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Mycobacterium Tuberculosis Lineage 4 Comprises Globally Distributed And Geographically Restricted Sublineages, David Stucki, Daniela Brites, Leïla Jeljeli, Mireia Coscolla, Gunturu Revathi Jan 2016

Mycobacterium Tuberculosis Lineage 4 Comprises Globally Distributed And Geographically Restricted Sublineages, David Stucki, Daniela Brites, Leïla Jeljeli, Mireia Coscolla, Gunturu Revathi

Pathology, East Africa

Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most …


A Healthy Herd: Addressing The Justifications For Vaccine Denial And Applying The Health Belief Model To The Current Anti-Vaccination Movement, Sarah L. Mchugh Jan 2016

A Healthy Herd: Addressing The Justifications For Vaccine Denial And Applying The Health Belief Model To The Current Anti-Vaccination Movement, Sarah L. Mchugh

Honors Program Theses

The purpose of this thesis is to explore and analyze the existing literature regarding the refusal to receive vaccinations designed specifically to prevent Measles-Mumps-Rubella (MMR), which has spurred a serious public health issue that puts every unvaccinated person at risk. It will investigate the reasons people refuse to get vaccinations for themselves or their children. The analysis of the current situation and the application of the Health Belief Model to the related factors will provide potential explanations regarding how the decision-making process may strengthen efforts towards increasing vaccination rates.


Where Is Pain In The Brain?, Marshall Devor Jan 2016

Where Is Pain In The Brain?, Marshall Devor

Animal Sentience

Key argues that fish cannot experience pain based on (1) brain imaging in humans, (2) consequences of lesions and (3) direct brain stimulation. Imaging indeed shows that pain-relevant signals reach the cortex, but not that they underlie the subjective experience of pain. Lesions and stimulation data are more to the point, but Key paints an idiosyncratic and misleading picture of their effects. S1 and S2 ablation does not eliminate evoked or spontaneous pain, although there may be up- or down-modulation. Likewise, stimulation of pain-associated cortical areas rarely induces pain, and pain almost never occurs at the onset of epileptic seizures. …


The Role Of Oxidative Stress In The Establishment Of Resistance To Cisplatin In Epithelial Ovarian Cancer Cells, Jimmy Belotte Jan 2016

The Role Of Oxidative Stress In The Establishment Of Resistance To Cisplatin In Epithelial Ovarian Cancer Cells, Jimmy Belotte

Wayne State University Dissertations

Epithelial ovarian cancer is the deadliest of all gynecologic cancers with an estimated 22,280 new cases and 14,240 deaths expected in 2016 in the US alone. This high mortality rate can be partially attributed to a lack of universal screening and the development of resistance to the recommended chemotherapeutics. Typically, the treatment of ovarian cancer requires both cytoreductive surgery (CRS) and platinum/taxane combination chemotherapy. Initially, 50–80% of patients with advanced disease will achieve complete clinical response. Unfortunately, most will relapse within 18 months with chemoresistant disease. Thus, understanding the mechanisms of platinum resistance is critical in order to improve the …


Incidence And Factors Associated With Nonalcoholic Fatty Liver Disease Among Patients With Rheumatoid Arthritis, Ani K. John Jan 2016

Incidence And Factors Associated With Nonalcoholic Fatty Liver Disease Among Patients With Rheumatoid Arthritis, Ani K. John

Walden Dissertations and Doctoral Studies

Nonalcoholic fatty liver disease (NAFLD) has become one of the most common hepatic diseases worldwide, making the diagnosis and management of NAFLD an emerging public health issue. Theories associated with NAFLD surmise that inflammation may be the root cause, along with the complex interplay of other chronic conditions such as obesity, metabolic syndrome, diabetes, dyslipidemia, and cardiovascular disease (CVD). It is unknown if other inflammatory conditions such as rheumatoid arthritis (RA), along with the use of methotrexate (MTX), might confer increased risk for NAFLD. Longitudinal data collected from a retrospective cohort of 17,481 adult RA patients in the United States …


