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Metabolic Effects Of Fgf-21: Thermoregulation And Beyond, Bin Ni, Jared S. Farrar, Janina A. Vaitkus, Francesco S. Celi

Internal Medicine Publications

Fibroblast growth factor (FGF)-21, a member of the FGF family, is a novel hormone involved in the control of metabolism by modulating glucose homeostasis, insulin sensitivity, ketogenesis, and promoting adipose tissue “browning.” Recent studies demonstrated that brown adipose tissue is not only a target for FGF-21, but is also a potentially important source of systemic FGF-21. These findings support the hypothesis that FGF-21 plays a physiologic role in thermogenesis and thermogenic recruitment of white adipose tissue by an autocrine–paracrine axis. This review examines the role of FGF-21 in thermogenesis from the perspective of cell-based, animal model, and human studies. We …

Increased Eicosanoid Levels In The Sugen/Chronic Hypoxia Model Of Severe Pulmonary Hypertension, Aysar A. Al-Husseini, Dayanjan S. Wijesinghe, Laszlo Farkas, Donatas Kraskauskas, Jennifer I. Drake, Ben Van Tassel, Antonio Abbate, Charles E. Chalfant, Norbert F. Voelkel

Internal Medicine Publications

Inflammation and altered immunity are recognized components of severe pulmonary arterial hypertension in human patients and in animal models of PAH. While eicosanoid metabolites of cyclooxygenase and lipoxygenase pathways have been identified in the lungs from pulmonary hypertensive animals their role in the pathogenesis of severe angioobliterative PAH has not been examined. Here we investigated whether a cyclooxygenase-2 (COX-2) inhibitor or diethylcarbamazine (DEC), that is known for its 5-lipoxygenase inhibiting and antioxidant actions, modify the development of PAH in the Sugen 5416/hypoxia (SuHx) rat model. The COX-2 inhibitor SC-58125 had little effect on the right ventricular pressure and did not …

Dysregulated Hepatic Methionine Metabolism Drives Homocysteine Elevation In Diet-Induced Nonalcoholic Fatty Liver Disease, Tommy Pacana, Sophie Cazanave, Aurora Verdianelli, Vaishali Patel, Hae-Ki Min, Faridoddin Mirshahi, Eoin Quinlivan, Arun J. Sanyal

Internal Medicine Publications

Methionine metabolism plays a central role in methylation reactions, production of glutathione and methylarginines, and modulating homocysteine levels. The mechanisms by which these are affected in NAFLD are not fully understood. The aim is to perform a metabolomic, molecular and epigenetic analyses of hepatic methionine metabolism in diet-induced NAFLD. Female 129S1/SvlmJ;C57Bl/6J mice were fed a chow (n = 6) or high-fat high-cholesterol (HFHC) diet (n = 8) for 52 weeks. Metabolomic study, enzymatic expression and DNA methylation analyses were performed. HFHC diet led to weight gain, marked steatosis and extensive fibrosis. In the methionine cycle, hepatic methionine was depleted (30%, …

An International Survey On Taking Up A Career In Cardiovascular Research: Opportunities And Biases Toward Would-Be Physician-Scientists, Giuseppe Biondi-Zoccai, Enrico Cerrato, Mariangela Peruzzi, Fabrizio D'Ascenzo, Elena De Falco, Isotta Chimenti, Sebastiano Sciarretta, Antonio G. M. Marullo, Elena Cavarretta, Ernesto Greco, Umberto Benedetto, Giulio Pompilio, Javier Escaned, Antonio Abbate, Alain Carpentier, Juan Carlos Chachques, Giacomo Frati

Internal Medicine Publications

Background

Cardiovascular research is the main shaper of clinical evidence underpinning decision making, with its cyclic progression of junior researchers to mature faculty members. Despite efforts at improving cardiovascular research training, several unmet needs persist. We aimed to appraise current perceptions on cardiovascular research training with an international survey.

