samples, the %Ptotal of cTnI from non-failing donor (n=4), and end-stage failing hearts (n=10) were 49.5±5.9% and 18.8±2.9%, respectively. Top-down MS with electron capture dissociation unequivocally localized the altered phosphorylation sites to Ser22/23 and determined the order of phosphorylation/dephosphorylation. This study represents the first clinical application of top-down MS-based quantitative proteomics for biomarker discovery from tissues, highlighting the potential of PTM as disease biomarkers. PMID:21751783

A DNA methylation fingerprint of 1628 human samples

PubMed Central

Fernandez, Agustin F.; Assenov, Yassen; Martin-Subero, Jose Ignacio; Balint, Balazs; Siebert, Reiner; Taniguchi, Hiroaki; Yamamoto, Hiroyuki; Hidalgo, Manuel; Tan, Aik-Choon; Galm, Oliver; Ferrer, Isidre; Sanchez-Cespedes, Montse; Villanueva, Alberto; Carmona, Javier; Sanchez-Mut, Jose V.; Berdasco, Maria; Moreno, Victor; Capella, Gabriel; Monk, David; Ballestar, Esteban; Ropero, Santiago; Martinez, Ramon; Sanchez-Carbayo, Marta; Prosper, Felipe; Agirre, Xabier; Fraga, Mario F.; Graña, Osvaldo; Perez-Jurado, Luis; Mora, Jaume; Puig, Susana; Prat, Jaime; Badimon, Lina; Puca, Annibale A.; Meltzer, Stephen J.; Lengauer, Thomas; Bridgewater, John; Bock, Christoph; Esteller, Manel

2012-01-01

Most of the studies characterizing DNA methylation patterns have been restricted to particular genomic loci in a limited number of human samples and pathological conditions. Herein, we present a compromise between an extremely comprehensive study of a human sample population with an intermediate level of resolution of CpGs at the genomic level. We obtained a DNA methylation fingerprint of 1628 human samples in which we interrogated 1505 CpG sites. The DNA methylation patterns revealed show this epigenetic mark to be critical in tissue-type definition and stemness, particularly around transcription start sites that are not within a CpG island. For disease, the generated DNA methylation fingerprints show that, during tumorigenesis, human cancer cells underwent a progressive gain of promoter CpG-island hypermethylation and a loss of CpG methylation in non-CpG-island promoters. Although transformed cells are those in which DNA methylation disruption is more obvious, we observed that other common human diseases, such as neurological and autoimmune disorders, had their own distinct DNA methylation profiles. Most importantly, we provide proof of principle that the DNA methylation fingerprints obtained might be useful for translational purposes by showing that we are able to identify the tumor type origin of cancers of unknown primary origin (CUPs). Thus, the DNA methylation patterns identified across the largest spectrum of samples, tissues, and diseases reported to date constitute a baseline for developing higher-resolution DNA methylation maps and provide important clues concerning the contribution of CpG methylation to tissue identity and its changes in the most prevalent human diseases. PMID:21613409

Preliminary Evidence for the Validity of the New Test of Everyday Reading Comprehension

ERIC Educational Resources Information Center

Wheldall, Kevin; McMurtry, Sarah

2014-01-01

The Test of Everyday Reading Comprehension (TERC) has recently been presented as an addition to the armoury of tests available for assessing the skills of low-progress readers. While comparison data for students of different ages are presented together with evidence for high test reliability, there is, as yet, no published evidence for its…

Context Dependence of One-Question-per-Passage Measures of Reading Comprehension.

ERIC Educational Resources Information Center

Oaster, T. R. F.; And Others

This study hypothesized that items in the one-question-per-passage format would be less easily answered when administered without their associated contexts than conventional reading comprehension items. A total of 256 seventh and eighth grade students were administered both Forms 3A and 3B of the Sequential Tests of Educational Progress (STEP 11).…

Indian Health Service: A Comprehensive Health Care Program for American Indians and Alaska Natives.

ERIC Educational Resources Information Center

Indian Health Service (PHS/HSA), Rockville, MD.

Comprehensive health care (preventive, curative, rehabilitative, and environmental) for more than 930,000 eligible American Indians and Alaska Natives is the responsibility of the Indian Health Service (IHS). Since 1955, this agency of the U.S. Public Health Service has made notable progress in raising the health status of Indians and Alaska…

Word Knowledge and Comprehension Effects of an Academic Vocabulary Intervention for Middle School Students

ERIC Educational Resources Information Center

McKeown, Margaret G.; Crosson, Amy C.; Moore, Debra W.; Beck, Isabel L.

2018-01-01

This article presents findings from an intervention across sixth and seventh grades to teach academic words to middle school students. The goals included investigating a progression of outcomes from word knowledge to comprehension and investigating the processes students use in establishing word meaning. Participants in Year 1 were two sixth-grade…

Beyond Grand Rounds: A Comprehensive and Sequential Intervention to Improve Identification of Delirium

ERIC Educational Resources Information Center

Ramaswamy, Ravishankar; Dix, Edward F.; Drew, Janet E.; Diamond, James J.; Inouye, Sharon K.; Roehl, Barbara J. O.

2011-01-01

Purpose of the Study: Delirium is a widespread concern for hospitalized seniors, yet is often unrecognized. A comprehensive and sequential intervention (CSI) aiming to effect change in clinician behavior by improving knowledge about delirium was tested. Design and Methods: A 2-day CSI program that consisted of progressive 4-part didactic series,…

Vascularisation to improve translational potential of tissue engineering systems for cardiac repair.

PubMed

Dilley, Rodney J; Morrison, Wayne A

2014-11-01

Cardiac tissue engineering is developing as an alternative approach to heart transplantation for treating heart failure. Shortage of organ donors and complications arising after orthotopic transplant remain major challenges to the modern field of heart transplantation. Engineering functional myocardium de novo requires an abundant source of cardiomyocytes, a biocompatible scaffold material and a functional vasculature to sustain the high metabolism of the construct. Progress has been made on several fronts, with cardiac cell biology, stem cells and biomaterials research particularly promising for cardiac tissue engineering, however currently employed strategies for vascularisation have lagged behind and limit the volume of tissue formed. Over ten years we have developed an in vivo tissue engineering model to construct vascularised tissue from various cell and tissue sources, including cardiac tissue. In this article we review the progress made with this approach and others, together with their potential to support a volume of engineered tissue for cardiac tissue engineering where contractile mass impacts directly on functional outcomes in translation to the clinic. It is clear that a scaled-up cardiac tissue engineering solution required for clinical treatment of heart failure will include a robust vascular supply for successful translation. This article is part of a directed issue entitled: Regenerative Medicine: the challenge of translation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Applications of condensed matter understanding to medical tissues and disease progression: Elemental analysis and structural integrity of tissue scaffolds

NASA Astrophysics Data System (ADS)

Bradley, D. A.; Farquharson, M. J.; Gundogdu, O.; Al-Ebraheem, Alia; Che Ismail, Elna; Kaabar, W.; Bunk, O.; Pfeiffer, F.; Falkenberg, G.; Bailey, M.

2010-02-01

The investigations reported herein link tissue structure and elemental presence with issues of environmental health and disease, exemplified by uptake and storage of potentially toxic elements in the body, the osteoarthritic condition and malignancy in the breast and other soft tissues. Focus is placed on application of state-of-the-art ionizing radiation techniques, including, micro-synchrotron X-ray fluorescence (μ-SXRF) and particle-induced X-ray emission/Rutherford backscattering mapping (μ-PIXE/RBS), coherent small-angle X-ray scattering (cSAXS) and X-ray phase-contrast imaging, providing information on elemental make-up, the large-scale organisation of collagen and anatomical features of moderate and low atomic number media. For the particular situations under investigation, use of such facilities is allowing information to be obtained at an unprecedented level of detail, yielding new understanding of the affected tissues and the progression of disease.

The Magnitude of a Community's Health Needs and Nonprofit Hospitals' Progress in Meeting Those Needs: Are We Faced With a Paradox?

PubMed

Singh, Simone R; Cramer, Geri R; Young, Gary J

Although most nonprofit hospitals are required to conduct periodic community health needs assessments (CHNAs), such assessments arguably are most critical for communities with substantial health needs. The objective of this study was to describe differences in progress in conducting CHNAs between hospitals located in communities with the greatest compared with the fewest health needs. We used data on CHNA activity from the 2013 tax filings of 1331 US hospitals combined with data on community health needs from the County Health Rankings. We used bivariate and multivariate analyses to examine differences in hospitals' progress in implementing comprehensive CHNAs using 4 activities: (1) strategies to address identified needs, (2) participation in developing community-wide plans, (3) including CHNA into a hospital's operational plan, and (4) developing a budget to address identified needs. We compared progress in communities with the greatest and the fewest health needs using a comprehensive indicator comprising a community's socioeconomic factors, health behaviors, access to medical care, and physical environment. In 2013, nonprofit hospitals serving communities with the greatest health needs conducted an average of 2.5 of the 4 CHNA activities, whereas hospitals serving communities with the fewest health needs conducted an average of 2.7 activities. Multivariate analysis, however, showed a negative but not significant relationship between the magnitude of a community's health needs and a hospital's progress in implementing comprehensive CHNAs. Hospitals serving communities with the greatest health needs face high demand for free and reduced-cost care, which may limit their ability to invest more of their community benefit dollars in initiatives aimed at improving the health of the community.

Parry-Romberg syndrome (progressive hemifacial atrophy) with spasmodic dysphonia--a rare association.

PubMed

Mugundhan, K; Selvakumar, C J; Gunasekaran, K; Thiruvarutchelvan, K; Sivakumar, S; Anguraj, M; Arun, S

2014-04-01

Parry-Romberg syndrome is a rare clinical entity characterised by progressive hemifacial atrophy with appearance of 'saber'. Various neurological and otorhinolaryngological disorders are associated with this syndrome. The association of Parry -Romberg syndrome with Spasmodic dysphonia has rarely been reported. A 37 year old female presented with progressive atrophy of tissues of left side of face for 10 years and change in voice for 1 year. On examination, wasting and atrophy of tissues including tongue was noted on left side of the face. ENT examination revealed adductor spasmodic dysphonia. We report the rare association of Parry -Romberg syndrome with spasmodic dysphonia.

Recent progress in tissue optical clearing for spectroscopic application

NASA Astrophysics Data System (ADS)

Sdobnov, A. Yu.; Darvin, M. E.; Genina, E. A.; Bashkatov, A. N.; Lademann, J.; Tuchin, V. V.

2018-05-01

This paper aims to review recent progress in optical clearing of the skin and over naturally turbid biological tissues and blood using this technique in vivo and in vitro with multiphoton microscopy, confocal Raman microscopy, confocal microscopy, NIR spectroscopy, optical coherence tomography, and laser speckle contrast imaging. Basic principles of the technique, its safety, advantages and limitations are discussed. The application of optical clearing agent on a tissue allows for controlling the optical properties of tissue. Optical clearing-induced reduction of tissue scattering significantly facilitates the observation of deep-located tissue regions, at the same time improving the resolution and image contrast for a variety of optical imaging methods suitable for clinical applications, such as diagnostics and laser treatment of skin diseases, mucosal tumor imaging, laser disruption of pathological abnormalities, etc. Structural images of different skin layers obtained ex vivo for porcine ear skin samples at application of Omnipaque™ and glycerol solutions during 60 min. Red color corresponds to TPEAF signal channel. Green color corresponds to SHG signal channel.

Tissue response to silicone rubber when used as a root canal filling.

PubMed

Kasman, F G; Goldman, M

1977-04-01

To test the tissue compatibility of silicone rubber when it is used as a root canal filler, excess material was intentionally forced into the apical tissues in primates. The tissue response was one of general acceptance, with the usual response being fibrotic encapsulation. A low degree of inflammation was noted. Further studies are in progress.

Education for Wholeness in an Age of Global Citizenship: Staying with the Problem of Value(s)

ERIC Educational Resources Information Center

O'Shea, Andrew

2013-01-01

Education for wholeness continues to remain a contentious issue within a liberal and progressively democratic culture. McLaughlin's work can help us conceptualise wholeness as it has been understood in traditional and progressive education, what he describes as "wholeness as comprehensiveness" and "wholeness as integration".…

Where the Girls Are: The Facts about Gender Equity in Education

ERIC Educational Resources Information Center

Corbett, Christianne; Hill, Catherine; St. Rose, Andresse

2008-01-01

This report presents a comprehensive look at girls' educational achievement during the past 35 years, paying special attention to the relationship between girls' and boys' progress. Analyses of results from national standardized tests, such as the National Assessment of Educational Progress (NAEP) and the SAT and ACT college entrance examinations,…

The National Education Goals Report. Volume One: National Data.

ERIC Educational Resources Information Center

National Education Goals Panel, Washington, DC.

The "1994 National Education Goals Report" consists of three documents, a central report focusing on core indicators, a volume of state data, and this volume of national data about the educational progress the nation and states are making. This volume contains comprehensive sets of measures to describe national progress toward the eight…

Psycholinguistic Correlates of Progress in Literature of Students of Russian Vocational Training School

ERIC Educational Resources Information Center

Nuriakhmetov, Aidar

2012-01-01

The article describes psycholinguistic correlates of progress in literature, discovered on the basis of correlation analysis of grades, and results of several psychological and psycholinguistic tests were taken in the context of comprehensive psycholinguistic research based on one of Russian vocational training schools. Analysis revealed a list of…

Educational Progress Indicator (E.P.I.): Synthetic Indicator for Monitoring Education. Contribution to Education for All.

ERIC Educational Resources Information Center

Camara, Boubacar

This publication complements the "Education for All" program and is intended to provide a comprehensive and operational indicator for monitoring education. As a synthetic tool, the Educational Progress Indicator (EPI) facilitates the analytical assessment and projection work of educational planners, managers, actors, and policymakers. The EPI…

The Time Course of Neurolinguistic and Neuropsychological Symptoms in Three Cases of Logopenic Primary Progressive Aphasia

ERIC Educational Resources Information Center

Etcheverry, Louise; Seidel, Barbara; Grande, Marion; Schulte, Stephanie; Pieperhoff, Peter; Sudmeyer, Martin; Minnerop, Martina; Binkofski, Ferdinand; Huber, Walter; Grodzinsky, Yosef; Amunts, Katrin; Heim, Stefan

2012-01-01

Primary progressive aphasia (PPA) is a rare clinical dementia syndrome affecting predominantly language abilities. Word-finding difficulties and comprehension deficits despite relatively preserved cognitive functions are characteristic symptoms during the first two years, and distinguish PPA from other dementia types like Alzheimer's disease.…

Training and Generalization Effects of a Reading Comprehension Learning Strategy on Computer and Paper-Pencil Assessments

ERIC Educational Resources Information Center

Worrell, Jamie; Duffy, Mary Lou; Brady, Michael P.; Dukes, Charles; Gonzalez-DeHass, Alyssa

2016-01-01

Many schools use computer-based testing to measure students' progress for end-of-the-year and statewide assessments. There is little research to support whether computer-based testing accurately reflects student progress, particularly among students with learning, performance, and generalization difficulties. This article summarizes an…

A Discrepancy in Comprehension and Production in Early Language Development in ASD: Is it Clinically Relevant?

PubMed

Davidson, Meghan M; Ellis Weismer, Susan

2017-07-01

This study examined the extent to which a discrepant comprehension-production profile (i.e., relatively more delayed comprehension than production) is characteristic of the early language phenotype in autism spectrum disorders (ASD) and tracked the developmental progression of the profile. Our findings indicated that a discrepant comprehension-production profile distinguished toddlers (30 months) with ASD from late talkers without ASD (91% sensitivity, 100% specificity) in groups that were comparable on expressive language, age, and socioeconomic status. Longitudinal data for children with ASD revealed that the discrepant profile steadily decreased from 30 to 44 months until there was no significant comprehension-production difference at 66 months. In conclusion, results suggest that lower comprehension than production may be an age-specific marker of toddlers with ASD.

Why does it matter how we regulate the use of human body parts?

PubMed

Goold, Imogen

2014-01-01

Human tissue and body parts have been used in one way or another for millennia. They have been preserved and displayed, both in museums and public shows. Real human hair is used for wigs, while some artists even use human tissue in their works. Blood, bone marrow, whole organs and a host of other structures and human substances are all transplanted into living persons to treat illness. New life can be created from gametes through in vitro fertilisation (IVF), while the creation of cell lines keeps tissue alive indefinitely. These uses create significant challenges for the legal system in the UK. The major challenge for the law is to balance the competing demands of those groups who have vested interests in human tissue-researchers, medical practitioners, patients, families, the community and the police, among many others. It must provide sufficient control to users of tissue, but also take account of the fact that our bodies hold psychological importance for us while we live and, after we die, for those we leave behind. To some degree the law has been successful, but we still lack a comprehensive, coherent approach to the regulation of human tissue. Partially as a reaction to this lack of a comprehensive approach, some commentators have turned to applying the concept of property to human tissue means to achieve regulatory outcomes they support.

A Comprehensive Specimen-Specific Multiscale Data Set for Anatomical and Mechanical Characterization of the Tibiofemoral Joint

PubMed Central

Chokhandre, Snehal; Colbrunn, Robb; Bennetts, Craig; Erdemir, Ahmet

2015-01-01

Understanding of tibiofemoral joint mechanics at multiple spatial scales is essential for developing effective preventive measures and treatments for both pathology and injury management. Currently, there is a distinct lack of specimen-specific biomechanical data at multiple spatial scales, e.g., joint, tissue, and cell scales. Comprehensive multiscale data may improve the understanding of the relationship between biomechanical and anatomical markers across various scales. Furthermore, specimen-specific multiscale data for the tibiofemoral joint may assist development and validation of specimen-specific computational models that may be useful for more thorough analyses of the biomechanical behavior of the joint. This study describes an aggregation of procedures for acquisition of multiscale anatomical and biomechanical data for the tibiofemoral joint. Magnetic resonance imaging was used to acquire anatomical morphology at the joint scale. A robotic testing system was used to quantify joint level biomechanical response under various loading scenarios. Tissue level material properties were obtained from the same specimen for the femoral and tibial articular cartilage, medial and lateral menisci, anterior and posterior cruciate ligaments, and medial and lateral collateral ligaments. Histology data were also obtained for all tissue types to measure specimen-specific cell scale information, e.g., cellular distribution. This study is the first of its kind to establish a comprehensive multiscale data set for a musculoskeletal joint and the presented data collection approach can be used as a general template to guide acquisition of specimen-specific comprehensive multiscale data for musculoskeletal joints. PMID:26381404

Comprehensive gene expression analysis of canine invasive urothelial bladder carcinoma by RNA-Seq.

PubMed

Maeda, Shingo; Tomiyasu, Hirotaka; Tsuboi, Masaya; Inoue, Akiko; Ishihara, Genki; Uchikai, Takao; Chambers, James K; Uchida, Kazuyuki; Yonezawa, Tomohiro; Matsuki, Naoaki

2018-04-27

Invasive urothelial carcinoma (iUC) is a major cause of death in humans, and approximately 165,000 individuals succumb to this cancer annually worldwide. Comparative oncology using relevant animal models is necessary to improve our understanding of progression, diagnosis, and treatment of iUC. Companion canines are a preferred animal model of iUC due to spontaneous tumor development and similarity to human disease in terms of histopathology, metastatic behavior, and treatment response. However, the comprehensive molecular characterization of canine iUC is not well documented. In this study, we performed transcriptome analysis of tissue samples from canine iUC and normal bladders using an RNA sequencing (RNA-Seq) approach to identify key molecular pathways in canine iUC. Total RNA was extracted from bladder tissues of 11 dogs with iUC and five healthy dogs, and RNA-Seq was conducted. Ingenuity Pathway Analysis (IPA) was used to assign differentially expressed genes to known upstream regulators and functional networks. Differential gene expression analysis of the RNA-Seq data revealed 2531 differentially expressed genes, comprising 1007 upregulated and 1524 downregulated genes, in canine iUC. IPA revealed that the most activated upstream regulator was PTGER2 (encoding the prostaglandin E 2 receptor EP2), which is consistent with the therapeutic efficiency of cyclooxygenase inhibitors in canine iUC. Similar to human iUC, canine iUC exhibited upregulated ERBB2 and downregulated TP53 pathways. Biological functions associated with cancer, cell proliferation, and leukocyte migration were predicted to be activated, while muscle functions were predicted to be inhibited, indicating muscle-invasive tumor property. Our data confirmed similarities in gene expression patterns between canine and human iUC and identified potential therapeutic targets (PTGER2, ERBB2, CCND1, Vegf, and EGFR), suggesting the value of naturally occurring canine iUC as a relevant animal model for human iUC.

A comprehensive glycome profiling of Huntington's disease transgenic mice.

PubMed

Gizaw, Solomon T; Koda, Toshiaki; Amano, Maho; Kamimura, Keiko; Ohashi, Tetsu; Hinou, Hiroshi; Nishimura, Shin-Ichiro

2015-09-01

Huntington's disease (HD) is an autosomal, dominantly inherited and progressive neurodegenerative disease, nosologically classified as the presence of intranuclear inclusion bodies and the loss of GABA-containing neurons in the neostriatum and subsequently in the cerebellar cortex. Abnormal processing of neuronal proteins can result in the misfolding of proteins and altered post-translational modification of newly synthesized proteins. Total glycomics, namely, N-glycomics, O-glycomics, and glycosphingolipidomics (GSL-omics) of HD transgenic mice would be a hallmark for central nervous system disorders in order to discover disease specific biomarkers. Glycoblotting method, a high throughput glycomic protocol, and matrix-assisted laser desorption ionization-time of flight/mass spectrometry (MALDI-TOF/MS) were used to study the total glycome expression levels in the brain tissue (3 mice of each sex) and sera (5 mice of each sex) of HD transgenic and control mice. All experiments were performed twice and differences in the expression levels of major glycoforms were compared between HD transgenic and control mice. We estimated the structure and expression levels of 87 and 58N-glycans in brain tissue and sera, respectively, of HD transgenic and control mice. The present results clearly indicated that the brain glycome and their expression levels are significantly gender specific when compared with those of other tissues and serum. Core-fucosylated and bisecting-GlcNAc types of N-glycans were found in increased levels in the brain tissue HD transgenic mice. Accordingly, core-fucosylated and sialic acid (particularly N-glycolylneuraminic acid, NeuGc) for biantennary type glycans were found in increased amounts in the sera of HD transgenic mice compared to that of control mice. Core 3 type O-glycans were found in increased levels in male and in decreased levels in both the striatum and cortexes of female HD transgenic mice. Furthermore, serum levels of core 1 type O-glycans decreased and were undetected for core 2 type O-glycans for HD transgenic mice. In glycosphingolipids, GD1a in brain tissue and GM2-NeuGc serum levels were found to have increased and decreased, respectively, in HD transgenic mice compared to those of the control group mice. Total glycome expression levels are significantly different between HD transgenic and control group mice. Glycoblotting combined with MALDI-TOF/MS total glycomics warrants a comprehensive, effective, novel and versatile technique for qualitative and quantitative analysis of total glycome expression levels. Furthermore, glycome-focused studies of both environmentally and genetically rooted neurodegenerative diseases are promising candidates for the discovery of potential disease glyco-biomarkers in the post-genome era. Copyright © 2015 Elsevier B.V. All rights reserved.

Toll-Like Receptor and Accessory Molecule mRNA Expression in Humans and Mice as Well as in Murine Autoimmunity, Transient Inflammation, and Progressive Fibrosis

PubMed Central

Ramaiah, Santhosh Kumar Vankayala; Günthner, Roman; Lech, Maciej; Anders, Hans-Joachim

2013-01-01

The cell type-, organ-, and species-specific expression of the Toll-like receptors (TLRs) are well described, but little is known about the respective expression profiles of their accessory molecules. We therefore determined the mRNA expression levels of LBP, MD2, CD36, CD14, granulin, HMGB1, LL37, GRP94, UNC93b1, TRIL, PRAT4A, AP3B1, AEP and the respective TLRs in human and mouse solid organs. Humans and mice displayed significant differences between their respective mRNA expression patterns of these factors. In addition, the expression profiles in transient tissue inflammation upon renal ischemia-reperfusion injury, in spleens and kidneys from mice with lupus-like systemic autoimmunity, and in progressive tissue fibrosis upon unilateral ureteral obstruction were studied. Several TLR co-factors were specifically regulated during the different phases of these disease entities, suggesting a functional involvement in the disease process. Thus, the organ- and species-specific expression patterns need to be considered in the design and interpretation of studies related to TLR-mediated innate immunity, which seems to be involved in the tissue injury phase, in the phase of tissue regeneration, and in progressive tissue remodelling. PMID:23803655

Gas gangrene (image)

MedlinePlus

Gas gangrene is a severe form of gangrene (tissue death) caused by the bacterium Clostridium perfringens. It generally ... causing painful swelling and destruction of involved tissue. Gas gangrene is rapidly progressive and often fatal.

Oxidative Damage in Parkinson’s Disease

DTIC Science & Technology

2005-01-01

inhibitors of MMPs, TIMP-1 and TIMP-2 in postmortem brain tissue of progressive supranuclear palsy . J Neurol Sci 2004; 218:39-45. Martinat C, Shendelman S...inhibitors of MMPs, TIMP-1 and TIMP-2 in postmortem brain tissue of progressive supranuclear palsy . J Neurol Sci 2004; 218:39-45. Martinat C...excess can have serious neurologi- effects at the higher dosages needed to overcome the In Viva Iron Chelation Prevents MPTP Toxicity 905 A 0 20 in

Improved mathematical and computational tools for modeling photon propagation in tissue

NASA Astrophysics Data System (ADS)

Calabro, Katherine Weaver

Light interacts with biological tissue through two predominant mechanisms: scattering and absorption, which are sensitive to the size and density of cellular organelles, and to biochemical composition (ex. hemoglobin), respectively. During the progression of disease, tissues undergo a predictable set of changes in cell morphology and vascularization, which directly affect their scattering and absorption properties. Hence, quantification of these optical property differences can be used to identify the physiological biomarkers of disease with interest often focused on cancer. Diffuse reflectance spectroscopy is a diagnostic tool, wherein broadband visible light is transmitted through a fiber optic probe into a turbid medium, and after propagating through the sample, a fraction of the light is collected at the surface as reflectance. The measured reflectance spectrum can be analyzed with appropriate mathematical models to extract the optical properties of the tissue, and from these, a set of physiological properties. A number of models have been developed for this purpose using a variety of approaches -- from diffusion theory, to computational simulations, and empirical observations. However, these models are generally limited to narrow ranges of tissue and probe geometries. In this thesis, reflectance models were developed for a much wider range of measurement parameters, and influences such as the scattering phase function and probe design were investigated rigorously for the first time. The results provide a comprehensive understanding of the factors that influence reflectance, with novel insights that, in some cases, challenge current assumptions in the field. An improved Monte Carlo simulation program, designed to run on a graphics processing unit (GPU), was built to simulate the data used in the development of the reflectance models. Rigorous error analysis was performed to identify how inaccuracies in modeling assumptions can be expected to affect the accuracy of extracted optical property values from experimentally-acquired reflectance spectra. From this analysis, probe geometries that offer the best robustness against error in estimation of physiological properties from tissue, are presented. Finally, several in vivo studies demonstrating the use of reflectance spectroscopy for both research and clinical applications are presented.

Predicted Hematologic and Plasma Volume Responses Following Rapid Ascent to Progressive Altitudes

DTIC Science & Technology

2014-06-01

of these changes, and define baseline demographics and physiologic descriptors that are important in predicting these changes. The overall impact of... physiologic descriptors that are important in predicting these changes. Using general linear mixed models and a comprehensive relational database...accomplished using a comprehensive relational database containing individual ascent profiles, demographics, and physiologic subject descriptors as well as

Student Monitoring through Performance Matters and the Florida Comprehensive Assessment Exam: A Regression Analysis of Student Reading Achievement

ERIC Educational Resources Information Center

Cassidy-Floyd, Juliet

2017-01-01

Florida, from 1971 to 2014 has used the Florida Comprehensive Assessment Test (FCAT) as a yearly accountability tool throughout the education system in the state (Bureau of K-12 Assessment, 2005). Schools use their own assessments to determine if students are making progress throughout the year. In one school district within Florida, Performance…

Report of the Comprehensive Study of the Department of Defense Dependents Schools.

ERIC Educational Resources Information Center

Bartell, Ted; And Others

As part of the 1978 amendments to the Elementary and Secondary Education Act of 1965, a comprehensive study of the Department of Defense Dependents Schools (DoDDS) was mandated by the 96th Congress. The objectives were to determine the educational quality of DoDDS, the relation of student progress to expectations, the availability of resources and…

Eye movements during listening reveal spontaneous grammatical processing.

PubMed

Huette, Stephanie; Winter, Bodo; Matlock, Teenie; Ardell, David H; Spivey, Michael

2014-01-01

Recent research using eye-tracking typically relies on constrained visual contexts in particular goal-oriented contexts, viewing a small array of objects on a computer screen and performing some overt decision or identification. Eyetracking paradigms that use pictures as a measure of word or sentence comprehension are sometimes touted as ecologically invalid because pictures and explicit tasks are not always present during language comprehension. This study compared the comprehension of sentences with two different grammatical forms: the past progressive (e.g., was walking), which emphasizes the ongoing nature of actions, and the simple past (e.g., walked), which emphasizes the end-state of an action. The results showed that the distribution and timing of eye movements mirrors the underlying conceptual structure of this linguistic difference in the absence of any visual stimuli or task constraint: Fixations were shorter and saccades were more dispersed across the screen, as if thinking about more dynamic events when listening to the past progressive stories. Thus, eye movement data suggest that visual inputs or an explicit task are unnecessary to solicit analog representations of features such as movement, that could be a key perceptual component to grammatical comprehension.

Loss of pericyte smoothened activity in mice with genetic deficiency of leptin.

PubMed

Xie, Guanhua; Swiderska-Syn, Marzena; Jewell, Mark L; Machado, Mariana Verdelho; Michelotti, Gregory A; Premont, Richard T; Diehl, Anna Mae

2017-04-20

Obesity is associated with multiple diseases, but it is unclear how obesity promotes progressive tissue damage. Recovery from injury requires repair, an energy-expensive process that is coupled to energy availability at the cellular level. The satiety factor, leptin, is a key component of the sensor that matches cellular energy utilization to available energy supplies. Leptin deficiency signals energy depletion, whereas activating the Hedgehog pathway drives energy-consuming activities. Tissue repair is impaired in mice that are obese due to genetic leptin deficiency. Tissue repair is also blocked and obesity enhanced by inhibiting Hedgehog activity. We evaluated the hypothesis that loss of leptin silences Hedgehog signaling in pericytes, multipotent leptin-target cells that regulate a variety of responses that are often defective in obesity, including tissue repair and adipocyte differentiation. We found that pericytes from liver and white adipose tissue require leptin to maintain expression of the Hedgehog co-receptor, Smoothened, which controls the activities of Hedgehog-regulated Gli transcription factors that orchestrate gene expression programs that dictate pericyte fate. Smoothened suppression prevents liver pericytes from being reprogrammed into myofibroblasts, but stimulates adipose-derived pericytes to become white adipocytes. Progressive Hedgehog pathway decay promotes senescence in leptin-deficient liver pericytes, which, in turn, generate paracrine signals that cause neighboring hepatocytes to become fatty and less proliferative, enhancing vulnerability to liver damage. Leptin-responsive pericytes evaluate energy availability to inform tissue construction by modulating Hedgehog pathway activity and thus, are at the root of progressive obesity-related tissue pathology. Leptin deficiency inhibits Hedgehog signaling in pericytes to trigger a pericytopathy that promotes both adiposity and obesity-related tissue damage.

Preclinical Magnetic Resonance Imaging and Systems Biology in Cancer Research

PubMed Central

Albanese, Chris; Rodriguez, Olga C.; VanMeter, John; Fricke, Stanley T.; Rood, Brian R.; Lee, YiChien; Wang, Sean S.; Madhavan, Subha; Gusev, Yuriy; Petricoin, Emanuel F.; Wang, Yue

2014-01-01

Biologically accurate mouse models of human cancer have become important tools for the study of human disease. The anatomical location of various target organs, such as brain, pancreas, and prostate, makes determination of disease status difficult. Imaging modalities, such as magnetic resonance imaging, can greatly enhance diagnosis, and longitudinal imaging of tumor progression is an important source of experimental data. Even in models where the tumors arise in areas that permit visual determination of tumorigenesis, longitudinal anatomical and functional imaging can enhance the scope of studies by facilitating the assessment of biological alterations, (such as changes in angiogenesis, metabolism, cellular invasion) as well as tissue perfusion and diffusion. One of the challenges in preclinical imaging is the development of infrastructural platforms required for integrating in vivo imaging and therapeutic response data with ex vivo pathological and molecular data using a more systems-based multiscale modeling approach. Further challenges exist in integrating these data for computational modeling to better understand the pathobiology of cancer and to better affect its cure. We review the current applications of preclinical imaging and discuss the implications of applying functional imaging to visualize cancer progression and treatment. Finally, we provide new data from an ongoing preclinical drug study demonstrating how multiscale modeling can lead to a more comprehensive understanding of cancer biology and therapy. PMID:23219428

Integral pharmacological management of bone mineral disorders in chronic kidney disease (part I): from treatment of phosphate imbalance to control of PTH and prevention of progression of cardiovascular calcification.

PubMed

Bover, J; Ureña-Torres, P; Lloret, M J; Ruiz-García, C; DaSilva, I; Diaz-Encarnacion, M M; Mercado, C; Mateu, S; Fernández, E; Ballarin, J

2016-06-01

Chronic kidney disease-mineral and bone disorders (CKD-MBD), involving a triad of laboratory and bone abnormalities, and tissue calcifications, are associated with dismal hard-outcomes. In two comprehensive articles, we review contemporary and future pharmacological options for treatment of phosphate (P) imbalance (this part 1) and hyperparathyroidism (part 2), taking into account CKD-accelerated atheromatosis/atherosclerosis and/or cardiovascular calcification (CVC) processes. Improvements in CKD-MBD require an integral approach, addressing all three components of the CKD-MBD triad. Individualization of treatment with P-binders and combinations of anti-parathyroid agents may improve biochemical control with lower incidence of undesirable effects. Isolated biochemical parameters do not accurately reflect calcium or P load or bone activity and do not stratify high cardiovascular risk patients with CKD. Initial guidance is provided on reasonable therapeutic strategies which consider the presence of CVC. This part reflects that although there is not an absolute evidence, many studies point to the need to improve P imbalance while trying to, at least, avoid progression of CVC by restriction of Ca-based P-binders if economically feasible. The availability of new drugs (i.e. inhibitors of intestinal transporters), and studies including early CKD should ultimately lead to clearer and more cost/effective clinical targets for CKD-MBD.

A Comprehensive Repository of Normal and Tumor Human Breast Tissues and Cells

DTIC Science & Technology

1999-07-01

mother was reported to have had cancer of the uterine cervix at the age of 22. Both maternal grandparents had died of colon cancer in their sixties...1 mutation). The repository also includes breast epithelial and stromal cell strains derived from non cancerous breast tissue as well as peripheral...tissue banks. 14. SUBJECT TERMS Breast Cancer 17. SECURITY CLASSIFICATION OF REPORT Unclassified 18. SECURITY CLASSIFICATION OF THIS PAGE

Limited utility of tissue micro-arrays in detecting intra-tumoral heterogeneity in stem cell characteristics and tumor progression markers in breast cancer.

PubMed

Kündig, Pascale; Giesen, Charlotte; Jackson, Hartland; Bodenmiller, Bernd; Papassotirolopus, Bärbel; Freiberger, Sandra Nicole; Aquino, Catharine; Opitz, Lennart; Varga, Zsuzsanna

2018-05-08

Intra-tumoral heterogeneity has been recently addressed in different types of cancer, including breast cancer. A concept describing the origin of intra-tumoral heterogeneity is the cancer stem-cell hypothesis, proposing the existence of cancer stem cells that can self-renew limitlessly and therefore lead to tumor progression. Clonal evolution in accumulated single cell genomic alterations is a further possible explanation in carcinogenesis. In this study, we addressed the question whether intra-tumoral heterogeneity can be reliably detected in tissue-micro-arrays in breast cancer by comparing expression levels of conventional predictive/prognostic tumor markers, tumor progression markers and stem cell markers between central and peripheral tumor areas. We analyzed immunohistochemical expression and/or gene amplification status of conventional prognostic tumor markers (ER, PR, HER2, CK5/6), tumor progression markers (PTEN, PIK3CA, p53, Ki-67) and stem cell markers (mTOR, SOX2, SOX9, SOX10, SLUG, CD44, CD24, TWIST) in 372 tissue-micro-array samples from 72 breast cancer patients. Expression levels were compared between central and peripheral tumor tissue areas and were correlated to histopathological grading. 15 selected cases additionally underwent RNA sequencing for transcriptome analysis. No significant difference in any of the analyzed between central and peripheral tumor areas was seen with any of the analyzed methods/or results that showed difference. Except mTOR, PIK3CA and SOX9 (nuclear) protein expression, all markers correlated significantly (p < 0.05) with histopathological grading both in central and peripheral areas. Our results suggest that intra-tumoral heterogeneity of stem-cell and tumor-progression markers cannot be reliably addressed in tissue-micro-array samples in breast cancer. However, most markers correlated strongly with histopathological grading confirming prognostic information as expression profiles were independent on the site of the biopsy was taken.

Where the Girls Are: The Facts about Gender Equity in Education. Executive Summary

ERIC Educational Resources Information Center

Corbett, Christianne; Hill, Catherine; St. Rose, Andresse

2008-01-01

This document summarizes the full report, which presents a comprehensive look at girls' educational achievement during the past 35 years, paying special attention to the relationship between girls' and boys' progress. Analyses of results from national standardized tests such as the National Assessment of Educational Progress (NAEP) and the SAT and…

Domain Definition and Exercise Generation as Functions of the National Assessment of Educational Progress.

ERIC Educational Resources Information Center

Haertel, Edward H.

It has been recommended that the National Assessment of Educational Progress (NAEP) specify comprehensive exercise domains to measure academic achievement, and provide a national item pool to measure the objectives in these domains. These domain specifications and item pools would serve to satisfy the increasing demand for valid, accurate, and…

Results from the Fourth Mathematics Assessment of the National Assessment of Educational Progress.

ERIC Educational Resources Information Center

Lindquist, Mary Montgomery, Ed.

The National Assessment of Educational Progress (NAEP) completed its fourth mathematics assessment during the 1985-86 school year and finished the analyses of the results in 1988. This monograph, prepared by an interpretive team of the National Council of Teachers of Mathematics, represents a comprehensive discussion of the results of the fourth…

A Compendium of Tests, Scales and Questionnaires: The Practitioner's Guide to Measuring Outcomes after Acquired Brain Impairment

ERIC Educational Resources Information Center

Tate, Robyn L.

2010-01-01

This "Compendium" is a comprehensive reference manual containing an extensive selection of instruments developed to measure signs and symptoms commonly encountered in neurological conditions, both progressive and non-progressive. It provides a repository of established instruments, as well as newly-developed scales, and covers all aspects of the…

A Canine Audience: The Effect of Animal-Assisted Therapy on Reading Progress among Students Identified with Learning Disabilities

ERIC Educational Resources Information Center

Griess, Julie Omodio

2010-01-01

This study explored the use of animal-assisted therapy with students identified with a learning disability and limited reading success. Initially, reading progress was defined as the participants' comprehension rate obtained from an oral Informal Reading Inventory (IRI) passage. The nature of the Informal Reading Inventory requires the…

Loss of Word-Meaning with Spared Object Semantics in a Case of Mixed Primary Progressive Aphasia

ERIC Educational Resources Information Center

Knels, Christina; Danek, Adrian

2010-01-01

This article provides a detailed assessment of patient HT with a history of progressive language deterioration of approximately 6 years presenting now as a fluent jargon aphasic with severe impairment of both speech production and comprehension. Neuropsychological testing of non-verbal cognitive functions showed no impairment, leading to the…

Compartments, Customers, or Convergence?: Evolving Challenges to IT Progress

ERIC Educational Resources Information Center

Jackson, Gregory A.

2007-01-01

For most of the past decade, IT leaders in higher education felt on top of things. Challenges were usually comprehensible and addressable, doing reasonable things yielded reasonable results, and for the most part, IT was a substantial contributor to institutional progress. But these days, IT leaders rarely feel on top of things. Instead, some days…

Information Theoretical Analysis of a Bovine Gene Atlas Reveals Chromosomal Regions with Tissue Specific Gene Expression.