Characterization Of The Protective Role Of Regulatory T Cells In Experimental Periapical Lesions Development And Its Chemoattraction Manipulation As A Therapeutic Tool, Carolina Favaro Francisconi, Andreia Espindola Vieira, Cláudia Cristina Biguetti, Andrew J. Glowacki, Ana Paula Favaro Trombone, Ariadne Letra, Renato Menezes Silva, Charles S. Sfeir, Steven R. Little, Gustavo P. Garlet Jan 2016

Characterization Of The Protective Role Of Regulatory T Cells In Experimental Periapical Lesions Development And Its Chemoattraction Manipulation As A Therapeutic Tool, Carolina Favaro Francisconi, Andreia Espindola Vieira, Cláudia Cristina Biguetti, Andrew J. Glowacki, Ana Paula Favaro Trombone, Ariadne Letra, Renato Menezes Silva, Charles S. Sfeir, Steven R. Little, Gustavo P. Garlet

School of Podiatric Medicine Publications

Introduction

The pathogenesis of periapical lesions is determined by the balance between host pro-inflammatory immune response and counteracting anti-inflammatory and reparative responses, which include regulatory T cells (Tregs) as potential immunoregulatory agents. In this study, we investigated (in a cause-and-effect manner) the involvement of CCL22-CCR4 axis in Tregs migration to the periapical area and the role of Tregs in the determination of outcomes in periapical lesions.

Methods

Periapical lesions were induced in C57Bl/6 (WT) and CCR4KO mice (pulp exposure and bacterial inoculation), and treated with anti-GITR to inhibit Tregs function or alternatively with CCL22-releasing, PLGA particles to induce site-specific migration …


Synthesis Of Neoglycoproteins/Neoglycopeptides And Their Immunological Evaluation In The Context Of Chagas Disease, Nathaniel Scott Schocker Jan 2016

Synthesis Of Neoglycoproteins/Neoglycopeptides And Their Immunological Evaluation In The Context Of Chagas Disease, Nathaniel Scott Schocker

Open Access Theses & Dissertations

The protozoan parasite, Trypanosoma cruzi, the etiologic agent of Chagas disease (ChD), has a cell surface covered by immunogenic glycoconjugates. A synthetic glycoarray containing non-reducing α-galactopyranosyl moieties related to mucin O-glycans of the parasite T. cruzi was evaluated by a chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA) with sera from patients with chronic ChD, revealing the disaccharide Galα(1,3)Galβ as the immunodominant glycotope (Chapter 2). This disaccharide comprises the two terminal sugars of the known immunodominant glycotope Galα(1,3)Galβ(1,4)GlcNAcα, which is expressed on glycosylphosphatidylinositol-anchored mucins of the infective trypomastigote stage of T. cruzi and triggers high levels of protective anti-α-Gal antibodies (Abs) in infected …


Perception Of Differences In Lip Profile Between 2-D And 3-D, Andrew Hansen Jan 2016

Perception Of Differences In Lip Profile Between 2-D And 3-D, Andrew Hansen

Theses and Dissertations

Past studies evaluating the esthetics of orthodontic treatment have been done using 2-D images. New 3-D imaging offers an improved, real-life representation of a subject. The purpose of this study was to determine how laypeople perceived differences in lip position (flat versus ideal lip fullness) in 2-D compared to 3-D.

3dMD images of 8 Caucasian subjects were adjusted to an ideal and flat lip position in 3-D and then in 2-D from the profile view. 2 surveys were created with paired ideal and flat images on the screen, either in 2-D or 3-D, and evaluators were asked to choose which …


Eeg Interictal Spike Detection Using Artificial Neural Networks, Howard J. Carey Iii Jan 2016

Eeg Interictal Spike Detection Using Artificial Neural Networks, Howard J. Carey Iii

Theses and Dissertations

Epilepsy is a neurological disease causing seizures in its victims and affects approximately 50 million people worldwide. Successful treatment is dependent upon correct identification of the origin of the seizures within the brain. To achieve this, electroencephalograms (EEGs) are used to measure a patient’s brainwaves. This EEG data must be manually analyzed to identify interictal spikes that emanate from the afflicted region of the brain. This process can take a neurologist more than a week and a half per patient. This thesis presents a method to extract and process the interictal spikes in a patient, and use them to reduce …