Methods and Results

We administered a 20-closed-question survey to mentors and mentees belonging to different international institutions. A total of 247 (12%) surveys were available (out of 2,000 invitations). Overall, mentees and mentors were reasonably satisfied with the educational and research resources. Significant differences were found analyzing results according to gender, …

Thyroid Hormone Mediated Modulation Of Energy Expenditure, Janina A. Vaitkus, Jared S. Farrar, Francesco S. Celi

Internal Medicine Publications

Thyroid hormone (TH) has diverse effects on mitochondria and energy expenditure (EE), generating great interest and research effort into understanding and harnessing these actions for the amelioration and treatment of metabolic disorders, such as obesity and diabetes. Direct effects on ATP utilization are a result of TH’s actions on metabolic cycles and increased cell membrane ion permeability. However, the majority of TH induced EE is thought to be a result of indirect effects, which, in turn, increase capacity for EE. This review discusses the direct actions of TH on EE, and places special emphasis on the indirect actions of TH, …

Dysregulated Hepatic Methionine Metabolism Drives Homocysteine Elevation In Diet-Induced Nonalcoholic Fatty Liver Disease, Tommy Pacana, Sophie Cazanave, Aurora Verdianelli, Viashali Patel, Hae-Ki Min, Faridoddin Mirshahi, Eoin Quinlavin, Arun J. Sanyal

Internal Medicine Publications

Methionine metabolism plays a central role in methylation reactions, production of glutathione and methylarginines, and modulating homocysteine levels. The mechanisms by which these are affected in NAFLD are not fully understood. The aim is to perform a metabolomic, molecular and epigenetic analyses of hepatic methionine metabolism in diet-induced NAFLD. Female 129S1/SvlmJ;C57Bl/6J mice were fed a chow (n = 6) or high-fat high-cholesterol (HFHC) diet (n = 8) for 52 weeks. Metabolomic study, enzymatic expression and DNA methylation analyses were performed. HFHC diet led to weight gain, marked steatosis and extensive fibrosis. In the methionine cycle, hepatic methionine was depleted (30%, …

State Of The Art On The Evidence Base In Cardiac Regenerative Therapy: Overview Of 41 Systematic Reviews, Mariangela Peruzzi, Elena De Falco, Antonio Abbate, Giuseppe Biondi-Zoccai, Isotta Chementi, Marzia Lotrionte, Umberto Benedetto, Ronak Delewi, Antonino G. M. Marullo, Giacomo Frati

Internal Medicine Publications

Objectives. To provide a comprehensive appraisal of the evidence from secondary research on cardiac regenerative therapy. Study Design and Setting. Overview of systematic reviews of controlled clinical trials concerning stem cell administration or mobilization in patients with cardiovascular disease. Results. After a systematic database search, we short-listed 41 reviews (660 patients). Twenty-two (54%) reviews focused on acute myocardial infarction (AMI), 19 (46%) on chronic ischemic heart disease (IHD) or heart failure (HF), 29 (71%) on bone marrow-derived stem-cells (BMSC), and 36 (88%) to randomized trials only. Substantial variability among reviews was found for validity (AMSTAR score: median 9 [minimum …

Intermittent Hypoxia In Childhood: The Harmful Consequences Versus Potential Benefits Of Therapeutic Uses, Tatiana V. Serebrovskaya, Lei Xi

Internal Medicine Publications

Intermittent hypoxia (IH) often occurs in early infancy in both preterm and term infants and especially at 36–44 weeks postmenstrual age. These episodes of IH could result from sleep-disordered breathing or may be temporally unrelated to apnea or bradycardia events. There are numerous reports indicating adverse effects of IH on development, behavior, academic achievement, and cognition in children with sleep apnea syndrome. It remains uncertain about the exact causative relationship between the neurocognitive and behavioral morbidities and IH and/or its associated sleep fragmentation. On the other hand, well-controlled and moderate IH conditioning/training has been used in sick children for treating …

Use Of Probe-Based Confocal Laser Endomicroscopy (Pcle) In Gastrointestinal Applications. A Consensus Report Based On Clinical Evidence, Kenneth K. Wang, David L. Carr-Locke, Satish K. Singh, Helmut Neumann, Helga Bertani, Jean-Paul Galmiche, Razvan I. Arsenescu, Fabrice Caillol, Kenneth J. Chang, Stanislas Chaussade, Emmanuel Coron, Guida Costamagna, Aldona Dlugosz, S Ian Gan, Marc Giovannini, Frank G. Gress, Oleh Haluszka, Khek Y. Ho, Michel Kahaleh, Vani J. Konda, Frederic Prat, Raj J. Shah, Prateek Sharma, Adam Slivka, Herbert C. Wolfsen, Alvin Zfass

Internal Medicine Publications

Background

Probe-based confocal laser endomicroscopy (pCLE) provides microscopic imaging during an endoscopic procedure. Its introduction as a standard modality in gastroenterology has brought significant progress in management strategies, affecting many aspects of clinical care and requiring standardisation of practice and training.