USDA-ARS?s Scientific Manuscript database

An essential step to understanding the genomic biology of any organism is to comprehensively survey its transcriptome. We present the Bovine Gene Atlas (BGA) a compendium of over 7.2 million unique 20 base Illumina DGE tags representing 100 tissue transcriptomes collected primarily from L1 Dominette...

A Digital Gene Expression-Based Bovine Gene Atlas Evaluating 92 Adult, Juvenile and Fetal Cattle Tissues

USDA-ARS?s Scientific Manuscript database

A comprehensive transcriptome survey, or “Gene Atlas,” provides information essential for a complete understanding of the genomic biology of an organism. Using a digital gene expression approach, we developed a Gene Atlas of RNA abundance in 92 adult, juvenile and fetal cattle tissues. The samples...

An atlas of bovine gene expression reveals novel distinctive tissue characteristics and evidence for improving genome annotation

USDA-ARS?s Scientific Manuscript database

Background A comprehensive transcriptome survey, or gene atlas, provides information essential for a complete understanding of the genomic biology of an organism. We present an atlas of RNA abundance for 92 adult, juvenile and fetal cattle tissues and three cattle cell lines. Results The Bovine Gene...

Critical Role for Monocytes/Macrophages in Rapid Progression to AIDS in Pediatric Simian Immunodeficiency Virus-Infected Rhesus Macaques.

PubMed

Sugimoto, Chie; Merino, Kristen M; Hasegawa, Atsuhiko; Wang, Xiaolei; Alvarez, Xavier A; Wakao, Hiroshi; Mori, Kazuyasu; Kim, Woong-Ki; Veazey, Ronald S; Didier, Elizabeth S; Kuroda, Marcelo J

2017-09-01

Infant humans and rhesus macaques infected with the human or simian immunodeficiency virus (HIV or SIV), respectively, express higher viral loads and progress more rapidly to AIDS than infected adults. Activated memory CD4 + T cells in intestinal tissues are major primary target cells for SIV/HIV infection, and massive depletion of these cells is considered a major cause of immunodeficiency. Monocytes and macrophages are important cells of innate immunity and also are targets of HIV/SIV infection. We reported previously that a high peripheral blood monocyte turnover rate was predictive for the onset of disease progression to AIDS in SIV-infected adult macaques. The purpose of this study was to determine if earlier or higher infection of monocytes/macrophages contributes to the more rapid progression to AIDS in infants. We observed that uninfected infant rhesus macaques exhibited higher physiologic baseline monocyte turnover than adults. Early after SIV infection, the monocyte turnover further increased, and it remained high during progression to AIDS. A high percentage of terminal deoxynucleotidyltransferase dUTP nick end label (TUNEL)-positive macrophages in the lymph nodes (LNs) and intestine corresponded with an increasing number of macrophages derived from circulating monocytes (bromodeoxyuridine positive [BrdU + ] CD163 + ), suggesting that the increased blood monocyte turnover was required to rapidly replenish destroyed tissue macrophages. Immunofluorescence analysis further demonstrated that macrophages were a significant portion of the virus-producing cells found in LNs, intestinal tissues, and lungs. The higher baseline monocyte turnover in infant macaques and subsequent macrophage damage by SIV infection may help explain the basis of more rapid disease progression to AIDS in infants. IMPORTANCE HIV infection progresses much more rapidly in pediatric cases than in adults; however, the mechanism for this difference is unclear. Using the rhesus macaque model, this work was performed to address why infants infected with SIV progress more quickly to AIDS than do adults. Earlier we reported that in adult rhesus macaques, increasing monocyte turnover reflected tissue macrophage damage by SIV and was predictive of terminal disease progression to AIDS. Here we report that uninfected infant rhesus macaques exhibited a higher physiological baseline monocyte turnover rate than adults. Furthermore, once infected with SIV, infants displayed further increased monocyte turnover that may have facilitated the accelerated progression to AIDS. These results support a role for monocytes and macrophages in the pathogenesis of SIV/HIV and begin to explain why infants are more prone to rapid disease progression. Copyright © 2017 American Society for Microbiology.

Critical Role for Monocytes/Macrophages in Rapid Progression to AIDS in Pediatric Simian Immunodeficiency Virus-Infected Rhesus Macaques

PubMed Central

Sugimoto, Chie; Merino, Kristen M.; Hasegawa, Atsuhiko; Wang, Xiaolei; Alvarez, Xavier A.; Wakao, Hiroshi; Kim, Woong-Ki; Veazey, Ronald S.; Didier, Elizabeth S.

2017-01-01

ABSTRACT Infant humans and rhesus macaques infected with the human or simian immunodeficiency virus (HIV or SIV), respectively, express higher viral loads and progress more rapidly to AIDS than infected adults. Activated memory CD4+ T cells in intestinal tissues are major primary target cells for SIV/HIV infection, and massive depletion of these cells is considered a major cause of immunodeficiency. Monocytes and macrophages are important cells of innate immunity and also are targets of HIV/SIV infection. We reported previously that a high peripheral blood monocyte turnover rate was predictive for the onset of disease progression to AIDS in SIV-infected adult macaques. The purpose of this study was to determine if earlier or higher infection of monocytes/macrophages contributes to the more rapid progression to AIDS in infants. We observed that uninfected infant rhesus macaques exhibited higher physiologic baseline monocyte turnover than adults. Early after SIV infection, the monocyte turnover further increased, and it remained high during progression to AIDS. A high percentage of terminal deoxynucleotidyltransferase dUTP nick end label (TUNEL)-positive macrophages in the lymph nodes (LNs) and intestine corresponded with an increasing number of macrophages derived from circulating monocytes (bromodeoxyuridine positive [BrdU+] CD163+), suggesting that the increased blood monocyte turnover was required to rapidly replenish destroyed tissue macrophages. Immunofluorescence analysis further demonstrated that macrophages were a significant portion of the virus-producing cells found in LNs, intestinal tissues, and lungs. The higher baseline monocyte turnover in infant macaques and subsequent macrophage damage by SIV infection may help explain the basis of more rapid disease progression to AIDS in infants. IMPORTANCE HIV infection progresses much more rapidly in pediatric cases than in adults; however, the mechanism for this difference is unclear. Using the rhesus macaque model, this work was performed to address why infants infected with SIV progress more quickly to AIDS than do adults. Earlier we reported that in adult rhesus macaques, increasing monocyte turnover reflected tissue macrophage damage by SIV and was predictive of terminal disease progression to AIDS. Here we report that uninfected infant rhesus macaques exhibited a higher physiological baseline monocyte turnover rate than adults. Furthermore, once infected with SIV, infants displayed further increased monocyte turnover that may have facilitated the accelerated progression to AIDS. These results support a role for monocytes and macrophages in the pathogenesis of SIV/HIV and begin to explain why infants are more prone to rapid disease progression. PMID:28566378

A comprehensive study on the fabrication and properties of biocomposites of poly(lactic acid)/ceramics for bone tissue engineering.

PubMed

Tajbakhsh, Saeid; Hajiali, Faezeh

2017-01-01

The fabrication of a suitable scaffold material is one of the major challenges for bone tissue engineering. Poly(lactic acid) (PLA) is one of the most favorable matrix materials in bone tissue engineering owing to its biocompatibility and biodegradability. However, PLA suffers from some shortcomings including low degradation rate, low cell adhesion caused by its hydrophobic property, and inflammatory reactions in vivo due to its degradation product, lactic acid. Therefore, the incorporation of bioactive reinforcements is considered as a powerful method to improve the properties of PLA. This review presents a comprehensive study on recent advances in the synthesis of PLA-based biocomposites containing ceramic reinforcements, including various methods of production and the evaluation of the scaffolds in terms of porosity, mechanical properties, in vitro and in vivo biocompatibility and bioactivity for bone tissue engineering applications. The production routes range from traditional approaches such as the use of porogens to provide porosity in the scaffolds to novel methods such as solid free-form techniques. Copyright © 2016 Elsevier B.V. All rights reserved.

Blood Poisoning: When to See a Doctor

MedlinePlus

... However, bacteremia and infection can potentially progress to sepsis and septic shock, serious illnesses that require prompt ... valves or other tissues, or progress to severe sepsis and septic shock, which may be life-threatening. ...

White grain mycetoma caused by Scedosporium apiospermum in North India: a case report.

PubMed

Gupta, Munesh Kumar; Banerjee, Tuhina; Kumar, Dhirendra; Rastogi, Amit; Tilak, Ragini

2013-12-01

Mycetoma is chronic granulomatous infection of skin and subcutaneous tissue caused by both bacteria and fungi. We report a case of mycetoma caused by Scedosporium apiospermum in the right foot of a 45-year-old farmer in north India. The patient had a history of trauma in the sole of the right foot followed by discharge of white granules along with proximal progression. Scedosporium apiospermum was identified based on colony characteristics and microscopic features on slide culture. Mycetoma is a progressive disease. Foot is commonly affected in persons who walk barefoot, especially in south India. Untreated mycetoma progress and involve the underlying fasciae and tissues along with bones often resulting in loss of limb. By prompt and reliable diagnosis with corresponding antimicrobial administration, we can prevent further progression and limb disability.

Potential Anticancer Properties of Osthol: A Comprehensive Mechanistic Review

PubMed Central

Shokoohinia, Yalda; Jafari, Fataneh; Mohammadi, Zeynab; Bazvandi, Leili; Hosseinzadeh, Leila; Chow, Nicholas; Bhattacharyya, Piyali; Farzaei, Mohammad Hosein; Farooqi, Ammad Ahmad; Nabavi, Seyed Mohammad; Bishayee, Anupam

2018-01-01

Cancer is caused by uncontrolled cell proliferation which has the potential to occur in different tissues and spread into surrounding and distant tissues. Despite the current advances in the field of anticancer agents, rapidly developing resistance against different chemotherapeutic drugs and significantly higher off-target effects cause millions of deaths every year. Osthol is a natural coumarin isolated from Apiaceaous plants which has demonstrated several pharmacological effects, such as antineoplastic, anti-inflammatory and antioxidant properties. We have attempted to summarize up-to-date information related to pharmacological effects and molecular mechanisms of osthol as a lead compound in managing malignancies. Electronic databases, including PubMed, Cochrane library, ScienceDirect and Scopus were searched for in vitro, in vivo and clinical studies on anticancer effects of osthol. Osthol exerts remarkable anticancer properties by suppressing cancer cell growth and induction of apoptosis. Osthol’s protective and therapeutic effects have been observed in different cancers, including ovarian, cervical, colon and prostate cancers as well as chronic myeloid leukemia, lung adenocarcinoma, glioma, hepatocellular, glioblastoma, renal and invasive mammary carcinoma. A large body of evidence demonstrates that osthol regulates apoptosis, proliferation and invasion in different types of malignant cells which are mediated by multiple signal transduction cascades. In this review, we set spotlights on various pathways which are targeted by osthol in different cancers to inhibit cancer development and progression. PMID:29301373

Non-viral gene activated matrices for mesenchymal stem cells based tissue engineering of bone and cartilage.

PubMed

Raisin, Sophie; Belamie, Emmanuel; Morille, Marie

2016-10-01

Recent regenerative medicine and tissue engineering strategies for bone and cartilage repair have led to fascinating progress of translation from basic research to clinical applications. In this context, the use of gene therapy is increasingly being considered as an important therapeutic modality and regenerative technique. Indeed, in the last 20 years, nucleic acids (plasmid DNA, interferent RNA) have emerged as credible alternative or complement to proteins, which exhibited major issues including short half-life, loss of bioactivity in pathologic environment leading to high dose requirement and therefore high production costs. The relevance of gene therapy strategies in combination with a scaffold, following a so-called "Gene-Activated Matrix (GAM)" approach, is to achieve a direct, local and sustained delivery of nucleic acids from a scaffold to ensure efficient and durable cell transfection. Among interesting cells sources, Mesenchymal Stem Cells (MSC) are promising for a rational use in gene/cell therapy with more than 1700 clinical trials approved during the last decade. The aim of the present review article is to provide a comprehensive overview of recent and ongoing work in non-viral genetic engineering of MSC combined with scaffolds. More specifically, we will show how this inductive strategy can be applied to orient stem cells fate for bone and cartilage repair. Copyright © 2016 Elsevier Ltd. All rights reserved.

tRNA modification profiles of the fast-proliferating cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, Chao; Niu, Leilei; Song, Wei

Despite the recent progress in RNA modification study, a comprehensive modification profile is still lacking for mammalian cells. Using a quantitative HPLC/MS/MS assay, we present here a study where RNA modifications are examined in term of the major RNA species. With paired slow- and fast-proliferating cell lines, distinct RNA modification profiles are first revealed for diverse RNA species. Compared to mRNAs, increased ribose and nucleobase modifications are shown for the highly-structured tRNAs and rRNAs, lending support to their contribution to the formation of high-order structures. This study also reveals a dynamic tRNA modification profile in the fast-proliferating cells. In additionmore » to cultured cells, this unique tRNA profile has been further confirmed with endometrial cancers and their adjacent normal tissues. Taken together, the results indicate that tRNA is a actively regulated RNA species in the fast-proliferating cancer cells, and suggest that they may play a more active role in biological process than expected. -- Highlights: •RNA modifications were first examined in term of the major RNA species. •A dynamic tRNA modifications was characterized for the fast-proliferating cells. •The unique tRNA profile was confirmed with endometrial cancers and their adjacent normal tissues. •tRNA was predicted as an actively regulated RNA species in the fast-proliferating cancer cells.« less

Connective tissue growth factor immunohistochemical expression is associated with gallbladder cancer progression.

PubMed

Garcia, Patricia; Leal, Pamela; Alvarez, Hector; Brebi, Priscilla; Ili, Carmen; Tapia, Oscar; Roa, Juan C

2013-02-01

Gallbladder cancer (GBC) is an aggressive neoplasia associated with late diagnosis, unsatisfactory treatment, and poor prognosis. Molecular mechanisms involved in GBC pathogenesis remain poorly understood. Connective tissue growth factor (CTGF) is thought to play a role in the pathologic processes and is overexpressed in several human cancers, including GBC. No information is available about CTGF expression in early stages of gallbladder carcinogenesis. Objective.- To evaluate the expression level of CTGF in benign and malignant lesions of gallbladder and its correlation with clinicopathologic features and GBC prognosis. Connective tissue growth factor protein was examined by immunohistochemistry on tissue microarrays containing tissue samples of chronic cholecystitis (n = 51), dysplasia (n = 15), and GBC (n = 169). The samples were scored according to intensity of staining as low/absent and high CTGF expressers. Statistical analysis was performed using the χ(2) test or Fisher exact probability test with a significance level of P < .05. Survival analysis was assessed by the Kaplan-Meier method and the log-rank test. Connective tissue growth factor expression showed a progressive increase from chronic cholecystitis to dysplasia and then to early and advanced carcinoma. Immunohistochemical expression (score ≥2) was significantly higher in advanced tumors, in comparison with chronic cholecystitis (P < .001) and dysplasia (P = .03). High levels of CTGF expression correlated with better survival (P = .04). Our results suggest a role for CTGF in GBC progression and a positive association with better prognosis. In addition, they underscore the importance of considering the involvement of inflammation on GBC development.

Use of Mesothelial Cells and Biological Matrices for Tissue Engineering of Simple Epithelium Surrogates.

PubMed

Lachaud, Christian Claude; Rodriguez-Campins, Berta; Hmadcha, Abdelkrim; Soria, Bernat

2015-01-01

Tissue-engineering technologies have progressed rapidly through last decades resulting in the manufacture of quite complex bioartificial tissues with potential use for human organ and tissue regeneration. The manufacture of avascular monolayered tissues such as simple squamous epithelia was initiated a few decades ago and is attracting increasing interest. Their relative morphostructural simplicity makes of their biomimetization a goal, which is currently accessible. The mesothelium is a simple squamous epithelium in nature and is the monolayered tissue lining the walls of large celomic cavities (peritoneal, pericardial, and pleural) and internal organs housed inside. Interestingly, mesothelial cells can be harvested in clinically relevant numbers from several anatomical sources and not less important, they also display high transdifferentiation capacities and are low immunogenic characteristics, which endow these cells with therapeutic interest. Their combination with a suitable scaffold (biocompatible, degradable, and non-immunogenic) may allow the manufacture of tailored serosal membranes biomimetics with potential spanning a wide range of therapeutic applications, principally for the regeneration of simple squamous-like epithelia such as the visceral and parietal mesothelium vascular endothelium and corneal endothelium among others. Herein, we review recent research progresses in mesothelial cells biology and their clinical sources. We make a particular emphasis on reviewing the different types of biological scaffolds suitable for the manufacture of serosal mesothelial membranes biomimetics. Finally, we also review progresses made in mesothelial cells-based therapeutic applications and propose some possible future directions.

Use of Mesothelial Cells and Biological Matrices for Tissue Engineering of Simple Epithelium Surrogates

PubMed Central

Lachaud, Christian Claude; Rodriguez-Campins, Berta; Hmadcha, Abdelkrim; Soria, Bernat

2015-01-01

Tissue-engineering technologies have progressed rapidly through last decades resulting in the manufacture of quite complex bioartificial tissues with potential use for human organ and tissue regeneration. The manufacture of avascular monolayered tissues such as simple squamous epithelia was initiated a few decades ago and is attracting increasing interest. Their relative morphostructural simplicity makes of their biomimetization a goal, which is currently accessible. The mesothelium is a simple squamous epithelium in nature and is the monolayered tissue lining the walls of large celomic cavities (peritoneal, pericardial, and pleural) and internal organs housed inside. Interestingly, mesothelial cells can be harvested in clinically relevant numbers from several anatomical sources and not less important, they also display high transdifferentiation capacities and are low immunogenic characteristics, which endow these cells with therapeutic interest. Their combination with a suitable scaffold (biocompatible, degradable, and non-immunogenic) may allow the manufacture of tailored serosal membranes biomimetics with potential spanning a wide range of therapeutic applications, principally for the regeneration of simple squamous-like epithelia such as the visceral and parietal mesothelium vascular endothelium and corneal endothelium among others. Herein, we review recent research progresses in mesothelial cells biology and their clinical sources. We make a particular emphasis on reviewing the different types of biological scaffolds suitable for the manufacture of serosal mesothelial membranes biomimetics. Finally, we also review progresses made in mesothelial cells-based therapeutic applications and propose some possible future directions. PMID:26347862

Inflammation Fuels Tumor Progress and Metastasis

PubMed Central

Liu, Jingyi; Lin, Pengnian Charles; Zhou, Binhua P.

2017-01-01

Inflammation is a beneficial response that can remove pathogens, repair injured tissue and restore homeostasis to damaged tissues and organs. However, increasing evidence indicate that chronic inflammation plays a pivotal role in tumor development, as well as progression, metastasis, and resistance to chemotherapy. We will review the current knowledge regarding the contribution of inflammation to epithelial mesenchymal transition. We will also provide some perspectives on the relationship between ER-stress signals and metabolism, and the role of these processes in the development of inflammation. PMID:26004407

Nasal erosion as an uncommon sign of child abuse.

PubMed

Culotta, Paige A; Isaac, Reena; Sarpong, Kwabena; Chandy, Binoy; Cruz, Andrea; Donaruma-Kwoh, Marcella

2018-05-01

While various forms of facial trauma, bruising, burns, and fractures are frequently seen in cases of child abuse, purposeful nasal erosion has rarely been identified as a form of abusive injury. Progressive destruction of nasal tissue in children provokes a wide differential diagnosis crossing multiple subspecialties: infectious, primary immunodeficiencies, inflammatory conditions, malignancy, and genetic disorders. Progressive nasal erosion also can be a manifestation of child abuse. The proposed mechanism is repetitive mechanical denudation of the soft tissue and cartilage resulting in chronic inflammation, bleeding, and ultimately destruction of the insulted tissue. We report 6 cases of child abuse manifesting as overt nasal destruction. Copyright © 2018 Elsevier B.V. All rights reserved.

Orchestrating liver development.

PubMed

Gordillo, Miriam; Evans, Todd; Gouon-Evans, Valerie

2015-06-15

The liver is a central regulator of metabolism, and liver failure thus constitutes a major health burden. Understanding how this complex organ develops during embryogenesis will yield insights into how liver regeneration can be promoted and how functional liver replacement tissue can be engineered. Recent studies of animal models have identified key signaling pathways and complex tissue interactions that progressively generate liver progenitor cells, differentiated lineages and functional tissues. In addition, progress in understanding how these cells interact, and how transcriptional and signaling programs precisely coordinate liver development, has begun to elucidate the molecular mechanisms underlying this complexity. Here, we review the lineage relationships, signaling pathways and transcriptional programs that orchestrate hepatogenesis. © 2015. Published by The Company of Biologists Ltd.

Monitoring/Imaging and Regenerative Agents for Enhancing Tissue Engineering Characterization and Therapies.

PubMed

Santiesteban, Daniela Y; Kubelick, Kelsey; Dhada, Kabir S; Dumani, Diego; Suggs, Laura; Emelianov, Stanislav

2016-03-01

The past three decades have seen numerous advances in tissue engineering and regenerative medicine (TERM) therapies. However, despite the successes there is still much to be done before TERM therapies become commonplace in clinic. One of the main obstacles is the lack of knowledge regarding complex tissue engineering processes. Imaging strategies, in conjunction with exogenous contrast agents, can aid in this endeavor by assessing in vivo therapeutic progress. The ability to uncover real-time treatment progress will help shed light on the complex tissue engineering processes and lead to development of improved, adaptive treatments. More importantly, the utilized exogenous contrast agents can double as therapeutic agents. Proper use of these Monitoring/Imaging and Regenerative Agents (MIRAs) can help increase TERM therapy successes and allow for clinical translation. While other fields have exploited similar particles for combining diagnostics and therapy, MIRA research is still in its beginning stages with much of the current research being focused on imaging or therapeutic applications, separately. Advancing MIRA research will have numerous impacts on achieving clinical translations of TERM therapies. Therefore, it is our goal to highlight current MIRA progress and suggest future research that can lead to effective TERM treatments.

Laser-induced autofluorescence-based objective evaluation of burn tissue repair in mice.

PubMed

Rathnakar, Bharath; Rao, Bola Sadashiva Satish; Prabhu, Vijendra; Chandra, Subhash; Mahato, Krishna Kishore

2018-05-01

Management of burn injuries are a growing concern, especially in determining the progression of healing. Several techniques are being practiced in clinics and have been considered all-time standard approaches to determine pre- and post-treatment outcomes of a healthy healing. However, these kinds of methods involve repeated biopsies and thereby hindering tissue repair. In view of this, our perspective was to develop a non-invasive tool in an attempt to provide a solution to determine the progression of healing, in vivo. Hence, the present study was designed to investigate the ability of laser-induced fluorescence (LIF) to monitor the variations in collagen intensity at various time points (0, 2, 6, 12, 18, 24, and 30 days) during burn tissue repair in mice, post low-power laser therapy (LPLT). The spectral findings demonstrated a significant change in collagen intensity as observed on day 24 (p < 0.05) and 30 (p < 0.01), when treated with LPLT (830 nm 3 J/cm 2 ) as compared to untreated control. From the observation, it was evident that the LIF could objectively monitor the progression of burn tissue repair in vivo.

Bioencapsulation technologies in tissue engineering

PubMed Central

Majewski, Rebecca L.; Zhang, Wujie; Ma, Xiaojun; Cui, Zhanfeng; Ren, Weiping; Markel, David C.

2017-01-01

Bioencapsulation technologies have played an important role in the developing successes of tissue engineering. Besides offering immunoisolation, they also show promise for cell/tissue banking and the directed differentiation of stem cells, by providing a unique microenvironment. This review describes bioencapsulation technologies and summarizes their recent progress in research into tissue engineering. The review concludes with a brief outlook regarding future research directions in this field. PMID:27716872

Gene Expression Profiling Reveals Novel Candidate Markers of Ovarian Carcinoma Intraperitoneal Metastasis.

PubMed

Elsnerova, Katerina; Bartakova, Alena; Tihlarik, Josef; Bouda, Jiri; Rob, Lukas; Skapa, Petr; Hruda, Martin; Gut, Ivan; Mohelnikova-Duchonova, Beatrice; Soucek, Pavel; Vaclavikova, Radka

2017-01-01

Epithelial ovarian cancer (EOC) has the highest mortality among gynecological carcinomas. The lack of specific markers for prognostic determination of EOC progression hinders the search for novel effective therapies. The aim of the present study was (i) to explore differences in expressions of ATP-binding cassette (ABC) and solute carrier (SLC) transporter genes, genes associated with drug metabolism and cell cycle regulation between control ovarian tissues (n = 14), primary EOCs (n = 44) and intraperitoneal metastases (n = 29); (ii) to investigate associations of gene expression levels with prognosis of patients with intraperitoneal metastases. In all tissue samples, transcript levels of the above target genes were assessed using quantitative real-time PCR. Gene expression levels were compared between particular tissue types and evaluated with regard to progression-free survival (PFS) and drug-resistance status of patients with metastases. Gene expression of ABCA7 significantly increased and that of ESR2 decreased in the order control ovarian tissues - primary EOCs - metastases. High expressions of ABCA2 / 8 / 9 / 10 , ABCB1 , ABCC9 , ABCG2 , ATP7A , SLC16A14 , and SOD3 genes were significantly associated with longer progression-free survival of patients. In intraperitoneal metastases, expression of all of these genes highly correlated and indicated prognostic profile. Transporters from the ABCA family, ABCG2, and ESR2 are involved mainly in lipid metabolism, membrane transport, and cell proliferation. These processes are thus probably the most important for EOC progression. Based on these results, we have proposed novel markers of ovarian carcinoma progression and metastatic spread which might be potentially useful as therapeutic targets. Their significance should be further explored on a larger independent set of patients.

Evaluation of new antibiotic cocktails against contaminating bacteria found in allograft tissues.

PubMed

Serafini, Agnese; Riello, Erika; Trojan, Diletta; Cogliati, Elisa; Palù, Giorgio; Manganelli, Riccardo; Paolin, Adolfo

2016-12-01

Contamination of retrieved tissues is a major problem for allograft safety. Consequently, tissue banks have implemented decontamination protocols to eliminate microorganisms from tissues. Despite the widespread adoption of these protocols, few comprehensive studies validating such methods have been published. In this manuscript we compare the bactericidal activity of different antibiotic cocktails at different temperatures against a panel of bacterial species frequently isolated in allograft tissues collected at the Treviso Tissue Bank Foundation, a reference organization of the Veneto Region in Italy that was instituted to select, recover, process, store and distribute human tissues. We were able to identify at least two different formulations capable of killing most of the bacteria during prolonged incubation at 4 °C.

Proteomic Analysis of Altered Extracellular Matrix Turnover in Bleomycin-induced Pulmonary Fibrosis

PubMed Central

Decaris, Martin L.; Gatmaitan, Michelle; FlorCruz, Simplicia; Luo, Flora; Li, Kelvin; Holmes, William E.; Hellerstein, Marc K.; Turner, Scott M.; Emson, Claire L.

2014-01-01

Fibrotic disease is characterized by the pathological accumulation of extracellular matrix (ECM) proteins. Surprisingly, very little is known about the synthesis and degradation rates of the many proteins and proteoglycans that constitute healthy or pathological extracellular matrix. A comprehensive understanding of altered ECM protein synthesis and degradation during the onset and progression of fibrotic disease would be immensely valuable. We have developed a dynamic proteomics platform that quantifies the fractional synthesis rates of large numbers of proteins via stable isotope labeling and LC/MS-based mass isotopomer analysis. Here, we present the first broad analysis of ECM protein kinetics during the onset of experimental pulmonary fibrosis. Mice were labeled with heavy water for up to 21 days following the induction of lung fibrosis with bleomycin. Lung tissue was subjected to sequential protein extraction to fractionate cellular, guanidine-soluble ECM proteins and residual insoluble ECM proteins. Fractional synthesis rates were calculated for 34 ECM proteins or protein subunits, including collagens, proteoglycans, and microfibrillar proteins. Overall, fractional synthesis rates of guanidine-soluble ECM proteins were faster than those of insoluble ECM proteins, suggesting that the insoluble fraction reflected older, more mature matrix components. This was confirmed through the quantitation of pyridinoline cross-links in each protein fraction. In fibrotic lung tissue, there was a significant increase in the fractional synthesis of unique sets of matrix proteins during early (pre-1 week) and late (post-1 week) fibrotic response. Furthermore, we isolated fast turnover subpopulations of several ECM proteins (e.g. type I collagen) based on guanidine solubility, allowing for accelerated detection of increased synthesis of typically slow-turnover protein populations. This establishes the presence of multiple kinetic pools of pulmonary collagen in vivo with altered turnover rates during evolving fibrosis. These data demonstrate the utility of dynamic proteomics in analyzing changes in ECM protein turnover associated with the onset and progression of fibrotic disease. PMID:24741116

Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression

PubMed Central

Wechalekar, Mihir D.; Cole, Suzanne; Yin, Xuefeng; Scott, Brittney; Loza, Mathew; Orr, Carl; McGarry, Trudy; Bombardieri, Michele; Humby, Frances; Proudman, Susanna M.; Pitzalis, Costantino; Smith, Malcolm D.; Friedman, Joshua R.; Anderson, Ian; Madakamutil, Loui; Veale, Douglas J.; Fearon, Ursula

2018-01-01

Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development. We demonstrate that the expression of PD-1 was increased in early and established RA synovial tissue compared to normal and OA synovium, whereas that of its ligands, programmed death ligand-1 (PD-L1) and PD-L2, was increased at all the stages of RA disease progression, namely arthralgia, IA/undifferentiated arthritis, early RA and established RA. Further, we show that RA patients expressed PD-1 on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells. Moreover, enrichment of Nivolumab gene signature was observed in IA and RA, indicating that the PD-1 pathway was downregulated during RA disease progression. Furthermore, serum soluble (s) PD-1 levels were increased in autoantibody positive early RA patients. Interestingly, most of the early RA synovium tissue sections showed negative PD-L1 staining by immunohistochemistry. Therefore, downregulation in PD-1 inhibitory signaling in RA could be attributed to increased serum sPD-1 and decreased synovial tissue PD-L1 levels. Taken together, these data suggest that agonistic PD1 antibody-based therapeutics may show efficacy in RA treatment and interception. PMID:29489833

Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression.

PubMed

Guo, Yanxia; Walsh, Alice M; Canavan, Mary; Wechalekar, Mihir D; Cole, Suzanne; Yin, Xuefeng; Scott, Brittney; Loza, Mathew; Orr, Carl; McGarry, Trudy; Bombardieri, Michele; Humby, Frances; Proudman, Susanna M; Pitzalis, Costantino; Smith, Malcolm D; Friedman, Joshua R; Anderson, Ian; Madakamutil, Loui; Veale, Douglas J; Fearon, Ursula; Nagpal, Sunil

2018-01-01

Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development. We demonstrate that the expression of PD-1 was increased in early and established RA synovial tissue compared to normal and OA synovium, whereas that of its ligands, programmed death ligand-1 (PD-L1) and PD-L2, was increased at all the stages of RA disease progression, namely arthralgia, IA/undifferentiated arthritis, early RA and established RA. Further, we show that RA patients expressed PD-1 on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells. Moreover, enrichment of Nivolumab gene signature was observed in IA and RA, indicating that the PD-1 pathway was downregulated during RA disease progression. Furthermore, serum soluble (s) PD-1 levels were increased in autoantibody positive early RA patients. Interestingly, most of the early RA synovium tissue sections showed negative PD-L1 staining by immunohistochemistry. Therefore, downregulation in PD-1 inhibitory signaling in RA could be attributed to increased serum sPD-1 and decreased synovial tissue PD-L1 levels. Taken together, these data suggest that agonistic PD1 antibody-based therapeutics may show efficacy in RA treatment and interception.

Evaluating the potential effect on fetal tissue after exposure to granisetron during pregnancy.

PubMed

Smith, Judith A; Julius, Justin M; Gaikwad, Anjali; Berens, Pamela D; Alcorn, Joseph; Moise, Kenneth J; Refuerzo, Jerrie S

2015-06-01

The objective of this study was to elucidate the possible toxic effects on the fetal tissues after exposure to two clinically relevant concentrations of granisetron. Primary cells were isolated from human fetal organs of 16-19 weeks gestational age and treated with 3 ng/mL or 30 ng/mL of granisetron. Cell cycle progression was evaluated by flow cytometry. ELISA was used to detect alterations in major apoptotic proteins. Up to 10% apoptosis in cardiac tissue was observed following treatment with 30 ng/mL granisetron. Neither concentration of granisetron caused alteration in cell cycle progression or alterations in apoptotic proteins in any of the other tissues. At 30 ng/mL granisetron concentration had the potential to induce up to 10% apoptosis in cardiac tissue; clinical significance needs further evaluation. At granisetron 3 ng/mL there was no detectable toxicity or on any fetal tissue in this study. Further research is needed to confirm these preliminary findings and determine if clinically significant. Copyright © 2015 Elsevier Inc. All rights reserved.

Plain packaging: a logical progression for tobacco control in one of the world's ‘darkest markets’

PubMed Central

Scollo, Michelle; Bayly, Megan; Wakefield, Melanie

2015-01-01

The Australian approach to tobacco control has been a comprehensive one, encompassing mass media campaigns, consumer information, taxation policy, access for smokers to smoking cessation advice and pharmaceutical treatments, protection from exposure to tobacco smoke and regulation of promotion. World-first legislation to standardise the packaging of tobacco was a logical next step to further reduce misleadingly reassuring promotion of a product known for the past 50 years to kill a high proportion of its long-term users. Similarly, refreshed, larger pack warnings which started appearing on packs at the end of 2012 were a logical progression of efforts to ensure that consumers are better informed about the health risks associated with smoking. Regardless of the immediate effects of legislation, further progress will continue to require a comprehensive approach to maintain momentum and ensure that government efforts on one front are not undermined by more vigorous efforts and greater investment by tobacco companies elsewhere. PMID:28407604

Properties of young massive clusters obtained with different massive-star evolutionary models

NASA Astrophysics Data System (ADS)

Wofford, Aida; Charlot, Stéphane

We undertake a comprehensive comparative test of seven widely-used spectral synthesis models using multi-band HST photometry of a sample of eight YMCs in two galaxies. We provide a first quantitative estimate of the accuracies and uncertainties of new models, show the good progress of models in fitting high-quality observations, and highlight the need of further comprehensive comparative tests.

A comprehensive comparison of perpendicular distance sampling methods for sampling downed coarse woody debris

Treesearch

Jeffrey H. Gove; Mark J. Ducey; Harry T. Valentine; Michael S. Williams

2013-01-01

Many new methods for sampling down coarse woody debris have been proposed in the last dozen or so years. One of the most promising in terms of field application, perpendicular distance sampling (PDS), has several variants that have been progressively introduced in the literature. In this study, we provide an overview of the different PDS variants and comprehensive...

3D Printing of Tissue Engineered Constructs for In Vitro Modeling of Disease Progression and Drug Screening.

PubMed

Vanderburgh, Joseph; Sterling, Julie A; Guelcher, Scott A

2017-01-01

2D cell culture and preclinical animal models have traditionally been implemented for investigating the underlying cellular mechanisms of human disease progression. However, the increasing significance of 3D vs. 2D cell culture has initiated a new era in cell culture research in which 3D in vitro models are emerging as a bridge between traditional 2D cell culture and in vivo animal models. Additive manufacturing (AM, also known as 3D printing), defined as the layer-by-layer fabrication of parts directed by digital information from a 3D computer-aided design file, offers the advantages of simultaneous rapid prototyping and biofunctionalization as well as the precise placement of cells and extracellular matrix with high resolution. In this review, we highlight recent advances in 3D printing of tissue engineered constructs that recapitulate the physical and cellular properties of the tissue microenvironment for investigating mechanisms of disease progression and for screening drugs.

3D Printing of Tissue Engineered Constructs for in vitro Modeling of Disease Progression and Drug Screening

PubMed Central

Vanderburgh, Joseph; Sterling, Julie A.

2016-01-01

2D cell culture and preclinical animal models have traditionally been implemented for investigating the underlying cellular mechanisms of human disease progression. However, the increasing significance of 3D versus 2D cell culture has initiated a new era in cell culture research in which 3D in vitro models are emerging as a bridge between traditional 2D cell culture and in vivo animal models. Additive manufacturing (AM, also known as 3D printing), defined as the layer-by-layer fabrication of parts directed by digital information from a 3D computer-aided design (CAD) file, offers the advantages of simultaneous rapid prototyping and biofunctionalization as well as the precise placement of cells and extracellular matrix with high resolution. In this review, we highlight recent advances in 3D printing of tissue engineered constructs (TECs) that recapitulate the physical and cellular properties of the tissue microenvironment for investigating mechanisms of disease progression and for screening drugs. PMID:27169894

A novel mitochondrial DNA deletion in a patient with Pearson syndrome and neonatal diabetes mellitus provides insight into disease etiology, severity and progression.

PubMed

Chen, Xin-Yu; Zhao, Si-Yu; Wang, Yan; Wang, Dong; Dong, Chang-Hu; Yang, Ying; Wang, Zhi-Hua; Wu, Yuan-Ming

2016-07-01

Pearson syndrome (PS) is a rare, mitochondrial DNA (mtDNA) deletion disorder mainly affecting hematopoietic system and exocrine pancreas in early infancy, which is characterized by multi-organ involvement, variable manifestations and poor prognosis. Since the clinical complexity and uncertain outcome of PS, the ability to early diagnose and anticipate disease progression is of great clinical importance. We described a patient with severe anemia and hyperglycinemia at birth was diagnosed with neonatal diabetes mellitus, and later with PS. Genetic testing revealed that a novel mtDNA deletion existed in various non-invasive tissues from the patient. The disease course was monitored by mtDNA deletion heteroplasmy and mtDNA/nucleus DNA genome ratio in different tissues and at different time points, showing a potential genotype-phenotype correlation. Our findings suggest that for patient suspected for PS, it may be therapeutically important to first perform detailed mtDNA analysis on non-invasive tissues at the initial diagnosis and during disease progression.

Circulating tumor DNA functions as an alternative for tissue to overcome tumor heterogeneity in advanced gastric cancer.

PubMed

Gao, Jing; Wang, Haixing; Zang, Wanchun; Li, Beifang; Rao, Guanhua; Li, Lei; Yu, Yang; Li, Zhongwu; Dong, Bin; Lu, Zhihao; Jiang, Zhi; Shen, Lin

2017-09-01

Overcoming tumor heterogeneity is a major challenge for personalized treatment of gastric cancer, especially for human epidermal growth factor receptor-2 targeted therapy. Analysis of circulating tumor DNA allows a more comprehensive analysis of tumor heterogeneity than traditional biopsies in lung cancer and breast cancer, but little is known in gastric cancer. We assessed mutation profiles of ctDNA and primary tumors from 30 patients with advanced gastric cancer, then performed a comprehensive analysis of tumor mutations by multiple biopsies from five patients, and finally analyzed the concordance of HER2 amplification in ctDNA and paired tumor tissues in 70 patients. By comparing with a single tumor sample, ctDNA displayed a low concordance of mutation profile, only approximately 50% (138/275) somatic mutations were found in paired tissue samples, however, when compared with multiple biopsies, most DNA mutations in ctDNA were also shown in paired tumor tissues. ctDNA had a high concordance (91.4%, Kappa index = 0.784, P < 0.001) of HER2 amplification with tumor tissues, suggesting it might be an alternative for tissue. It implied that ctDNA-based assessment could partially overcome the tumor heterogeneity, and might serve as a potential surrogate for HER2 analysis in gastric cancer. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

[Research progress of cell-scaffold complex in tendon tissue engineering].

PubMed

Zhu, Ying; Li, Min

2013-04-01

To review the research progress of cell-scaffold complex in the tendon tissue engineering. Recent literature concerning cell-scaffold complex in the tendon tissue engineering was reviewed, the research situation of the cell-scaffold complex was elaborated in the aspects of seed cells, scaffolds, cell culture, and application. In tendon tissue engineering, a cell-scaffold complex is built by appropriate seed cells and engineered scaffolds. Experiments showed that modified seed cells had better therapeutic effects. Further, scaffold functionality could be improved through surface modification, growth factor cure, mechanical stimulation, and contact guidance. Among these methods, mechanical stimulation revealed the most significant results in promoting cell proliferation and function. Through a variety of defect models, it is demonstrated that the use of cell-scaffold complex could achieve satisfactory results for tendon regeneration. The cell-scaffold complex for tendon tissue engineering is a popular research topic. Although it has not yet met the requirement of clinical use, it has broad application prospects.

Bioprinting technologies for disease modeling.