Nutritional Status And Tuberculosis Risk In Adult And Pediatric Household Contacts, Omowunmi Aibana, Xeno Acharya, Chuan-Chin Huang, Mercedes C Becerra, Jerome T Galea, Silvia S Chiang, Carmen Contreras, Roger Calderon, Rosa Yataco, Gustavo E Velásquez, Karen Tintaya, Judith Jimenez, Leonid Lecca, Megan B Murray Jan 2016

Nutritional Status And Tuberculosis Risk In Adult And Pediatric Household Contacts, Omowunmi Aibana, Xeno Acharya, Chuan-Chin Huang, Mercedes C Becerra, Jerome T Galea, Silvia S Chiang, Carmen Contreras, Roger Calderon, Rosa Yataco, Gustavo E Velásquez, Karen Tintaya, Judith Jimenez, Leonid Lecca, Megan B Murray

Faculty, Staff and Student Publications

BACKGROUND: Studies show obesity decreases risk of tuberculosis (TB) disease. There is limited evidence on whether high body mass index also protects against TB infection; how very high body mass indices influence TB risk; or whether nutritional status predicts this risk in children. We assessed the impact of body mass index on incident TB infection and disease among adults and children.

METHODS AND FINDINGS: We conducted a prospective cohort study among household contacts of pulmonary TB cases in Lima, Peru. We determined body mass index at baseline and followed participants for one year for TB infection and disease. We used …


Endothelial Cells Expressing Endothelial And Mesenchymal Cell Gene Products In Lung Tissue From Patients With Systemic Sclerosis-Associated Interstitial Lung Disease., Fabian A. Mendoza, Sonsoles Piera-Velazquez, John L. Farber, Carol Feghali-Bostwick, Sergio A. Jimenez Jan 2016

Endothelial Cells Expressing Endothelial And Mesenchymal Cell Gene Products In Lung Tissue From Patients With Systemic Sclerosis-Associated Interstitial Lung Disease., Fabian A. Mendoza, Sonsoles Piera-Velazquez, John L. Farber, Carol Feghali-Bostwick, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: To examine whether lung endothelial cells (ECs) from patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) express mesenchymal cell-specific proteins and gene transcripts, indicative of the occurrence of endothelial-to-mesenchymal phenotypic transition (EndoMT).

METHODS: Lung tissue from 6 patients with SSc-associated pulmonary fibrosis was examined by histopathology and immunohistochemistry. Confocal laser microscopy was utilized to assess the simultaneous expression of EC and myofibroblast molecular markers. CD31+CD102+ ECs were isolated from the lung tissue of 2 patients with SSc-associated ILD and 2 normal control subjects, and the expression of EC and mesenchymal cell markers and other relevant genes was analyzed …


Breastfeeding Education For Women With Diabetes, Pregnancy-Induced Hypertension And Multiple Gestations, Oluwapelumi Adefunmike Adeboyejo Jan 2016

Breastfeeding Education For Women With Diabetes, Pregnancy-Induced Hypertension And Multiple Gestations, Oluwapelumi Adefunmike Adeboyejo

Walden Dissertations and Doctoral Studies

Breastfeeding is considered a public health concern due to increased maternal/infant mortality and morbidity rates associated with persistent low rates in breastfeeding. Providing early breastfeeding education for women with diabetic, pregnancy-induced hypertension and multiple gestations can result in higher persistence rates and a decrease in maternal and infant mortality and morbidity rates. This quality improvement project provided early prenatal breastfeeding education for women with diabetes, pregnancy-induce hypertension and multiple gestations at a private clinic in Long Beach, Southern California. Evidence-based literature reviews were conducted through CINAHL and Medline (2009-2014). The descriptive study used for the project was made up questionnaires …


Expression And Functions Of Il-24 And Socs3 In Pseudomonas Aeruginosa Keratitis In A C57bl/6 Mouse Model, Bing Xu Jan 2016

Expression And Functions Of Il-24 And Socs3 In Pseudomonas Aeruginosa Keratitis In A C57bl/6 Mouse Model, Bing Xu