Objective

This study aimed to provide guidance on the standardisation of its practice and training in Barrett’s oesophagus, biliary strictures, colorectal lesions and inflammatory bowel diseases.

Methods

Initial statements were developed by five group leaders, based on the available clinical evidence. These statements were then voted and edited by the 26 participants, using a modified Delphi approach. After two …

Rational Combinations Of Targeted Agents In Aml, Prithviraj Bose, Steven Grant

Internal Medicine Publications

Despite modest improvements in survival over the last several decades, the treatment of AML continues to present a formidable challenge. Most patients are elderly, and these individuals, as well as those with secondary, therapy-related, or relapsed/refractory AML, are particularly difficult to treat, owing to both aggressive disease biology and the high toxicity of current chemotherapeutic regimens. It has become increasingly apparent in recent years that coordinated interruption of cooperative survival signaling pathways in malignant cells is necessary for optimal therapeutic results. The modest efficacy of monotherapy with both cytotoxic and targeted agents in AML testifies to this. As the complex …

State Of The Art On The Evidence Base In Cardiac Regenerative Therapy: Overview Of 41 Systematic Reviews, Mariangela Peruzzi, Elena De Falco, Antonio Abbate, Giuseppe Biondi-Zoccai, Isotta Chimenti, Marzia Lotrionte, Umberto Benedetto, Ronak Delewi, Antonino G. M. Marullo, Giacomo Frati

Internal Medicine Publications

Objectives. To provide a comprehensive appraisal of the evidence from secondary research on cardiac regenerative therapy. Study Design and Setting. Overview of systematic reviews of controlled clinical trials concerning stem cell administration or mobilization in patients with cardiovascular disease. Results. After a systematic database search, we short-listed 41 reviews (660 patients). Twenty-two (54%) reviews focused on acute myocardial infarction (AMI), 19 (46%) on chronic ischemic heart disease (IHD) or heart failure (HF), 29 (71%) on bone marrow-derived stem-cells (BMSC), and 36 (88%) to randomized trials only. Substantial variability among reviews was found for validity (AMSTAR score: median …

An International Survey On Taking Up A Career In Cardiovascular Research: Opportunities And Biases Toward Would-Be Physician-Scientists, Giuseppe Biondi-Zoccai, Enrico Cerrato, Mariangela Peruzzi, Fabrizio D'Ascenzo, Elena De Falco, Isotta Chimenti, Sebastiano Sciarretta, Antonino G. M. Marullo, Elena Cavarretta, Ernesto Greco, Umberto Benedetto, Giulio Pompilio, Javier Escaned, Antonio Abbate, Alain Carpentier, Juan Carlos Chachques, Giacomo Frati

Internal Medicine Publications

Background

Cardiovascular research is the main shaper of clinical evidence underpinning decision making, with its cyclic progression of junior researchers to mature faculty members. Despite efforts at improving cardiovascular research training, several unmet needs persist. We aimed to appraise current perceptions on cardiovascular research training with an international survey.

Methods and Results

We administered a 20-closed-question survey to mentors and mentees belonging to different international institutions. A total of 247 (12%) surveys were available (out of 2,000 invitations). Overall, mentees and mentors were reasonably satisfied with the educational and research resources. Significant differences were found analyzing results according to gender, …

Dysregulated Hepatic Methionine Metabolism Drives Homocysteine Elevation In Diet-Induced Nonalcoholic Fatty Liver Disease, Tommy Pacana, Sophie Cazanave, Aurora Verdianelli, Vaishali Patel, Hae-Ki Min, Faridoddin Mirshahi, Eoin Quinlivan, Arun J. Sanyal