PubMed

Memic, Adnan; Navaei, Ali; Mirani, Bahram; Cordova, Julio Alvin Vacacela; Aldhahri, Musab; Dolatshahi-Pirouz, Alireza; Akbari, Mohsen; Nikkhah, Mehdi

2017-09-01

There is a great need for the development of biomimetic human tissue models that allow elucidation of the pathophysiological conditions involved in disease initiation and progression. Conventional two-dimensional (2D) in vitro assays and animal models have been unable to fully recapitulate the critical characteristics of human physiology. Alternatively, three-dimensional (3D) tissue models are often developed in a low-throughput manner and lack crucial native-like architecture. The recent emergence of bioprinting technologies has enabled creating 3D tissue models that address the critical challenges of conventional in vitro assays through the development of custom bioinks and patient derived cells coupled with well-defined arrangements of biomaterials. Here, we provide an overview on the technological aspects of 3D bioprinting technique and discuss how the development of bioprinted tissue models have propelled our understanding of diseases' characteristics (i.e. initiation and progression). The future perspectives on the use of bioprinted 3D tissue models for drug discovery application are also highlighted.

Does administering a comprehensive examination affect pass rates on the Registered Health Information Administrator certification examination?

PubMed

McNeill, Marjorie H

2009-01-01

The purpose of this research study was to determine whether the administration of a comprehensive examination before graduation increases the percentage of students passing the Registered Health Information Administrator certification examination. A t-test for independent means yielded a statistically significant difference between the Registered Health Information Administrator certification examination pass rates of health information administration programs that administer a comprehensive examination and programs that do not administer a comprehensive examination. Programs with a high certification examination pass rate do not require a comprehensive examination when compared with those programs with a lower pass rate. It is concluded that health information administration faculty at the local level should perform program self-analysis to improve student progress toward achievement of learning outcomes and entry-level competencies.

Needle-tissue interactive mechanism and steering control in image-guided robot-assisted minimally invasive surgery: a review.

PubMed

Li, Pan; Yang, Zhiyong; Jiang, Shan

2018-06-01

Image-guided robot-assisted minimally invasive surgery is an important medicine procedure used for biopsy or local target therapy. In order to reach the target region not accessible using traditional techniques, long and thin flexible needles are inserted into the soft tissue which has large deformation and nonlinear characteristics. However, the detection results and therapeutic effect are directly influenced by the targeting accuracy of needle steering. For this reason, the needle-tissue interactive mechanism, path planning, and steering control are investigated in this review by searching literatures in the last 10 years, which results in a comprehensive overview of the existing techniques with the main accomplishments, limitations, and recommendations. Through comprehensive analyses, surgical simulation for insertion into multi-layer inhomogeneous tissue is verified as a primary and propositional aspect to be explored, which accurately predicts the nonlinear needle deflection and tissue deformation. Investigation of the path planning of flexible needles is recommended to an anatomical or a deformable environment which has characteristics of the tissue deformation. Nonholonomic modeling combined with duty-cycled spinning for needle steering, which tracks the tip position in real time and compensates for the deviation error, is recommended as a future research focus in the steering control in anatomical and deformable environments. Graphical abstract a Insertion force when the needle is inserted into soft tissue. b Needle deflection model when the needle is inserted into soft tissue [68]. c Path planning in anatomical environments [92]. d Duty-cycled spinning incorporated in nonholonomic needle steering [64].

Tissue classification for laparoscopic image understanding based on multispectral texture analysis

NASA Astrophysics Data System (ADS)

Zhang, Yan; Wirkert, Sebastian J.; Iszatt, Justin; Kenngott, Hannes; Wagner, Martin; Mayer, Benjamin; Stock, Christian; Clancy, Neil T.; Elson, Daniel S.; Maier-Hein, Lena

2016-03-01

Intra-operative tissue classification is one of the prerequisites for providing context-aware visualization in computer-assisted minimally invasive surgeries. As many anatomical structures are difficult to differentiate in conventional RGB medical images, we propose a classification method based on multispectral image patches. In a comprehensive ex vivo study we show (1) that multispectral imaging data is superior to RGB data for organ tissue classification when used in conjunction with widely applied feature descriptors and (2) that combining the tissue texture with the reflectance spectrum improves the classification performance. Multispectral tissue analysis could thus evolve as a key enabling technique in computer-assisted laparoscopy.

Energy-Based Tissue Fusion for Sutureless Closure: Applications, Mechanisms, and Potential for Functional Recovery.

PubMed

Kramer, Eric A; Rentschler, Mark E

2018-06-04

As minimally invasive surgical techniques progress, the demand for efficient, reliable methods for vascular ligation and tissue closure becomes pronounced. The surgical advantages of energy-based vessel sealing exceed those of traditional, compression-based ligatures in procedures sensitive to duration, foreign bodies, and recovery time alike. Although the use of energy-based devices to seal or transect vasculature and connective tissue bundles is widespread, the breadth of heating strategies and energy dosimetry used across devices underscores an uncertainty as to the molecular nature of the sealing mechanism and induced tissue effect. Furthermore, energy-based techniques exhibit promise for the closure and functional repair of soft and connective tissues in the nervous, enteral, and dermal tissue domains. A constitutive theory of molecular bonding forces that arise in response to supraphysiological temperatures is required in order to optimize and progress the use of energy-based tissue fusion. While rapid tissue bonding has been suggested to arise from dehydration, dipole interactions, molecular cross-links, or the coagulation of cellular proteins, long-term functional tissue repair across fusion boundaries requires that the reaction to thermal damage be tailored to catalyze the onset of biological healing and remodeling. In this review, we compile and contrast findings from published thermal fusion research in an effort to encourage a molecular approach to characterization of the prevalent and promising energy-based tissue bond.

Public policy action and CCC implementation: benefits and hurdles

PubMed Central

Daniel, Kelley; Gurian, Gary L.; Petherick, J. T.; Stockmyer, Chris; David, Annette M.; Miller, Sara E.

2010-01-01

Policy change continues to be an increasingly effective means of advancing the agenda of comprehensive cancer control. Efforts have moved progressively from describing how public policy can enhance the comprehensive cancer control agenda to implementation of public policy best practices at both the state and federal levels. The current political and economic contexts bring additional challenges and opportunities to the efforts surrounding comprehensive cancer control and policy. The purpose of this paper is to highlight recent policy successes, to illustrate the importance of policy as a means of advancing the comprehensive cancer control agenda, and to discuss continued policy action as we move forward in a time of healthcare reform and continuing economic uncertainty. PMID:21086034

Public policy action and CCC implementation: benefits and hurdles.

PubMed

Steger, Carter; Daniel, Kelley; Gurian, Gary L; Petherick, J T; Stockmyer, Chris; David, Annette M; Miller, Sara E

2010-12-01

Policy change continues to be an increasingly effective means of advancing the agenda of comprehensive cancer control. Efforts have moved progressively from describing how public policy can enhance the comprehensive cancer control agenda to implementation of public policy best practices at both the state and federal levels. The current political and economic contexts bring additional challenges and opportunities to the efforts surrounding comprehensive cancer control and policy. The purpose of this paper is to highlight recent policy successes, to illustrate the importance of policy as a means of advancing the comprehensive cancer control agenda, and to discuss continued policy action as we move forward in a time of healthcare reform and continuing economic uncertainty.

Lineage-specific splicing of a brain-enriched alternative exon promotes glioblastoma progression

PubMed Central

Ferrarese, Roberto; Harsh, Griffith R.; Yadav, Ajay K.; Bug, Eva; Maticzka, Daniel; Reichardt, Wilfried; Dombrowski, Stephen M.; Miller, Tyler E.; Masilamani, Anie P.; Dai, Fangping; Kim, Hyunsoo; Hadler, Michael; Scholtens, Denise M.; Yu, Irene L.Y.; Beck, Jürgen; Srinivasasainagendra, Vinodh; Costa, Fabrizio; Baxan, Nicoleta; Pfeifer, Dietmar; von Elverfeldt, Dominik; Backofen, Rolf; Weyerbrock, Astrid; Duarte, Christine W.; He, Xiaolin; Prinz, Marco; Chandler, James P.; Vogel, Hannes; Chakravarti, Arnab; Rich, Jeremy N.; Carro, Maria S.; Bredel, Markus

2014-01-01

Tissue-specific alternative splicing is critical for the emergence of tissue identity during development, yet the role of this process in malignant transformation is undefined. Tissue-specific splicing involves evolutionarily conserved, alternative exons that represent only a minority of the total alternative exons identified. Many of these conserved exons have functional features that influence signaling pathways to profound biological effect. Here, we determined that lineage-specific splicing of a brain-enriched cassette exon in the membrane-binding tumor suppressor annexin A7 (ANXA7) diminishes endosomal targeting of the EGFR oncoprotein, consequently enhancing EGFR signaling during brain tumor progression. ANXA7 exon splicing was mediated by the ribonucleoprotein PTBP1, which is normally repressed during neuronal development. PTBP1 was highly expressed in glioblastomas due to loss of a brain-enriched microRNA (miR-124) and to PTBP1 amplification. The alternative ANXA7 splicing trait was present in precursor cells, suggesting that glioblastoma cells inherit the trait from a potential tumor-initiating ancestor and that these cells exploit this trait through accumulation of mutations that enhance EGFR signaling. Our data illustrate that lineage-specific splicing of a tissue-regulated alternative exon in a constituent of an oncogenic pathway eliminates tumor suppressor functions and promotes glioblastoma progression. This paradigm may offer a general model as to how tissue-specific regulatory mechanisms can reprogram normal developmental processes into oncogenic ones. PMID:24865424

CHST14/D4ST1 deficiency: New form of Ehlers-Danlos syndrome.

PubMed

Kosho, Tomoki

2016-02-01

Carbohydrate sulfotransferase 14/dermatan 4-O-sulfotransferase-1 (CHST14/D4ST1) deficiency represents a specific form of Ehlers-Danlos syndrome (EDS) caused by recessive loss-of-function mutations in CHST14. The disorder has been independently termed "adducted thumb-clubfoot syndrome", "EDS, Kosho type", and "EDS, musculocontractural type". To date, 31 affected patients from 21 families have been described. Clinically, CHST14/D4ST1 deficiency is characterized by multiple congenital malformations (craniofacial features including large fontanelle, hypertelorism, short and downslanting palpebral fissures, blue sclerae, short nose with hypoplastic columella, low-set and rotated ears, high palate, long philtrum, thin upper lip vermilion, small mouth, and micro-retrognathia; multiple congenital contractures including adduction-flexion contractures and talipes equinovarus as well as other visceral or ophthalmological malformations) and progressive multisystem fragility-related complications (skin hyperextensibility, bruisability, and fragility with atrophic scars; recurrent dislocations; progressive talipes or spinal deformities; pneumothorax or pneumohemothorax; large subcutaneous hematomas; and diverticular perforation). Etiologically, multisystem fragility is presumably caused by impaired assembly of collagen fibrils resulting from loss of dermatan sulfate (DS) in the decorin glycosaminoglycan side chain that promotes electrostatic binding between collagen fibrils. This is the first reported human disorder that specifically affects biosynthesis of DS. Its clinical characteristics indicate that CHST14/D4ST1 and, more fundamentally, DS, play a critical role in fetal development and maintenance of connective tissues in multiple organs. Considering that patients with CHST14/D4ST1 deficiency develop progressive multisystem fragility-related manifestations, establishment of a comprehensive and detailed natural history and health-care guidelines as well as further elucidation of the pathophysiology in view of future etiology-based therapy are crucial. © 2015 Japan Pediatric Society.

Elevated Levels of Innate Immune Modulators in Lymph Nodes and Blood Are Associated with More-Rapid Disease Progression in Simian Immunodeficiency Virus-Infected Monkeys▿

PubMed Central

Durudas, Andre; Milush, Jeffrey M.; Chen, Hui-Ling; Engram, Jessica C.; Silvestri, Guido; Sodora, Donald L.

2009-01-01

Cytokines and chemokines are critical for establishing tissue-specific immune responses and play key roles in modulating disease progression in simian immunodeficiency virus (SIV)-infected macaques and human immunodeficiency virus (HIV)-infected humans. The goal here was to characterize the innate immune response at different tissue sites and to correlate these responses to clinical outcome, initially focusing on rhesus macaques orally inoculated with SIV and monitored until onset of simian AIDS. Cytokine and chemokine mRNA transcripts were assessed at lymph nodes (LN) and peripheral blood cells utilizing quantitative real-time PCR at different time points postinfection. The mRNA expression of four immune modulators—alpha interferon (IFN-α), oligoadenylate synthetase (OAS), CXCL9, and CXCL10—was positively associated with disease progression within LN tissue. Elevated cytokine/chemokine expression in LN did not result in any observed beneficial outcome since the numbers of CXCR3+ cells were not increased, nor were the SIV RNA levels decreased. In peripheral blood, increased OAS and CXCL10 expression were elevated in SIV+ monkeys that progress the fastest to simian AIDS. Our results indicate that higher IFN-α, OAS, CXCL9, and CXCL10 mRNA expression in LN was associated with rapid disease progression and a LN environment that may favor SIV replication. Furthermore, higher expression of CXCL10 and OAS in peripheral blood could potentially serve as a diagnostic marker for hosts that are likely to progress to AIDS. Understanding the expression patterns of key innate immune modulators will be useful in assessing the disease state and potential rates of disease progression in HIV+ patients, which could lead to novel therapy and vaccine approaches. PMID:19759147

Elevated levels of innate immune modulators in lymph nodes and blood are associated with more-rapid disease progression in simian immunodeficiency virus-infected monkeys.

PubMed

Durudas, Andre; Milush, Jeffrey M; Chen, Hui-Ling; Engram, Jessica C; Silvestri, Guido; Sodora, Donald L

2009-12-01

Cytokines and chemokines are critical for establishing tissue-specific immune responses and play key roles in modulating disease progression in simian immunodeficiency virus (SIV)-infected macaques and human immunodeficiency virus (HIV)-infected humans. The goal here was to characterize the innate immune response at different tissue sites and to correlate these responses to clinical outcome, initially focusing on rhesus macaques orally inoculated with SIV and monitored until onset of simian AIDS. Cytokine and chemokine mRNA transcripts were assessed at lymph nodes (LN) and peripheral blood cells utilizing quantitative real-time PCR at different time points postinfection. The mRNA expression of four immune modulators-alpha interferon (IFN-alpha), oligoadenylate synthetase (OAS), CXCL9, and CXCL10-was positively associated with disease progression within LN tissue. Elevated cytokine/chemokine expression in LN did not result in any observed beneficial outcome since the numbers of CXCR3(+) cells were not increased, nor were the SIV RNA levels decreased. In peripheral blood, increased OAS and CXCL10 expression were elevated in SIV(+) monkeys that progress the fastest to simian AIDS. Our results indicate that higher IFN-alpha, OAS, CXCL9, and CXCL10 mRNA expression in LN was associated with rapid disease progression and a LN environment that may favor SIV replication. Furthermore, higher expression of CXCL10 and OAS in peripheral blood could potentially serve as a diagnostic marker for hosts that are likely to progress to AIDS. Understanding the expression patterns of key innate immune modulators will be useful in assessing the disease state and potential rates of disease progression in HIV(+) patients, which could lead to novel therapy and vaccine approaches.

Evaluating the Progress of the School Reading Program. Learning Package No. 17.

ERIC Educational Resources Information Center

Nelson, Carol; Smith, Carl, Comp.

Originally developed for the Department of Defense Schools (DoDDS) system, this learning package on evaluating the progress of the school reading program is designed for teachers who wish to upgrade or expand their teaching skills on their own. The package includes a comprehensive search of the ERIC database; a lecture giving an overview on the…

Civics Framework for the 1998 National Assessment of Educational Progress.

ERIC Educational Resources Information Center

Center for Civic Education, Calabasas, CA.

The material provides a comprehensive look at the design, goals, and methods to be used in the 1998 National Assessment of Educational Progress (NAEP) Civics Assessment. This assessment will attempt to gauge the civic knowledge and skills of the nation's 4th, 8th, and 12th grade students. To do well on the assessment, students will have to show…

Maine Assessment of Educational Progress, Report 2. Results Report 1: Citizenship and Writing, 1972.

ERIC Educational Resources Information Center

Maine State Dept. of Educational and Cultural Services, Augusta.

The purpose of the Maine Assessment of Educational Progress (MAEP) in 1972 was to complete the first phase of a 10-year comprehensive needs assessment program involving students in public and non-public schools of the state. The total program is designed to provide specific information about knowledge, skills, understandings, and attitudes in 10…

Damaging effects of visible light. Comprehensive progress report

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

1981-01-01

Research progress is reported on studies of retinal light damage. A myriad of variables effect the production of light damage. These include age, prior light history, body temperature, vitamin A status, intensity, wavelength and duration of light. The intensity-duration function and the age function have been studied in detail in rats. Studies have been begun on the wavelength variable. (ACR)

A Self-Evaluation Report of Wisconsin Public Schools, 1991-92: Comprehensive Alcohol and Other Drug Abuse Programs.

ERIC Educational Resources Information Center

Wisconsin State Dept. of Public Instruction, Madison.

This publication reports the progress Wisconsin school districts have made toward providing programs that address alcohol and other drug abuse. It begins with an explanation of the problem and a description of Wisconsin's model for addressing the problem. Progress within districts is measured using the model as a standard. Results are presented…

Curriculum-Based Measurement: Developing a Computer-Based Assessment Instrument for Monitoring Student Reading Progress on Multiple Indicators

ERIC Educational Resources Information Center

Forster, Natalie; Souvignier, Elmar

2011-01-01

The purpose of this study was to examine the technical adequacy of a computer-based assessment instrument which is based on hierarchical models of text comprehension for monitoring student reading progress following the Curriculum-Based Measurement (CBM) approach. At intervals of two weeks, 120 third-grade students finished eight CBM tests. To…

Next-generation sequencing reveals a Novel NSCLC ALK F1174V mutation and confirms ALK G1202R mutation confers high-level resistance to alectinib (CH5424802/RO5424802) in ALK-rearranged NSCLC patients who progressed on crizotinib.

PubMed

Ignatius Ou, Sai-Hong; Azada, Michele; Hsiang, David J; Herman, June M; Kain, Tatiana S; Siwak-Tapp, Christina; Casey, Cameron; He, Jie; Ali, Siraj M; Klempner, Samuel J; Miller, Vincent A

2014-04-01

Acquired secondary mutations in the anaplastic lymphoma kinase (ALK) gene have been identified in ALK-rearranged (ALK+) non-small-cell lung cancer (NSCLC) patients who developed disease progression while on crizotinib treatment. Here, we identified a novel secondary acquired NSCLC ALK F1174V mutation by comprehensive next-generation sequencing in one ALK+ NSCLC patient who progressed on crizotinib after a prolonged partial response to crizotinib. In a second case, we identified a secondary acquired ALK G1202R, which also confers resistance to alectinib (CH5424802/RO5424802), a second-generation ALK inhibitor that can inhibit ALK gatekeeper L1196M mutation in vitro. ALK G1202R is located at the solvent front of the ALK kinase domain and exhibits a high level of resistance to all other ALK inhibitors currently in clinical development in vitro. Comprehensive genomic profiling of resistant tumor is increasingly important in tailoring treatment decisions after disease progression on crizotinib in ALK+ NSCLC given the promise of second-generation ALK inhibitors and other therapeutic strategies.

Assessment of Individuals with Primary Progressive Aphasia.

PubMed

Henry, Maya L; Grasso, Stephanie M

2018-07-01

Speech-language pathologists play a crucial role in the assessment and treatment of individuals with primary progressive aphasia (PPA). The speech-language evaluation is a critical aspect of the diagnostic and rehabilitative process, informing differential diagnosis as well as intervention planning and monitoring of cognitive-linguistic status over time. The evaluation should include a thorough case history and interview and a detailed assessment of speech-language and cognitive functions, with tasks designed to detect core and associated deficits outlined in current diagnostic criteria. In this paper, we review assessments that can be utilized to examine communication and cognition in PPA, including general aphasia batteries designed for stroke and/or progressive aphasia as well as tests of specific cognitive-linguistic functions, including naming, object/person knowledge, single-word and sentence comprehension, repetition, spontaneous speech/language production, motor speech, written language, and nonlinguistic cognitive domains. The comprehensive evaluation can inform diagnostic decision making and facilitate planning of interventions that are tailored to the patient's current status and likely progression of deficits. As such, the speech-language evaluation allows the medical team to provide individuals with PPA and their families with appropriate recommendations for the present and the future. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Finding Patterns of Emergence in Science and Technology

DTIC Science & Technology

2012-09-24

formal evaluation scheduled – Case Studies, Eight Examples: Tissue Engineering, Cold Fusion, RF Metamaterials, DNA Microarrays, Genetic Algorithms, RNAi...emerging capabilities Case Studies, Eight Examples: • Tissue Engineering, Cold Fusion, RF Metamaterials, DNA Microarrays, Genetic Algorithms...Evidence Quality (i.e., the rubric ) and deliver comprehensible evidential support for nomination • Demonstrate proof-of-concept nomination for Chinese

Fully integrated reflection-mode photoacoustic, two-photon, and second harmonic generation microscopy in vivo

NASA Astrophysics Data System (ADS)

Song, Wei; Xu, Qiang; Zhang, Yang; Zhan, Yang; Zheng, Wei; Song, Liang

2016-08-01

The ability to obtain comprehensive structural and functional information from intact biological tissue in vivo is highly desirable for many important biomedical applications, including cancer and brain studies. Here, we developed a fully integrated multimodal microscopy that can provide photoacoustic (optical absorption), two-photon (fluorescence), and second harmonic generation (SHG) information from tissue in vivo, with intrinsically co-registered images. Moreover, using a delicately designed optical-acoustic coupling configuration, a high-frequency miniature ultrasonic transducer was integrated into a water-immersion optical objective, thus allowing all three imaging modalities to provide a high lateral resolution of ~290 nm with reflection-mode imaging capability, which is essential for studying intricate anatomy, such as that of the brain. Taking advantage of the complementary and comprehensive contrasts of the system, we demonstrated high-resolution imaging of various tissues in living mice, including microvasculature (by photoacoustics), epidermis cells, cortical neurons (by two-photon fluorescence), and extracellular collagen fibers (by SHG). The intrinsic image co-registration of the three modalities conveniently provided improved visualization and understanding of the tissue microarchitecture. The reported results suggest that, by revealing complementary tissue microstructures in vivo, this multimodal microscopy can potentially facilitate a broad range of biomedical studies, such as imaging of the tumor microenvironment and neurovascular coupling.

The Origin and Significance of Mammary Intraductal Foam Cells

DTIC Science & Technology

2005-09-01

hematopoeitic origin developed in mammary tissue with both benign and malignant differentiation, depending on environmental cues. Progression of the cells...contribution of hematopoeitic precursors to the heterogeneity of cell types in benign and malignant mammary tissue.

Tissue- and age-specific DNA replication patterns at the CTG/CAG-expanded human myotonic dystrophy type 1 locus.

PubMed

Cleary, John D; Tomé, Stéphanie; López Castel, Arturo; Panigrahi, Gagan B; Foiry, Laurent; Hagerman, Katharine A; Sroka, Hana; Chitayat, David; Gourdon, Geneviève; Pearson, Christopher E

2010-09-01

Myotonic dystrophy, caused by DM1 CTG/CAG repeat expansions, shows varying instability levels between tissues and across ages within patients. We determined DNA replication profiles at the DM1 locus in patient fibroblasts and tissues from DM1 transgenic mice of various ages showing different instability. In patient cells, the repeat is flanked by two replication origins demarcated by CTCF sites, with replication diminished at the expansion. In mice, the expansion replicated from only the downstream origin (CAG as lagging template). In testes from mice of three different ages, replication toward the repeat paused at the earliest age and was relieved at later ages-coinciding with increased instability. Brain, pancreas and thymus replication varied with CpG methylation at DM1 CTCF sites. CTCF sites between progressing forks and repeats reduced replication depending on chromatin. Thus, varying replication progression may affect tissue- and age-specific repeat instability.

The peritumoural adipose tissue microenvironment and cancer. The roles of fatty acid binding protein 4 and fatty acid binding protein 5.

PubMed

Guaita-Esteruelas, S; Gumà, J; Masana, L; Borràs, J

2018-02-15

The adipose tissue microenvironment plays a key role in tumour initiation and progression because it provides fatty acids and adipokines to tumour cells. The fatty acid-binding protein (FABP) family is a group of small proteins that act as intracellular fatty acid transporters. Adipose-derived FABPs include FABP4 and FABP5. Both have an important role in lipid-related metabolic processes and overexpressed in many cancers, such as breast, prostate, colorectal and ovarian. Moreover, their expression in peritumoural adipose tissue is deregulated, and their circulating levels are upregulated in some tumours. In this review, we discuss the role of the peritumoural adipose tissue and the related adipokines FABP4 and FABP5 in cancer initiation and progression and the possible pathways implicated in these processes. Copyright © 2017 Elsevier B.V. All rights reserved.

Next-Generation Pathology.

PubMed

Caie, Peter D; Harrison, David J

2016-01-01

The field of pathology is rapidly transforming from a semiquantitative and empirical science toward a big data discipline. Large data sets from across multiple omics fields may now be extracted from a patient's tissue sample. Tissue is, however, complex, heterogeneous, and prone to artifact. A reductionist view of tissue and disease progression, which does not take this complexity into account, may lead to single biomarkers failing in clinical trials. The integration of standardized multi-omics big data and the retention of valuable information on spatial heterogeneity are imperative to model complex disease mechanisms. Mathematical modeling through systems pathology approaches is the ideal medium to distill the significant information from these large, multi-parametric, and hierarchical data sets. Systems pathology may also predict the dynamical response of disease progression or response to therapy regimens from a static tissue sample. Next-generation pathology will incorporate big data with systems medicine in order to personalize clinical practice for both prognostic and predictive patient care.

Cellular proliferation and regeneration following tissue damage. Progress report. [Eyes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harding, C.V.

1976-10-01

Results are reported from a study of wound healing in tissues of the eye, particularly lens, cornea, and surrounding tissues. The reactions of these tissues to mechanical injuries, as well as injuries induced by chemotoxic agents were studied. It is postulated that a better understanding of the basic reactions of the eye to injurious agents may be of importance in the evaluation of potential environmental hazards.

Lung extracellular matrix and redox regulation

PubMed Central

Watson, Walter H.; Ritzenthaler, Jeffrey D.; Roman, Jesse

2016-01-01

Pulmonary fibrosis affects millions worldwide and, even though there has been a significant investment in understanding the processes involved in wound healing and maladaptive repair, a complete understanding of the mechanisms responsible for lung fibrogenesis eludes us, and interventions capable of reversing or halting disease progression are not available. Pulmonary fibrosis is characterized by the excessive expression and uncontrolled deposition of extracellular matrix (ECM) proteins resulting in erosion of the tissue structure. Initially considered an ‘end-stage’ process elicited after injury, these events are now considered pathogenic and are believed to contribute to the course of the disease. By interacting with integrins capable of signal transduction and by influencing tissue mechanics, ECM proteins modulate processes ranging from cell adhesion and migration to differentiation and growth factor expression. In doing so, ECM proteins help orchestrate complex developmental processes and maintain tissue homeostasis. However, poorly controlled deposition of ECM proteins promotes inflammation, fibroproliferation, and aberrant differentiation of cells, and has been implicated in the pathogenesis of pulmonary fibrosis, atherosclerosis and cancer. Considering their vital functions, ECM proteins are the target of investigation, and oxidation–reduction (redox) reactions have emerged as important regulators of the ECM. Oxidative stress invariably accompanies lung disease and promotes ECM expression directly or through the overproduction of pro-fibrotic growth factors, while affecting integrin binding and activation. In vitro and in vivo investigations point to redox reactions as targets for intervention in pulmonary fibrosis and related disorders, but studies in humans have been disappointing probably due to the narrow impact of the interventions tested, and our poor understanding of the factors that regulate these complex reactions. This review is not meant to provide a comprehensive review of this field, but rather to highlight what has been learned and to raise interest in this area in need of much attention. PMID:26938939

A Revised Hemodynamic Theory of Age-Related Macular Degeneration

PubMed Central

Gelfand, Bradley D.; Ambati, Jayakrishna

2016-01-01

Age-related macular degeneration (AMD) afflicts one out of every 40 individuals worldwide, causing irreversible central blindness in millions. The transformation of various tissue layers within the macula in the retina has led to competing conceptual models of the molecular pathways, cell types, and tissues responsible for the onset and progression of AMD. A model that has persisted for over 6 decades is the hemodynamic, or vascular theory of AMD progression, which states that vascular dysfunction of the choroid underlies AMD pathogenesis. Here, we re-evaluate this hypothesis in light of recent advances on molecular, anatomic, and hemodynamic changes underlying choroidal dysfunction in AMD. We propose an updated, detailed model of hemodynamic dysfunction as a mechanism of AMD development and progression. PMID:27423265

Connective tissue growth factor (CTGF) and cancer progression.

PubMed

Chu, Chia-Yu; Chang, Cheng-Chi; Prakash, Ekambaranellore; Kuo, Min-Liang

2008-11-01

Connective tissue growth factor (CTGF) is a member of the CCN family of secreted, matrix-associated proteins encoded by immediate early genes that play various roles in angiogenesis and tumor growth. CCN family proteins share uniform modular structure which mediates various cellular functions such as regulation of cell division, chemotaxis, apoptosis, adhesion, motility, angiogenesis, neoplastic transformation, and ion transport. Recently, CTGF expression has been shown to be associated with tumor development and progression. There is growing body of evidence that CTGF may regulate cancer cell migration, invasion, angiogenesis, and anoikis. In this review, we will highlight the influence of CTGF expression on the biological behavior and progression of various cancer cells, as well as its regulation on various types of protein signals and their mechanisms.

Association and regulation of protein factors of field effect in prostate tissues

PubMed Central

Gabriel, Kristin N.; Jones, Anna C.; Nguyen, Julie P.T.; Antillon, Kresta S.; Janos, Sara N.; Overton, Heidi N.; Jenkins, Shannon M.; Frisch, Emily H.; Trujillo, Kristina A.; Bisoffi, Marco

2016-01-01

Field effect or field cancerization denotes the presence of molecular aberrations in structurally intact cells residing in histologically normal tissues adjacent to solid tumors. Currently, the etiology of prostate field-effect formation is unknown and there is a prominent lack of knowledge of the underlying cellular and molecular pathways. We have previously identified an upregulated expression of several protein factors representative of prostate field effect, i.e., early growth response-1 (EGR-1), platelet-derived growth factor-A (PDGF-A), macrophage inhibitory cytokine-1 (MIC-1), and fatty acid synthase (FASN) in tissues at a distance of 1 cm from the visible margin of intracapsule prostate adenocarcinomas. We have hypothesized that the transcription factor EGR-1 could be a key regulator of prostate field-effect formation by controlling the expression of PDGF-A, MIC-1, and FASN. Taking advantage of our extensive quantitative immunofluorescence data specific for EGR-1, PDGF-A, MIC-1, and FASN generated in disease-free, tumor-adjacent, and cancerous human prostate tissues, we chose comprehensive correlation as our major approach to test this hypothesis. Despite the static nature and sample heterogeneity of association studies, we show here that sophisticated data generation, such as by spectral image acquisition, linear unmixing, and digital quantitative imaging, can provide meaningful indications of molecular regulations in a physiologically relevant in situ environment. Our data suggest that EGR-1 acts as a key regulator of prostate field effect through induction of pro-proliferative (PDGF-A and FASN), and suppression of pro-apoptotic (MIC-1) factors. These findings were corroborated by computational promoter analyses and cell transfection experiments in non-cancerous prostate epithelial cells with ectopically induced and suppressed EGR-1 expression. Among several clinical applications, a detailed knowledge of pathways of field effect may lead to the development of targeted intervention strategies preventing progression from pre-malignancy to cancer. PMID:27634112

Recent progress in interfacial tissue engineering approaches for osteochondral defects.

PubMed

Castro, Nathan J; Hacking, S Adam; Zhang, Lijie Grace

2012-08-01

This review provides a brief synopsis of the anatomy and physiology of the osteochondral interface, scaffold-based and non-scaffold based approaches for engineering both tissues independently as well as recent developments in the manufacture of gradient constructs. Novel manufacturing techniques and nanotechnology will be discussed with potential application in osteochondral interfacial tissue engineering.

White adipose tissue cells and the progression of cachexia: inflammatory pathways

PubMed Central

Neves, Rodrigo X.; Rosa‐Neto, José Cesar; Yamashita, Alex S.; Matos‐Neto, Emidio M.; Riccardi, Daniela M. R.; Lira, Fabio S.; Batista, Miguel L.

2015-01-01

Abstract Background Cachexia is a systemic syndrome leading to body wasting, systemic inflammation, and to metabolic chaos. It is a progressive condition, and little is known about its dynamics. Detection of the early signs of the disease may lead to the attenuation of the associated symptoms. The white adipose tissue is an organ with endocrine functions, capable of synthesising and secreting a plethora of proteins, including cytokines, chemokines, and adipokines. It is well established that different adipose tissue depots demonstrate heterogeneous responses to physiological and pathological stimuli. The present study aimed at providing insight into adipocyte involvement in inflammation along the progression of cachexia. Methods Eight‐weeks‐old male rats were subcutaneously inoculated with a Walker 256 carcinosarcoma cell suspension (2 × 107 cells in 1.0 mL; tumour‐bearing, T) or Phosphate‐buffered saline (control, C). The retroperitoneal, epididymal, and mesenteric adipose pads were excised on Days 0, 7, and 14 post‐tumour cell injection, and the adipocytes were isolated. Results Mesenteric and epididymal adipocytes showed up‐regulation of IL‐1β protein expression and activation of the inflammasome pathway, contributing for whole tissue inflammation. The stromal vascular fraction of the retroperitoneal adipose tissue, on the other hand, seems to be the major contributor for the inflammation in this specific pad. Conclusion Adipocytes seem to play a relevant role in the establishment of white adipose tissue inflammation, through the activation of the NF‐κB and inflammasome pathways. In epididymal adipocytes, induction of the inflammasome may be detected already on Day 7 post‐tumour cell inoculation. PMID:27493872

Comprehensive proteomic profiles of mouse AApoAII amyloid fibrils provide insights into the involvement of lipoproteins in the pathology of amyloidosis.

PubMed

Miyahara, Hiroki; Sawashita, Jinko; Ishikawa, Eri; Yang, Mu; Ding, Xin; Liu, Yingye; Hachiya, Naomi; Kametani, Fuyuki; Yazaki, Masahide; Mori, Masayuki; Higuchi, Keiichi

2018-02-10

Amyloidosis is a disorder characterized by extracellular fibrillar deposits of misfolded proteins. The amyloid deposits commonly contain several non-fibrillar proteins as amyloid-associated proteins, but their roles in amyloidosis pathology are still unknown. In mouse senile amyloidosis, apolipoprotein A-II (ApoA-II) forms extracellular amyloid fibril (AApoAII) deposits with other proteins (AApoAII-associated proteins) in many organs. We previously reported that R1.P1-Apoa2 c mice provide a reproducible model of AApoAII amyloidosis. In order to investigate the sequential alterations of AApoAII-associated protein, we performed a proteomic analysis of amyloid fibrils extracted from mouse liver tissues that contained different levels of AApoAII deposition. We identified 6 AApoAII-associated proteins that constituted 20 of the top-ranked proteins in mice with severe AApoAII deposition. Although the amount of AApoAII-associated proteins increased with the progression of amyloidosis, the relative abundance of AApoAII-associated proteins changed little throughout the progression of amyloidosis. On the other hand, plasma levels of these proteins showed dramatic changes during the progression of amyloidosis. In addition, we confirmed that AApoAII-associated proteins were significantly associated with lipid metabolism based on functional enrichment analysis, and lipids were co-deposited with AApoAII fibrils from early stages of development of amyloidosis. Thus, these results demonstrate that lipoproteins are involved in AApoAII amyloidosis pathology. This study presented proteomic profiles of AApoAII amyloidosis during disease progression and it revealed co-deposition of lipids with AApoAII deposits based on functional analyses. The relative abundance of AApoAII-associated proteins in the amyloid fibril fractions did not change over the course of development of AApoAII amyloidosis pathology. However, their concentrations in plasma changed dramatically with progression of the disease. Interestingly, several AApoAII-associated proteins have been found as constituents of lipid-rich lesions of other degenerative diseases, such as atherosclerosis and age-related macular degeneration. The common protein components among these diseases with lipid-rich deposits could be accounted for by a lipoprotein retention model. Copyright © 2017 Elsevier B.V. All rights reserved.

Comprehensive MS and Solid-State NMR Metabolomic Profiling Reveals Molecular Variations in Native Periderms from Four Solanum tuberosum Potato Cultivars.

PubMed

Huang, Wenlin; Serra, Olga; Dastmalchi, Keyvan; Jin, Liqing; Yang, Lijia; Stark, Ruth E

2017-03-15

The potato (Solanum tuberosum L.) ranks third in worldwide consumption among food crops. Whereas disposal of potato peels poses significant challenges for the food industry, secondary metabolites in these tissues are also bioactive and essential to crop development. The diverse primary and secondary metabolites reported in whole tubers and wound-healing tissues prompted a comprehensive profiling study of native periderms from four cultivars with distinctive skin morphologies and commercial food uses. Polar and nonpolar soluble metabolites were extracted concurrently, analyzed chromatographically, and characterized with mass spectrometry; the corresponding solid interfacial polymeric residue was examined by solid-state 13 C NMR. In total, 112 secondary metabolites were found in the phellem tissues; multivariate analysis identified 10 polar and 30 nonpolar potential biomarkers that distinguish a single cultivar among Norkotah Russet, Atlantic, Chipeta, and Yukon Gold cultivars which have contrasting russeting features. Compositional trends are interpreted in the context of periderm protective function.

Estrogen synthesis and signaling pathways during ageing: from periphery to brain

PubMed Central

Cui, Jie; Shen, Yong; Li, Rena

2012-01-01

Estrogens are the primary female sex hormones and play important roles in both reproductive and non-reproductive systems. Estrogens can be synthesized in non-reproductive tissue as liver, heart, muscle, bone and brain. The tissue-specific estrogen synthesis is consistent with a diversity of estrogen actions. Here, we will focus on tissue and cell-specific estrogen synthesis and estrogen receptor signaling. This review will include three parts: (I) tissue and cell-specific estrogen synthesis and metabolism, (II) tissue and cell-specific distribution of estrogen receptors and signaling and (III) tissue-specific estrogen function and related disorders, including cardiovascular diseases, osteoporosis, Alzheimer's disease and Parkinson disease. This comprehensive review provides new insights into estrogens by giving a better understanding of the tissue-specific estrogen effects and their roles in various diseases. PMID:23348042

Linear and Nonlinear Growth Models for Value-Added Assessment: An Application to Spanish Primary and Secondary Schools' Progress in Reading Comprehension

ERIC Educational Resources Information Center

Lopez-Martin, Esther; Kuosmanen, Timo; Gaviria, Jose Luis

2014-01-01

Value-added models are considered one of the best alternatives not only for accountability purposes but also to improve the school system itself. The estimates provided by these models measure the contribution of schools to students' academic progress, once the effect of other factors outside school control are eliminated. The functional form for…

Following the Mobile Student: Can We Develop the Capacity for a Comprehensive Database To Assess Student Progression? Research Report.

ERIC Educational Resources Information Center

Ewell, Peter T.; Schild, Paula R.; Paulson, Karen

A major problem in measuring student success in postsecondary education is the difficulty in tracking students' progress as they transfer from one institution to another. National studies have shown that more than half of students attend more than one institution in their pursuit of a bachelor's degree. This study examined existing state-level…

Pieces of the Puzzle: Factors in the Improvement of Urban School Districts on the National Assessment of Educational Progress. Abstract

ERIC Educational Resources Information Center

Casserly, Michael; Price-Baugh, Ricki; Corcoran, Amanda; Lewis, Sharon; Uzzell, Renata; Simon, Candace; Heppen, Jessica; Leinwand, Steve; Salinger, Terry; de Mello, Victor Bandeira; Dogan, Enis; Novotny, Laura

2011-01-01

This is an abridged, summary report of selected findings from "Pieces of the Puzzle: Factors in the Improvement of Urban School Districts on the National Assessment of Educational Progress"--a comprehensive study prepared by the Council of the Great City Schools in collaboration with the American Institutes for Research (AIR) and with…

Spatial Mapping of Lipids at Cellular Resolution in Embryos of Cotton[W][OA

PubMed Central

Horn, Patrick J.; Korte, Andrew R.; Neogi, Purnima B.; Love, Ebony; Fuchs, Johannes; Strupat, Kerstin; Borisjuk, Ljudmilla; Shulaev, Vladimir; Lee, Young-Jin; Chapman, Kent D.

2012-01-01

Advances in mass spectrometry (MS) have made comprehensive lipidomics analysis of complex tissues relatively commonplace. These compositional analyses, although able to resolve hundreds of molecular species of lipids in single extracts, lose the original cellular context from which these lipids are derived. Recently, high-resolution MS of individual lipid droplets from seed tissues indicated organelle-to-organelle variation in lipid composition, suggesting that heterogeneity of lipid distributions at the cellular level may be prevalent. Here, we employed matrix-assisted laser desorption/ionization–MS imaging (MALDI-MSI) approaches to visualize lipid species directly in seed tissues of upland cotton (Gossypium hirsutum). MS imaging of cryosections of mature cotton embryos revealed a distinct, heterogeneous distribution of molecular species of triacylglycerols and phosphatidylcholines, the major storage and membrane lipid classes in cotton embryos. Other lipids were imaged, including phosphatidylethanolamines, phosphatidic acids, sterols, and gossypol, indicating the broad range of metabolites and applications for this chemical visualization approach. We conclude that comprehensive lipidomics images generated by MALDI-MSI report accurate, relative amounts of lipid species in plant tissues and reveal previously unseen differences in spatial distributions providing for a new level of understanding in cellular biochemistry. PMID:22337917

Microenvironmental Regulation of Mammary Carcinogenesis

DTIC Science & Technology

2008-06-01

cells. These models share many of the hallmarks of multistage human breast cancer development including histological disease progression and immune cell... developed by Muller and colleagues20, represents a reasonable recapitulation of late-stage human breast cancer as determined by histological progression ...Annual Progress Report d. Develop a profile of proteolytic activities in normal and neoplastic mammary tissues from mouse models of mammary

DNA methylome profiling identifies novel methylated genes in African American patients with colorectal neoplasia.

PubMed

Ashktorab, Hassan; Daremipouran, M; Goel, Ajay; Varma, Sudhir; Leavitt, R; Sun, Xueguang; Brim, Hassan

2014-04-01

The identification of genes that are differentially methylated in colorectal cancer (CRC) has potential value for both diagnostic and therapeutic interventions specifically in high-risk populations such as African Americans (AAs). However, DNA methylation patterns in CRC, especially in AAs, have not been systematically explored and remain poorly understood. Here, we performed DNA methylome profiling to identify the methylation status of CpG islands within candidate genes involved in critical pathways important in the initiation and development of CRC. We used reduced representation bisulfite sequencing (RRBS) in colorectal cancer and adenoma tissues that were compared with DNA methylome from a healthy AA subject's colon tissue and peripheral blood DNA. The identified methylation markers were validated in fresh frozen CRC tissues and corresponding normal tissues from AA patients diagnosed with CRC at Howard University Hospital. We identified and validated the methylation status of 355 CpG sites located within 16 gene promoter regions associated with CpG islands. Fifty CpG sites located within CpG islands-in genes ATXN7L1 (2), BMP3 (7), EID3 (15), GAS7 (1), GPR75 (24), and TNFAIP2 (1)-were significantly hypermethylated in tumor vs. normal tissues (P<0.05). The methylation status of BMP3, EID3, GAS7, and GPR75 was confirmed in an independent, validation cohort. Ingenuity pathway analysis mapped three of these markers (GAS7, BMP3 and GPR) in the insulin and TGF-β1 network-the two key pathways in CRC. In addition to hypermethylated genes, our analysis also revealed that LINE-1 repeat elements were progressively hypomethylated in the normal-adenoma-cancer sequence. We conclude that DNA methylome profiling based on RRBS is an effective method for screening aberrantly methylated genes in CRC. While previous studies focused on the limited identification of hypermethylated genes, ours is the first study to systematically and comprehensively identify novel hypermethylated genes, as well as hypomethylated LINE-1 sequences, which may serve as potential biomarkers for CRC in African Americans. Our discovered biomarkers were intimately linked to the insulin/TGF-B1 pathway, further strengthening the association of diabetic disorders with colon oncogenic transformation.

miR-17 inhibitor suppressed osteosarcoma tumor growth and metastasis via increasing PTEN expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Yong, E-mail: gaoyongunion@163.com; Luo, Ling-hui; Li, Shuai

2014-02-07

Highlights: • miR-17 was increased in OS tissues and cell lines. • Inhibition of miR-17 suppressed OS cell proliferation. • Inhibition of miR-17 suppressed OS cell migration and invasion. • PTEN was a target of miR-17. • miR-17 was negatively correlated with PTEN in OS tissues. - Abstract: MicroRNAs (miRNAs) play essential roles in cancer development and progression. Here, we investigated the role of miR-17 in the progression and metastasis of osteosarcoma (OS). miR-17 was frequently increased in OS tissues and cell lines. Inhibition of miR-17 in OS cell lines substantially suppressed cell proliferation, migration, and invasion. Phosphatase and tensinmore » homolog (PTEN) was identified as a target of miR-17, and ectopic expression of miR-17 inhibited PTEN by direct binding to its 3′-untranslated region (3′-UTR). Expression of miR-17 was negatively correlated with PTEN in OS tissues. Together, these findings indicate that miR-17 acts as an oncogenic miRNA and may contribute to the progression and metastasis of OS, suggesting miR-17 as a potential novel diagnostic and therapeutic target of OS.« less

Matrix MetalloProteinases (MMPs) andTissue Inhibitors of MetalloProteinases (TIMPs): positive and negative regulators intumor cell adhesion

PubMed Central

Bourboulia, Dimitra; Stetler-Stevenson, William G.

2010-01-01

Cells adhere to one another and/or to matrices that surround them. Regulation of cell-cell (intercellular) and cell-matrix adhesion is tightly controlled in normal cells, however, defects in cell adhesion are common in the majority of humancancers. Multilateral communication among tumor cells with the extracellular matrix (ECM) and neighbor cells is accomplished through adhesion molecules, ECM components, proteolytic enzymes and their endogenous inhibitors. There is sufficient evidence to suggest that reduced adherence is a tumor cell propertyengaged during tumor progression. Tumor cells acquire the ability to change shape, detach and easily move through spaces disorganizing the normal tissue architecture. This property is due to changes in expression levels of adhesion molecules and/or due to elevated levels of secreted proteolytic enzymes, including matrix metalloproteinases (MMPs). Among other roles, MMPsdegrade the ECMand, therefore, prepare the path for tumor cells to migrate, invade and spread to distant secondary areas, where they form metastasis. Tissue Inhibitors of Metalloproteinases or TIMPs control MMP activities and, therefore, minimize matrix degradation. Both MMPs and TIMPs are involved in tissue remodeling and decisively regulate tumor cell progression including tumor angiogenesis. In this review, we describe and discuss data that support the important role of MMPs and TIMPs in cancer cell adhesion and tumor progression. PMID:20470890

Current progress in tissue engineering of heart valves: multiscale problems, multiscale solutions.

PubMed

Cheung, Daniel Y; Duan, Bin; Butcher, Jonathan T

2015-01-01

Heart valve disease is an increasingly prevalent and clinically serious condition. There are no clinically effective biological diagnostics or treatment strategies. The only recourse available is replacement with a prosthetic valve, but the inability of these devices to grow or respond biologically to their environments necessitates multiple resizing surgeries and life-long coagulation treatment, especially in children. Tissue engineering has a unique opportunity to impact heart valve disease by providing a living valve conduit, capable of growth and biological integration. This review will cover current tissue engineering strategies in fabricating heart valves and their progress towards the clinic, including molded scaffolds using naturally derived or synthetic polymers, decellularization, electrospinning, 3D bioprinting, hybrid techniques, and in vivo engineering. Whereas much progress has been made to create functional living heart valves, a clinically viable product is not yet realized. The next leap in engineered living heart valves will require a deeper understanding of how the natural multi-scale structural and biological heterogeneity of the tissue ensures its efficient function. Related, improved fabrication strategies must be developed that can replicate this de novo complexity, which is likely instructive for appropriate cell differentiation and remodeling whether seeded with autologous stem cells in vitro or endogenously recruited cells.

Current Progress in Tissue Engineering of Heart Valves: Multiscale Problems, Multiscale Solutions

PubMed Central

Cheung, Daniel Y; Duan, Bin; Butcher, Jonathan T.

2016-01-01

Introduction Heart valve disease is an increasingly prevalent and clinically serious condition. There are no clinically effective biological diagnostics or treatment strategies. The only recourse available is replacement with a prosthetic valve, but the inability of these devices to grow or respond biologically to their environments necessitates multiple resizing surgeries and life-long coagulation treatment, especially in children. Tissue engineering has a unique opportunity to impact heart valve disease by providing a living valve conduit, capable of growth and biological integration. Areas covered This review will cover current tissue engineering strategies in fabricating heart valves and their progress towards the clinic, including molded scaffolds using naturally-derived or synthetic polymers, decellularization, electrospinning, 3D bioprinting, hybrid techniques, and in vivo engineering. Expert opinion While much progress has been made to create functional living heart valves, a clinically viable product is not yet realized. The next leap in engineered living heart valves will require a deeper understanding of how the natural multi-scale structural and biological heterogeneity of the tissue ensures its efficient function. Related, improved fabrication strategies must be developed that can replicate this de novo complexity, which is likely instructive for appropriate cell differentiation and remodeling whether seeded with autologous stem cells in vitro or endogenously recruited cells. PMID:26027436

Stockpiling and Comprehensive Utilization of Red Mud Research Progress

PubMed Central

Liu, Dong-Yan; Wu, Chuan-Sheng

2012-01-01

With increasing production of red mud, the environmental problems caused by it are increasingly serious, and thus the integrated treatment of red mud is imminent. This article provides an overview of the composition and the basic characteristics of red mud. The research progress of safe stockpiling and comprehensive utilization of red mud is summarized. The safe stockpiling of red mud can be divided into two aspects: the design and safe operation of the stocking yard. The comprehensive utilization of red mud can be further divided into three aspects: the effective recycling of components, resource utilization and application in the field of environmental protection. This paper points out that the main focus of previous studies on red mud stockpiling is cost reproduction and land tenure. The recovery of resources from red mud has a high value-added, but low level industrialization. The use of red mud as a building material and filler material is the most effective way to reduce the stockpiling of red mud. Red mud used for environmental remediation materials is a new hotspot and worth promoting for its simple processing and low cost.

Proteolytic roles of matrix metalloproteinase (MMP)-13 during progression of chronic periodontitis: initial evidence for MMP-13/MMP-9 activation cascade.

PubMed

Hernández Ríos, Marcela; Sorsa, Timo; Obregón, Fabián; Tervahartiala, Taina; Valenzuela, María Antonieta; Pozo, Patricia; Dutzan, Nicolás; Lesaffre, Emmanuel; Molas, Marek; Gamonal, Jorge

2009-12-01

Matrix metalloproteinases (MMP)-13 can initiate bone resorption and activate proMMP-9 in vitro, and both these MMPs have been widely implicated in tissue destruction associated with chronic periodontitis. We studied whether MMP-13 activity and TIMP-1 levels in gingival crevicular fluid (GCF) associated with progression of chronic periodontitis assessed clinically and by measuring carboxy-terminal telopeptide of collagen I (ICTP) levels. We additionally addressed whether MMP-13 could potentiate gelatinase activation in diseased gingival tissue. In this prospective study, GCF samples from subjects undergoing clinical progression of chronic periodontitis and healthy controls were screened for ICTP levels, MMP-13 activity and TIMP-1. Diseased gingival explants were cultured, treated or not with MMP-13 with or without adding CL-82198, a synthetic MMP-13 selective inhibitor, and assayed by gelatin zymography and densitometric analysis. Active sites demonstrated increased ICTP levels and MMP-13 activity (p<0.05) in progression subjects. The MMP-9 activation rate was elevated in MMP-13-treated explants (p<0.05) and MMP-13 inhibitor prevented MMP-9 activation. MMP-13 could be implicated in the degradation of soft and hard supporting tissues and proMMP-9 activation during progression of chronic periodontitis. MMP-13 and -9 can potentially form an activation cascade overcoming the protective TIMP-1 shield, which may become useful for diagnostic aims and a target for drug development.

Early Prediction of Cancer Progression by Depth-Resolved Nanoscale Mapping of Nuclear Architecture from Unstained Tissue Specimens.

PubMed

Uttam, Shikhar; Pham, Hoa V; LaFace, Justin; Leibowitz, Brian; Yu, Jian; Brand, Randall E; Hartman, Douglas J; Liu, Yang

2015-11-15

Early cancer detection currently relies on screening the entire at-risk population, as with colonoscopy and mammography. Therefore, frequent, invasive surveillance of patients at risk for developing cancer carries financial, physical, and emotional burdens because clinicians lack tools to accurately predict which patients will actually progress into malignancy. Here, we present a new method to predict cancer progression risk via nanoscale nuclear architecture mapping (nanoNAM) of unstained tissue sections based on the intrinsic density alteration of nuclear structure rather than the amount of stain uptake. We demonstrate that nanoNAM detects a gradual increase in the density alteration of nuclear architecture during malignant transformation in animal models of colon carcinogenesis and in human patients with ulcerative colitis, even in tissue that appears histologically normal according to pathologists. We evaluated the ability of nanoNAM to predict "future" cancer progression in patients with ulcerative colitis who did and did not develop colon cancer up to 13 years after their initial colonoscopy. NanoNAM of the initial biopsies correctly classified 12 of 15 patients who eventually developed colon cancer and 15 of 18 who did not, with an overall accuracy of 85%. Taken together, our findings demonstrate great potential for nanoNAM in predicting cancer progression risk and suggest that further validation in a multicenter study with larger cohorts may eventually advance this method to become a routine clinical test. ©2015 American Association for Cancer Research.

A Computational Clonal Analysis of the Developing Mouse Limb Bud

PubMed Central

Marcon, Luciano; Arqués, Carlos G.; Torres, Miguel S.; Sharpe, James

2011-01-01

A comprehensive spatio-temporal description of the tissue movements underlying organogenesis would be an extremely useful resource to developmental biology. Clonal analysis and fate mappings are popular experiments to study tissue movement during morphogenesis. Such experiments allow cell populations to be labeled at an early stage of development and to follow their spatial evolution over time. However, disentangling the cumulative effects of the multiple events responsible for the expansion of the labeled cell population is not always straightforward. To overcome this problem, we develop a novel computational method that combines accurate quantification of 2D limb bud morphologies and growth modeling to analyze mouse clonal data of early limb development. Firstly, we explore various tissue movements that match experimental limb bud shape changes. Secondly, by comparing computational clones with newly generated mouse clonal data we are able to choose and characterize the tissue movement map that better matches experimental data. Our computational analysis produces for the first time a two dimensional model of limb growth based on experimental data that can be used to better characterize limb tissue movement in space and time. The model shows that the distribution and shapes of clones can be described as a combination of anisotropic growth with isotropic cell mixing, without the need for lineage compartmentalization along the AP and PD axis. Lastly, we show that this comprehensive description can be used to reassess spatio-temporal gene regulations taking tissue movement into account and to investigate PD patterning hypothesis. PMID:21347315

A Functional High-Throughput Assay of Myelination in Vitro

DTIC Science & Technology

2013-07-01

feasibility of developing microengineered human neural tissues that can be assessed non-invasively. A population of neurons has been derived from human...physiological responses in microengineered tissue constructs has been demonstrated. This works represents a unique combination of enabling...and recording from microengineered tissues. All progress and results discussed in this report are in regard to the revised Statement of Work

Alzheimer's disease: neuroprogesterone, epoxycholesterol, and ABC transporters as determinants of neurodesmosterol tissue levels and its role in amyloid protein processing.

PubMed

Javitt, Norman B

2013-01-01

Evidence is emerging that during the development of Alzheimer's disease (AD), changes in the synthesis and metabolism of cholesterol and progesterone are occurring that may or may not affect the progression of the disease. The concept arose from the recognition that dehydrocholesterol 24-reductase (DHCR24/Seladin-1), one of the nine enzymes in the endoplasmic reticulum that determines the transformation of lanosterol to cholesterol, is selectively reduced in late AD. As a consequence, the tissue level of desmosterol increases, affecting the expression of ABC transporters and the structure of lipid rafts, both determinants of amyloid-β processing. However, the former effect is considered beneficial and the latter detrimental to processing. Other determinants of desmosterol tissue levels are 24,25 epoxycholesterol and the ABCG1 and ABCG4 transporters. Progesterone and its metabolites are determinants of tissue levels of desmosterol and several other sterol intermediates in cholesterol synthesis. Animal models indicate marked elevations in the tissue levels of these sterols at early time frames in the progression of neurodegenerative diseases. The low level of neuroprogesterone and metabolites in AD are consonant with the low level of desmosterol and may have a role in amyloid-β processing. The sparse data that has accumulated appears to be a sufficient basis for proposing a systematic evaluation of the biologic roles of sterol intermediates in the slowly progressive neurodegeneration characteristic of AD.

Progress in reflectance confocal microscopy for imaging oral tissues in vivo

NASA Astrophysics Data System (ADS)

Peterson, Gary; Zanoni, Daniella K.; Migliacci, Jocelyn; Cordova, Miguel; Rajadhyaksha, Milind; Patel, Snehal

2016-02-01

We report progress in development and feasibility testing of reflectance confocal microscopy (RCM) for imaging in the oral cavity of humans. We adapted a small rigid relay telescope (120mm long x 14mm diameter) and a small water immersion objective lens (12mm diameter, NA 0.7) to a commercial handheld RCM scanner (Vivascope 3000, Caliber ID, Rochester NY). This scanner is designed for imaging skin but we adapted the front end (the objective lens and the stepper motor that axially translates) for intra-oral use. This adaption required a new approach to address the loss of the automated stepper motor for acquisition of images in depth. A helical spring-like cap (with a coverslip to contact tissue) was designed for approximately 150 um of travel. Additionally other methods for focusing optics were designed and evaluated. The relay telescope optics is being tested in a clinical setting. With the capture of video and "video-mosaicing", extended areas can be imaged. The feasibility of imaging oral tissues was initially investigated in volunteers. RCM imaging in buccal mucosa in vivo shows nuclear and cellular detail in the epithelium and epithelial junction, and connective tissue and blood flow in the underlying lamina propria. Similar detail, including filiform and fungiform papillae, can be seen on the tongue in vivo. Clinical testing during head and neck surgery is now in progress and patients are being imaged for both normal tissue and cancerous margins in lip and tongue mucosa.

Crosstalk between the heart and peripheral organs in heart failure

PubMed Central

Jahng, James Won Suk; Song, Erfei; Sweeney, Gary

2016-01-01

Mediators from peripheral tissues can influence the development and progression of heart failure (HF). For example, in obesity, an altered profile of adipokines secreted from adipose tissue increases the incidence of myocardial infarction (MI). Less appreciated is that heart remodeling releases cardiokines, which can strongly impact various peripheral tissues. Inflammation, and, in particular, activation of the nucleotide-binding oligomerization domain-like receptors with pyrin domain (NLRP3) inflammasome are likely to have a central role in cardiac remodeling and mediating crosstalk with other organs. Activation of the NLRP3 inflammasome in response to cardiac injury induces the production and secretion of the inflammatory cytokines interleukin (IL)-1β and IL-18. In addition to having local effects in the myocardium, these pro-inflammatory cytokines are released into circulation and cause remodeling in the spleen, kidney, skeletal muscle and adipose tissue. The collective effects of various cardiokines on peripheral organs depend on the degree and duration of myocardial injury, with systematic inflammation and peripheral tissue damage observed as HF progresses. In this article, we review mechanisms regulating myocardial inflammation in HF and the role of factors secreted by the heart in communication with peripheral tissues. PMID:26964833

Effectiveness of comprehensive fixed appliance treatment used with the Forsus Fatigue Resistant Device in Class II patients.

PubMed

Franchi, Lorenzo; Alvetro, Lisa; Giuntini, Veronica; Masucci, Caterina; Defraia, Efisio; Baccetti, Tiziano

2011-07-01

To assess the dental, skeletal, and soft tissue effects of comprehensive fixed appliance treatment combined with the Forsus Fatigue Resistant Device (FRD) in Class II patients. Thirty-two Class II patients (mean age 12.7 ± 1.2 years) were treated consecutively with the FRD protocol and compared with a matched sample of 27 untreated Class II subjects (mean age 12.8 ± 1.3 years). Lateral cephalograms were taken before therapy and at the completion of comprehensive therapy. The mean duration of comprehensive treatment was 2.4 ± 0.4 years. Statistical comparisons were carried out with the Student's t-test (P < .05). The success rate was 87.5%. The FRD group showed a significant restraint in the sagittal skeletal position of the maxilla (also at the soft tissue level), a significant increase in mandibular length, and a significant improvement in maxillo-mandibular sagittal skeletal relationships. The treated group exhibited a significant reduction in overjet and a significant increase in molar relationship. The lower incisors were significantly proclined and intruded, while the lower first molars moved significantly in a mesial and vertical direction. The FRD protocol is effective in correcting Class II malocclusion with a combination of skeletal (mainly maxillary) and dentoalveolar (mainly mandibular) modifications.

Cartilage Dysfunction in ALS Patients as Side Effect of Motion Loss: 3D Mechano-Electrochemical Computational Model

PubMed Central

Gaffney, Eamonn A.; Doblaré, Manuel

2014-01-01

Amyotrophic lateral sclerosis (ALS) is a debilitating motor neuron disease characterized by progressive weakness, muscle atrophy, and fasciculation. This fact results in a continuous degeneration and dysfunction of articular soft tissues. Specifically, cartilage is an avascular and nonneural connective tissue that allows smooth motion in diarthrodial joints. Due to the avascular nature of cartilage tissue, cells nutrition and by-product exchange are intermittently occurring during joint motions. Reduced mobility results in a change of proteoglycan density, osmotic pressure, and permeability of the tissue. This work aims to demonstrate the abnormal cartilage deformation in progressive immobilized articular cartilage for ALS patients. For this aim a novel 3D mechano-electrochemical model based on the triphasic theory for charged hydrated soft tissues is developed. ALS patient parameters such as tissue porosity, osmotic coefficient, and fixed anions were incorporated. Considering different mobility reduction of each phase of the disease, results predicted the degree of tissue degeneration and the reduction of its capacity for deformation. The present model can be a useful tool to predict the evolution of joints in ALS patients and the necessity of including specific cartilage protectors, drugs, or maintenance physical activities as part of the symptomatic treatment in amyotrophic lateral sclerosis. PMID:24991537

Using the cavitation collapse time to indicate the extent of histotripsy-induced tissue fractionation

NASA Astrophysics Data System (ADS)

Macoskey, J. J.; Choi, S. W.; Hall, T. L.; Vlaisavljevich, E.; Lundt, J. E.; Lee, F. T., Jr.; Johnsen, E.; Cain, C. A.; Xu, Z.

2018-03-01

Histotripsy is an ultrasonic tissue ablation method based on acoustic cavitation. It has been shown that cavitation dynamics change depending on the mechanical properties of the host medium. During histotripsy treatment, the target-tissue is gradually fractionated and eventually liquefied to acellular homogenate. In this study, the change in the collapse time (t col) of the cavitation bubble cloud over the course of histotripsy treatment is investigated as an indicator for progression of the tissue fractionation process throughout treatment. A 500 kHz histotripsy transducer is used to generate single-location lesions within tissue-mimicking agar phantoms of varying stiffness levels as well as ex vivo bovine liver samples. Cavitation collapse signals are acquired with broadband hydrophones, and cavitation is imaged optically using a high-speed camera in transparent tissue-mimicking phantoms. The high-speed-camera-acquired measurements of t col validate the acoustic hydrophone measurements. Increases in t col are observed both with decreasing phantom stiffness and throughout histotripsy treatment with increasing number of pulses applied. The increasing trend of t col throughout the histotripsy treatment correlates well with the progression of lesion formation generated in tissue-mimicking phantoms (R 2  =  0.87). Finally, the increasing trend of t col over the histotripsy treatment is validated in ex vivo bovine liver.

From in vitro to in vivo Models of Bacterial Biofilm-Related Infections

PubMed Central

Lebeaux, David; Chauhan, Ashwini; Rendueles, Olaya; Beloin, Christophe

2013-01-01

The influence of microorganisms growing as sessile communities in a large number of human infections has been extensively studied and recognized for 30–40 years, therefore warranting intense scientific and medical research. Nonetheless, mimicking the biofilm-life style of bacteria and biofilm-related infections has been an arduous task. Models used to study biofilms range from simple in vitro to complex in vivo models of tissues or device-related infections. These different models have progressively contributed to the current knowledge of biofilm physiology within the host context. While far from a complete understanding of the multiple elements controlling the dynamic interactions between the host and biofilms, we are nowadays witnessing the emergence of promising preventive or curative strategies to fight biofilm-related infections. This review undertakes a comprehensive analysis of the literature from a historic perspective commenting on the contribution of the different models and discussing future venues and new approaches that can be merged with more traditional techniques in order to model biofilm-infections and efficiently fight them. PMID:25437038

Oxidative Stress and Epigenetic Regulation in Ageing and Age-Related Diseases

PubMed Central

Cencioni, Chiara; Spallotta, Francesco; Martelli, Fabio; Valente, Sergio; Mai, Antonello; Zeiher, Andreas M.; Gaetano, Carlo

2013-01-01

Recent statistics indicate that the human population is ageing rapidly. Healthy, but also diseased, elderly people are increasing. This trend is particularly evident in Western countries, where healthier living conditions and better cures are available. To understand the process leading to age-associated alterations is, therefore, of the highest relevance for the development of new treatments for age-associated diseases, such as cancer, diabetes, Alzheimer and cardiovascular accidents. Mechanistically, it is well accepted that the accumulation of intracellular damage determined by reactive oxygen species (ROS) might orchestrate the progressive loss of control over biological homeostasis and the functional impairment typical of aged tissues. Here, we review how epigenetics takes part in the control of stress stimuli and the mechanisms of ageing physiology and physiopathology. Alteration of epigenetic enzyme activity, histone modifications and DNA-methylation is, in fact, typically associated with the ageing process. Specifically, ageing presents peculiar epigenetic markers that, taken altogether, form the still ill-defined “ageing epigenome”. The comprehension of mechanisms and pathways leading to epigenetic modifications associated with ageing may help the development of anti-ageing therapies. PMID:23989608

Use of diagnostics in wound management.

PubMed

Romanelli, Marco; Miteva, Maria; Romanelli, Paolo; Barbanera, Sabrina; Dini, Valentina

2013-03-01

Wound healing research has progressed impressively over the past years. New insights into the pathogenesis of different chronic wounds and the study of novel treatment have made wound healing a model disorder and have revealed basic cellular and molecular mechanisms underlying chronic wounds. Although the observation is so obvious and simple, the interpretations by different observers can be quite variable. The interpretations of severity and change in severity by treatment may differ considerably between patient and practitioners. In this review we provide comprehensive view on different aspects of wound diagnostic, including clinical measurement, new biomarkers in wound pathology, proteases evaluation, and future noninvasive sensor-based devices. Wound caregivers are in the unique position of being able to observe the wound changes and describe these with knowledge and strict methodology, but also with the wide range of available wound diagnostic devices. The complexity of severity assessment in wound healing is reflected by the multiple clinical scores available. The best objective methods used to evaluate cutaneous tissue repair should have a high specificity and sensitivity and a low inter and intraobserver variation.

Application of NMR-based metabolomics to the study of gut microbiota in obesity.

PubMed

Calvani, Riccardo; Brasili, Elisa; Praticò, Giulia; Sciubba, Fabio; Roselli, Marianna; Finamore, Alberto; Marini, Federico; Marzetti, Emanuele; Miccheli, Alfredo

2014-01-01

Lifestyle habits, host gene repertoire, and alterations in the intestinal microbiota concur to the development of obesity. A great deal of research has recently been focused on investigating the role gut microbiota plays in the pathogenesis of metabolic dysfunctions and increased adiposity. Altered microbiota can affect host physiology through several pathways, including enhanced energy harvest, and perturbations in immunity, metabolic signaling, and inflammatory pathways. A broad range of "omics" technologies is now available to help decipher the interactions between the host and the gut microbiota at detailed genetic and functional levels. In particular, metabolomics--the comprehensive analysis of metabolite composition of biological fluids and tissues--could provide breakthrough insights into the links among the gut microbiota, host genetic repertoire, and diet during the development and progression of obesity. Here, we briefly review the most insightful findings on the involvement of gut microbiota in the pathogenesis of obesity. We also discuss how metabolomic approaches based on nuclear magnetic resonance spectroscopy could help understand the activity of gut microbiota in relation to obesity, and assess the effects of gut microbiota modulation in the treatment of this condition.

Acquire: an open-source comprehensive cancer biobanking system.

PubMed

Dowst, Heidi; Pew, Benjamin; Watkins, Chris; McOwiti, Apollo; Barney, Jonathan; Qu, Shijing; Becnel, Lauren B

2015-05-15

The probability of effective treatment of cancer with a targeted therapeutic can be improved for patients with defined genotypes containing actionable mutations. To this end, many human cancer biobanks are integrating more tightly with genomic sequencing facilities and with those creating and maintaining patient-derived xenografts (PDX) and cell lines to provide renewable resources for translational research. To support the complex data management needs and workflows of several such biobanks, we developed Acquire. It is a robust, secure, web-based, database-backed open-source system that supports all major needs of a modern cancer biobank. Its modules allow for i) up-to-the-minute 'scoreboard' and graphical reporting of collections; ii) end user roles and permissions; iii) specimen inventory through caTissue Suite; iv) shipping forms for distribution of specimens to pathology, genomic analysis and PDX/cell line creation facilities; v) robust ad hoc querying; vi) molecular and cellular quality control metrics to track specimens' progress and quality; vii) public researcher request; viii) resource allocation committee distribution request review and oversight and ix) linkage to available derivatives of specimen. © The Author 2015. Published by Oxford University Press.

HNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancer

PubMed Central

Ross-Adams, Helen; Ball, Stephen; Lawrenson, Kate; Halim, Silvia; Russell, Roslin; Wells, Claire; Strand, Siri H.; Ørntoft, Torben F.; Larson, Melissa; Armasu, Sebastian; Massie, Charles E.; Asim, Mohammad; Mortensen, Martin M.; Borre, Michael; Woodfine, Kathryn; Warren, Anne Y.; Lamb, Alastair D.; Kay, Jonathan; Whitaker, Hayley; Ramos-Montoya, Antonio; Murrell, Adele; Sørensen, Karina D.; Fridley, Brooke L.; Goode, Ellen L.; Gayther, Simon A.; Masters, John

2016-01-01

Two independent regions within HNF1B are consistently identified in prostate and ovarian cancer genome-wide association studies (GWAS); their functional roles are unclear. We link prostate cancer (PC) risk SNPs rs11649743 and rs3760511 with elevated HNF1B gene expression and allele-specific epigenetic silencing, and outline a mechanism by which common risk variants could effect functional changes that increase disease risk: functional assays suggest that HNF1B is a pro-differentiation factor that suppresses epithelial-to-mesenchymal transition (EMT) in unmethylated, healthy tissues. This tumor-suppressor activity is lost when HNF1B is silenced by promoter methylation in the progression to PC. Epigenetic inactivation of HNF1B in ovarian cancer also associates with known risk SNPs, with a similar impact on EMT. This represents one of the first comprehensive studies into the pleiotropic role of a GWAS-associated transcription factor across distinct cancer types, and is the first to describe a conserved role for a multi-cancer genetic risk factor. PMID:27732966

The Interplay of LncRNA-H19 and Its Binding Partners in Physiological Process and Gastric Carcinogenesis

PubMed Central

Zhang, Li; Zhou, Yuhang; Huang, Tingting; Cheng, Alfred S. L.; Yu, Jun; Kang, Wei; To, Ka Fai

2017-01-01

Long non-coding RNA (lncRNA), a novel and effective modulator in carcinogenesis, has become a study hotspot in recent years. The imprinted oncofetal lncRNA H19 is one of the first identified imprinted lncRNAs with a high expression level in embryogenesis but is barely detectable in most tissues after birth. Aberrant alterations of H19 expression have been demonstrated in various tumors, including gastric cancer (GC), implicating a crucial role of H19 in cancer progression. As one of the top malignancies in the world, GC has already become a serious concern to public health with poor prognosis. The regulatory roles of H19 in gastric carcinogenesis have been explored by various research groups, which leads to the development of GC therapy. This review comprehensively summarizes the current knowledge of H19 in tumorigenesis, especially in GC pathogenesis, with emphasis on the underneath molecular mechanisms depicted from its functional partners. Furthermore, the accumulated knowledge of H19 will provide better understanding on targeted therapy of GC. PMID:28230721

Use of a Lysine-Derived Urethane Surgical Adhesive as an Alternative to Progressive Tension Sutures in Abdominoplasty Patients: A Cohort Study.

PubMed

Spring, Michelle A

2018-04-07

Fluid accumulation is a common complication after abdominoplasty procedures, and is typically managed by the placement of post-surgical drains. Progressive tension sutures (PTS) have been shown to be an effective approach to reduce the dead space by point-wise mechanical fixation, allowing for drain-free procedures. Lysine-derived urethane surgical adhesive provides an alternative approach for mechanical fixation and reduction of dead space, and may reduce surgery time compared to PTS. This prospective, controlled, single center clinical study compared progressive tension suture wound closure technique without drains (control) to tissue adhesive wound closure technique without drains (test) during abdominoplasty surgery. The objective was to determine if lysine-derived urethane surgical adhesive is an effective alternative to PTS for drain-free abdominoplasty procedures. Patients undergoing abdominoplasty who met the established inclusion/exclusion criteria were consented and enrolled in the study. Ten PTS (control) cases were performed, followed immediately by ten tissue adhesive (test) cases. Drains were not used in any procedures. Key outcome measures included all major and minor post-surgical complications requiring any intervention, the time to place progressive tension sutures versus time for tissue adhesive application, and number of PTS attachments versus number of adhesive drops applied. Surgeries were completed over an 8-month period. No statistical differences were identified between the two groups with regard to age, BMI, dissection surface area or flap weight. No clinical seroma formation was observed in either group. In the control (PTS) group, two patients developed small areas of dermal closure suture abscess requiring removal of suture material. One control patient developed drainage and fat necrosis thought to be related to PTS above the incision and later required a scar revision. One tissue adhesive patient developed hypertrophic scars of both her breast reduction and abdominoplasty scars requiring additional treatment. The average time to place PTS in the control group was 10.7 minutes (range, 7-18 minutes) and the average number of sutures placed was 16.6 (range, 12-22 sutures). In the test group, the average time to place the tissue adhesive and hold pressure was 5.9 minutes (range 5.5-8.0 minutes). The average number of tissue adhesive drops applied was 69.6 (range: 63-78 drops). In the tissue adhesive group, both the reduction in time for flap adhesion and the increased number of adhesive points were statistically significant when compared to PTS. Lysine-derived urethane surgical adhesive was applied in less time than progressive tension sutures, even after accounting for holding pressure for 5 minutes. The tissue adhesive provided four times the number of attachment points compared to PTS, although the significance of this is not clear. There were no postoperative clinical seromas detected in either group and there were no major complications in either group. Based on these results, the use of lysine-derived urethane surgical adhesive was found to be a safe and effective alternative to progressive tension sutures to reduce seroma formation in drain-free abdominoplasty procedures.

Comprehensive Study of Acute Effects and Recovery After Concussion

DTIC Science & Technology

2015-10-01

1 AD______________ AWARD NUMBER: W81XWH-14-1-0561 TITLE: Comprehensive Study of Acute Effects and Recovery After Concussion PRINCIPAL... Concussion 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Michael McCrea, PhD, ABPP 5d. PROJECT NUMBER Professor & Director of Brain Injury Research...course of 3 years, the project is progressing on schedule. We baseline tested 545 football athletes from July 13, 2015 to Aug 21, 2015. We enrolled

[Pulmonary involvement in connective tissue disease].

PubMed

Bartosiewicz, Małgorzata

2016-01-01

The connective tissue diseases are a variable group of autoimmune mediated disorders characterized by multiorgan damage. Pulmonary complications are common, usually occur after the onset of joint symptoms, but can also be initially presenting complaint. The respiratory system may be involved in all its component: airways, vessels, parenchyma, pleura and respiratory muscles. Lung involvement is an increasing cause of morbidity and mortality in the connective tissue diseases. Clinical course is highly variable - can range from mild to rapidly progressive, some processes are reversible, while others are irreversible. Thus, the identification of reversible disease , and separately progressive disease, are important clinical issues. The frequency, clinical presentation, prognosis and responce to therapy are different, depending on the pattern of involvement as well as on specyfic diagnostic method used to identify it. High- resolution computed tompography plays an important role in identifying patients with respiratory involvement. Pulmonary function tests are a sensitive tool detecting interstitial lung disease. In this article, pulmonary lung involvement accompanying most frequently apperaing connective tissue diseases - rheumatoid arthritis, systemic sclerosis, lupus erythematosus, polymyositis/dermatomyositis, Sjögrens syndrome and mixed connective tissue disaese are reviewed.

[RESEARCH PROGRESS OF THREE-DIMENSIONAL PRINTING POROUS SCAFFOLDS FOR BONE TISSUE ENGINEERING].

PubMed

Wu, Tianqi; Yang, Chunxi

2016-04-01

To summarize the research progress of several three-dimensional (3-D)-printing scaffold materials in bone tissue engineering. The recent domestic and international articles about 3-D printing scaffold materials were reviewed and summarized. Compared with conventional manufacturing methods, 3-D printing has distinctive advantages, such as enhancing the controllability of the structure and increasing the productivity. In addition to the traditional metal and ceramic scaffolds, 3-D printing scaffolds carrying seeding cells and tissue factors as well as scaffolds filling particular drugs for special need have been paid more and more attention. The development of 3-D printing porous scaffolds have revealed new perspectives in bone repairing. But it is still at the initial stage, more basic and clinical researches are still needed.

Maggot therapy in treatment of a complex hand injury complicated by mycotic infection.

PubMed

Bohac, M; Cambal, M; Zamborsky, R; Takac, P; Fedeles, J

2015-01-01

Complex injuries of the hand remain a therapeutic challenge for surgeons. We present the case of a male who suffered a devastating injury of the hand caused by a conveyor belt. The patient developed a progressive Absidia corymbifera infection of the affected soft tissues. Initial treatments with serial surgical debridement and topical and intravenous itraconazole were unsuccessful in eliminating the infection. We decided to use maggot debridement therapy in a new special design to debride all necrotic, devitalized tissue and preserve only healthy tissue and functioning structures. This maneuverer followed by negative pressure therapy allowed progressive healing. In such complex hand injuries, maggot debridement combined with negative pressure therapy could be considered to achieve effective and considerable results, although future functional morbidity may occur (Fig. 4, Ref. 18).

Cancer as a changed tissue's way of life (when to treat, when to watch and when to think).

PubMed

Demicheli, Romano; Quiton, Dinah Faith T; Fornili, Marco; Hrushesky, William Jm

2016-03-01

The profound scientific and commercial success of molecular biology, the progress of 'cancer gene' investigation technologies, together, pushed forward the postulate that genes explain 'everything'. Yet, during the last few years the microenvironments of solid tumors have emerged as key modulators of initiation, progression and metastasis and as essential to the therapeutic response. In the present review, we provide a synthetic examination of the main traits of cells embedded into the cancer stroma and emphasize several evidences that all components of the tumor tissue cooperate in space and time. Then we turn to discuss the epitheliocentric somatic mutational view and other new paradigms assuming that disturbed tissue interactions among cell populations are critical to cancer causation, growth and spread.

Radiation injury to the temporal bone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guida, R.A.; Finn, D.G.; Buchalter, I.H.

1990-01-01

Osteoradionecrosis of the temporal bone is an unusual sequela of radiation therapy to the head and neck. Symptoms occur many years after the radiation is administered, and progression of the disease is insidious. Hearing loss (sensorineural, conductive, or mixed), otalgia, otorrhea, and even gross tissue extrusion herald this condition. Later, intracranial complications such as meningitis, temporal lobe or cerebellar abscess, and cranial neuropathies may occur. Reported here are five cases of this rare malady representing varying degrees of the disease process. They include a case of radiation-induced necrosis of the tympanic ring with persistent squamous debris in the external auditorymore » canal and middle ear. Another case demonstrates the progression of radiation otitis media to mastoiditis with bony sequestration. Further progression of the disease process is seen in a third case that evolved into multiple cranial neuropathies from skull base destruction. Treatment includes systemic antibiotics, local wound care, and debridement in cases of localized tissue involvement. More extensive debridement with removal of sequestrations, abscess drainage, reconstruction with vascularized tissue from regional flaps, and mastoid obliteration may be warranted for severe cases. Hyperbaric oxygen therapy has provided limited benefit.« less

The dark side of hippo signaling: A cancer promoter role.