Internal Medicine Publications

Methionine metabolism plays a central role in methylation reactions, production of glutathione and methylarginines, and modulating homocysteine levels. The mechanisms by which these are affected in NAFLD are not fully understood. The aim is to perform a metabolomic, molecular and epigenetic analyses of hepatic methionine metabolism in diet-induced NAFLD. Female 129S1/SvlmJ;C57Bl/6J mice were fed a chow (n = 6) or high-fat high-cholesterol (HFHC) diet (n = 8) for 52 weeks. Metabolomic study, enzymatic expression and DNA methylation analyses were performed. HFHC diet led to weight gain, marked steatosis and extensive fibrosis. In the methionine cycle, hepatic methionine was depleted (30%, …

Time And Temperature Dependent Surface Tension Measurements Of Responsive Protein-Based Polymer Surfactant Solutions, Hakan Celik

ETD Archive

A three-armed star elastin-like polypeptide (ELP-foldon) has thermoreversible character which exhibits phase separation above a transition temperature (Tt) in physiologic salt concentrations. At lower salt concentration, the ELP-foldon behaves like a thermoresponsive surfactant, exhibiting micelle formation above its Tt. The purpose of this study is characterize the surfactant behavior of the ELP-foldon at air-liquid interface by measuring the surface tension. The surface tension is measured as a function of time for different ELP concentrations from 10 nM to 50 ℗æM and over range of temperatures from 25 to 35 ℗¿ using the axisymmetric drop shape analysis (ADSA). The ADSA is …

Solute Partitioning In Elastin-Like Polypeptides: A Foundation For Drug Delivery Applications, Eric Helm

ETD Archive

No abstract provided.

Characterization Of Highly Concentrated Elastin-Like Polypeptide Solutions: Rheometric Properties And Phase Separation Analysis, Kevin Michael Otto

ETD Archive

Elastin-like polypeptides (ELPs) are environmentally responsive biopolymers. These protein based polymers are specific in that they exhibit phase separation in response to a number of stimuli. Some of these stimuli include temperature, light, and pH. There are a large number of factors to consider when designing ELP constructs that allow for control of the transitioning behavior, some of which include amino acid sequences, protein concentration, salt concentration, and the polymer chain length. Elastin-like polypeptides are soluble in water at low temperatures, however, upon an increase in temperature, the proteins become insoluble in water and phase separate. This point of temperature …

Assessment Of The Freshwater Mussel Community Of The Upper Mahoning River Watershed And Factors Influencing Diversity And Abundance In Small Streams, Matthew T. Begley

ETD Archive

Freshwater mussel communities have experienced drastic declines in diversity and abundance in many streams throughout North America. Among the reasons for these declines is the human-driven alteration of the landscape, as urban and agricultural use impart many known stressors to aquatic systems. Impairments include increased sedimentation, increased pollutants, increased flood frequency and intensity, and decreased diversity and abundance of many organisms, including fish, macroinvertebrates, and mussels. Attempts to explain the abundance and diversity of mussel communities using small-scale factors such as substrate type and flow velocity provided little to no predictive power. Instead, reach-scale variables, such as stream morphology and …

A Cross Sectional Comparison Of Flexibility And Balance In Children 10-14 Years Of Age, Allison Anne Lowe

ETD Archive

To determine the effects of age on flexibility and balance in children ages 10-14. This study also determined the validity of the Y-balance test by comparing it to the standard back-saver sit and reach (BSSR) and the balance error scoring system test (BESS). Methods: 84 participants males (n=41) and females (n=43) ages 10-14 years old from a school in Chardon, Ohio, volunteered through a convenience sample to complete the study. Each subject had to complete three different tests in a randomized order during their regular physical education class. To compare the results of the three tests, gender and the age …

Teaching Universal Design In Computer Science, Damian Gordon, Ciaran O'Leary

Theme 1: Delivering Universal Design in Technical Subjects

No abstract provided.

Epigenetic Modifications Of The Pgc-1Α Promoter During Exercise Induced Expression In Mice, Timothy L. Lochmann, Ravindar R. Thomas, James P. Bennett, Shirley M. Taylor

Massey Comprehensive Cancer Center Publications

The transcriptional coactivator, PGC-1α, is known for its role in mitochondrial biogenesis. Although originally thought to exist as a single protein isoform, recent studies have identified additional promoters which produce multiple mRNA transcripts. One of these promoters (promoter B), approximately 13.7kb upstream of the canonical PGC-1α promoter (promoter A), yields alternative transcripts present at levels much lower than the canonical PGC-1α mRNA transcript. In skeletal muscle, exercise resulted in a substantial, rapid increase of mRNA of these alternative PGC-1α transcripts. Although the β2-adrenergic receptor was identified as a signaling pathway that activates transcription from PGC-1α promoter B, it is not …

Dismira: Prioritization Of Disease Candidates In Mirna-Disease Associations Based On Maximum Weighted Matching Inference Model And Motif-Based Analysis, Joseph J. Nalluri, Bhanu K. Kamapantula, Debmalya Barh, Neha Jain, Antaripa Bhattacharya, Sintia Silva De Almeida, Rommel Thiago Juca Ramos, Artur Silva, Vasco Azevedo, Preetam Ghosh

Computer Science Publications

Background

MicroRNAs (miRNAs) have increasingly been found to regulate diseases at a significant level. The interaction of miRNA and diseases is a complex web of multilevel interactions, given the fact that a miRNA regulates upto 50 or more diseases and miRNAs/diseases work in clusters. The clear patterns of miRNA regulations in a disease are still elusive.

Methods

In this work, we approach the miRNA-disease interactions from a network scientific perspective and devise two approaches - maximum weighted matching model (a graph theoretical algorithm which provides the result by solving an optimization equation of selecting the most prominent set of diseases) …

Use Of A Green Familiar Faces Paradigm Improves P300-Speller Brain-Computer Interface Performance, Qi Li, Shuai Lu, Jian Li, Ou Bai

Computer Science Publications

Background

A recent study showed improved performance of the P300-speller when the flashing row or column was overlaid with translucent pictures of familiar faces (FF spelling paradigm). However, the performance of the P300-speller is not yet satisfactory due to its low classification accuracy and information transfer rate.

Objective

To investigate whether P300-speller performance is further improved when the chromatic property and the FF spelling paradigm are combined.

Methods

We proposed a new spelling paradigm in which the flashing row or column is overlaid with translucent green pictures of familiar faces (GFF spelling paradigm). We analyzed the ERP waveforms elicited by …

Transcriptional Network Growing Models Using Motif-Based Preferential Attachment, Ahmed F. Abdelzaher, Ahmad F. Al-Musawi, Preetam Ghosh, Michael L. Mayo, Edward J. Perkins

Computer Science Publications

Understanding relationships between architectural properties of gene-regulatory networks (GRNs) has been one of the major goals in systems biology and bioinformatics, as it can provide insights into, e.g., disease dynamics and drug development. Such GRNs are characterized by their scale-free degree distributions and existence of network motifs – i.e., small-node subgraphs that occur more abundantly in GRNs than expected from chance alone. Because these transcriptional modules represent “building blocks” of complex networks and exhibit a wide range of functional and dynamical properties, they may contribute to the remarkable robustness and dynamical stability associated with the whole of GRNs. Here, we …

Miregulome: A Knowledge-Base Of Mirna Regulomics And Analysis, Debmalya Barh, Bhanu Kamapantula, Neha Jain, Joseph Nalluri, Antaripa Bhattacharya, Lucky Juneja, Neha Barve, Sandeep Tiwari, Anderson Miyoshi, Vasco Azevedo, Kenneth Blum, Anil Kumar, Artur Silva, Preetam Ghosh

Computer Science Publications

miRNAs regulate post transcriptional gene expression by targeting multiple mRNAs and hence can modulate multiple signalling pathways, biological processes, and patho-physiologies. Therefore, understanding of miRNA regulatory networks is essential in order to modulate the functions of a miRNA. The focus of several existing databases is to provide information on specific aspects of miRNA regulation. However, an integrated resource on the miRNA regulome is currently not available to facilitate the exploration and understanding of miRNA regulomics. miRegulome attempts to bridge this gap. The current version of miRegulome v1.0 provides details on the entire regulatory modules of miRNAs altered in response to …

Self-Organizing Feature Maps Identify Proteins Critical To Learning In A Mouse Model Of Down Syndrome, Clara Higuera, Katheleen J. Gardiner, Krzysztof J. Cios