PubMed

Dunn, Brandon; Ma, Xianjue

2017-10-02

The Hippo signaling pathway regulates organ size and tissue homeostasis. Given this role it is unsurprising that dysregulation of this pathway has implications for cancer progression. A convincing body of literature shows that the Hippo pathway serves a tumor suppressive function with its inactivation leading to massive overgrowth. However, additional studies have also shown that activation of Hippo signaling can promote tumor progression. It remains unknown how a single pathway can produce such diametrically opposed effects. This lack of knowledge is in part due to our inability to make meaningful comparisons from studies which have taken place in a variety of cell types, tissues, and organisms. Recently however, we have published 2 studies using the Drosophila wing disk to study the Hippo pathway and have found that Hippo pathway activation can promote cell migration and invasion while Hippo pathway inactivation leads to overgrowth. Thus we propose here that Drosophila can provide a research platform with which to begin addressing how the Hippo pathway can both enhance and suppress tumor progression due to published pro- and anti-tumor functionalities of the Hippo pathway in the same tissue.

At the Crossroads of Clinical and Preclinical Research for Muscular Dystrophy-Are We Closer to Effective Treatment for Patients?

PubMed

Gawlik, Kinga I

2018-05-16

Among diseases affecting skeletal muscle, muscular dystrophy is one of the most devastating and complex disorders. The term 'muscular dystrophy' refers to a heterogeneous group of genetic diseases associated with a primary muscle defect that leads to progressive muscle wasting and consequent loss of muscle function. Muscular dystrophies are accompanied by numerous clinical complications and abnormalities in other tissues that cause extreme discomfort in everyday life. The fact that muscular dystrophy often takes its toll on babies and small children, and that many patients die at a young age, adds to the cruel character of the disease. Clinicians all over the world are facing the same problem: they have no therapy to offer except for symptom-relieving interventions. Patients, their families, but also clinicians, are in urgent need of an effective cure. Despite advances in genetics, increased understanding of molecular mechanisms underlying muscle disease, despite a sweeping range of successful preclinical strategies and relative progress of their implementation in the clinic, therapy for patients is currently out of reach. Only a greater comprehension of disease mechanisms, new preclinical studies, development of novel technologies, and tight collaboration between scientists and physicians can help improve clinical treatment. Fortunately, inventiveness in research is rapidly extending the limits and setting new standards for treatment design. This review provides a synopsis of muscular dystrophy and considers the steps of preclinical and clinical research that are taking the muscular dystrophy community towards the fundamental goal of combating the traumatic disease.

Progress and promises of human cardiac magnetic resonance at ultrahigh fields: a physics perspective.

PubMed

Niendorf, Thoralf; Graessl, Andreas; Thalhammer, Christof; Dieringer, Matthias A; Kraus, Oliver; Santoro, Davide; Fuchs, Katharina; Hezel, Fabian; Waiczies, Sonia; Ittermann, Bernd; Winter, Lukas

2013-04-01

A growing number of reports eloquently speak about explorations into cardiac magnetic resonance (CMR) at ultrahigh magnetic fields (B0≥7.0 T). Realizing the progress, promises and challenges of ultrahigh field (UHF) CMR this perspective outlines current trends in enabling MR technology tailored for cardiac MR in the short wavelength regime. For this purpose many channel radiofrequency (RF) technology concepts are outlined. Basic principles of mapping and shimming of transmission fields including RF power deposition considerations are presented. Explorations motivated by the safe operation of UHF-CMR even in the presence of conductive implants are described together with the physics, numerical simulations and experiments, all of which detailing antenna effects and RF heating induced by intracoronary stents at 7.0 T. Early applications of CMR at 7.0 T and their clinical implications for explorations into cardiovascular diseases are explored including assessment of cardiac function, myocardial tissue characterization, MR angiography of large and small vessels as well as heteronuclear MR of the heart and the skin. A concluding section ventures a glance beyond the horizon and explores future directions. The goal here is not to be comprehensive but to inspire the biomedical and diagnostic imaging communities to throw further weight behind the solution of the many remaining unsolved problems and technical obstacles of UHF-CMR with the goal to transfer MR physics driven methodological advancements into extra clinical value. Copyright © 2012 Elsevier Inc. All rights reserved.

Data-Based Interval Throwing Programs for Collegiate Softball Players

PubMed Central

Axe, Michael J.; Windley, Thomas C.; Snyder-Mackler, Lynn

2002-01-01

Objective: To construct interval throwing programs followed by a simulated game for collegiate softball players at all positions. The programs are intended to be used as functional progressions within a comprehensive rehabilitation program for an injured athlete or to augment off-season conditioning workouts. Design and Setting: We collected data over a single season of National Collegiate Athletic Association softball at the University of Delaware and Goldey Beacom College. We observed 220 half-innings of play and 2785 pitches during data collection. Subjects: The subjects were collegiate-level softball players at all positions of play. Measurements: We recorded the number of pitches for pitchers. For catchers, we recorded the number of sprints to back up a play, time in the squat stance, throws back to the pitcher, and the perceived effort and distance of all other throws. We also collected the perceived effort and distance of all throws for infielders and outfielders. Results: Pitchers threw an average of 89.61 pitches per game; catchers were in the squat stance 14.13 minutes per game; infielders threw the ball between 4.28 times per game and 6.30 times per game; and outfielders threw distances of up to 175 feet. Conclusions: We devised the interval throwing programs from the data collected, field dimensions, the types of injuries found to occur in softball, and a general understanding of tissue healing. We designed programs that allow a safe and efficient progressive return to sport. PMID:12937435

Preclinical magnetic resonance imaging and systems biology in cancer research: current applications and challenges.

PubMed

Albanese, Chris; Rodriguez, Olga C; VanMeter, John; Fricke, Stanley T; Rood, Brian R; Lee, YiChien; Wang, Sean S; Madhavan, Subha; Gusev, Yuriy; Petricoin, Emanuel F; Wang, Yue

2013-02-01

Biologically accurate mouse models of human cancer have become important tools for the study of human disease. The anatomical location of various target organs, such as brain, pancreas, and prostate, makes determination of disease status difficult. Imaging modalities, such as magnetic resonance imaging, can greatly enhance diagnosis, and longitudinal imaging of tumor progression is an important source of experimental data. Even in models where the tumors arise in areas that permit visual determination of tumorigenesis, longitudinal anatomical and functional imaging can enhance the scope of studies by facilitating the assessment of biological alterations, (such as changes in angiogenesis, metabolism, cellular invasion) as well as tissue perfusion and diffusion. One of the challenges in preclinical imaging is the development of infrastructural platforms required for integrating in vivo imaging and therapeutic response data with ex vivo pathological and molecular data using a more systems-based multiscale modeling approach. Further challenges exist in integrating these data for computational modeling to better understand the pathobiology of cancer and to better affect its cure. We review the current applications of preclinical imaging and discuss the implications of applying functional imaging to visualize cancer progression and treatment. Finally, we provide new data from an ongoing preclinical drug study demonstrating how multiscale modeling can lead to a more comprehensive understanding of cancer biology and therapy. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Relationship between antioxidants, lipid peroxidation and aging.

PubMed

Barja de Quiroga, G; López-Torres, M; Pérez-Campo, R

1992-01-01

Experiments performed on species as different as flies, rats and frogs are not conclusive about the possibility that antioxidant defenses decrease in old animals. Even when these decreases are found, their physiological meaning is far from clear. Furthermore, a constancy of antioxidant capacity in old age is consistent with the fact that aging is a progressive phenomenon which occurs at a rather constant rate from the mature young to the very old animal, without showing a great acceleration rate in the aged. Nevertheless, experimental results strongly suggest that the maintenance of an appropriate antioxidant/prooxidant balance does have an important role in maintaining health in the aging animal. It is possible that the continuous presence of small amounts of free radicals in the adult tissues of both mature adults and old animals is an important factor in aging (a progressive phenomenon) and susceptibility to disease. Since, similarly to what occurs in procariota, the whole antioxidant system seems to be under homeostatic control in vertebrates, it is imperative to perform comprehensive and detailed studies on the effects of carefully controlled doses of antioxidants on biomarkers of health as well as on the different endogenous cellular antioxidant and prooxidant systems. These studies should have as a final goal the knowledge of which doses of antioxidants are high enough to increase antioxidant protection but low enough to avoid feedback depression of other endogenous antioxidants; this could further improve the health state of humans situated in the middle and last phases of their life span.

Future Perspective of Single-Molecule FRET Biosensors and Intravital FRET Microscopy.

PubMed

Hirata, Eishu; Kiyokawa, Etsuko

2016-09-20

Förster (or fluorescence) resonance energy transfer (FRET) is a nonradiative energy transfer process between two fluorophores located in close proximity to each other. To date, a variety of biosensors based on the principle of FRET have been developed to monitor the activity of kinases, proteases, GTPases or lipid concentration in living cells. In addition, generation of biosensors that can monitor physical stresses such as mechanical power, heat, or electric/magnetic fields is also expected based on recent discoveries on the effects of these stressors on cell behavior. These biosensors can now be stably expressed in cells and mice by transposon technologies. In addition, two-photon excitation microscopy can be used to detect the activities or concentrations of bioactive molecules in vivo. In the future, more sophisticated techniques for image acquisition and quantitative analysis will be needed to obtain more precise FRET signals in spatiotemporal dimensions. Improvement of tissue/organ position fixation methods for mouse imaging is the first step toward effective image acquisition. Progress in the development of fluorescent proteins that can be excited with longer wavelength should be applied to FRET biosensors to obtain deeper structures. The development of computational programs that can separately quantify signals from single cells embedded in complicated three-dimensional environments is also expected. Along with the progress in these methodologies, two-photon excitation intravital FRET microscopy will be a powerful and valuable tool for the comprehensive understanding of biomedical phenomena. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

P650Influence of fetunin-a level on progression of calcific aortic valve stenosis The COFRASA - GENERAC Study.

PubMed

Kubota, N; David Messika-Zeitoun, Dmz

2016-12-01

In recent years, pathophysiology of aortic stenosis (AS) has been considered as a possibly active inflammatory process, but its determinants remain unclear. Calcium tissue deposition observed in dilaysis patients have been linked to low level of Fetuin-A, a powerful inhibitor of ectopic calcification. It is thus suspected to play a role in development of aortic stenosis. To assess correlation between Fetuin-A level and AS progression in a prospective cohort of AS patients, COFRASA (clinicalTrial.gov_number_NCT00338676) and GENERAC (clinicalTrial.gov_number_NCT00647088). A comprehensive clinical evaluation and Fetuin-A plasma level measurement was performed at baseline. AS severity was evaluated at baseline and yearly thereafter using echocardiography (mean pressure gradient (MPG)) and computed tomography (degree of aortic valve calcification or AVC). Annual progression was calculated as [(final measurement - baseline measurement)/follow-up duration] for both MPG and AVC measurements. We enrolled 296 patients with at least 1 year of follow-up. Mean age was 74±10 years, 217 (73%) were men. Mean Fetuin-A level was 0.55±0.15 g/L. After a mean follow-up of 3.0±1.7 years, no correlation was found between AS progression and Fetuin-A level, using either MPG (r=0.015, p=0.82) or AVC (r=0.014, p=0.82). This was also true when comparing patients with lower level of Fetuin-A (≤0.53 g/L, the median in our cohort) with patients with higher level(+3±5 mmHg/year (median 2, [0-5] vs +4±4 mmHg/year (median 2, [1-6]) p=0.06, and +205±290 AUC/year (median 122, [32-269]) vs +240±310 AUC/year (median 145, [50-313], p=0.24). This was true also after adjustment for baseline severity and valve antomy. In our prospective cohortot of AS patients we found no impact of Fetuin-A on both hemodynamic and anatomic AS progression. Despite strong capacity to inhibit ectopic calcium deposition, Fetuin-A plasma level seems to have minor influence on AS progression. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: Journals.permissions@oup.com.

3D Bio-Printing Review

NASA Astrophysics Data System (ADS)

Du, Xianbin

2018-01-01

Ultimate goal of tissue engineering is to replace pathological or necrotic body tissue or organ by artificial tissue or organ and tissue engineering is a very promising research field. 3D bio-printing is a kind of emerging technologies and a branch of tissue engineering. It has made significant progress in the past decade. 3D bio-printing can realize tissue and organ construction in vitro and has wide application in basic research and pharmacy. This paper is to make an analysis and review on 3D bio-printing from the perspectives of bioink, printing technology and technology application.

Current state of cartilage tissue engineering

PubMed Central

Tuli, Richard; Li, Wan-Ju; Tuan, Rocky S

2003-01-01

Damage to cartilage is of great clinical consequence given the tissue's limited intrinsic potential for healing. Current treatments for cartilage repair are less than satisfactory, and rarely restore full function or return the tissue to its native normal state. The rapidly emerging field of tissue engineering holds great promise for the generation of functional cartilage tissue substitutes. The general approach involves a biocompatible, structurally and mechanically sound scaffold, with an appropriate cell source, which is loaded with bioactive molecules that promote cellular differentiation and/or maturation. This review highlights aspects of current progress in cartilage tissue engineering. PMID:12932283

RUNX3 methylation in normal surrounding urothelium of patients with non-muscle-invasive bladder cancer: potential role in the prediction of tumor progression.

PubMed

Jeong, P; Min, B D; Ha, Y S; Song, P H; Kim, I Y; Ryu, K H; Kim, J H; Yun, S J; Kim, W J

2012-11-01

Previously, we reported a causal relationship between RUNX3 methylation and bladder tumor development. Thus, in order to clarify its role in tumorigenesis, this study aims to identify the function of RUNX3 methylation in normal adjacent urothelium of patients with non-muscle invasive bladder cancer (NMIBC). Tumor tissue and donor-matched normal adjacent tissue from 55 patients who underwent transurethral resection (TUR) were selected for the study, and RUNX3 promoter methylation was assessed using methylation-specific polymerase chain reaction (MS-PCR). RUNX3 promoter methylation occurred more frequently in tumor samples than in histologically normal urothelium in patients with NMIBC (P = 0.02). The methylation rates for the RUNX3 promoter in normal adjacent urothelium and tumor tissue were 47% and 69%, respectively. Interestingly, RUNX3 methylation in normal adjacent urothelium was associated with tumor number (P = 0.022) and progression (P = 0.035). Kaplan-Meier estimates revealed that RUNX3 methylation in normal urothelium showed a significant association with time to progression (P = 0.017) in NMIBC patients. Stratifying the patients into 'both methylation', 'one methylation' and 'no methylation' groups for tumors and normal urothelium revealed that no progression occurred in the 'no methylation' group during follow-up. Multivariate Cox regression analysis demonstrated that RUNX3 methylation in normal urothelium [hazards ratio (HR): 5.692, P = 0.042] was an independent predictor of progression. RUNX3 methylation was associated with transition from normal urothelium to bladder tumor. More importantly, RUNX3 methylation in normal adjacent urothelium may predict progression in NMIBC patients who have undergone TUR. Copyright © 2012 Elsevier Ltd. All rights reserved.

Fibulin-1 Predicts Disease Progression in Patients With Idiopathic Pulmonary Fibrosis

PubMed Central

Unger, Sofia; Corte, Tamera J.; Keller, Michael; Wolters, Paul J.; Richeldi, Luca; Cerri, Stefania; Prêle, Cecilia M.; Hansbro, Philip M.; Argraves, William Scott; Oliver, Rema A.; Oliver, Brian G.; Black, Judith L.; Burgess, Janette K.

2014-01-01

BACKGROUND: The underlying mechanisms of idiopathic pulmonary fibrosis (IPF) are unknown. This progressive disease has high mortality rates, and current models for prediction of mortality have limited value in identifying which patients will progress. We previously showed that the glycoprotein fibulin-1 is involved in enhanced proliferation and wound repair by mesenchymal cells and, thus, may contribute to lung fibrosis in IPF. METHODS: Serum, lung tissue, and lung function values were obtained from four independent locations (Sydney, NSW, and Perth, WA, Australia; San Francisco, CA; and Modena, Italy). Patients with IPF were followed for a minimum of 1 year and progression was defined as a significant decline in lung function or death. Primary parenchymal lung fibroblasts of 15 patients with and without IPF were cultured under nonstimulatory conditions. Fibulin-1 levels in serum, and secreted or deposited by fibroblasts, were measured by western blot and in lung tissue by immunohistochemistry. RESULTS: Serum fibulin-1 levels were increased in patients with IPF compared with subjects without lung disease (P = .006). Furthermore, tissue fibulin-1 levels were increased in patients with IPF (P = .02) and correlated negatively with lung function (r = −0.9, P < .05). Primary parenchymal fibroblasts from patients with IPF produced more fibulin-1 than those from subjects without IPF (P < .05). Finally, serum fibulin-1 levels at first blood draw predicted disease progression in IPF within 1 year (area under the curve , 0.71; 95% CI, 0.57-0.86; P = .012). CONCLUSIONS: Fibulin-1 is a novel potential biomarker for disease progression in IPF and raises the possibility that it could be used as a target for the development of new treatments. PMID:24832167

A Tissue Systems Pathology Assay for High-Risk Barrett's Esophagus.

PubMed

Critchley-Thorne, Rebecca J; Duits, Lucas C; Prichard, Jeffrey W; Davison, Jon M; Jobe, Blair A; Campbell, Bruce B; Zhang, Yi; Repa, Kathleen A; Reese, Lia M; Li, Jinhong; Diehl, David L; Jhala, Nirag C; Ginsberg, Gregory; DeMarshall, Maureen; Foxwell, Tyler; Zaidi, Ali H; Lansing Taylor, D; Rustgi, Anil K; Bergman, Jacques J G H M; Falk, Gary W

2016-06-01

Better methods are needed to predict risk of progression for Barrett's esophagus. We aimed to determine whether a tissue systems pathology approach could predict progression in patients with nondysplastic Barrett's esophagus, indefinite for dysplasia, or low-grade dysplasia. We performed a nested case-control study to develop and validate a test that predicts progression of Barrett's esophagus to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), based upon quantification of epithelial and stromal variables in baseline biopsies. Data were collected from Barrett's esophagus patients at four institutions. Patients who progressed to HGD or EAC in ≥1 year (n = 79) were matched with patients who did not progress (n = 287). Biopsies were assigned randomly to training or validation sets. Immunofluorescence analyses were performed for 14 biomarkers and quantitative biomarker and morphometric features were analyzed. Prognostic features were selected in the training set and combined into classifiers. The top-performing classifier was assessed in the validation set. A 3-tier, 15-feature classifier was selected in the training set and tested in the validation set. The classifier stratified patients into low-, intermediate-, and high-risk classes [HR, 9.42; 95% confidence interval, 4.6-19.24 (high-risk vs. low-risk); P < 0.0001]. It also provided independent prognostic information that outperformed predictions based on pathology analysis, segment length, age, sex, or p53 overexpression. We developed a tissue systems pathology test that better predicts risk of progression in Barrett's esophagus than clinicopathologic variables. The test has the potential to improve upon histologic analysis as an objective method to risk stratify Barrett's esophagus patients. Cancer Epidemiol Biomarkers Prev; 25(6); 958-68. ©2016 AACR. ©2016 American Association for Cancer Research.

Fibulin-1 predicts disease progression in patients with idiopathic pulmonary fibrosis.

PubMed

Jaffar, Jade; Unger, Sofia; Corte, Tamera J; Keller, Michael; Wolters, Paul J; Richeldi, Luca; Cerri, Stefania; Prêle, Cecilia M; Hansbro, Philip M; Argraves, William Scott; Oliver, Rema A; Oliver, Brian G; Black, Judith L; Burgess, Janette K

2014-10-01

The underlying mechanisms of idiopathic pulmonary fibrosis (IPF) are unknown. This progressive disease has high mortality rates, and current models for prediction of mortality have limited value in identifying which patients will progress. We previously showed that the glycoprotein fibulin-1 is involved in enhanced proliferation and wound repair by mesenchymal cells and, thus, may contribute to lung fibrosis in IPF. Serum, lung tissue, and lung function values were obtained from four independent locations (Sydney, NSW, and Perth, WA, Australia; San Francisco, CA; and Modena, Italy). Patients with IPF were followed for a minimum of 1 year and progression was defined as a significant decline in lung function or death. Primary parenchymal lung fibroblasts of 15 patients with and without IPF were cultured under nonstimulatory conditions. Fibulin-1 levels in serum, and secreted or deposited by fibroblasts, were measured by western blot and in lung tissue by immunohistochemistry. Serum fibulin-1 levels were increased in patients with IPF compared with subjects without lung disease (P = .006). Furthermore, tissue fibulin-1 levels were increased in patients with IPF (P = .02) and correlated negatively with lung function (r = -0.9, P < .05). Primary parenchymal fibroblasts from patients with IPF produced more fibulin-1 than those from subjects without IPF (P < .05). Finally, serum fibulin-1 levels at first blood draw predicted disease progression in IPF within 1 year (area under the curve , 0.71; 95% CI, 0.57-0.86; P = .012). Fibulin-1 is a novel potential biomarker for disease progression in IPF and raises the possibility that it could be used as a target for the development of new treatments.

Management of thoracolumbar spine trauma: An overview

PubMed Central

Rajasekaran, S; Kanna, Rishi Mugesh; Shetty, Ajoy Prasad

2015-01-01

Thoracolumbar spine fractures are common injuries that can result in significant disability, deformity and neurological deficit. Controversies exist regarding the appropriate radiological investigations, the indications for surgical management and the timing, approach and type of surgery. This review provides an overview of the epidemiology, biomechanical principles, radiological and clinical evaluation, classification and management principles. Literature review of all relevant articles published in PubMed covering thoracolumbar spine fractures with or without neurologic deficit was performed. The search terms used were thoracolumbar, thoracic, lumbar, fracture, trauma and management. All relevant articles and abstracts covering thoracolumbar spine fractures with and without neurologic deficit were reviewed. Biomechanically the thoracolumbar spine is predisposed to a higher incidence of spinal injuries. Computed tomography provides adequate bony detail for assessing spinal stability while magnetic resonance imaging shows injuries to soft tissues (posterior ligamentous complex [PLC]) and neurological structures. Different classification systems exist and the most recent is the AO spine knowledge forum classification of thoracolumbar trauma. Treatment includes both nonoperative and operative methods and selected based on the degree of bony injury, neurological involvement, presence of associated injuries and the integrity of the PLC. Significant advances in imaging have helped in the better understanding of thoracolumbar fractures, including information on canal morphology and injury to soft tissue structures. The ideal classification that is simple, comprehensive and guides management is still elusive. Involvement of three columns, progressive neurological deficit, significant kyphosis and canal compromise with neurological deficit are accepted indications for surgical stabilization through anterior, posterior or combined approaches. PMID:25593358

Carotenoids in Staple Cereals: Metabolism, Regulation, and Genetic Manipulation

PubMed Central

Zhai, Shengnan; Xia, Xianchun; He, Zhonghu

2016-01-01

Carotenoids play a critical role in animal and human health. Animals and humans are unable to synthesize carotenoids de novo, and therefore rely upon diet as sources of these compounds. However, major staple cereals often contain only small amounts of carotenoids in their grains. Consequently, there is considerable interest in genetic manipulation of carotenoid content in cereal grain. In this review, we focus on carotenoid metabolism and regulation in non-green plant tissues, as well as genetic manipulation in staple cereals such as rice, maize, and wheat. Significant progress has been made in three aspects: (1) seven carotenogenes play vital roles in carotenoid regulation in non-green plant tissues, including 1-deoxyxylulose-5-phosphate synthase influencing isoprenoid precursor supply, phytoene synthase, β-cyclase, and ε-cyclase controlling biosynthesis, 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase and carotenoid cleavage dioxygenases responsible for degradation, and orange gene conditioning sequestration sink; (2) provitamin A-biofortified crops, such as rice and maize, were developed by either metabolic engineering or marker-assisted breeding; (3) quantitative trait loci for carotenoid content on chromosomes 3B, 7A, and 7B were consistently identified, eight carotenogenes including 23 loci were detected, and 10 gene-specific markers for carotenoid accumulation were developed and applied in wheat improvement. A comprehensive and deeper understanding of the regulatory mechanisms of carotenoid metabolism in crops will be beneficial in improving our precision in improving carotenoid contents. Genomic selection and gene editing are emerging as transformative technologies for provitamin A biofortification. PMID:27559339

Arthrofibrosis Associated With Total Knee Arthroplasty.

PubMed

Cheuy, Victor A; Foran, Jared R H; Paxton, Roger J; Bade, Michael J; Zeni, Joseph A; Stevens-Lapsley, Jennifer E

2017-08-01

Arthrofibrosis is a debilitating postoperative complication of total knee arthroplasty (TKA). It is one of the leading causes of hospital readmission and a predominant reason for TKA failure. The prevalence of arthrofibrosis will increase as the annual incidence of TKA in the United States rises into the millions. In a narrative review of the literature, the etiology, economic burden, treatment strategies, and future research directions of arthrofibrosis after TKA are examined. Characterized by excessive proliferation of scar tissue during an impaired wound healing response, arthrofibrotic stiffness causes functional deficits in activities of daily living. Postoperative, supervised physiotherapy remains the first line of defense against the development of arthrofibrosis. Also, adjuncts to traditional physiotherapy such as splinting and augmented soft tissue mobilization can be beneficial. The effectiveness of rehabilitation on functional outcomes depends on the appropriate timing, intensity, and progression of the program, accounting for the patient's ability and level of pain. Invasive treatments such as manipulation under anesthesia, debridement, and revision arthroplasty improve range of motion, but can be traumatic and costly. Future studies investigating novel treatments, early diagnosis, and potential preoperative screening for risk of arthrofibrosis will help target those patients who will need additional attention and tailored rehabilitation to improve TKA outcomes. Arthrofibrosis is a multi-faceted complication of TKA, and is difficult to treat without an early, tailored, comprehensive rehabilitation program. Understanding the risk factors for its development and the benefits and shortcomings of various interventions are essential to best restore mobility and function. Copyright © 2017 Elsevier Inc. All rights reserved.

Mild Myopathy Is Associated with COMP but Not MATN3 Mutations in Mouse Models of Genetic Skeletal Diseases

PubMed Central

Piróg, Katarzyna A.; Katakura, Yoshihisa; Mironov, Aleksandr; Briggs, Michael D.

2013-01-01

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are skeletal disorders resulting from mutations in COMP, matrilin-3 or collagen IX and are characterised by short-limbed dwarfism and premature osteoarthritis. Interestingly, recent reports suggest patients can also manifest with muscle weakness. Here we present a detailed analysis of two mouse models of the PSACH/MED disease spectrum; ΔD469 T3-COMP (PSACH) and V194D matrilin-3 (MED). In grip test experiments T3-COMP mice were weaker than wild-type littermates, whereas V194D mice behaved as controls, confirming that short-limbed dwarfism alone does not contribute to PSACH/MED-related muscle weakness. Muscles from T3-COMP mice showed an increase in centronuclear fibers at the myotendinous junction. T3-COMP tendons became more lax in cyclic testing and showed thicker collagen fibers when compared with wild-type tissue; matrilin-3 mutant tissues were indistinguishable from controls. This comprehensive study of the myopathy associated with PSACH/MED mutations enables a better understanding of the disease progression, confirms that it is genotype specific and that the limb weakness originates from muscle and tendon pathology rather than short-limbed dwarfism itself. Since some patients are primarily diagnosed with neuromuscular symptoms, this study will facilitate better awareness of the differential diagnoses that might be associated with the PSACH/MED spectrum and subsequent care of PSACH/MED patients. PMID:24312420

Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma: A report from the International DLBCL Rituximab-CHOP Consortium Program Study

PubMed Central

Visco, Carlo; Li, Yan; Xu-Monette, Zijun Y.; Miranda, Roberto N.; Green, Tina M.; Li, Yong; Tzankov, Alexander; Wen, Wei; Liu, Wei-min; Kahl, Brad S.; d’Amore, Emanuele S. G.; Montes-Moreno, Santiago; Dybkær, Karen; Chiu, April; Tam, Wayne; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Winter, Jane N.; Wang, Huan-You; O’Neill, Stacey; Dunphy, Cherie H.; Hsi, Eric D.; Zhao, X. Frank; Go, Ronald S.; Choi, William W. L.; Zhou, Fan; Czader, Magdalena; Tong, Jiefeng; Zhao, Xiaoying; van Krieken, J. Han; Huang, Qing; Ai, Weiyun; Etzell, Joan; Ponzoni, Maurilio; Ferreri, Andres J. M.; Piris, Miguel A.; Møller, Michael B.; Bueso-Ramos, Carlos E.; Medeiros, L. Jeffrey; Wu, Lin; Young, Ken H.

2013-01-01

Gene expression profiling (GEP) has stratified diffuse large B-cell lymphoma (DLBCL) into molecular subgroups that correspond to different stages of lymphocyte development - namely germinal center B-cell-like and activated B-cell-like. This classification has prognostic significance, but GEP is expensive and not readily applicable into daily practice, which has lead to immunohistochemical algorithms proposed as a surrogate for GEP analysis. We assembled tissue microarrays from 475 de novo DLBCL patients who were treated with rituximab-CHOP chemotherapy. All cases were successfully profiled by GEP on formalin-fixed, paraffin-embedded tissue samples. Sections were stained with antibodies reactive with CD10, GCET1, FOXP1, MUM1, and BCL6 and cases were classified following a rationale of sequential steps of differentiation of B-cells. Cutoffs for each marker were obtained using receiver operating characteristic curves, obviating the need for any arbitrary method. An algorithm based on the expression of CD10, FOXP1, and BCL6 was developed that had a simpler structure than other recently proposed algorithms and 92.6% concordance with GEP. In multivariate analysis, both the International Prognostic Index and our proposed algorithm were significant independent predictors of progression-free and overall survival. In conclusion, this algorithm effectively predicts prognosis of DLBCL patients matching GEP subgroups in the era of rituximab therapy. PMID:22437443

Novel in vivo techniques to visualize kidney anatomy and function.

PubMed

Peti-Peterdi, János; Kidokoro, Kengo; Riquier-Brison, Anne

2015-07-01

Intravital imaging using multiphoton microscopy (MPM) has become an increasingly popular and widely used experimental technique in kidney research over the past few years. MPM allows deep optical sectioning of the intact, living kidney tissue with submicron resolution, which is unparalleled among intravital imaging approaches. MPM has solved a long-standing critical technical barrier in renal research to study several complex and inaccessible cell types and anatomical structures in vivo in their native environment. Comprehensive and quantitative kidney structure and function MPM studies helped our better understanding of the cellular and molecular mechanisms of the healthy and diseased kidney. This review summarizes recent in vivo MPM studies with a focus on the glomerulus and the filtration barrier, although select, glomerulus-related renal vascular and tubular functions are also mentioned. The latest applications of serial MPM of the same glomerulus in vivo, in the intact kidney over several days, during the progression of glomerular disease are discussed. This visual approach, in combination with genetically encoded fluorescent markers of cell lineage, has helped track the fate and function (e.g., cell calcium changes) of single podocytes during the development of glomerular pathologies, and provided visual proof for the highly dynamic, rather than static, nature of the glomerular environment. Future intravital imaging applications have the promise to further push the limits of optical microscopy, and to advance our understanding of the mechanisms of kidney injury. Also, MPM will help to study new mechanisms of tissue repair and regeneration, a cutting-edge area of kidney research.

Status of the NASA Balloon Program

NASA Astrophysics Data System (ADS)

Needleman, H. C.; Nock, R. S.; Bawcom, D. W.

1993-02-01

In the early 1980's the U.S. National Aeronautics and Space Administration (NASA) Balloon Program was faced with a problem of catastrophic balloon failures. In 1986 a balloon recovery program was initiated. This program included qualification of new balloon films, and investigations into materials, processing, structures and performance of balloons. This recovery program has been very successful. To date, more than 100 balloons manufactured of newly developed films have been flown with unprecedented success. There has been much progress made across the spectrum of balloon related disciplines. A new design philosophy has been developed and is being used for all NASA balloons. An updated balloon reliability and quality assurance program is in effect. The long duration balloon development project has been initiated with the first flight test having been conducted in December 1989 from Antarctica. A comprehensive research and development (R&D) effort has been initiated and is progressing well. The progress, status and future plans for these and other aspects of the NASA program, along with a description of the comprehensive balloon R&D activity, will be presented.

Is oxygen availability a limiting factor for in vitro folliculogenesis?

PubMed Central

Sudhakaran, Sam; Barbato, Vincenza; Merolla, Anna; Braun, Sabrina; Di Nardo, Maddalena; Costanzo, Valentina; Ferraro, Raffaele; Iannantuoni, Nicola

2018-01-01

Transplantation of ovarian tissue for the preservation of fertility in oncological patients is becoming an accepted clinical practice. However, the risk of re-introducing tumour cells at transplantation has stirred an increased interest for complete in vitro folliculogenesis. This has not yet been achieved in humans possibly for the lack of knowledge on the environmental milieu that orchestrates folliculogenesis in vivo. The main aim of this study was to investigate the effect of oxygen availability on follicle health and growth during in vitro culture of ovarian tissue strips. To this end, a model was developed to predict the dissolved oxygen concentration in tissue under varying culture conditions. Ovarian cortical strips of bovine, adopted as an animal model, and human tissue were cultured in conventional (CD) and gas permeable (PD) dishes under different media column heights and gaseous oxygen tensions for 3, 6 and 9 days. Follicle quality, activation of primordial follicles to the primary stage, and progression to the secondary stage were analysed through histology. Follicle viability was assessed through a live-dead assay at the confocal scanning laser microscope. Findings showed a higher follicle quality and viability after culture of bovine ovarian strips in PD in adequate medium height and oxygen tensions. The best culture conditions found in the bovine were adopted for human ovarian strip culture and promoted a higher follicle quality, viability and progression. Overall, data demonstrated that modulation of oxygen availability in tissue plays a key role in maintaining follicles’ health and their ability to survive and progress to the secondary stage during ovarian tissue in vitro culture. Such culture conditions could increase the yield of healthy secondary follicles for subsequent dissection and individual culture to obtain competent oocytes. PMID:29425251

Decreased expression of 14-3-3 σ, an early event of malignant transformation of respiratory epithelium, also facilitates progression of squamous cell lung cancer

PubMed Central

Sun, Nan; Wu, Yongkai; Huang, Bo; Liu, Qian; Dong, Yinan; Ding, Jianqiao; Liu, Yongyu

2015-01-01

Background It has been shown that 14-3-3 σ serves as a tumor suppressor gene, and is downregulated in various tumor tissues. However, the role of 14-3-3 σ during the initiation and progression of lung squamous cell carcinoma (SqCC) is not well understood. Methods The expression status of 14-3-3 σ in archival tissue samples from 40 lung SqCC patients (36 with normal bronchia, 19 squamous metaplasia, and 17 dysplasia/carcinoma in situ, in their tissue samples) was examined by immunohistochemical analysis. The proliferation rate and tumor formation ability of the H520 cell transfected with 14-3-3 σ was tested with methyl thiazolyl tetrazolium assay and nude mice subcutaneous injection, respectively. Results In the normal bronchial epithelia, 14-3-3 σ was highly expressed, whereas it was significantly decreased in precancerous and cancerous tissues. Compared with matched invasive cancer tissues, the expression level of 14-3-3 σ in squamous metaplasia was significantly higher (P = 0.049), while that in dysplasia/carcinoma in situ showed no significant changes (P = 0.135). Statistical analysis showed that the expression level of 14-3-3 σ in tumor tissue was associated with the differentiation grade of the tumor (P = 0.001) and the prognosis of the patient (P = 0.003). The overexpression of 14-3-3 σ significantly suppressed the proliferation of H520 cells in vitro and in vivo. Conclusion The inactivation of 14-3-3 σ may be a very early event in tumorigenesis and could facilitate the initiation and progression of lung SqCC in a sustainable way. PMID:26557909

Real-time, haptics-enabled simulator for probing ex vivo liver tissue.

PubMed

Lister, Kevin; Gao, Zhan; Desai, Jaydev P

2009-01-01

The advent of complex surgical procedures has driven the need for realistic surgical training simulators. Comprehensive simulators that provide realistic visual and haptic feedback during surgical tasks are required to familiarize surgeons with the procedures they are to perform. Complex organ geometry inherent to biological tissues and intricate material properties drive the need for finite element methods to assure accurate tissue displacement and force calculations. Advances in real-time finite element methods have not reached the state where they are applicable to soft tissue surgical simulation. Therefore a real-time, haptics-enabled simulator for probing of soft tissue has been developed which utilizes preprocessed finite element data (derived from accurate constitutive model of the soft-tissue obtained from carefully collected experimental data) to accurately replicate the probing task in real-time.

Comprehensive Genetic Analysis of Early Host Body Reactions to the Bioactive and Bio-Inert Porous Scaffolds

PubMed Central

Ehashi, Tomo; Takemura, Taro; Hanagata, Nobutaka; Minowa, Takashi; Kobayashi, Hisatoshi; Ishihara, Kazuhiko; Yamaoka, Tetsuji

2014-01-01

To design scaffolds for tissue regeneration, details of the host body reaction to the scaffolds must be studied. Host body reactions have been investigated mainly by immunohistological observations for a long time. Despite of recent dramatic development in genetic analysis technologies, genetically comprehensive changes in host body reactions are hardly studied. There is no information about host body reactions that can predict successful tissue regeneration in the future. In the present study, porous polyethylene scaffolds were coated with bioactive collagen or bio-inert poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB) and were implanted subcutaneously and compared the host body reaction to those substrates by normalizing the result using control non-coat polyethylene scaffold. The comprehensive analyses of early host body reactions to the scaffolds were carried out using a DNA microarray assay. Within numerous genes which were expressed differently among these scaffolds, particular genes related to inflammation, wound healing, and angiogenesis were focused upon. Interleukin (IL)-1β and IL-10 are important cytokines in tissue responses to biomaterials because IL-1β promotes both inflammation and wound healing and IL-10 suppresses both of them. IL-1β was up-regulated in the collagen-coated scaffold. Collagen-specifically up-regulated genes contained both M1- and M2-macrophage-related genes. Marked vessel formation in the collagen-coated scaffold was occurred in accordance with the up-regulation of many angiogenesis-inducible factors. The DNA microarray assay provided global information regarding the host body reaction. Interestingly, several up-regulated genes were detected even on the very bio-inert PMB-coated surfaces and those genes include inflammation-suppressive and wound healing-suppressive IL-10, suggesting that not only active tissue response but also the inert response may relates to these genetic regulations. PMID:24454803

Development of a systems-based in situ multiplex biomarker screening approach for the assessment of immunopathology and neural tissue plasticity in male rats after traumatic brain injury.

PubMed

Bogoslovsky, Tanya; Bernstock, Joshua D; Bull, Greg; Gouty, Shawn; Cox, Brian M; Hallenbeck, John M; Maric, Dragan

2018-04-01

Traumatic brain injuries (TBIs) pose a massive burden of disease and continue to be a leading cause of morbidity and mortality throughout the world. A major obstacle in developing effective treatments is the lack of comprehensive understanding of the underlying mechanisms that mediate tissue damage and recovery after TBI. As such, our work aims to highlight the development of a novel experimental platform capable of fully characterizing the underlying pathobiology that unfolds after TBI. This platform encompasses an empirically optimized multiplex immunohistochemistry staining and imaging system customized to screen for a myriad of biomarkers required to comprehensively evaluate the extent of neuroinflammation, neural tissue damage, and repair in response to TBI. Herein, we demonstrate that our multiplex biomarker screening platform is capable of evaluating changes in both the topographical location and functional states of resident and infiltrating cell types that play a role in neuropathology after controlled cortical impact injury to the brain in male Sprague-Dawley rats. Our results demonstrate that our multiplex biomarker screening platform lays the groundwork for the comprehensive characterization of changes that occur within the brain after TBI. Such work may ultimately lead to the understanding of the governing pathobiology of TBI, thereby fostering the development of novel therapeutic interventions tailored to produce optimal tissue protection, repair, and/or regeneration with minimal side effects, and may ultimately find utility in a wide variety of other neurological injuries, diseases, and disorders that share components of TBI pathobiology. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

The self-assembling process and applications in tissue engineering

PubMed Central

Lee, Jennifer K.; Link, Jarrett M.; Hu, Jerry C. Y.; Athanasiou, Kyriacos A.

2018-01-01

Tissue engineering strives to create neotissues capable of restoring function. Scaffold-free technologies have emerged that can recapitulate native tissue function without the use of an exogenous scaffold. This chapter will survey, in particular, the self-assembling and self-organization processes as scaffold-free techniques. Characteristics and benefits of each process are described, and key examples of tissues created using these scaffold-free processes are examined to provide guidance for future tissue engineering developments. This chapter aims to explore the potential of self-assembly and self-organization scaffold-free approaches, detailing the recent progress in the in vitro tissue engineering of biomimetic tissues with these methods, toward generating functional tissue replacements. PMID:28348174

Near-infrared Raman spectroscopy for assessing biochemical changes of cervical tissue associated with precarcinogenic transformation.

PubMed

Duraipandian, Shiyamala; Mo, Jianhua; Zheng, Wei; Huang, Zhiwei

2014-11-07

Raman spectroscopy measures the inelastically scattered light from tissue that is capable of identifying native tissue biochemical constituents and their changes associated with disease transformation. This study aims to characterize the Raman spectroscopic properties of cervical tissue associated with the multi-stage progression of cervical precarcinogenic sequence. A rapid-acquisition fiber-optic near-infrared (NIR) Raman diagnostic system was employed for tissue Raman spectral measurements at 785 nm excitation. A total of 68 Raman spectra (23 benign, 29 low-grade squamous intraepithelial lesions (LSIL) and 16 high grade squamous intraepithelial lesions (HSIL)) were measured from 25 cervical tissue biopsy specimens, as confirmed by colposcopy-histopathology. The semi-quantitative biochemical modeling based on the major biochemicals (i.e., DNA, proteins (histone, collagen), lipid (triolein) and carbohydrates (glycogen)) in cervical tissue uncovers the stepwise accumulation of biomolecular changes associated with progressive cervical precarcinogenesis. Multi-class partial least squares-discriminant analysis (PLS-DA) together with leave-one tissue site-out, cross-validation yielded the diagnostic sensitivities of 95.7%, 82.8% and 81.3%; specificities of 100.0%, 92.3% and 88.5%,for discrimination among benign, LSIL and HSIL cervical tissues, respectively. This work suggests that the Raman spectral biomarkers have identified the potential to be used for monitoring the multi-stage cervical precarcinogenesis, forming the foundation of applying NIR Raman spectroscopy for the early diagnosis of cervical precancer in vivo at the molecular level.

Paradigms and progress in vocal fold restoration.

PubMed

Ford, Charles N

2008-09-01

Science advances occur through orderly steps, puzzle-solving leaps, or divergences from the accepted disciplinary matrix that occasionally result in a revolutionary paradigm shift. Key advances must overcome bias, criticism, and rejection. Examples in biological science include use of embryonic stem cells, recognition of Helicobacter pylori in the etiology of ulcer disease, and the evolution of species. Our work in vocal fold restoration reflects these patterns. We progressed through phases of tissue replacement with fillers and biological implants, to current efforts at vocal fold regeneration through tissue engineering, and face challenges of a new "systems biology" paradigm embracing genomics and proteomics.

A hypothetical pathogenesis model for androgenic alopecia: clarifying the dihydrotestosterone paradox and rate-limiting recovery factors.

PubMed

English, Robert S

2018-02-01

Androgenic alopecia, also known as pattern hair loss, is a chronic progressive condition that affects 80% of men and 50% of women throughout a lifetime. But despite its prevalence and extensive study, a coherent pathology model describing androgenic alopecia's precursors, biological step-processes, and physiological responses does not yet exist. While consensus is that androgenic alopecia is genetic and androgen-mediated by dihydrotestosterone, questions remain regarding dihydrotestosterone's exact role in androgenic alopecia onset. What causes dihydrotestosterone to increase in androgenic alopecia-prone tissues? By which mechanisms does dihydrotestosterone miniaturize androgenic alopecia-prone hair follicles? Why is dihydrotestosterone also associated with hair growth in secondary body and facial hair? Why does castration (which decreases androgen production by 95%) stop pattern hair loss, but not fully reverse it? Is there a relationship between dihydrotestosterone and tissue remodeling observed alongside androgenic alopecia onset? We review evidence supporting and challenging dihydrotestosterone's causal relationship with androgenic alopecia, then propose an evidence-based pathogenesis model that attempts to answer the above questions, account for additionally-suspected androgenic alopecia mediators, identify rate-limiting recovery factors, and elucidate better treatment targets. The hypothesis argues that: (1) chronic scalp tension transmitted from the galea aponeurotica induces an inflammatory response in androgenic alopecia-prone tissues; (2) dihydrotestosterone increases in androgenic alopecia-prone tissues as part of this inflammatory response; and (3) dihydrotestosterone does not directly miniaturize hair follicles. Rather, dihydrotestosterone is a co-mediator of tissue dermal sheath thickening, perifollicular fibrosis, and calcification - three chronic, progressive conditions concomitant with androgenic alopecia progression. These conditions remodel androgenic alopecia-prone tissues - restricting follicle growth space, oxygen, and nutrient supply - leading to the slow, persistent hair follicle miniaturization characterized in androgenic alopecia. If true, this hypothetical model explains the mechanisms by which dihydrotestosterone miniaturizes androgenic alopecia-prone hair follicles, describes a rationale for androgenic alopecia progression and patterning, makes sense of dihydrotestosterone's paradoxical role in hair loss and hair growth, and identifies targets to further improve androgenic alopecia recovery rates: fibrosis, calcification, and chronic scalp tension. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

Peri-implantitis.

PubMed

Schwarz, Frank; Derks, Jan; Monje, Alberto; Wang, Hom-Lay

2018-06-01

This narrative review provides an evidence-based overview on peri-implantitis for the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. A literature review was conducted addressing the following topics: 1) definition of peri-implantitis; 2) conversion from peri-implant mucositis to peri-implantitis, 3) onset and pattern of disease progression, 4) characteristics of peri-implantitis, 5) risk factors/indicators for peri-implantitis, and 6) progressive crestal bone loss in the absence of soft tissue inflammation. 1)Peri-implantitis is a pathological condition occurring in tissues around dental implants, characterized by inflammation in the peri-implant connective tissue and progressive loss of supporting bone. 2)The histopathologic and clinical conditions leading to the conversion from peri-implant mucositis to peri-implantitis are not completely understood. 3)The onset of peri-implantitis may occur early during follow-up and the disease progresses in a non-linear and accelerating pattern. 4a)Peri-implantitis sites exhibit clinical signs of inflammation and increased probing depths compared to baseline measurements. 4b)At the histologic level, compared to periodontitis sites, peri-implantitis sites often have larger inflammatory lesions. 4c)Surgical entry at peri-implantitis sites often reveals a circumferential pattern of bone loss. 5a)There is strong evidence that there is an increased risk of developing peri-implantitis in patients who have a history of chronic periodontitis, poor plaque control skills, and no regular maintenance care after implant therapy. Data identifying "smoking" and "diabetes" as potential risk factors/indicators for peri-implantitis are inconclusive. 5b)There is some limited evidence linking peri-implantitis to other factors such as: post-restorative presence of submucosal cement, lack of peri-implant keratinized mucosa and positioning of implants that make it difficult to perform oral hygiene and maintenance. 6)Evidence suggests that progressive crestal bone loss around implants in the absence of clinical signs of soft tissue inflammation is a rare event. © 2018 American Academy of Periodontology and European Federation of Periodontology.

77 FR 27781 - Agency Information Collection Activities: Proposed Collection: Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-11

... progress towards a high-quality home visiting program or embedding their home visiting program into a comprehensive, high-quality early childhood system. Thirteen States were awarded Development Grants, and nine...

Stuck in Neutral: Stalled Progress in Statewide Comprehensive Smoke-Free Laws and Cigarette Excise Taxes, United States, 2000–2014

PubMed Central

King, Brian A.; Babb, Stephen D.

2016-01-01

Introduction Increasing tobacco excise taxes and implementing comprehensive smoke-free laws are two of the most effective population-level strategies to reduce tobacco use, prevent tobacco use initiation, and protect nonsmokers from secondhand smoke. We examined state laws related to smoke-free buildings and to cigarette excise taxes from 2000 through 2014 to see how implementation of these laws from 2000 through 2009 differs from implementation in more recent years (2010–2014). Methods We used legislative data from LexisNexis, an online legal research database, to examine changes in statewide smoke-free laws and cigarette excise taxes in effect from January 1, 2000, through December 31, 2014. A comprehensive smoke-free law was defined as a statewide law prohibiting smoking in all indoor areas of private work sites, restaurants, and bars. Results From 2000 through 2009, 21 states and the District of Columbia implemented comprehensive smoke-free laws prohibiting smoking in work sites, restaurants, and bars. In 2010, 4 states implemented comprehensive smoke-free laws. The last state to implement a comprehensive smoke-free law was North Dakota in 2012, bringing the total number to 26 states and the District of Columbia. From 2000 through 2009, 46 states and the District of Columbia implemented laws increasing their cigarette excise tax, which increased the national average state excise tax rate by $0.92. However, from 2010 through 2014, only 14 states and the District of Columbia increased their excise tax, which increased the national average state excise tax rate by $0.20. Conclusion The recent stall in progress in enacting and implementing statewide comprehensive smoke-free laws and increasing cigarette excise taxes may undermine tobacco prevention and control efforts in the United States, undercutting efforts to reduce tobacco use, exposure to secondhand smoke, health disparities, and tobacco-related illness and death. PMID:27309417

Stuck in Neutral: Stalled Progress in Statewide Comprehensive Smoke-Free Laws and Cigarette Excise Taxes, United States, 2000-2014.

PubMed

Holmes, Carissa Baker; King, Brian A; Babb, Stephen D

2016-06-16

Increasing tobacco excise taxes and implementing comprehensive smoke-free laws are two of the most effective population-level strategies to reduce tobacco use, prevent tobacco use initiation, and protect nonsmokers from secondhand smoke. We examined state laws related to smoke-free buildings and to cigarette excise taxes from 2000 through 2014 to see how implementation of these laws from 2000 through 2009 differs from implementation in more recent years (2010-2014). We used legislative data from LexisNexis, an online legal research database, to examine changes in statewide smoke-free laws and cigarette excise taxes in effect from January 1, 2000, through December 31, 2014. A comprehensive smoke-free law was defined as a statewide law prohibiting smoking in all indoor areas of private work sites, restaurants, and bars. From 2000 through 2009, 21 states and the District of Columbia implemented comprehensive smoke-free laws prohibiting smoking in work sites, restaurants, and bars. In 2010, 4 states implemented comprehensive smoke-free laws. The last state to implement a comprehensive smoke-free law was North Dakota in 2012, bringing the total number to 26 states and the District of Columbia. From 2000 through 2009, 46 states and the District of Columbia implemented laws increasing their cigarette excise tax, which increased the national average state excise tax rate by $0.92. However, from 2010 through 2014, only 14 states and the District of Columbia increased their excise tax, which increased the national average state excise tax rate by $0.20. The recent stall in progress in enacting and implementing statewide comprehensive smoke-free laws and increasing cigarette excise taxes may undermine tobacco prevention and control efforts in the United States, undercutting efforts to reduce tobacco use, exposure to secondhand smoke, health disparities, and tobacco-related illness and death.

E-cadherin suppression accelerates squamous cell carcinoma progression in three-dimensional, human tissue constructs.

PubMed

Margulis, Alexander; Zhang, Weitian; Alt-Holland, Addy; Crawford, Howard C; Fusenig, Norbert E; Garlick, Jonathan A

2005-03-01

We studied the link between loss of E-cadherin-mediated adhesion and acquisition of malignant properties in three-dimensional, human tissue constructs that mimicked the initial stages of squamous cell cancer progression. Suppression of E-cadherin expression in early-stage, skin-derived tumor cells (HaCaT-II-4) was induced by cytoplasmic sequestration of beta-catenin upon stable expression of a dominant-negative E-cadherin fusion protein (H-2Kd-Ecad). In monolayer cultures, expression of H-2Kd-Ecad resulted in decreased levels of E-cadherin, redistribution of beta-catenin to the cytoplasm, and complete loss of intercellular adhesion when compared with control II-4 cells. This was accompanied by a 7-fold decrease in beta-catenin-mediated transcription and a 12-fold increase in cell migration. In three-dimensional constructs, E-cadherin-deficient tissues showed disruption of architecture, loss of adherens junctional proteins from cell contacts, and focal tumor cell invasion. Invasion was linked to activation of matrix metalloproteinase (MMP)-mediated degradation of basement membrane in H-2Kd-Ecad-expressing tissue constructs that was blocked by MMP inhibition (GM6001). Quantitative reverse transcription-PCR showed a 2.5-fold increase in MMP-2 and an 8-fold increase in MMP-9 in cells expressing the H-2Kd-Ecad fusion protein when compared with controls, and gel zymography showed increased MMP protein levels. Following surface transplantation of three-dimensional tissues, suppression of E-cadherin expression greatly accelerated tumorigenesis in vivo by inducing a switch to high-grade carcinomas that resulted in a 5-fold increase in tumor size after 4 weeks. Suppression of E-cadherin expression and loss of its function fundamentally modified squamous cell carcinoma progression by activating a highly invasive, aggressive tumor phenotype, whereas maintenance of E-cadherin prevented invasion in vitro and limited tumor progression in vivo.

Full scattering profile for detecting physiological tissue properties

NASA Astrophysics Data System (ADS)

Duadi, Hamootal; Fixler, Dror

2017-02-01

Light reflectance and transmission from soft tissue has been utilized in noninvasive clinical measurement devices such as the photoplethysmograph (PPG) and reflectance pulse oximeter. Most methods of near infrared (NIR) spectroscopy focus on the volume reflectance from a semi-infinite sample, while very few measure transmission. We have previously shown that examining the full scattering profile (FSP), which is the angular distribution of exiting photons, provides more comprehensive information when measuring from a cylindrical tissue, such as earlobe, fingertip and pinched tissue. Our hypothesis is that the change in blood vessel diameter is more significant than the change in optical properties. The findings of this work demonstrate a realistic model for optical tissue measurements such as NIR spectroscopy, PPG and pulse oximetery.

[Progress in application of 3D bioprinting in cartilage regeneration and reconstruction for tissue engineering].

PubMed

Liao, Junlin; Wang, Shaohua; Chen, Jia; Xie, Hongju; Zhou, Jianda

2017-02-28

Three-dimensional (3D) bioprinting provides an advanced technology for tissue engineering and regenerative medicine because of its ability to produce the models or organs with higher precision and more suitable for human body. It has been successfully used to produce a variety of cartilage scaffold materials. In addition, 3D bioprinter can directly to print tissue and organs with live chondrocytes. In conclusion, 3D bioprinting may have broad prospect for cartilage regeneration and reconstruction in tissue engineering.

Tissue-Engineering for the Study of Cardiac Biomechanics

PubMed Central

Ma, Stephen P.; Vunjak-Novakovic, Gordana

2016-01-01

The notion that both adaptive and maladaptive cardiac remodeling occurs in response to mechanical loading has informed recent progress in cardiac tissue engineering. Today, human cardiac tissues engineered in vitro offer complementary knowledge to that currently provided by animal models, with profound implications to personalized medicine. We review here recent advances in the understanding of the roles of mechanical signals in normal and pathological cardiac function, and their application in clinical translation of tissue engineering strategies to regenerative medicine and in vitro study of disease. PMID:26720588

A Prospective Evaluation of Circulating Tumor Cells and Cell-Free DNA in EGFR-Mutant Non-Small Cell Lung Cancer Patients Treated with Erlotinib on a Phase II Trial.

PubMed

Yanagita, Masahiko; Redig, Amanda J; Paweletz, Cloud P; Dahlberg, Suzanne E; O'Connell, Allison; Feeney, Nora; Taibi, Myriam; Boucher, David; Oxnard, Geoffrey R; Johnson, Bruce E; Costa, Daniel B; Jackman, David M; Jänne, Pasi A

2016-12-15

Genotype-directed therapy is the standard of care for advanced non-small cell lung cancer (NSCLC), but obtaining tumor tissue for genotyping remains a challenge. Circulating tumor cell (CTC) or cell-free DNA (cfDNA) analysis may allow for noninvasive evaluation. This prospective trial evaluated CTCs and cfDNA in EGFR-mutant NSCLC patients treated with erlotinib until progression. EGFR-mutant NSCLC patients were enrolled in a phase II trial of erlotinib. Blood was collected at baseline, every 2 months on study, and at disease progression. Plasma genotyping was performed by droplet digital PCR for EGFR19del, L858R, and T790M. CTCs were isolated by CellSave, enumerated, and analyzed by immunofluorescence for CD45 and pan-cytokeratin and EGFR and MET FISH were also performed. Rebiopsy was performed at disease progression. Sixty patients were enrolled; 44 patients discontinued therapy for disease progression. Rebiopsy occurred in 35 of 44 patients (80%), with paired CTC/cfDNA analysis in 41 of 44 samples at baseline and 36 of 44 samples at progression. T790M was identified in 23 of 35 (66%) tissue biopsies and 9 of 39 (23%) cfDNA samples. CTC analysis at progression identified MET amplification in 3 samples in which tissue analysis could not be performed. cfDNA analysis identified T790M in 2 samples in which rebiopsy was not possible. At diagnosis, high levels of cfDNA but not high levels of CTCs correlated with progression-free survival. cfDNA and CTCs are complementary, noninvasive assays for evaluation of acquired resistance to first-line EGFR TKIs and may expand the number of patients in whom actionable genetic information can be obtained at acquired resistance. Serial cfDNA monitoring may offer greater clinical utility than serial monitoring of CTCs. Clin Cancer Res; 22(24); 6010-20. ©2016 AACR. ©2016 American Association for Cancer Research.

Comprehensive, comprehensible, distributed and intelligent databases: current status.

PubMed

Frishman, D; Heumann, K; Lesk, A; Mewes, H W

1998-01-01

It is only a matter of time until a user will see not many but one integrated database of information for molecular biology. Is this true? Is it a good thing? Why will it happen? Where are we now? What developments are fostering and what developments are impeding progress towards this end? A list of WWW resources devoted to database issues in molecular biology is available at http://www.mips.biochem.mpg.de frishman@mips.biochem.mpg.de

Further Research on Speeded Speech as an Educational Medium. Effects of Listening Aids and Self-Pacing on Comprehension and the Use of Compressed Speech for Review. Progress Report Number 4.

ERIC Educational Resources Information Center

Friedman, Herbert L.; And Others

The studies reported here are a continuation of research into the comprehension of time-compressed speech by normal college students. In the Listening Aid Study II, an experiment was designed to retest the advantages of the precis as a listening aid when the precis expressed the overall meaning of a passage. Also, a new listening aid was…

[The phonological variant of primary progressive aphasia, a single case study].

PubMed

Diesfeldt, H F A

2011-04-01

Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by an insidious onset and gradual progression of deficits that can involve any aspect of language, including word finding, object naming, fluency, syntax, phonology and word comprehension. The initial symptoms occur in the absence of major deficits in other cognitive domains, including episodic memory, visuospatial abilities and visuoconstruction. According to recent diagnostic guidelines, PPA is typically divided into three variants: nonfluent variant PPA (also termed progressive nonfluent aphasia), semantic variant PPA (also termed semantic dementia) and logopenic/phonological variant PPA (also termed logopenic progressive aphasia). The paper describes a 79-yr old man, who presented with normal motor speech and production rate, impaired single word retrieval and phonemic errors in spontaneous speech and confrontational naming. Confrontation naming was strongly affected by lexical frequency. He was impaired on repetition of sentences and phrases. Reading was intact for regularly spelled words but not for irregular words (surface dyslexia). Comprehension was spared at the single word level, but impaired for complex sentences. He performed within the normal range on the Dutch equivalent of the Pyramids and Palm Trees (PPT) Pictures Test, indicating that semantic processing was preserved. There was, however, a slight deficiency on the PPT Words Test, which appeals to semantic knowledge of verbal associations. His core deficit was interpreted as an inability to retrieve stored lexical-phonological information for spoken word production in spontaneous speech, confrontation naming, repetition and reading aloud.

Bi-directional signaling: Extracellular Matrix and Integrin Regulation of Breast Tumor Progression

PubMed Central

Gehler, Scott; Ponik, Suzanne M.; Riching, Kristin M; Keely, Patricia J.

2016-01-01

Cell transformation and tumor progression involves a common set of acquired capabilities, including increased proliferation, failure of cell death, self-sufficiency in growth, angiogenesis, and tumor cell invasion and metastasis (1). The stromal environment consists of many cell types, including fibroblasts, macrophages, and endothelial cells, in addition to various extracellular matrix (ECM) proteins that function to support normal tissue maintenance, but have also been implicated in tumor progression (2). Both the chemical and mechanical properties of the ECM have been shown to influence normal and malignant cell behavior. For instance, mesenchymal stem cells differentiate into specific lineages that are dependent on matrix stiffness (3), while tumor cells undergo changes in cell behavior and gene expression in response to matrix stiffness (4). ECM remodeling is implicated in tumor progression and includes changes in both the chemical and mechanical properties of the ECM (5) that can be a result of 1.) increased deposition of stromal ECM, 2.) enhanced contraction of ECM fibrils, and 3.) altered collagen alignment and ECM stiffness. In addition, remodeling of the ECM may alter whether tumor cells employ proteolytic degradation mechanisms during invasion and metastasis. Tumor cells respond to such changes in ECM remodeling through altered intracellular signaling and cell cycle control that lead to enhanced proliferation, loss of normal tissue architecture, and local tumor cell migration and invasion into the surrounding stromal tissue (6). This review will focus on the bi-directional interplay between the mechanical properties of the ECM and changes in integrin-mediated signal transduction events in an effort to elucidate cell behaviors during tumor progression. PMID:23582036

Combined Secretomics and Transcriptomics Revealed Cancer-Derived GDF15 is Involved in Diffuse-Type Gastric Cancer Progression and Fibroblast Activation.

PubMed

Ishige, Takayuki; Nishimura, Motoi; Satoh, Mamoru; Fujimoto, Mai; Fukuyo, Masaki; Semba, Toshihisa; Kado, Sayaka; Tsuchida, Sachio; Sawai, Setsu; Matsushita, Kazuyuki; Togawa, Akira; Matsubara, Hisahiro; Kaneda, Atsushi; Nomura, Fumio

2016-02-19

Gastric cancer is classified into two subtypes, diffuse and intestinal. The diffuse-type gastric cancer (DGC) has poorer prognosis, and the molecular pathology is not yet fully understood. The purpose of this study was to identify functional secreted molecules involved in DGC progression. We integrated the secretomics of six gastric cancer cell lines and gene expression analysis of gastric cancer tissues with publicly available microarray data. Hierarchical clustering revealed characteristic gene expression differences between diffuse- and intestinal-types. GDF15 was selected as a functional secreted molecule owing to high expression only in fetal tissues. Protein expression of GDF15 was higher in DGC cell lines and tissues. Serum levels of GDF15 were significant higher in DGC patients as compared with healthy individuals and chronic gastritis patients, and positively correlated with wall invasion and lymph node metastasis. In addition, the stimulation of GDF15 on NIH3T3 fibroblast enhanced proliferation and up-regulated expression of extracellular matrix genes, which were similar to TGF-β stimulation. These results indicate that GDF15 contributes to fibroblast activation. In conclusion, this study revealed that GDF15 may be a novel functional secreted molecule for DGC progression, possibly having important roles for cancer progression via the affecting fibroblast function, as well as TGF-β.

Predicting reading outcomes with progress monitoring slopes among middle grade students

PubMed Central

Tolar, Tammy D.; Barth, Amy E.; Fletcher, Jack M.; Francis, David J.; Vaughn, Sharon

2013-01-01

Effective implementation of response-to-intervention (RTI) frameworks depends on efficient tools for monitoring progress. Evaluations of growth (i.e., slope) may be less efficient than evaluations of status at a single time point, especially if slopes do not add to predictions of outcomes over status. We examined progress monitoring slope validity for predicting reading outcomes among middle school students by evaluating latent growth models for different progress monitoring measure-outcome combinations. We used multi-group modeling to evaluate the effects of reading ability, reading intervention, and progress monitoring administration condition on slope validity. Slope validity was greatest when progress monitoring was aligned with the outcome (i.e., word reading fluency slope was used to predict fluency outcomes in contrast to comprehension outcomes), but effects varied across administration conditions (viz., repeated reading of familiar vs. novel passages). Unless the progress monitoring measure is highly aligned with outcome, slope may be an inefficient method for evaluating progress in an RTI context. PMID:24659899

Recent Advances in Laser-Ablative Synthesis of Bare Au and Si Nanoparticles and Assessment of Their Prospects for Tissue Engineering Applications.

PubMed

Al-Kattan, Ahmed; Nirwan, Viraj P; Popov, Anton; Ryabchikov, Yury V; Tselikov, Gleb; Sentis, Marc; Fahmi, Amir; Kabashin, Andrei V

2018-05-24

Driven by surface cleanness and unique physical, optical and chemical properties, bare (ligand-free) laser-synthesized nanoparticles (NPs) are now in the focus of interest as promising materials for the development of advanced biomedical platforms related to biosensing, bioimaging and therapeutic drug delivery. We recently achieved significant progress in the synthesis of bare gold (Au) and silicon (Si) NPs and their testing in biomedical tasks, including cancer imaging and therapy, biofuel cells, etc. We also showed that these nanomaterials can be excellent candidates for tissue engineering applications. This review is aimed at the description of our recent progress in laser synthesis of bare Si and Au NPs and their testing as functional modules (additives) in innovative scaffold platforms intended for tissue engineering tasks.

Bmi-1 expression modulates non-small cell lung cancer progression

PubMed Central

Xiong, Dan; Ye, Yunlin; Fu, Yujie; Wang, Jinglong; Kuang, Bohua; Wang, Hongbo; Wang, Xiumin; Zu, Lidong; Xiao, Gang; Hao, Mingang; Wang, Jianhua

2015-01-01

Previous studies indicate that the role of B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is responsible for multiple cancer progression. However, Bmi-1 in controlling gene expression in non-small cell lung cancer (NSCLC) development is not well explored. Here we report that the Bmi-1 level is highly increased in primary NSCLC tissues compared to matched adjacent non-cancerous tissues and required for lung tumor growth in xenograft model. Furthermore, we also demonstrate that Bmi-1 level is lower in matched involved lymph node cancerous tissues than the respective primary NSCLC tissues. We find that Bmi-1 does not affect cell cycle and apoptosis in lung cancer cell lines as it does not affect the expression of p16/p19, Pten, AKT and P-AKT. Mechanistic analyses note that reduction of Bmi-1 expression inversely regulates invasion and metastasis of NSCLC cells in vitro and in vivo, followed by induction of epithelial-mesenchymal transition (EMT). Using genome microarray assays, we find that RNAi-mediated silence of Bmi-1 modulates some important molecular genetics or signaling pathways, potentially associated with NSCLC development. Taken together, our findings disclose for the first time that Bmi-1 level accumulates strongly in early stage and then declines in late stage, which is potentially important for NSCLC cell invasion and metastasis during progression. PMID:25880371

Omentum and bone marrow: how adipocyte-rich organs create tumour microenvironments conducive for metastatic progression

PubMed Central

Gusky, H. Chkourko; Diedrich, J.; MacDougald, O. A.; Podgorski, I.

2016-01-01

Summary A number of clinical studies have linked adiposity with increased cancer incidence, progression and metastasis, and adipose tissue is now being credited with both systemic and local effects on tumour development and survival. Adipocytes, a major component of benign adipose tissue, represent a significant source of lipids, cytokines and adipokines, and their presence in the tumour microenvironment substantially affects cellular trafficking, signalling and metabolism. Cancers that have a high predisposition to metastasize to the adipocyte-rich host organs are likely to be particularly affected by the presence of adipocytes. Although our understanding of how adipocytes influence tumour progression has grown significantly over the last several years, the mechanisms by which adipocytes regulate the meta-static niche are not well-understood. In this review, we focus on the omentum, a visceral white adipose tissue depot, and the bone, a depot for marrow adipose tissue, as two distinct adipocyte-rich organs that share common characteristic: they are both sites of significant metastatic growth. We highlight major differences in origin and function of each of these adipose depots and reveal potential common characteristics that make them environments that are attractive and conducive to secondary tumour growth. Special attention is given to how omental and marrow adipocytes modulate the tumour microenvironment by promoting angiogenesis, affecting immune cells and altering metabolism to support growth and survival of metastatic cancer cells. PMID:27432523

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): Positive and negative regulators in tumor cell adhesion.

PubMed

Bourboulia, Dimitra; Stetler-Stevenson, William G

2010-06-01

Cells adhere to one another and/or to matrices that surround them. Regulation of cell-cell (intercellular) and cell-matrix adhesion is tightly controlled in normal cells, however, defects in cell adhesion are common in the majority of human cancers. Multilateral communication among tumor cells with the extracellular matrix (ECM) and neighbor cells is accomplished through adhesion molecules, ECM components, proteolytic enzymes and their endogenous inhibitors. There is sufficient evidence to suggest that reduced adherence is a tumor cell property engaged during tumor progression. Tumor cells acquire the ability to change shape, detach and easily move through spaces disorganizing the normal tissue architecture. This property is due to changes in expression levels of adhesion molecules and/or due to elevated levels of secreted proteolytic enzymes, including matrix metalloproteinases (MMPs). Among other roles, MMPs degrade the ECM and, therefore, prepare the path for tumor cells to migrate, invade and spread to distant secondary areas, where they form metastasis. Tissue inhibitors of metalloproteinases or TIMPs control MMP activities and, therefore, minimize matrix degradation. Both MMPs and TIMPs are involved in tissue remodeling and decisively regulate tumor cell progression including tumor angiogenesis. In this review, we describe and discuss data that support the important role of MMPs and TIMPs in cancer cell adhesion and tumor progression. Published by Elsevier Ltd.

Autosomal Recessive Mental Retardation, Deafness, Ankylosis, and Mild Hypophosphatemia Associated with a Novel ANKH Mutation in a Consanguineous Family

PubMed Central

Morava, Eva; Kühnisch, Jirko; Drijvers, Jefte M.; Robben, Joris H.; Cremers, Cor; van Setten, Petra; Branten, Amanda; Stumpp, Sabine; de Jong, Alphons; Voesenek, Krysta; Vermeer, Sascha; Heister, Angelien; Claahsen-van der Grinten, Hedi L.; O'Neill, Charles W.; Willemsen, Michèl A.; Lefeber, Dirk; Deen, Peter M. T.; Kornak, Uwe; Kremer, Hannie; Wevers, Ron A.

2011-01-01

Context: Mutations in ANKH cause the highly divergent conditions familial chondrocalcinosis and craniometaphyseal dysplasia. The gene product ANK is supposed to regulate tissue mineralization by transporting pyrophosphate to the extracellular space. Objective: We evaluated several family members of a large consanguineous family with mental retardation, deafness, and ankylosis. We compared their skeletal, metabolic, and serological parameters to that of the autosomal recessive progressive ankylosis (ank) mouse mutant, caused by a loss-of-function mutation in the murine ortholog Ank. Participants: The studied patients had painful small joint soft-tissue calcifications, progressive spondylarthropathy, osteopenia, mild hypophosphatemia, mixed hearing loss, and mental retardation. Results: After mapping the disease gene to 5p15, we identified the novel homozygous ANK missense mutation L244S in all patients. Although L244 is a highly conserved amino acid, the mutated ANK protein was detected at normal levels at the plasma membrane in primary patient fibroblasts. The phenotype was highly congruent with the autosomal recessive progressive ankylosis (ank) mouse mutant. This indicates a loss-of-function effect of the L244S mutation despite normal ANK protein expression. Interestingly, our analyses revealed that the primary step of joint degeneration is fibrosis and mineralization of articular soft tissues. Moreover, heterozygous carriers of the L244S mutation showed mild osteoarthritis without metabolic alterations, pathological calcifications, or central nervous system involvement. Conclusion: Beyond the description of the first human progressive ankylosis phenotype, our results indicate that ANK influences articular soft tissues commonly involved in degenerative joint disorders. Furthermore, this human disorder provides the first direct evidence for a role of ANK in the central nervous system. PMID:20943778

Autosomal recessive mental retardation, deafness, ankylosis, and mild hypophosphatemia associated with a novel ANKH mutation in a consanguineous family.

PubMed

Morava, Eva; Kühnisch, Jirko; Drijvers, Jefte M; Robben, Joris H; Cremers, Cor; van Setten, Petra; Branten, Amanda; Stumpp, Sabine; de Jong, Alphons; Voesenek, Krysta; Vermeer, Sascha; Heister, Angelien; Claahsen-van der Grinten, Hedi L; O'Neill, Charles W; Willemsen, Michèl A; Lefeber, Dirk; Deen, Peter M T; Kornak, Uwe; Kremer, Hannie; Wevers, Ron A

2011-01-01

Mutations in ANKH cause the highly divergent conditions familial chondrocalcinosis and craniometaphyseal dysplasia. The gene product ANK is supposed to regulate tissue mineralization by transporting pyrophosphate to the extracellular space. We evaluated several family members of a large consanguineous family with mental retardation, deafness, and ankylosis. We compared their skeletal, metabolic, and serological parameters to that of the autosomal recessive progressive ankylosis (ank) mouse mutant, caused by a loss-of-function mutation in the murine ortholog Ank. The studied patients had painful small joint soft-tissue calcifications, progressive spondylarthropathy, osteopenia, mild hypophosphatemia, mixed hearing loss, and mental retardation. After mapping the disease gene to 5p15, we identified the novel homozygous ANK missense mutation L244S in all patients. Although L244 is a highly conserved amino acid, the mutated ANK protein was detected at normal levels at the plasma membrane in primary patient fibroblasts. The phenotype was highly congruent with the autosomal recessive progressive ankylosis (ank) mouse mutant. This indicates a loss-of-function effect of the L244S mutation despite normal ANK protein expression. Interestingly, our analyses revealed that the primary step of joint degeneration is fibrosis and mineralization of articular soft tissues. Moreover, heterozygous carriers of the L244S mutation showed mild osteoarthritis without metabolic alterations, pathological calcifications, or central nervous system involvement. Beyond the description of the first human progressive ankylosis phenotype, our results indicate that ANK influences articular soft tissues commonly involved in degenerative joint disorders. Furthermore, this human disorder provides the first direct evidence for a role of ANK in the central nervous system.

Overexpression of caldesmon is associated with tumor progression in patients with primary non-muscle-invasive bladder cancer

PubMed Central

Lee, Myung-Shin; Lee, Jisu; Kim, Joo Heon; Kim, Won Tae; Kim, Wun-Jae; Ahn, Hanjong; Park, Jinsung

2015-01-01

The expression and function of caldesmon (CAD) in urothelial bladder carcinoma (BC) have not been reported. Here, we investigated the expression, prognostic value, and potential functional mechanism of CAD in primary non-muscle-invasive bladder cancer (NMIBC). Protein profiling of tissue samples using antibody microarrays showed significantly higher CAD expression in muscle-invasive BC tissues compared with NMIBC tissues. We then validated the CAD expression in BC cells by immunohistochemistry analysis using paraffin-embedded tissue blocks and western blots using BC cell lines. In addition, we examined the expression of CAD variants by reverse transcription-polymerase chain reaction, and confirmed the expression of low-molecular-weight isoforms (L-CAD), specifically encoded by WI-38 L-CAD II (transcript variant 2), in BC cells. Survival analysis in an independent primary NMIBC cohort comprising 132 patients showed that positive CAD expression was significantly associated with poorer prognosis than no CAD expression with regard to recurrence- and progression-free survival (p = 0.001 and 0.014, respectively). Multivariate analyses further indicated that positive CAD expression was an independent predictor of progression-free survival (p = 0.032; HR = 5.983). Data obtained from in vitro silencing and overexpression studies indicated that L-CAD promotes migration and invasiveness of BC cells. Immunofluorescence assays showed dramatic structural changes in the actin cytoskeleton of BC cells after L-CAD overexpression. Our findings collectively suggest that L-CAD overexpression in primary NMIBC is significantly associated with tumor progression and that a possible mechanism for L-CAD's activity is implicated in increased cell motility and invasive characteristics through morphological changes in BC cells. PMID:26430961

Signaling Interplay between Bone Marrow Adipose Tissue and Multiple Myeloma cells.

PubMed

Falank, Carolyne; Fairfield, Heather; Reagan, Michaela R

2016-01-01

In the year 2000, Hanahan and Weinberg (1) defined the six Hallmarks of Cancer as: self-sufficiency in growth signals, evasion of apoptosis, insensitivity to antigrowth mechanisms, tissue invasion and metastasis, limitless replicative potential, and sustained angiogenesis. Eleven years later, two new Hallmarks were added to the list (avoiding immune destruction and reprograming energy metabolism) and two new tumor characteristics (tumor-promoting inflammation and genome instability and mutation) (2). In multiple myeloma (MM), a destructive cancer of the plasma cell that grows predominantly in the bone marrow (BM), it is clear that all these hallmarks and characteristics are in play, contributing to tumor initiation, drug resistance, disease progression, and relapse. Bone marrow adipose tissue (BMAT) is a newly recognized contributor to MM oncogenesis and disease progression, potentially affecting MM cell metabolism, immune action, inflammation, and influences on angiogenesis. In this review, we discuss the confirmed and hypothetical contributions of BMAT to MM development and disease progression. BMAT has been understudied due to technical challenges and a previous lack of appreciation for the endocrine function of this tissue. In this review, we define the dynamic, responsive, metabolically active BM adipocyte. We then describe how BMAT influences MM in terms of: lipids/metabolism, hypoxia/angiogenesis, paracrine or endocrine signaling, and bone disease. We then discuss the connection between BMAT and systemic inflammation and potential treatments to inhibit the feedback loops between BM adipocytes and MM cells that support MM progression. We aim for researchers to use this review to guide and help prioritize their experiments to develop better treatments or a cure for cancers, such as MM, that associate with and may depend on BMAT.

Signaling Interplay between Bone Marrow Adipose Tissue and Multiple Myeloma cells

PubMed Central

Falank, Carolyne; Fairfield, Heather; Reagan, Michaela R.

2016-01-01

In the year 2000, Hanahan and Weinberg (1) defined the six Hallmarks of Cancer as: self-sufficiency in growth signals, evasion of apoptosis, insensitivity to antigrowth mechanisms, tissue invasion and metastasis, limitless replicative potential, and sustained angiogenesis. Eleven years later, two new Hallmarks were added to the list (avoiding immune destruction and reprograming energy metabolism) and two new tumor characteristics (tumor-promoting inflammation and genome instability and mutation) (2). In multiple myeloma (MM), a destructive cancer of the plasma cell that grows predominantly in the bone marrow (BM), it is clear that all these hallmarks and characteristics are in play, contributing to tumor initiation, drug resistance, disease progression, and relapse. Bone marrow adipose tissue (BMAT) is a newly recognized contributor to MM oncogenesis and disease progression, potentially affecting MM cell metabolism, immune action, inflammation, and influences on angiogenesis. In this review, we discuss the confirmed and hypothetical contributions of BMAT to MM development and disease progression. BMAT has been understudied due to technical challenges and a previous lack of appreciation for the endocrine function of this tissue. In this review, we define the dynamic, responsive, metabolically active BM adipocyte. We then describe how BMAT influences MM in terms of: lipids/metabolism, hypoxia/angiogenesis, paracrine or endocrine signaling, and bone disease. We then discuss the connection between BMAT and systemic inflammation and potential treatments to inhibit the feedback loops between BM adipocytes and MM cells that support MM progression. We aim for researchers to use this review to guide and help prioritize their experiments to develop better treatments or a cure for cancers, such as MM, that associate with and may depend on BMAT. PMID:27379019

Latest research progress on food waste management: a comprehensive review

NASA Astrophysics Data System (ADS)

Zhu, Shangzhen; Gao, Hetong; Duan, Lunbo

2018-05-01

Since a large amount of food supplying is provided as a basic line measuring increasing residents’ life standard, food waste has become progressively numeral considerable. Much attention has been drawn to this problem. This work gave an overview on latest researches about anaerobic digestion, composting, generalized management and other developments on management of food waste. Different technologies were introduced and evaluated. Further views on future research in such a field were proposed.

First year progress report on the development of the Texas flexible pavement database.

DOT National Transportation Integrated Search

2008-01-01

Comprehensive and reliable databases are essential for the development, validation, and calibration of any pavement : design and rehabilitation system. These databases should include material properties, pavement structural : characteristics, highway...

77 FR 33225 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-05

... progress towards a high-quality home visiting program or towards embedding their home visiting program into a comprehensive, high-quality early childhood system. Of State applicants to the competitive grant...

Technical issues affecting the implementation of US environmental protection agency's proposed fish tissue-based aquatic criterion for selenium

Treesearch

A. Dennis Lemly; Joseph P. Skorupa

2007-01-01

The US Environmental Protection Agency is developing a national water quality criterion for selenium that is based on concentrations of the element in fish tissue. Although this approach offers advantages over the current water-based regulations, it also presents new challenges with respect to implementation. A comprehensive protocol that answers the ‘‘what, where, and...