Computer Science Publications

Down syndrome (DS) is a chromosomal abnormality (trisomy of human chromosome 21) associated with intellectual disability and affecting approximately one in 1000 live births worldwide. The overexpression of genes encoded by the extra copy of a normal chromosome in DS is believed to be sufficient to perturb normal pathways and normal responses to stimulation, causing learning and memory deficits. In this work, we have designed a strategy based on the unsupervised clustering method, Self Organizing Maps (SOM), to identify biologically important differences in protein levels in mice exposed to context fear conditioning (CFC). We analyzed expression levels of 77 proteins …

Self-Organizing Feature Maps Identify Proteins Critical To Learning In A Mouse Model Of Down Syndrome, Clara Higuera, Katheleen J. Gardiner, Kryzysztof Cios

Computer Science Publications

Down syndrome (DS) is a chromosomal abnormality (trisomy of human chromosome 21) associated with intellectual disability and affecting approximately one in 1000 live births worldwide. The overexpression of genes encoded by the extra copy of a normal chromosome in DS is believed to be sufficient to perturb normal pathways and normal responses to stimulation, causing learning and memory deficits. In this work, we have designed a strategy based on the unsupervised clustering method, Self Organizing Maps (SOM), to identify biologically important differences in protein levels in mice exposed to context fear conditioning (CFC). We analyzed expression levels of 77 proteins …

Self-Organizing Feature Maps Identify Proteins Critical To Learning In A Mouse Model Of Down Syndrome, Clara Higuera, Kathleen J. Gardiner, Kryzysztof Cios

Computer Science Publications

Down syndrome (DS) is a chromosomal abnormality (trisomy of human chromosome 21) associated with intellectual disability and affecting approximately one in 1000 live births worldwide. The overexpression of genes encoded by the extra copy of a normal chromosome in DS is believed to be sufficient to perturb normal pathways and normal responses to stimulation, causing learning and memory deficits. In this work, we have designed a strategy based on the unsupervised clustering method, Self Organizing Maps (SOM), to identify biologically important differences in protein levels in mice exposed to context fear conditioning (CFC). We analyzed expression levels of 77 proteins …

Identifying Influential Nodes In A Wound Healing-Related Network Of Biological Processes Using Mean First-Passage Time, Tomasz Jakub Arodz, Danail Bonchev

Computer Science Publications

In this study we offer an approach to network physiology, which proceeds from transcriptomic data and uses gene ontology analysis to identify the biological processes most enriched in several critical time points of wound healing process (days 0, 3 and 7). The top-ranking differentially expressed genes for each process were used to build two networks: one with all proteins regulating the transcription of selected genes, and a second one involving the proteins from the signaling pathways that activate the transcription factors. The information from these networks is used to build a network of the most enriched processes with undirected links …

Communication For Development: Theory And Practice For Empowerment And Social Justice, Third Edition, Srinivas R. Melkote, H. Leslie Steeves

BGSU Faculty Books

This third edition features significantly revised and updated chapters to include the latest scholarship on, and practices of, media and communication for development. It explores empowerment and social justice to individuals and communities around the world in the context of increasing globalization. Tracing the history of development communication, it looks objectively at diverse approaches and their supporters, and goes on to provide models for the future. It also offers a new chapter presenting the authors' framework foregrounding empowerment and social justice as goals for development communication in the 21st century.

The earlier editions of this book, Communication for Development in …

Vedolizumab: An Α4Β7 Integrin Antagonist For Ulcerative Colitis And Crohn’S Disease, Lauren N. Cherry, Nancy S. Yunker, Erika R. Lambert, Dalemarie Vaughan, Denise K. Lowe

VCU Health Publications

Ulcerative colitis (UC) and Crohn’s disease (CD) are chronic, relapsing inflammatory bowel diseases associated with significant morbidity. Conventional therapies for these diseases include corticosteroids, aminosalicylates, immunomodulators, and monoclonal antibodies. Over the years tumor necrosis factor (TNF)-α antagonists alone or in combination with other therapies have emerged as the cornerstone of treatment for induction and maintenance of remission of moderate to severe UC and CD. Unfortunately, some patients with moderate to severe UC and CD are unable to attain or maintain remission with TNF-α antagonist treatment. Vedolizumab, a humanized monoclonal antibody, is the first integrin receptor antagonist approved that selectively antagonizes …