Corneal Tissue Engineering: Recent Advances and Future Perspectives

PubMed Central

Ghezzi, Chiara E.; Rnjak-Kovacina, Jelena

2015-01-01

To address the growing need for corneal transplants two main approaches are being pursued: allogenic and synthetic materials. Allogenic tissue from human donors is currently the preferred choice; however, there is a worldwide shortage in donated corneal tissue. In addition, tissue rejection often limits the long-term success of this approach. Alternatively, synthetic homologs to donor corneal grafts are primarily considered temporary replacements until suitable donor tissue becomes available, as they result in a high incidence of graft failure. Tissue engineered cornea analogs would provide effective cornea tissue substitutes and alternatives to address the need to reduce animal testing of commercial products. Recent progress toward these needs is reviewed here, along with future perspectives. PMID:25434371

Tissue engineering, stem cells, and cloning for the regeneration of urologic organs.

PubMed

Atala, Anthony

2003-10-01

Tissue engineering efforts are currently being undertaken for every type of tissue and organ within the urinary system. Most of the effort expended to engineer genitourinary tissues has occurred within the last decade. Tissue engineering techniques require a cell culture facility designed for human application. Personnel who have mastered the techniques of cell harvest, culture, and expansion as well as polymer design are essential for the successful application of this technology. Various engineered genitourinary tissues are at different stages of development, with some already being used clinically, a few in preclinical trials, and some in the discovery stage. Recent progress suggests that engineered urologic tissues may have an expanded clinical applicability in the future.

Identification of a Lipokine, a Lipid Hormone Linking Adipose Tissue to Systemic Metabolism

PubMed Central

Cao, Haiming; Gerhold, Kristin; Mayers, Jared R.; Wiest, Michelle M.; Watkins, Steve M.; Hotamisligil, Gökhan S.

2008-01-01

Dysregulation of lipid metabolism in individual tissues can lead to systemic disruption of insulin action and glucose metabolism. Utilizing a comprehensive lipidomic platform and mice deficient in adipose tissue lipid chaperones aP2 and mal1, we explored how metabolic alterations in adipose tissue are linked to whole-body metabolism through lipid signals. A robust increase in de novo lipogenesis rendered the adipose tissue of these mice resistant to the deleterious systemic effects of dietary lipid exposure. Systemic lipid profiling also led to identification of C16:1n7-palmitoleate as an adipose tissue-derived lipid hormone that strongly stimulates muscle insulin action and suppresses hepatosteatosis. Our data reveal a novel, lipid-mediated endocrine network and demonstrate that adipose tissue uses lipokines such as C16:1n7-palmitoleate to communicate with distant organs and regulate systemic metabolic homeostasis. PMID:18805087

A comprehensive model of the spatio-temporal stem cell and tissue organisation in the intestinal crypt.

PubMed

Buske, Peter; Galle, Jörg; Barker, Nick; Aust, Gabriela; Clevers, Hans; Loeffler, Markus

2011-01-06

We introduce a novel dynamic model of stem cell and tissue organisation in murine intestinal crypts. Integrating the molecular, cellular and tissue level of description, this model links a broad spectrum of experimental observations encompassing spatially confined cell proliferation, directed cell migration, multiple cell lineage decisions and clonal competition.Using computational simulations we demonstrate that the model is capable of quantitatively describing and predicting the dynamic behaviour of the intestinal tissue during steady state as well as after cell damage and following selective gain or loss of gene function manipulations affecting Wnt- and Notch-signalling. Our simulation results suggest that reversibility and flexibility of cellular decisions are key elements of robust tissue organisation of the intestine. We predict that the tissue should be able to fully recover after complete elimination of cellular subpopulations including subpopulations deemed to be functional stem cells. This challenges current views of tissue stem cell organisation.

Modelling the mechanics of partially mineralized collagen fibrils, fibres and tissue

PubMed Central

Liu, Yanxin; Thomopoulos, Stavros; Chen, Changqing; Birman, Victor; Buehler, Markus J.; Genin, Guy M.

2014-01-01

Progressive stiffening of collagen tissue by bioapatite mineral is important physiologically, but the details of this stiffening are uncertain. Unresolved questions about the details of the accommodation of bioapatite within and upon collagen's hierarchical structure have posed a central hurdle, but recent microscopy data resolve several major questions. These data suggest how collagen accommodates bioapatite at the lowest relevant hierarchical level (collagen fibrils), and suggest several possibilities for the progressive accommodation of bioapatite at higher hierarchical length scales (fibres and tissue). We developed approximations for the stiffening of collagen across spatial hierarchies based upon these data, and connected models across hierarchies levels to estimate mineralization-dependent tissue-level mechanics. In the five possible sequences of mineralization studied, percolation of the bioapatite phase proved to be an important determinant of the degree of stiffening by bioapatite. The models were applied to study one important instance of partially mineralized tissue, which occurs at the attachment of tendon to bone. All sequences of mineralization considered reproduced experimental observations of a region of tissue between tendon and bone that is more compliant than either tendon or bone, but the size and nature of this region depended strongly upon the sequence of mineralization. These models and observations have implications for engineered tissue scaffolds at the attachment of tendon to bone, bone development and graded biomimetic attachment of dissimilar hierarchical materials in general. PMID:24352669

Innovation and the future of advanced dosimetry: 2D to 5D

NASA Astrophysics Data System (ADS)

Oldham, Mark

2017-05-01

Recent years have witnessed a remarkable evolution in the techniques, capabilities and applications of 3D dosimetry. Initially the goal was simple: to innovate new techniques capable of comprehensively measuring and verifying exquisitely intricate dose distributions from a paradigm changing emerging new therapy, IMRT. Basic questions emerged: how well were treatment planning systems modelling the complex delivery, and how could treatments be verified for safe use on patients? Since that time, equally significant leaps of innovation have continued in the technology of treatment delivery. In addition, clinical practice has been transformed by the addition of on-board imaging capabilities, which tend to hypo-fractionation strategies and margin reduction. The net result is a high stakes treatment setting where the clinical morbidity of any unintended treatment deviation is exacerbated by the combination of highly conformal dose distributions given with reduced margins with fractionation regimens unfriendly to healthy tissue. Not surprisingly this scenario is replete with challenges and opportunities for new and improved dosimetry systems. In particular tremendous interest exists in comprehensive 3D dosimetry systems, and systems that can resolve the dose in moving structures (4D) and even in deforming structures (5D). Despite significant progress in the capability of multi-dimensional dosimetry systems, it is striking that true 3D dosimetry systems are today largely found in academic institutions or specialist clinics. The reasons will be explored. We will highlight innovations occurring both in treatment delivery and in advanced dosimetry methods designed to verify them, and explore current and future opportunities for advanced dosimetry tools in clinical practice and translational research.

Cellular Response to a Novel Fetal Acellular Collagen Matrix: Implications for Tissue Regeneration

PubMed Central

Rennert, Robert C.; Garg, Ravi K.; Gurtner, Geoffrey C.

2013-01-01

Introduction. PriMatrix (TEI Biosciences Inc., Boston, MA, USA) is a novel acellular collagen matrix derived from fetal bovine dermis that is designed for use in partial- and full-thickness wounds. This study analyzes the cellular response to PriMatrix in vivo, as well as the ability of this matrix to facilitate normal tissue regeneration. Methods. Five by five mm squares of rehydrated PriMatrix were implanted in a subcutaneous fashion on the dorsum of wild-type mice. Implant site tissue was harvested for histology, immunohistochemistry (IHC), and flow cytometric analyses at multiple time points until day 28. Results. PriMatrix implants were found to go through a biological progression initiated by a transient infiltrate of inflammatory cells, followed by mesenchymal cell recruitment and vascular development. IHC analysis revealed that the majority of the implanted fetal dermal collagen fibers persisted through day 28 but underwent remodeling and cellular repopulation to form tissue with a density and morphology consistent with healthy dermis. Conclusions. PriMatrix implants undergo progressive in vivo remodeling, facilitating the regeneration of histologically normal tissue through a mild inflammatory and progenitor cell response. Regeneration of normal tissue is especially important in a wound environment, and these findings warrant further investigation of PriMatrix in this setting. PMID:23970899

Cellular response to a novel fetal acellular collagen matrix: implications for tissue regeneration.

PubMed

Rennert, Robert C; Sorkin, Michael; Garg, Ravi K; Januszyk, Michael; Gurtner, Geoffrey C

2013-01-01

Introduction. PriMatrix (TEI Biosciences Inc., Boston, MA, USA) is a novel acellular collagen matrix derived from fetal bovine dermis that is designed for use in partial- and full-thickness wounds. This study analyzes the cellular response to PriMatrix in vivo, as well as the ability of this matrix to facilitate normal tissue regeneration. Methods. Five by five mm squares of rehydrated PriMatrix were implanted in a subcutaneous fashion on the dorsum of wild-type mice. Implant site tissue was harvested for histology, immunohistochemistry (IHC), and flow cytometric analyses at multiple time points until day 28. Results. PriMatrix implants were found to go through a biological progression initiated by a transient infiltrate of inflammatory cells, followed by mesenchymal cell recruitment and vascular development. IHC analysis revealed that the majority of the implanted fetal dermal collagen fibers persisted through day 28 but underwent remodeling and cellular repopulation to form tissue with a density and morphology consistent with healthy dermis. Conclusions. PriMatrix implants undergo progressive in vivo remodeling, facilitating the regeneration of histologically normal tissue through a mild inflammatory and progenitor cell response. Regeneration of normal tissue is especially important in a wound environment, and these findings warrant further investigation of PriMatrix in this setting.

Biomedical Applications of Mid-Infrared Spectroscopic Imaging and Multivariate Data Analysis: Contribution to the Understanding of Diabetes Pathogenesis

NASA Astrophysics Data System (ADS)

Aboualizadeh, Ebrahim

Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of adult vision loss. Although a great deal of progress has been made in ophthalmological examinations and clinical approaches to detect the signs of retinopathy in patients with diabetes, there still remain outstanding questions regarding the molecular and biochemical changes involved. To discover the biochemical mechanisms underlying the development and progression of changes in the retina as a result of diabetes, a more comprehensive understanding of the bio-molecular processes, in individual retinal cells subjected to hyperglycemia, is required. Animal models provide a suitable resource for temporal detection of the underlying pathophysiological and biochemical changes associated with DR, which is not fully attainable in human studies. In the present study, I aimed to determine the nature of diabetes-induced, highly localized biochemical changes in the retinal tissue from Ins2Akita/+ (Akita/+; a model of Type I diabetes) male mice with different duration of diabetes. Employing label-free, spatially resolved Fourier transform infrared (FT-IR) imaging engaged with chemometric tools enabled me to identify temporal-dependent reproducible biomarkers of the diabetic retinal tissue from mice with 6 or 12 weeks, and 6 or 10 months of diabetes. I report, for the first time, the origin of molecular changes in the biochemistry of individual retinal layers with different duration of diabetes. A robust classification between distinctive retinal layers - namely photoreceptor layer (PRL), outer plexiform layer (OPL), inner nuclear layer (INL), and inner plexiform layer (IPL) - and associated temporal-dependent spectral biomarkers, were delineated. Spatially-resolved super resolution chemical images revealed oxidative stress-induced structural and morphological alterations within the nucleus of the photoreceptors. Comparison among the PRL, OPL, INL, and IPL suggested that the photoreceptor layer is the most susceptible layer to the oxidative stress with short-duration of diabetes. Moreover, for the first time, we present the temporal-dependent molecular alterations for the PRL, OPL, INL, and IPL from Akita/+ mice, with progression of diabetes. These findings are potentially important and may be of particular benefit in understanding the molecular and biological activity of retinal cells during oxidative stress in diabetes. Our integrating paradigm provides a new conceptual framework and a significant rationale for a better understanding of the molecular and cellular mechanisms underlying the development and progression of DR. This approach may yield alternative and potentially complimentary methods for the assessment of diabetes changes. It is expected that the conclusions drawn from this work will bridge the gap in our knowledge regarding the biochemical mechanisms of the DR and address some critical needs in the biomedical community.

The bioink: A comprehensive review on bioprintable materials.

PubMed

Hospodiuk, Monika; Dey, Madhuri; Sosnoski, Donna; Ozbolat, Ibrahim T

This paper discusses "bioink", bioprintable materials used in three dimensional (3D) bioprinting processes, where cells and other biologics are deposited in a spatially controlled pattern to fabricate living tissues and organs. It presents the first comprehensive review of existing bioink types including hydrogels, cell aggregates, microcarriers and decellularized matrix components used in extrusion-, droplet- and laser-based bioprinting processes. A detailed comparison of these bioink materials is conducted in terms of supporting bioprinting modalities and bioprintability, cell viability and proliferation, biomimicry, resolution, affordability, scalability, practicality, mechanical and structural integrity, bioprinting and post-bioprinting maturation times, tissue fusion and formation post-implantation, degradation characteristics, commercial availability, immune-compatibility, and application areas. The paper then discusses current limitations of bioink materials and presents the future prospects to the reader. Copyright © 2017 Elsevier Inc. All rights reserved.

[New challenge of tissue repair and regenerative medicine: to achieve a perfect repair and regeneration of multiple tissues in wound sites].

PubMed

Fu, X B

2016-01-01

Great achievements in the study of tissue repair and regeneration have been made, and many of these successes have been shown to be beneficial to the patients in recent years. However, perfect tissue repair and regeneration of damaged tissues and organs remain to be great challenges in the management of trauma and diseases. Based on the progress in developmental biology in animals and advances in stem cell biology, it is possible to attain the aim of perfect repair and regeneration by means of somatic cell reprogramming and different inducing techniques.

3D culture models of tissues under tension.

PubMed

Eyckmans, Jeroen; Chen, Christopher S

2017-01-01

Cells dynamically assemble and organize into complex tissues during development, and the resulting three-dimensional (3D) arrangement of cells and their surrounding extracellular matrix in turn feeds back to regulate cell and tissue function. Recent advances in engineered cultures of cells to model 3D tissues or organoids have begun to capture this dynamic reciprocity between form and function. Here, we describe the underlying principles that have advanced the field, focusing in particular on recent progress in using mechanical constraints to recapitulate the structure and function of musculoskeletal tissues. © 2017. Published by The Company of Biologists Ltd.

Increased phosphatidylethanolamine N-methyltransferase gene expression in non-small-cell lung cancer tissue predicts shorter patient survival

PubMed Central

ZINRAJH, DAVID; HÖRL, GERD; JÜRGENS, GÜNTHER; MARC, JANJA; SOK, MIHA; CERNE, DARKO

2014-01-01

Lipid mobilization is of great importance for tumor growth and studies have suggested that cancer cells exhibit abnormal choline phospholipid metabolism. In the present study, we hypothesized that phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is increased in non-small-cell lung cancer (NSCLC) tissues and that increased gene expression acts as a predictor of shorter patient survival. Forty-two consecutive patients with resected NSCLC were enrolled in this study. Paired samples of lung cancer tissues and adjacent non-cancer lung tissues were collected from resected specimens for the estimation of PEMT expression. SYBR Green-based real-time polymerase chain reaction was used for quantification of PEMT mRNA in lung cancer tissues. Lipoprotein lipase (LPL) and fatty acid synthase (FASN) activities had already been measured in the same tissues. During a four-year follow-up, 21 patients succumbed to tumor progression. One patient did not survive due to non-cancer reasons and was not included in the analysis. Cox regression analysis was used to assess the prognostic value of PEMT expression. Our findings show that elevated PEMT expression in the cancer tissue, relative to that in the adjacent non-cancer lung tissue, predicts shorter patient survival independently of standard prognostic factors and also independently of increased LPL or FASN activity, the two other lipid-related predictors of shorter patient survival. These findings suggest that active phosphatidylcholine and/or choline metabolism are essential for tumor growth and progression. PMID:24932311

Increased phosphatidylethanolamine N-methyltransferase gene expression in non-small-cell lung cancer tissue predicts shorter patient survival.

PubMed

Zinrajh, David; Hörl, Gerd; Jürgens, Günther; Marc, Janja; Sok, Miha; Cerne, Darko

2014-06-01

Lipid mobilization is of great importance for tumor growth and studies have suggested that cancer cells exhibit abnormal choline phospholipid metabolism. In the present study, we hypothesized that phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is increased in non-small-cell lung cancer (NSCLC) tissues and that increased gene expression acts as a predictor of shorter patient survival. Forty-two consecutive patients with resected NSCLC were enrolled in this study. Paired samples of lung cancer tissues and adjacent non-cancer lung tissues were collected from resected specimens for the estimation of PEMT expression. SYBR Green-based real-time polymerase chain reaction was used for quantification of PEMT mRNA in lung cancer tissues. Lipoprotein lipase (LPL) and fatty acid synthase (FASN) activities had already been measured in the same tissues. During a four-year follow-up, 21 patients succumbed to tumor progression. One patient did not survive due to non-cancer reasons and was not included in the analysis. Cox regression analysis was used to assess the prognostic value of PEMT expression. Our findings show that elevated PEMT expression in the cancer tissue, relative to that in the adjacent non-cancer lung tissue, predicts shorter patient survival independently of standard prognostic factors and also independently of increased LPL or FASN activity, the two other lipid-related predictors of shorter patient survival. These findings suggest that active phosphatidylcholine and/or choline metabolism are essential for tumor growth and progression.

Improvements in Alzheimer's disease diagnosis using principle components analysis (PCA) in combination with Raman spectroscopy

NASA Astrophysics Data System (ADS)

Archer, John K. J.; Sudworth, Caroline D.; Williams, Rachel; How, Thien; Stone, Nicholas; Mann, David; Black, Richard A.

2007-07-01

The significant achievements of medical science over the last century are evident in the increasing age of the global population, however this now brings new problems, the most prominent being the growth in the number of people suffering from dementia. Over half the people with dementia in the UK are sufferers of Alzheimer's disease, a condition in which intraneuronal neurofibrillary tangles and extraneuronal senile tangles take over neurons prompting their death. A definitive diagnosis is still only currently available post-mortem, whilst current symptom based processes of elimination are far from perfect, especially when the only treatments available are symptom inhibiting drugs. Principal component analysis (PCA) of the Raman spectra taken from brain tissue has proved to be a potential tool in the diagnosis. However, this work now has to be refined in order to progress to tissue less associated with the symptoms of Alzheimer's disease. The first step of this has already been taken in progressing from frontal tissue to occipital tissue point spectra taken at random positions from bulk tissue. Now we present initial work into acquiring Raman spectral maps from across a tissue area, in pursuit of identifying unique plaque and tangle spectra. These spectra are presented alongside synthetic β-Amyloid spectra, in a study of the role that the peptide plays in the biomarker spectra, and how this information can aid the PCA of bulk tissue, and point towards a Raman spectroscopic test on less sensitive tissue, such as blood.

Analysis of molecular pathways in pancreatic ductal adenocarcinomas with a bioinformatics approach.

PubMed

Wang, Yan; Li, Yan

2015-01-01

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer death worldwide. Our study aimed to reveal molecular mechanisms. Microarray data of GSE15471 (including 39 matching pairs of pancreatic tumor tissues and patient-matched normal tissues) was downloaded from Gene Expression Omnibus (GEO) database. We identified differentially expressed genes (DEGs) in PDAC tissues compared with normal tissues by limma package in R language. Then GO and KEGG pathway enrichment analyses were conducted with online DAVID. In addition, principal component analysis was performed and a protein-protein interaction network was constructed to study relationships between the DEGs through database STRING. A total of 532 DEGs were identified in the 38 PDAC tissues compared with 33 normal tissues. The results of principal component analysis of the top 20 DEGs could differentiate the PDAC tissues from normal tissues directly. In the PPI network, 8 of the 20 DEGs were all key genes of the collagen family. Additionally, FN1 (fibronectin 1) was also a hub node in the network. The genes of the collagen family as well as FN1 were significantly enriched in complement and coagulation cascades, ECM-receptor interaction and focal adhesion pathways. Our results suggest that genes of collagen family and FN1 may play an important role in PDAC progression. Meanwhile, these DEGs and enriched pathways, such as complement and coagulation cascades, ECM-receptor interaction and focal adhesion may be important molecular mechanisms involved in the development and progression of PDAC.

Alzheimer's Disease. LC Science Tracer Bullet 87-2.

ERIC Educational Resources Information Center

Sammons, Vivian O., Comp.

Alzheimer's disease is characterized by a degeneration and shrinkage of brain tissue; the symptoms include progressive memory loss, bizarre behavior, difficulty in speaking and walking, incontinence, and confusion. Positive diagnosis is possible only upon examination of brain tissue at autopsy. The disease affects not only the patient but also the…

A laser primer for orthopaedic nurses.

PubMed

Michelson, S A

1990-01-01

Laser therapy is an efficient surgical intervention that minimizes tissue manipulation and destruction; however meticulous nursing care is required to safeguard the patient from potential hazards inherent in the procedure. A solid grounding in basic laser concepts including biophysics, correct operation of the equipment, safety, and maintenance will assist the nurse in providing comprehensive, high quality care. The emphasis of nursing practice should be oriented toward comprehensive patient education, psychosocial support, and safeguarding the patient from potential laser hazards.

Machine Learning and Data Mining for Comprehensive Test Ban Treaty Monitoring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russell, S; Vaidya, S

2009-07-30

The Comprehensive Test Ban Treaty (CTBT) is gaining renewed attention in light of growing worldwide interest in mitigating risks of nuclear weapons proliferation and testing. Since the International Monitoring System (IMS) installed the first suite of sensors in the late 1990's, the IMS network has steadily progressed, providing valuable support for event diagnostics. This progress was highlighted at the recent International Scientific Studies (ISS) Conference in Vienna in June 2009, where scientists and domain experts met with policy makers to assess the current status of the CTBT Verification System. A strategic theme within the ISS Conference centered on exploring opportunitiesmore » for further enhancing the detection and localization accuracy of low magnitude events by drawing upon modern tools and techniques for machine learning and large-scale data analysis. Several promising approaches for data exploitation were presented at the Conference. These are summarized in a companion report. In this paper, we introduce essential concepts in machine learning and assess techniques which could provide both incremental and comprehensive value for event discrimination by increasing the accuracy of the final data product, refining On-Site-Inspection (OSI) conclusions, and potentially reducing the cost of future network operations.« less

Ecological requirements for pallid sturgeon reproduction and recruitment in the Lower Missouri River: Annual report 2009

USGS Publications Warehouse

DeLonay, Aaron J.; Jacobson, Robert B.; Papoulias, Diana M.; Wildhaber, Mark L.; Chojnacki, Kimberly A.; Pherigo, Emily K.; Bergthold, Casey L.; Mestl, Gerald E.

2010-01-01

The Comprehensive Sturgeon Research Project is a multiyear, multiagency collaborative research framework developed to provide information to support pallid sturgeon recovery and Missouri River management decisions. The general Comprehensive Sturgeon Research Project strategy is to integrate field and laboratory studies of sturgeon reproductive ecology, habitat requirements, and physiology to produce a predictive understanding of sturgeon population dynamics. The project scope of work is developed annually with cooperating research partners and in collaboration with the U.S. Army Corps of Engineers, Missouri River Recovery-Integrated Science Program. The research consists of several interdependent and complementary research tasks engaging multiple disciplines that primarily address spawning as a probable limiting factor in reproduction and survival of the pallid sturgeon. The research is multifaceted and is designed to provide information needed for management decisions impacting habitat restoration, flow modification, and pallid sturgeon population augmentation on the Missouri River, and throughout the range of the species. Research activities and progress towards understanding of the species are reported to the U.S. Army Corps of Engineers annually. This annual report details the research effort and progress made by Comprehensive Sturgeon Research Project during 2009.

Effective osimertinib treatment in a patient with discordant T790 M mutation detection between liquid biopsy and tissue biopsy.

PubMed

Mambetsariev, Isa; Vora, Lalit; Yu, Kim Wai; Salgia, Ravi

2018-03-21

We report the successful treatment of the patient with osimertinib 80 mg/day following disease progression and a discordance in the detection of a mechanism of resistance epithelial growth factor receptor (EGFR) T790 M between liquid biopsy and tissue biopsy methods. A 57-year-old Hispanic male patient initially diagnosed with an EGFR 19 deletion positive lung adenocarcinoma and clinically responded to initial erlotinib treatment. The patient subsequently progressed on erlotinib 150 mg/day and repeat biopsies both tissue and liquid were sent for next-generation sequencing (NGS). A T790 M EGFR mutation was detected in the blood sample using a liquid biopsy technique, but the tissue biopsy failed to show a T790 M mutation in a newly biopsied tissue sample. He was then successfully treated with osimertinib 80 mg/day, has clinically and radiologically responded, and remains on osimertinib treatment after 10 months. Second-line osimertinib treatment, when administered at 80 mg/day, is both well tolerated and efficacious in a patient with previously erlotinib treated lung adenocarcinoma and a T790 M mutation detected by liquid biopsy.

Association of proteasomal activity with metastasis in luminal breast cancer

NASA Astrophysics Data System (ADS)

Shashova, E. E.; Fesik, E. A.; Doroshenko, A. V.

2017-09-01

Chimotrypsin-like (ChTL) and caspase-like (CL) proteasomal activities were investigated in different variants of the tumor progression of luminal breast cancer. Patients with primary luminal breast cancer (n = 123) in stage T1-3N0-2M0 who had not received neoadjuvant treatment were included in this study. Proteasome ChTL and CL activities were determined in the samples of tumor and adjacent tissues. The coefficients of chymotrypsin-like (kChTL) and caspase-like (kCL) proteasome activity were also calculated as the ratio of the corresponding activity in the tumor tissue to activity in the adjacent tissue. ChTL, CL, kChTL and kCL in the tissues of luminal A and B breast cancer with lymphogenic metastasis were compared, and their association with hematogenous metastasis was evaluated. On the one hand, CL activity of proteasomes increased in luminal A breast cancer with extensive lymphogenic metastasis (N2), on the other hand it decreased in the luminal B subtype of cancer. The ratio of proteasomal activity in the tumor and adjacent tissues plays a significant role in the hematogenic pathway of breast cancer progression and is associated with poor metastatic-free survival.

Necrotizing Fasciitis: How Reliable are the Cutaneous Signs?

PubMed Central

Kiat, Ho Jun; En Natalie, Yap Hui; Fatimah, Lateef

2017-01-01

Necrotizing fasciitis (NF) is a surgical emergency. It is often aggressive and characterized by the rapidly progressive inflammatory infection of the fascia that causes extensive necrosis of the subcutaneous tissue and fascia, relatively sparing the muscle and skin tissue. As the disease progresses, thrombosis of the affected cutaneous perforators subsequently devascularizes the overlying skin. The course indeed can be a fulminant one. The diagnosis of NF, especially in the early stages, is extremely challenging, and it can be very close in presentation to other skin and subcutaneous tissue infections. The primary site of the pathology is the deep fascia. Necrosis of the tissues and fascia may manifest as erythema without sharp margins, swelling, warmth, shiny, and exquisitely tender areas. Pain out of proportion to physical examination findings may be observed. The subcutaneous tissue may be firm and indurated such that the underlying muscle groups cannot be distinctly palpated. Eventually, as the overlying skin is stripped of its blood supply, skin necrosis ensues and hemorrhagic bullae form. Bacteremia and sepsis invariably develop when the infection is well established. This paper discusses some of issues related to the cutaneous signs found in NF and also provides a review the current, available literature on the subject matter. PMID:29097860

Cardiac rehabilitation: a comprehensive review

PubMed Central

Lear, Scott A; Ignaszewski, Andrew

2001-01-01

Cardiac rehabilitation (CR) is a commonly used treatment for men and women with cardiovascular disease. To date, no single study has conclusively demonstrated a comprehensive benefit of CR. Numerous individual studies, however, have demonstrated beneficial effects such as improved risk-factor profile, slower disease progression, decreased morbidity, and decreased mortality. This paper will review the evidence for the use of CR and discuss the implications and limitations of these studies. The safety, relevance to special populations, challenges, and future directions of CR will also be reviewed. PMID:11806801

[Fibromyalgia syndrome after comprehensive treatment of breast cancer: a case report].

PubMed

Ding, Xia; Li, Yan; Cui, Yiyi; Shen, Yingying; Gu, Jianzhong; Guo, Yong

2016-05-25

Fibromyalgia syndrome after comprehensive treatment of breast cancer is rare and seldom reported. Here we present a case of a 50-year-old female patient,who was admitted to the hospital because of generalized fibromyalgia for 3 months and brain metastasis after the right breast carcinoma surgery for 1 month, and the clinical diagnosis was brain metastasis from breast carcinoma combined with fibromyalgia syndrome. The fibromyalgia were relieved with proper symptomatic treatment but the patient eventually died of tumor progression.

Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus.

PubMed

Eckstrand, C D; Sparger, E E; Pitt, K A; Murphy, B G

2017-01-01

Feline immunodeficiency virus (FIV) infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN), and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC)-associated viral RNA (vRNA) by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs.

Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus

PubMed Central

Sparger, E. E.; Pitt, K. A.

2017-01-01

Feline immunodeficiency virus (FIV) infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN), and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC)-associated viral RNA (vRNA) by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs. PMID:28384338

[Research Progress of CircRNA and Its Application Prospect in Forensic Medicine].

PubMed

Tu, C Y; Jin, K D; Shao, C C; Liu, B N; Zhang, Y Q; Xie, J H; Shen, Y W

2018-02-01

Circular RNA （circRNA） is a type of noncoding RNA with tissue specificity and high stability, which forms a closed continuous loop and is abundantly expressed in tissue cells. According to recent research, the regulatory function of circRNA elucidating in the occurrence and development of disease shows a potential for diagnosing clinical disease and revealing disease mechanism. This paper reviews the biological characteristics, analysis methods of circRNA and its research progress in clinical application as biomarker, and outlooks its application in the field of forensic medicine. Copyright© by the Editorial Department of Journal of Forensic Medicine.

Spontaneous bilateral chylothorax with fatal outcome in a patient with melorheostosis.

PubMed

Leuenberger, Michèle; Braunwalder, Jan; Schmid, Ralph A; Stanga, Zeno

2008-11-01

We report a case of progressive, multifocal melorheostosis in a 28-year-old woman, with involvement of the left arm, chest, spine, and impressive soft tissue involvement. In the past, she had undergone multiple vascular interventions. She presented with spontaneous massive bilateral chylothorax. After conservative treatment without success, we conducted bilateral pleurodesis. This resulted in a clear reduction of pleural effusions, but her medical condition subsequently worsened due to progressive parenchymatous infiltrates, and increased interlobal pleural effusions. She ultimately died of global respiratory insufficiency. In patients with melorheostosis, involvement of the soft tissue can result in distinctive morbidity, and whenever possible, treatment should be conservative.

[A case of mixed connective tissue disease positive for proteinase 3 antineutrophil cytoplasmic antibody in a patient with slowly progressive type 1 diabetes mellitus and chronic thyroiditis].

PubMed

Michitsuji, Tohru; Horai, Yoshiro; Sako, Ayaka; Asano, Taro; Iwanaga, Nozomi; Izumi, Yasumori; Kawakami, Atsushi

2017-01-01

  A female in her sixties with slowly progressive type 1 diabetes mellitus (SPT1DM) and chronic thyroiditis was referred to our rheumatology department with swelling in her fingers. A prominent atherosclerotic lesion was revealed upon brain magnetic resonance imaging, and she was found to have mixed connective tissue disease (MCTD) positive for proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA). This rare case of MCTD accompanying SPT1DM and PR3-ANCA suggested that a synergy between MCTD and PR3-ANCA triggers atherosclerosis.

Stone Man: A Case Report

PubMed Central

Mortazavi, Hamed; Eshghpour, Majid; Niknami, Mahdi; Saeedi, Morteza

2012-01-01

Fibrodysplasia ossificans progressiva (FOP) is a rare hereditary connective tissue disease characterized by the progressive ectopic ossification of ligaments, tendons, and facial and skeletal muscles throughout life. Symptoms begin in childhood as localized soft tissue swellings. Immobility and articular dysfunction appear with involvement of the spine and proximal extremities. The temporomandibular joint (TMJ) is a critical component involved in the maxillofacial region, resulting in severe limitation of masticatory function, although TMJ involvement is rare. The aim of this article is to present a 28-year-old man with dental problems and slowly progressive limitation of motion in the jaw, knees, shoulders and hips as well as neck distortion. PMID:23599712

Lessons Learned Through the Follow-up of the Long-Term Effects of Over-Exposure to an Ir192 Industrial Radiography Source in Bangladesh

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jalil, A.; Rabbani, G.; Hossain, M. K.

2003-02-24

An industrial radiographer was accidentally over-exposed while taking the radiograph of weld-joints of gas pipe-lines in 1985 in Bangladesh. Symptoms of high radiation exposure occurred immediately after the accident and skin erythema developed leading to progressive tissue deterioration. The consequences of this over-exposure is being followed up to assess the long-term effects of ionizing radiation on the victim. Progressive tissue deteriorations have already led to multiple surgeries and successive amputations of the finger-tips so far. Lessons learned from this accident are also reported in this paper.

A new semiquantitative method for evaluation of metastasis progression.

PubMed

Volarevic, A; Ljujic, B; Volarevic, V; Milovanovic, M; Kanjevac, T; Lukic, A; Arsenijevic, N

2012-01-01

Although recent technical advancements are directed toward developing novel assays and methods for detection of micro and macro metastasis, there are still no reports of reliable, simple to use imaging software that could be used for the detection and quantification of metastasis in tissue sections. We herein report a new semiquantitative method for evaluation of metastasis progression in a well established 4T1 orthotopic mouse model of breast cancer metastasis. The new semiquantitative method presented here was implemented by using the Autodesk AutoCAD 2012 program, a computer-aided design program used primarily for preparing technical drawings in 2 dimensions. By using the Autodesk AutoCAD 2012 software- aided graphical evaluation we managed to detect each metastatic lesion and we precisely calculated the average percentage of lung and liver tissue parenchyma with metastasis in 4T1 tumor-bearing mice. The data were highly specific and relevant to descriptive histological analysis, confirming reliability and accuracy of the AutoCAD 2012 software as new method for quantification of metastatic lesions. The new semiquantitative method using AutoCAD 2012 software provides a novel approach for the estimation of metastatic progression in histological tissue sections.

Progressive polarity loss and luminal collapse disrupt tissue organization in carcinoma

PubMed Central

Halaoui, Ruba; Rejon, Carlis; Chatterjee, Sudipa June; Szymborski, Joseph; Meterissian, Sarkis; Muller, William J.; Omeroglu, Atilla; McCaffrey, Luke

2017-01-01

Epithelial cancers (carcinoma) account for 80%–90% of all cancers. The development of carcinoma is associated with disrupted epithelial organization and solid ductal structures. The mechanisms underlying the morphological development of carcinoma are poorly understood, but it is thought that loss of cell polarity is an early event. Here we report the characterization of the development of human breast lesions leading to carcinoma. We identified a unique mechanism that generates solid ducts in carcinoma through progressive loss of polarity and collapse of the luminal architecture. This program initiates with asymmetric divisions of polarized cells that generate a stratified epithelium containing both polarized and depolarized cells. Stratified regions form cords that penetrate into the lumen, subdividing it into polarized secondary lumina. The secondary lumina then collapse with a concomitant decrease in RhoA and myosin II activity at the apical membrane and ultimately lose apical–basal polarity. By restoring RhoA activity in mice, ducts maintained lumen and cell polarity. Notably, disrupted tissue architecture through luminal collapse was reversible, and ducts with a lumen were re-established after oncogene suppression in vivo. This reveals a novel and common mechanism that contributes to carcinoma development by progressively disrupting cell and tissue organization. PMID:28887414

Interactome Mapping Guided by Tissue-Specific Phosphorylation in Age-Related Macular Degeneration

PubMed Central

Sripathi, Srinivas R.; He, Weilue; Prigge, Cameron L.; Sylvester, O’Donnell; Um, Ji-Yeon; Powell, Folami L.; Neksumi, Musa; Bernstein, Paul S.; Choo, Dong-Won; Bartoli, Manuela; Gutsaeva, Diana R.; Jahng, Wan Jin

2017-01-01

The current study aims to determine the molecular mechanisms of age-related macular degeneration (AMD) using the phosphorylation network. Specifically, we examined novel biomarkers for oxidative stress by protein interaction mapping using in vitro and in vivo models that mimic the complex and progressive characteristics of AMD. We hypothesized that the early apoptotic reactions could be initiated by protein phosphorylation in region-dependent (peripheral retina vs. macular) and tissue-dependent (retinal pigment epithelium vs. retina) manner under chronic oxidative stress. The analysis of protein interactome and oxidative biomarkers showed the presence of tissue- and region-specific post-translational mechanisms that contribute to AMD progression and suggested new therapeutic targets that include ubiquitin, erythropoietin, vitronectin, MMP2, crystalline, nitric oxide, and prohibitin. Phosphorylation of specific target proteins in RPE cells is a central regulatory mechanism as a survival tool under chronic oxidative imbalance. The current interactome map demonstrates a positive correlation between oxidative stress-mediated phosphorylation and AMD progression and provides a basis for understanding oxidative stress-induced cytoskeletal changes and the mechanism of aggregate formation induced by protein phosphorylation. This information could provide an effective therapeutic approach to treat age-related neurodegeneration. PMID:28580316

Interactome Mapping Guided by Tissue-Specific Phosphorylation in Age-Related Macular Degeneration.

PubMed

Sripathi, Srinivas R; He, Weilue; Prigge, Cameron L; Sylvester, O'Donnell; Um, Ji-Yeon; Powell, Folami L; Neksumi, Musa; Bernstein, Paul S; Choo, Dong-Won; Bartoli, Manuela; Gutsaeva, Diana R; Jahng, Wan Jin

2017-02-01

The current study aims to determine the molecular mechanisms of age-related macular degeneration (AMD) using the phosphorylation network. Specifically, we examined novel biomarkers for oxidative stress by protein interaction mapping using in vitro and in vivo models that mimic the complex and progressive characteristics of AMD. We hypothesized that the early apoptotic reactions could be initiated by protein phosphorylation in region-dependent (peripheral retina vs. macular) and tissue-dependent (retinal pigment epithelium vs. retina) manner under chronic oxidative stress. The analysis of protein interactome and oxidative biomarkers showed the presence of tissue- and region-specific post-translational mechanisms that contribute to AMD progression and suggested new therapeutic targets that include ubiquitin, erythropoietin, vitronectin, MMP2, crystalline, nitric oxide, and prohibitin. Phosphorylation of specific target proteins in RPE cells is a central regulatory mechanism as a survival tool under chronic oxidative imbalance. The current interactome map demonstrates a positive correlation between oxidative stress-mediated phosphorylation and AMD progression and provides a basis for understanding oxidative stress-induced cytoskeletal changes and the mechanism of aggregate formation induced by protein phosphorylation. This information could provide an effective therapeutic approach to treat age-related neurodegeneration.

The Brain Revolution.

ERIC Educational Resources Information Center

Sylwester, Robert

1998-01-01

A cognitive-science revolution, reminiscent of Dewey's Progressive Education Movement, will profoundly affect future educational policy and practice. A comprehensive brain theory will emerge out of Darwin's discoveries about natural selection as a scientific explanation for biodiversity, Einstein's theoretical reconceptualization of…

BARATARIA-TERREBONNE NATIONAL ESTUARY PROGRAM IMPLEMENTATION REVIEW REPORT, 2001-2003

EPA Science Inventory

From January 2001 through December 2003, BTNEP made significant progress on implementation of its Comprehensive Conservation Management Plan (CCMP). Notable accomplishments during this period occurred in the areas of coordinated planning and implementation, ecological management,...

Study to Understand Cervical Cancer Early Endpoints and Determinants (SUCCEED)

Cancer.gov

A study to comprehensively assess biomarkers of risk for progressive cervical neoplasia, and thus develop a new set of biomarkers that can distinguish those at highest risk of cervical cancer from those with benign infection

What's New in Software? Computer Programs for Unobtrusive, Informal Evaluation.

ERIC Educational Resources Information Center

Hedley, Carolyn

1985-01-01

Teachers can use microcomputers in informal assessment of learning disabled students' academic achievement, math and science progress, reading comprehension, cognitive processes, motivation and social interaction. Selected software for unobtrusive, informal assessment is listed. (CL)

CETA Progress Report

ERIC Educational Resources Information Center

Kolberg, William H.

1974-01-01

The Comprehensive Employment and Training Act (CETA), less than one year old, represents a promising start and demonstrates that Federal, State, and local governments can work together to help people with serious employment problems compete more effectively for jobs. (Author/MW)

Systems Proteomics for Translational Network Medicine

PubMed Central

Arrell, D. Kent; Terzic, Andre

2012-01-01

Universal principles underlying network science, and their ever-increasing applications in biomedicine, underscore the unprecedented capacity of systems biology based strategies to synthesize and resolve massive high throughput generated datasets. Enabling previously unattainable comprehension of biological complexity, systems approaches have accelerated progress in elucidating disease prediction, progression, and outcome. Applied to the spectrum of states spanning health and disease, network proteomics establishes a collation, integration, and prioritization algorithm to guide mapping and decoding of proteome landscapes from large-scale raw data. Providing unparalleled deconvolution of protein lists into global interactomes, integrative systems proteomics enables objective, multi-modal interpretation at molecular, pathway, and network scales, merging individual molecular components, their plurality of interactions, and functional contributions for systems comprehension. As such, network systems approaches are increasingly exploited for objective interpretation of cardiovascular proteomics studies. Here, we highlight network systems proteomic analysis pipelines for integration and biological interpretation through protein cartography, ontological categorization, pathway and functional enrichment and complex network analysis. PMID:22896016

Exosomes as Novel microRNA-Delivery Vehicles to Modulate Prostate Cancer Progression

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-1-0548 TITLE: Exosomes as Novel microRNA-Delivery Vehicles to Modulate Prostate Cancer Progression PRINCIPAL...Sep 2015 4. TITLE AND SUBTITLE Exosomes as Novel microRNA-Delivery Vehicles to Modulate Prostate Cancer Progression 5a. CONTRACT NUMBER 5b. GRANT...they are produced, but can also signal intercellularly to other cells and tissues at distant sites via exosomal transport. We hypothesize that miRNAs

[Analysis and comprehensive evaluation on cold resistance of six varieties of Michelia].

PubMed

Li, Rui Xue; Jin, Xiao Ling; Hu, Xi Jun; Chai, Yi Xia; Cai, Meng Ying; Luo, Feng; Zhang, Fang Jing

2017-05-18

Taking six varieties of Michelia as test materials, their responses under cold situation in the field were investigated and the semilethal low temperatures were calculated by fitting Logistic equation. The nine structure indexes of leaf tissue were observed by paraffin section, and a comprehensive evaluation on cold resistance of different varieties was given according to subordinate function value analysis. The results showed that the relative electrical conductivity of six varieties of Michelia was significantly positively correlated with the semilethal low temperature (LT 50 ) of 3 h 0-25 ℃ treatment. From high to low, the order of LT 50 , which ranged between -20.48 ℃and -8.67 ℃, was M. maudiae ＞ M. maudiae var. rubicunda ＞ M. wilsonii ＞ M. 'liubanhanxiao' ♀× M. shiluensis ♂ ＞ M. platypetala ＞ M. 'liubanhanxiao'. The epidermal anticlinal walls of six varieties of Michelia leaves had 1-2 layers and showed slightly sinuated shape. The leaf had 1-3 layers of palisade tissue cells and the differences among the indexes of nine anatomical structures were extremely significant. The thickness of palisade tissue, ratio between palisade tissue and spongy tissue, and thickness of the vein were the key factors affecting cold resistance. The order of cold resistance of six varieties of Michelia, from the strong to the weak, was M. 'liubanhanxiao' ＞ M. platypetala ＞ M. 'liubanhanxiao' ♀× M. shiluensis ♂＞M. wilsonii ＞ M. maudiae var. rubicunda ＞ M. maudiae, which was basically consistent with the result of field investigation.

Qualitative and quantitative mass spectrometry imaging of drugs and metabolites in tissue at therapeutic levels.

PubMed

Sun, Na; Walch, Axel

2013-08-01

Mass spectrometry imaging (MSI) is a rapidly evolving technology that yields qualitative and quantitative distribution maps of small pharmaceutical-active molecules and their metabolites in tissue sections in situ. The simplicity, high sensitivity and ability to provide comprehensive spatial distribution maps of different classes of biomolecules make MSI a valuable tool to complement histopathology for diagnostics and biomarker discovery. In this review, qualitative and quantitative MSI of drugs and metabolites in tissue at therapeutic levels are discussed and the impact of this technique in drug discovery and clinical research is highlighted.

PROGRESS IN ACUTE MYELOID LEUKEMIA

PubMed Central

Kadia, Tapan M.; Ravandi, Farhad; O’Brien, Susan; Cortes, Jorge; Kantarjian, Hagop M.

2014-01-01

Significant progress has been made in the treatment of acute myeloid leukemia (AML). Steady gains in clinical research and a renaissance of genomics in leukemia have led to improved outcomes. The recognition of tremendous heterogeneity in AML has allowed individualized treatments of specific disease entities within the context of patient age, cytogenetics, and mutational analysis. The following is a comprehensive review of the current state of AML therapy and a roadmap of our approach to these distinct disease entities. PMID:25441110

Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue.

PubMed

Gautieri, Alfonso; Passini, Fabian S; Silván, Unai; Guizar-Sicairos, Manuel; Carimati, Giulia; Volpi, Piero; Moretti, Matteo; Schoenhuber, Herbert; Redaelli, Alberto; Berli, Martin; Snedeker, Jess G

2017-05-01

Concurrent with a progressive loss of regenerative capacity, connective tissue aging is characterized by a progressive accumulation of Advanced Glycation End-products (AGEs). Besides being part of the typical aging process, type II diabetics are particularly affected by AGE accumulation due to abnormally high levels of systemic glucose that increases the glycation rate of long-lived proteins such as collagen. Although AGEs are associated with a wide range of clinical disorders, the mechanisms by which AGEs contribute to connective tissue disease in aging and diabetes are still poorly understood. The present study harnesses advanced multiscale imaging techniques to characterize a widely employed in vitro model of ribose induced collagen aging and further benchmarks these data against experiments on native human tissues from donors of different age. These efforts yield unprecedented insight into the mechanical changes in collagen tissues across hierarchical scales from molecular, to fiber, to tissue-levels. We observed a linear increase in molecular spacing (from 1.45nm to 1.5nm) and a decrease in the D-period length (from 67.5nm to 67.1nm) in aged tissues, both using the ribose model of in vitro glycation and in native human probes. Multiscale mechanical analysis of in vitro glycated tendons strongly suggests that AGEs reduce tissue viscoelasticity by severely limiting fiber-fiber and fibril-fibril sliding. This study lays an important foundation for interpreting the functional and biological effects of AGEs in collagen connective tissues, by exploiting experimental models of AGEs crosslinking and benchmarking them for the first time against endogenous AGEs in native tissue. Copyright © 2016 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Matrix Metalloproteases and Tissue Inhibitors of Metalloproteinases in Medial Plica and Pannus-like Tissue Contribute to Knee Osteoarthritis Progression

PubMed Central

Yang, Chih-Chang; Lin, Cheng-Yu; Wang, Hwai-Shi; Lyu, Shaw-Ruey

2013-01-01

Osteoarthritis (OA) is characterized by degradation of the cartilage matrix, leading to pathologic changes in the joints. However, the pathogenic effects of synovial tissue inflammation on OA knees are not clear. To investigate whether the inflammation caused by the medial plica is involved in the pathogenesis of osteoarthritis, we examined the expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α in the medial plica and pannus-like tissue in the knees of patients with medial compartment OA who underwent either arthroscopic medial release (stage II; 15 knee joints from 15 patients) or total knee replacement (stage IV; 18 knee joints from 18 patients). MMP-2, MMP-3, MMP-9, IL-1β, and TNF-α mRNA and protein levels measured, respectively, by quantitative real-time PCR and Quantibody human MMP arrays, were highly expressed in extracts of medial plica and pannus-like tissue from stage IV knee joints. Immunohistochemical staining also demonstrated high expression of MMP-2, MMP-3, and MMP-9 in plica and pannus-like tissue of stage IV OA knees and not in normal cartilage. Some TIMP/MMP ratios decreased significantly in both medial plica and pannus-like tissue as disease progressed from stage II to stage IV. Furthermore, the migration of cells from the pannus-like tissue was enhanced by IL-1β, while plica cell migration was enhanced by TNF-α. The results suggest that medial plica and pannus-like tissue may be involved in the process of cartilage degradation in medial compartment OA of the knee. PMID:24223987

Matrix metalloproteases and tissue inhibitors of metalloproteinases in medial plica and pannus-like tissue contribute to knee osteoarthritis progression.

PubMed

Yang, Chih-Chang; Lin, Cheng-Yu; Wang, Hwai-Shi; Lyu, Shaw-Ruey

2013-01-01

Osteoarthritis (OA) is characterized by degradation of the cartilage matrix, leading to pathologic changes in the joints. However, the pathogenic effects of synovial tissue inflammation on OA knees are not clear. To investigate whether the inflammation caused by the medial plica is involved in the pathogenesis of osteoarthritis, we examined the expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α in the medial plica and pannus-like tissue in the knees of patients with medial compartment OA who underwent either arthroscopic medial release (stage II; 15 knee joints from 15 patients) or total knee replacement (stage IV; 18 knee joints from 18 patients). MMP-2, MMP-3, MMP-9, IL-1β, and TNF-α mRNA and protein levels measured, respectively, by quantitative real-time PCR and Quantibody human MMP arrays, were highly expressed in extracts of medial plica and pannus-like tissue from stage IV knee joints. Immunohistochemical staining also demonstrated high expression of MMP-2, MMP-3, and MMP-9 in plica and pannus-like tissue of stage IV OA knees and not in normal cartilage. Some TIMP/MMP ratios decreased significantly in both medial plica and pannus-like tissue as disease progressed from stage II to stage IV. Furthermore, the migration of cells from the pannus-like tissue was enhanced by IL-1β, while plica cell migration was enhanced by TNF-α. The results suggest that medial plica and pannus-like tissue may be involved in the process of cartilage degradation in medial compartment OA of the knee.

The role of adipose tissue in cancer-associated cachexia.

PubMed

Vaitkus, Janina A; Celi, Francesco S

2017-03-01

Adipose tissue (fat) is a heterogeneous organ, both in function and histology, distributed throughout the body. White adipose tissue, responsible for energy storage and more recently found to have endocrine and inflammation-modulatory activities, was historically thought to be the only type of fat present in adult humans. The recent demonstration of functional brown adipose tissue in adults, which is highly metabolic, shifted this paradigm. Additionally, recent studies demonstrate the ability of white adipose tissue to be induced toward the brown adipose phenotype - "beige" or "brite" adipose tissue - in a process referred to as "browning." While these adipose tissue depots are under investigation in the context of obesity, new evidence suggests a maladaptive role in other metabolic disturbances including cancer-associated cachexia, which is the topic of this review. This syndrome is multifactorial in nature and is an independent factor associated with poor prognosis. Here, we review the contributions of all three adipose depots - white, brown, and beige - to the development and progression of cancer-associated cachexia. Specifically, we focus on the local and systemic processes involving these adipose tissues that lead to increased energy expenditure and sustained negative energy balance. We highlight key findings from both animal and human studies and discuss areas within the field that need further exploration. Impact statement Cancer-associated cachexia (CAC) is a complex, multifactorial syndrome that negatively impacts patient quality of live and prognosis. This work reviews a component of CAC that lacks prior discussion: adipose tissue contributions. Uniquely, it discusses all three types of adipose tissue, white, beige, and brown, their interactions, and their contributions to the development and progression of CAC. Summarizing key bench and clinical studies, it provides information that will be useful to both basic and clinical researchers in designing experiments, studies, and clinical trials.

Infrared micro-spectroscopy of human tissue: principles and future promises.

PubMed

Diem, Max; Ergin, Ayşegül; Remiszewski, Stan; Mu, Xinying; Akalin, Ali; Raz, Dan

2016-06-23

This article summarizes the methods employed, and the progress achieved over the past two decades in applying vibrational (Raman and IR) micro-spectroscopy to problems of medical diagnostics and cellular biology. During this time, several research groups have verified the enormous information contained in vibrational spectra; in fact, information on protein, lipid and metabolic composition of cells and tissues can be deduced by decoding the observed vibrational spectra. This decoding process is aided by the availability of computer workstations and advanced algorithms for data analysis. Furthermore, commercial instrumentation for the fast collection of both Raman and infrared micro-spectral data has enabled the collection of images of cells and tissues based solely on vibrational spectroscopic data. The progress in the field has been manifested by a steady increase in the number and quality of publications submitted by established and new research groups in vibrational spectroscopy in the biological and biomedical arenas.

Oxidative stress and adipocyte biology: focus on the role of AGEs.

PubMed

Boyer, Florence; Vidot, Jennifer Baraka; Dubourg, Alexis Guerin; Rondeau, Philippe; Essop, M Faadiel; Bourdon, Emmanuel

2015-01-01

Diabetes is a major health problem that is usually associated with obesity, together with hyperglycemia and increased advanced glycation endproducts (AGEs) formation. Elevated AGEs elicit severe downstream consequences via their binding to receptors of AGEs (RAGE). This includes oxidative stress and oxidative modifications of biological compounds together with heightened inflammation. For example, albumin (major circulating protein) undergoes increased glycoxidation with diabetes and may represent an important biomarker for monitoring diabetic pathophysiology. Despite the central role of adipose tissue in many physiologic/pathologic processes, recognition of the effects of greater AGEs formation in this tissue is quite recent within the obesity/diabetes context. This review provides a brief background of AGEs formation and adipose tissue biology and thereafter discusses the impact of AGEs-adipocyte interactions in pathology progression. Novel data are included showing how AGEs (especially glycated albumin) may be involved in hyperglycemia-induced oxidative damage in adipocytes and its potential links to diabetes progression.

Expression profiling of peroxisome proliferator-activated receptor-delta (PPAR-delta) in mouse tissues using tissue microarray.

PubMed

Higashiyama, Hiroyuki; Billin, Andrew N; Okamoto, Yuji; Kinoshita, Mine; Asano, Satoshi

2007-05-01

Peroxisome proliferator-activated receptor-delta (PPAR-delta) is known as a transcription factor involved in the regulation of fatty acid oxidation and mitochondrial biogenesis in several tissues, such as skeletal muscle, liver and adipose tissues. In this study, to elucidate systemic physiological functions of PPAR-delta, we examined the tissue distribution and localization of PPAR-delta in adult mouse tissues using tissue microarray (TMA)-based immunohistochemistry. PPAR-delta positive signals were observed on variety of tissues/cells in multiple systems including cardiovascular, urinary, respiratory, digestive, endocrine, nervous, hematopoietic, immune, musculoskeletal, sensory and reproductive organ systems. In these organs, PPAR-delta immunoreactivity was generally localized on the nucleus, although cytoplasmic localization was observed on several cell types including neurons in the nervous system and cells of the islet of Langerhans. These expression profiling data implicate various physiological roles of PPAR-delta in multiple organ systems. TMA-based immunohistochemistry enables to profile comprehensive protein localization and distribution in a high-throughput manner.

Adipose-Derived Stem Cell Delivery for Adipose Tissue Engineering: Current Status and Potential Applications in a Tissue Engineering Chamber Model.

PubMed

Zhan, Weiqing; Tan, Shaun S; Lu, Feng

2016-08-01

In reconstructive surgery, there is a clinical need for adequate implants to repair soft tissue defects caused by traumatic injury, tumor resection, or congenital abnormalities. Adipose tissue engineering may provide answers to this increasing demand. This study comprehensively reviews current approaches to adipose tissue engineering, detailing different cell carriers under investigation, with a special focus on the application of adipose-derived stem cells (ASCs). ASCs act as building blocks for new tissue growth and as modulators of the host response. Recent studies have also demonstrated that the implantation of a hollow protected chamber, combined with a vascular pedicle within the fat flaps provides blood supply and enables the growth of large-volume of engineered soft tissue. Conceptually, it would be of value to co-regulate this unique chamber model with adipose-derived stem cells to obtain a greater volume of soft tissue constructs for clinical use. Our review provides a cogent update on these advances and details the generation of possible fat substitutes.

Tissue engineering for urinary tract reconstruction and repair: Progress and prospect in China.

PubMed

Zou, Qingsong; Fu, Qiang

2018-04-01

Several urinary tract pathologic conditions, such as strictures, cancer, and obliterations, require reconstructive plastic surgery. Reconstruction of the urinary tract is an intractable task for urologists due to insufficient autologous tissue. Limitations of autologous tissue application prompted urologists to investigate ideal substitutes. Tissue engineering is a new direction in these cases. Advances in tissue engineering over the last 2 decades may offer alternative approaches for the urinary tract reconstruction. The main components of tissue engineering include biomaterials and cells. Biomaterials can be used with or without cultured cells. This paper focuses on cell sources, biomaterials, and existing methods of tissue engineering for urinary tract reconstruction in China. The paper also details challenges and perspectives involved in urinary tract reconstruction.

[Regulation of terpene metabolism]. Annual progress report, March 15, 1988--March 14, 1989

DOE Office of Scientific and Technical Information (OSTI.GOV)

Croteau, R.

1989-12-31

Progress in understanding of the metabolism of monoterpenes by peppermint and spearmint is recorded including the actions of two key enzymes, geranyl pyrophosphate:limonene cyclase and a UDP-glucose dependent glucosyl transferase; concerning the ultrastructure of oil gland senescence; enzyme subcellular localization; regulation of metabolism; and tissue culture systems.

Development of Nitrogen Sensor for Determination of PN(2) in Body Tissues.

DTIC Science & Technology

1982-07-01

3) The progress of the reduction reaction (1) was followed by voltammetry. A single anodic potential sweep , starting from the open circuit...Graphite Electrode The progressive attachment of [Ru(NH3 ) 5 H2 0] +2 to PVP-coated graphite electrodes was observed by cyclic voltametry as an

Connective Tissue Mineralization in Abcc6−/− Mice, a Model for Pseudoxanthoma Elasticum

PubMed Central

Kavukcuoglu, N. Beril; Li, Qiaoli; Pleshko, Nancy; Uitto, Jouni

2012-01-01

Pseudoxanthoma elasticum (PXE) is a heritable multisystem disorder characterized by ectopic mineralization. However, the structure of the mineral deposits, their interactions with the connective tissue matrix, and the details of the progressive maturation of the mineral crystals are currently unknown. In this study, we examined the mineralization processes in Abcc6−/− mice, a model system for PXE, by energy dispersive X-ray, and Fourier transform infrared imaging spectroscopy (FT-IRIS). The results indicated that the principal components of the mineral deposits were calcium and phosphate which co-localized within the histologically demonstrable lesions determined by topographic mapping. The Ca/P ratio increased in samples with progressive mineralization reaching the value comparable to that in endochondral bone. A progressive increase in mineralization was also reflected by increased mineral-to-matrix ratio determined by FT-IRIS. Determination of the mineral phases by FT-IRIS suggested progressive maturation of the mineral deposits from amorphous calcium phosphate to hydroxyapatite. These results provide critical information of the mechanisms of mineralization in PXE, with potential pharmacologic implications. PMID:22421595

The molecular biology of WHO grade I astrocytomas.

PubMed

Marko, Nicholas F; Weil, Robert J

2012-12-01

World Health Organization (WHO) grade I astrocytomas include pilocytic astrocytoma (PA) and subependymal giant cell astrocytoma (SEGA). As technologies in pharmacologic neo-adjuvant therapy continue to progress and as molecular characteristics are progressively recognized as potential markers of both clinically significant tumor subtypes and response to therapy, interest in the biology of these tumors has surged. An updated review of the current knowledge of the molecular biology of these tumors is needed. We conducted a Medline search to identify published literature discussing the molecular biology of grade I astrocytomas. We then summarized this literature and discuss it in a logical framework through which the complex biology of these tumors can be clearly understood. A comprehensive review of the molecular biology of WHO grade I astrocytomas is presented. The past several years have seen rapid progress in the level of understanding of PA in particular, but the molecular literature regarding both PA and SEGA remains nebulous, ambiguous, and occasionally contradictory. In this review we provide a comprehensive discussion of the current understanding of the chromosomal, genomic, and epigenomic features of both PA and SEGA and provide a logical framework in which these data can be more readily understood.

Early Identification of Reading Comprehension Difficulties.

PubMed

Catts, Hugh W; Nielsen, Diane Corcoran; Bridges, Mindy Sittner; Liu, Yi-Syuan

2016-09-01

Most research on early identification of reading disabilities has focused on word reading problems and little attention has been given to reading comprehension difficulties. In this study, we investigated whether measures of language ability and/or response to language intervention in kindergarten uniquely predicted reading comprehension difficulties in third grade. A total of 366 children were administered a battery of screening measures at the beginning of kindergarten and progress monitoring probes across the school year. A subset of children also received a 26-week Tier 2 language intervention. Participants' achievement in word reading was assessed at the end of second grade, and their performance in reading comprehension was measured as the end of third grade. Results showed that measures of language ability in kindergarten significantly added to the prediction of reading comprehension difficulties over and above kindergarten word reading predictors and direct measures of word reading in second grade. Response to language intervention also proved to be a unique predictor of reading comprehension outcomes. Findings are discussed in terms of their relevance for the early identification of reading disabilities. © Hammill Institute on Disabilities 2014.

Lattice-based model of ductal carcinoma in situ suggests rules for breast cancer progression to an invasive state.

PubMed

Boghaert, Eline; Radisky, Derek C; Nelson, Celeste M

2014-12-01

Ductal carcinoma in situ (DCIS) is a heterogeneous group of non-invasive lesions of the breast that result from abnormal proliferation of mammary epithelial cells. Pathologists characterize DCIS by four tissue morphologies (micropapillary, cribriform, solid, and comedo), but the underlying mechanisms that distinguish the development and progression of these morphologies are not well understood. Here we explored the conditions leading to the emergence of the different morphologies of DCIS using a two-dimensional multi-cell lattice-based model that incorporates cell proliferation, apoptosis, necrosis, adhesion, and contractility. We found that the relative rates of cell proliferation and apoptosis governed which of the four morphologies emerged. High proliferation and low apoptosis favored the emergence of solid and comedo morphologies. In contrast, low proliferation and high apoptosis led to the micropapillary morphology, whereas high proliferation and high apoptosis led to the cribriform morphology. The natural progression between morphologies cannot be investigated in vivo since lesions are usually surgically removed upon detection; however, our model suggests probable transitions between these morphologies during breast cancer progression. Importantly, cribriform and comedo appear to be the ultimate morphologies of DCIS. Motivated by previous experimental studies demonstrating that tumor cells behave differently depending on where they are located within the mammary duct in vivo or in engineered tissues, we examined the effects of tissue geometry on the progression of DCIS. In agreement with our previous experimental work, we found that cells are more likely to invade from the end of ducts and that this preferential invasion is regulated by cell adhesion and contractility. This model provides additional insight into tumor cell behavior and allows the exploration of phenotypic transitions not easily monitored in vivo.

Is Science Logical?

ERIC Educational Resources Information Center

Pease, Craig M.; Bull, J. J.

1992-01-01

Offers a concise, abstract description of the scientific method different from the historical, philosophical, and case-study approaches, which lead to comprehension of this method. Discusses features of scientific models, dynamic interactions underlying scientific progress, ways that scientist successfully understand nature, mechanisms for…

MTSS Coaching: Bridging Knowing to Doing

ERIC Educational Resources Information Center

Freeman, Jennifer; Sugai, George; Simonsen, Brandi; Everett, Susannah

2017-01-01

Improving educator effectiveness and school functioning requires continuous attention to practice selection, implementation fidelity, and progress monitoring, especially in the context of systemic school reform efforts. As such, supporting professional development must be targeted, comprehensive, efficient, and relevant. In particular, coaching…

Quality management and accreditation of research tissue banks: experience of the National Center for Tumor Diseases (NCT) Heidelberg.

PubMed

Herpel, Esther; Röcken, Christoph; Manke, Heike; Schirmacher, Peter; Flechtenmacher, Christa

2010-12-01

Tissue banks are key resource and technology platforms in biomedical research that address the molecular pathogenesis of diseases as well as disease prevention, diagnosis, and treatment. Due to the central role of tissue banks in standardized collection, storage, and distribution of human tissues and their derivatives, quality management and its external assessment is becoming increasingly relevant for the maintenance, acceptance, and funding of tissue banks. Little experience exists regarding formalized external evaluation of tissue banks, especially regarding certification and accreditation. Based on the accreditation of the National Center of Tumor Diseases (NCT) tissue bank in Heidelberg (Germany), criteria, requirements, processes, and implications were compiled and evaluated. Accreditation formally approved professional competence and performance of the tissue bank in all steps involved in tissue collection, storage, handling as well as macroscopic and histologic examination and final (exit) examination of the tissue and transfer supervised by board-certified competent histopathologists. Thereby, accreditation provides a comprehensive measure to evaluate and document the quality standard of tissue research banks and may play a significant role in the future assessment of tissue banks. Furthermore, accreditation may support harmonization and standardization of tissue banking for biomedical research purposes.

The time course of neurolinguistic and neuropsychological symptoms in three cases of logopenic primary progressive aphasia.

PubMed

Etcheverry, Louise; Seidel, Barbara; Grande, Marion; Schulte, Stephanie; Pieperhoff, Peter; Südmeyer, Martin; Minnerop, Martina; Binkofski, Ferdinand; Huber, Walter; Grodzinsky, Yosef; Amunts, Katrin; Heim, Stefan

2012-06-01

Primary progressive aphasia (PPA) is a rare clinical dementia syndrome affecting predominantly language abilities. Word-finding difficulties and comprehension deficits despite relatively preserved cognitive functions are characteristic symptoms during the first two years, and distinguish PPA from other dementia types like Alzheimer's disease. However, the dynamics of changes in language and non-linguistic abilities are not well understood. Most studies on progression used cross-sectional designs, which provide only limited insight into the course of the disease. Here we report the results of a longitudinal study in three cases of logopenic PPA over a period of 18 months, with exemplary longitudinal data from one patient even over 46 months. A comprehensive battery of neurolinguistic and neuropsychological tests was applied four times at intervals of six months. Over this period, deterioration of verbal abilities such as picture naming, story retelling, and semantic word recall was found, and the individual decline was quantified and compared between the three patients. Furthermore, decrease in non-verbal skills such as divided attention and increasing apraxia was observed in all three patients. In addition, inter-subject variability in the progression with different focuses was observed, with one patient developing a non-fluent PPA variant. The longitudinal, multivariate investigation of logopenic PPA thus provides novel insights into the progressive deterioration of verbal as well as non-verbal abilities. These deficits may further interact and thus form a multi-causal basis for the patients' problems in every-day life which need to be considered when planning individually targeted intervention in PPA. Copyright © 2012 Elsevier Ltd. All rights reserved.

3D printing for clinical application in otorhinolaryngology.

PubMed

Zhong, Nongping; Zhao, Xia

2017-12-01

Three-dimensional (3D) printing is a promising technology that can use a patient's image data to create complex and personalized constructs precisely. It has made great progress over the past few decades and has been widely used in medicine including medical modeling, surgical planning, medical education and training, prosthesis and implants. Three-dimensional (3D) bioprinting is a powerful tool that has the potential to fabricate bioengineered constructs of the desired shape layer-by-layer using computer-aided deposition of living cells and biomaterials. Advances in 3D printed implants and future tissue-engineered constructs will bring great progress to the field of otolaryngology. By integrating 3D printing into tissue engineering and materials, it may be possible for otolaryngologists to implant 3D printed functional grafts into patients for reconstruction of a variety of tissue defects in the foreseeable future. In this review, we will introduce the current state of 3D printing technology and highlight the applications of 3D printed prosthesis and implants, 3D printing technology combined with tissue engineering and future directions of bioprinting in the field of otolaryngology.

Macrophage-mediated response to hypoxia in disease.

PubMed

Tazzyman, Simon; Murdoch, Craig; Yeomans, James; Harrison, Jack; Muthana, Munitta

2014-01-01

Hypoxia plays a critical role in the pathobiology of various inflamed, diseased tissues, including malignant tumors, atherosclerotic plaques, myocardial infarcts, the synovia of rheumatoid arthritic joints, healing wounds, and sites of bacterial infection. These areas of hypoxia form when the blood supply is occluded and/or the oxygen supply is unable to keep pace with cell growth and/or infiltration of inflammatory cells. Macrophages are ubiquitous in all tissues of the body and exhibit great plasticity, allowing them to perform divergent functions, including, among others, patrolling tissue, combating invading pathogens and tumor cells, orchestrating wound healing, and restoring homeostasis after an inflammatory response. The number of tissue macrophages increases markedly with the onset and progression of many pathological states, with many macrophages accumulating in avascular and necrotic areas, where they are exposed to hypoxia. Recent studies show that these highly versatile cells then respond rapidly to the hypoxia present by altering their expression of a wide array of genes. Here we review the evidence for hypoxia-driven macrophage inflammatory responses in various disease states, and how this influences disease progression and treatment.

Pattern of somatostatin receptors expression in normal and bladder cancer tissue samples.

PubMed

Karavitakis, Markos; Msaouel, Pavlos; Michalopoulos, Vassilis; Koutsilieris, Michael

2014-06-01

Known risks factors for bladder cancer progression and recurrence are limited regarding their prognostic ability. Therefore identification of molecular determinants of disease progression could provide with more specific prognostic information and could be translated into new approaches for biomarker development. In the present study we evaluated, the expression patterns of somatostatin receptors 1-5 (SSTRs) in normal and tumor bladder tissues. The expression of SSTR1-5 was characterized in 45 normal and bladder cancer tissue samples using reverse transcriptase-polymerase chain reaction (RT-PCR). SSTR1 was expressed in 24 samples, SSTR2 in 15, SSTR3 in 23, SSTR4 in 16 and SSTR5 in all but one sample. Bladder cancer tissue samples expressed lower levels of SSTR3. Co-expression of SSTRs was associated with superficial disease. Our results demonstrate, for the first time, that there is expression of SSTR in normal and bladder cancer urothelium. Further studies are required to evaluate the prognostic and therapeutic significance of these findings. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Decreased expression of Toll-like receptor 4 and 5 during progression of prostate transformation in transgenic adenocarcinoma of mouse prostate mice.

PubMed

Han, Ju-Hee; Park, Jong-Hwan; Kim, Bo-Yeon; Chang, Seo-Na; Kim, Tae-Hyoun; Park, Jae-Hak; Kim, Dong-Jae

2015-01-01

Chronic inflammation has been considered an important risk factor for development of prostate cancer. Toll-like receptors (TLRs) recognize microbial moieties or endogenous molecules and play an important role in the triggering and promotion of inflammation. In this study, we examined whether expression of TLR4 and TLR5 was associated with progression of prostate transformation in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. The expression of TLR4 and TLR5 was evaluated by immunohistochemisty in formalin-fixed paraffin-embedded prostate tissue from wild-type (WT) and TRAMP mice. Normal prostate tissue from WT mice showed strong expression of TLR4 and TLR5. However, TLR4 expression in the prostate tissue from TRAMP mice gradually decreased as pathologic grade became more aggressive. TLR5 expression in the prostate tissue from TRAMP mice also decreased in low-grade prostate intraepithelial neoplasia (PIN), high-grade PIN and poorly differentiated adenocarcinoma. Overall, our results suggest that decreased expression of TLR4 and TLR5 may contribute to prostate tumorigenesis.

Tissue factor expression in rheumatoid synovium: a potential role in pannus invasion of rheumatoid arthritis.

PubMed

Chen, Lujun; Lu, Yahua; Chu, Yang; Xie, Jun; Ding, Wen'ge; Wang, Fengming

2013-09-01

Angiogenesis, as well as pannus formation within the joint, plays an important role in the erosion of articular cartilage and bone in the pathological process of rheumatoid arthritis (RA). Tissue factor (TF), an essential initiator of the extrinsic pathway of blood coagulation, is also involved in the angiogenesis and the pannus formation of RA progression. In the present study, we used immunofluorescence and confocal scanning methods to characterize TF immunolocalization in RA synovium. We showed that positive staining of TF could be immunolocalized in synoviocytes, CD19(+) B cells and CD68(+) macrophages, whereas weak or negative staining of tissue factor could be found in CD34(+) endothelial cells of neo-vessels, CD3(+) T cells and CD14(+) monocytes in RA synovium tissues. Our study demonstrates a detailed local expression of TF in the rheumatoid synovium, and supports the notion that TF, expressed not only by the synoviocytes themselves, but also the infiltrating CD19(+) B cells and CD68(+) macrophages, is involved in the pannus invasion in the progression of rheumatoid arthritis. Copyright © 2013 Elsevier GmbH. All rights reserved.

Communicative competence in Alzheimer's disease: metaphor and sarcasm comprehension.

PubMed

Maki, Yohko; Yamaguchi, Tomoharu; Koeda, Tatsuya; Yamaguchi, Haruyasu

2013-02-01

The purpose of this study was to evaluate the deficits of metaphor and sarcasm comprehension in Alzheimer's disease (AD), as pragmatic interpretation such as metaphor and sarcasm comprehension is required in social communication. A total of 31 young normal controls, 104 aged normal controls (ANC), 42 patients with amnesic mild cognitive impairment (aMCI), and 30 patients with mild AD were evaluated by Metaphoric and Sarcastic Scenario Test, which consists of 5 metaphoric and 5 sarcastic questions with 5 answer choices. Scores were analyzed using the repeated measures analysis of variance (metaphor/sarcasm vs 4 participant groups). Sarcasm comprehension, which requires second-order Theory of Mind (ToM), started to deteriorate in ANC, and metaphor comprehension, which requires first-order ToM, started to deteriorate in aMCI, and both deteriorated as disease progressed. Literal interpretation of pragmatic language is characteristic in patients with mild AD. Such misinterpretation would result in social miscommunication, even if they still retained semantic-lexical competence.

Implementation of the Single European Code in a Multi-Tissue Bank.

PubMed

Schroeter, Jan; Schulz, Tino; Schroeter, Bernard; Fleischhauer, Katrin; Pruß, Axel

2017-11-01

The traceability of tissue and cells transplants is important to ensure a high level of safety for the recipients. With the final introduction of the Single European Code (SEC) in April 2017 in the EU a consistent system among all member states became mandatory. The regulations for the SEC on EU and national level were evaluated. An overview on the different parts of the SEC with detailed explanations is given. Our own experiences with the implementation of the SEC in our multi-tissue bank are reported in addition. The implementation of the SEC in our multi-tissue bank could be successfully realized. However, it revealed a number of difficulties, especially the sterile labeling of certain tissue transplants and the complex update of the existing database. The introduction of the SEC has made a contribution to the safety of recipients of tissue and cells transplants through a system of comprehensive and transparent traceability.

Chemical Probes for Visualizing Intact Animal and Human Brain Tissue.

PubMed

Lai, Hei Ming; Ng, Wai-Lung; Gentleman, Steve M; Wu, Wutian

2017-06-22

Newly developed tissue clearing techniques can be used to render intact tissues transparent. When combined with fluorescent labeling technologies and optical sectioning microscopy, this allows visualization of fine structure in three dimensions. Gene-transfection techniques have proved very useful in visualizing cellular structures in animal models, but they are not applicable to human brain tissue. Here, we discuss the characteristics of an ideal chemical fluorescent probe for use in brain and other cleared tissues, and offer a comprehensive overview of currently available chemical probes. We describe their working principles and compare their performance with the goal of simplifying probe selection for neuropathologists and stimulating probe development by chemists. We propose several approaches for the development of innovative chemical labeling methods which, when combined with tissue clearing, have the potential to revolutionize how we study the structure and function of the human brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

γδ T cells in homeostasis and host defence of epithelial barrier tissues.

PubMed

Nielsen, Morten M; Witherden, Deborah A; Havran, Wendy L

2017-12-01

Epithelial surfaces line the body and provide a crucial interface between the body and the external environment. Tissue-resident epithelial γδ T cells represent a major T cell population in the epithelial tissues and are ideally positioned to carry out barrier surveillance and aid in tissue homeostasis and repair. In this Review, we focus on the intraepithelial γδ T cell compartment of the two largest epithelial tissues in the body - namely, the epidermis and the intestine - and provide a comprehensive overview of the crucial contributions of intraepithelial γδ T cells to tissue integrity and repair, host homeostasis and protection in the context of the symbiotic relationship with the microbiome and during pathogen clearance. Finally, we describe epithelium-specific butyrophilin-like molecules and briefly review their emerging role in selectively shaping and regulating epidermal and intestinal γδ T cell repertoires.

Large-scale inference of protein tissue origin in gram-positive sepsis plasma using quantitative targeted proteomics

PubMed Central

Malmström, Erik; Kilsgård, Ola; Hauri, Simon; Smeds, Emanuel; Herwald, Heiko; Malmström, Lars; Malmström, Johan

2016-01-01

The plasma proteome is highly dynamic and variable, composed of proteins derived from surrounding tissues and cells. To investigate the complex processes that control the composition of the plasma proteome, we developed a mass spectrometry-based proteomics strategy to infer the origin of proteins detected in murine plasma. The strategy relies on the construction of a comprehensive protein tissue atlas from cells and highly vascularized organs using shotgun mass spectrometry. The protein tissue atlas was transformed to a spectral library for highly reproducible quantification of tissue-specific proteins directly in plasma using SWATH-like data-independent mass spectrometry analysis. We show that the method can determine drastic changes of tissue-specific protein profiles in blood plasma from mouse animal models with sepsis. The strategy can be extended to several other species advancing our understanding of the complex processes that contribute to the plasma proteome dynamics. PMID:26732734

A comprehensive review of cryogels and their roles in tissue engineering applications.

PubMed

Hixon, Katherine R; Lu, Tracy; Sell, Scott A

2017-10-15

The extracellular matrix is fundamental in providing an appropriate environment for cell interaction and signaling to occur. Replicating such a matrix is advantageous in the support of tissue ingrowth and regeneration through the field of tissue engineering. While scaffolds can be fabricated in many ways, cryogels have recently become a popular approach due to their macroporous structure and durability. Produced through the crosslinking of gel precursors followed by a subsequent controlled freeze/thaw cycle, the resulting cryogel provides a unique, sponge-like structure. Therefore, cryogels have proven advantageous for many tissue engineering applications including roles in bioreactor systems, cell separation, and scaffolding. Specifically, the matrix has been demonstrated to encourage the production of various molecules, such as antibodies, and has also been used for cryopreservation. Cryogels can pose as a bioreactor for the expansion of cell lines, as well as a vehicle for cell separation. Lastly, this matrix has shown excellent potential as a tissue engineered scaffold, encouraging regrowth at numerous damaged tissue sites in vivo. This review will briefly discuss the fabrication of cryogels, with an emphasis placed on their application in various facets of tissue engineering to provide an overview of this unique scaffold's past and future roles. Cryogels are unique scaffolds produced through the controlled freezing and thawing of a polymer solution. There is an ever-growing body of literature that demonstrates their applicability in the realm of tissue engineering as extracellular matrix analogue scaffolds; with extensive information having been provided regarding the fabrication, porosity, and mechanical integrity of the scaffolds. Additionally, cryogels have been reviewed with respect to their role in bioseparation and as cellular incubators. This all-inclusive view of the roles that cryogels can play is critical to advancing the technology and expanding its niche within biomaterials and tissue engineering research. To the best of the authors' knowledge, this is the first comprehensive review of cryogel applications in tissue engineering that includes specific looks at their growing roles as extracellular matrix analogues, incubators, and in bioseparation processes. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

MUC1, MUC2, MUC4, MUC5AC and MUC6 expression in the progression of prostate cancer.

PubMed

Cozzi, Paul J; Wang, Jian; Delprado, Warick; Perkins, Alan C; Allen, Barry J; Russell, Pamela J; Li, Yong

2005-01-01

Molecular changes are vital for the development of prognostic markers and therapeutic modalities of prostate cancer (CaP). There is growing interest in mucins as treatment targets in human malignancies, including CaP. The role of their expression in the progression of CaP is however unclear. We examined the expressions MUC1, MUC2, MUC4, MUC5AC and MUC6 in CaP tissues using tissue microarrays (TMAs) to look for tumor-associated antigens (TAAs) for targeted therapy. In this study, 120 paraffin-embedded specimens were selected from patients who underwent radical retro-pubic prostatectomy (RRP) or trans-urethral-resection of the prostate (TURP) for primary, untreated CaP and 10 matched lymph node metastases. A series of MUC monoclonal antibodies (mAbs) was used on TMAs by standard immunohistochemistry. Our results indicate that the over-expression of MUC1 was detected in 58% of primary CaP tissues and 90% of lymph node metastases but not in normal prostate or benign tissues, while the expression of MUC2, MUC4, MUC5AC and MUC6 was found to be negative in both normal and cancer tissues. Of the MUC1 positive tumors 86% were Gleason grade 7 or higher. Over-expression of MUC1 was found in late stage CaP while MUC2, 4, 5AC and 6 were negative in CaP. MUC1 is a TAA that is highly related to tumor progression in CaP patients. This antigen is ideal for targeted therapy to control micrometastases and hormone refractory disease but additional studies are necessary to assess its usefulness in patient biopsies and CaP bone metastases before clinical trial.