Wayne State University Dissertations

The aim of this study was to elucidate the expression and functions of interleukin (IL)-24 and suppressor of cytokine signaling 3 (SOCS3), and their regulatory relationship in C57BL/6 mouse corneas in response to Pseudomonas aeruginosa (PA) infection. Among IL-20R cytokines, only IL-24 was induced at both mRNA and protein levels by the infection, and this upregulation was dampened by flagellin pretreatment. Time course studies revealed that IL-24 expression was markedly elevated, followed by a subsidence and second elevation, a pattern shared with SOCS3 but not IL-1β or IL-6. Silencing of IL-24 enhanced S100A8/A9 expression, and suppressed SOCS3, IL-1β, IL-1RN, and …


Aβ-Related Memory Decline In Apoe Ε4 Noncarriers: Implications For Alzheimer Disease, Yen Ying Lim, Simon Laws, Victor Villemagne, Robert Pietrzak, Tenielle Porter, David Ames, Christoher Fowler, Stephanie Rainey-Smith, Peter Snyder, Ralph Martins, Olivier Salvado, Pierrick Bourgeat, Christopher Rowe, Colin Masters, Paul Maruff Jan 2016

Aβ-Related Memory Decline In Apoe Ε4 Noncarriers: Implications For Alzheimer Disease, Yen Ying Lim, Simon Laws, Victor Villemagne, Robert Pietrzak, Tenielle Porter, David Ames, Christoher Fowler, Stephanie Rainey-Smith, Peter Snyder, Ralph Martins, Olivier Salvado, Pierrick Bourgeat, Christopher Rowe, Colin Masters, Paul Maruff

Research outputs 2014 to 2021

Objective:

As the absence of Aβ-related memory decline in APOE ϵ4 noncarriers may be due to the relative brevity of previous studies, we aimed to characterize Aβ-related cognitive decline over 72 months in APOE ϵ4 carriers and noncarriers who were cognitively normal (CN).

Methods:

CN older adults (n 423) underwent Aβ imaging and APOE genotyping. Participants completed comprehensive neuropsychological testing at baseline 18-, 36-, 54-, and 72-month assessments.

Results:

Relative to Aβ- CN ϵ4 noncarriers, both Aβ+ CN ϵ4 carriers and noncarriers showed significantly increased decline in measures of memory, language, and executive function as well as higher rates of …


Consistent Prebiotic Effect On Gut Microbiota With Altered Fodmap Intake In Patients With Crohn's Disease: A Randomised, Controlled Cross-Over Trial Of Well-Defined Diets, Emma P. Halmos, Claus T. Christophersen, Anthony R. Bird, Susan J. Shepherd, Jane G. Muir, Peter R. Gibson Jan 2016

Consistent Prebiotic Effect On Gut Microbiota With Altered Fodmap Intake In Patients With Crohn's Disease: A Randomised, Controlled Cross-Over Trial Of Well-Defined Diets, Emma P. Halmos, Claus T. Christophersen, Anthony R. Bird, Susan J. Shepherd, Jane G. Muir, Peter R. Gibson

Research outputs 2014 to 2021

OBJECTIVES:

Altering FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) intake has substantial effects on gut microbiota. This study aimed to investigate effects of altering FODMAP intake on markers of colonic health in patients with Crohn’s disease.

METHODS:

After evaluation of their habitual diet, 9 patients with clinically quiescent Crohn’s disease were randomised to 21 days of provided low or typical (“Australian”) FODMAP diets with ≥ 21-day washout in between. Five-day fecal samples were collected at the end of each diet and analyzed for calprotectin, pH, short-chain fatty acids (SCFA) and bacterial abundance. Gastrointestinal symptoms were recorded daily.

RESULTS:

Eight participants …


Determinants Of Activity Levels In African Americans With Mild Cognitive Impairment., Barry W. Rovner, Md, Robin J. Casten, Phd, Benjamin E. Leiby, Phd Jan 2016

Determinants Of Activity Levels In African Americans With Mild Cognitive Impairment., Barry W. Rovner, Md, Robin J. Casten, Phd, Benjamin E. Leiby, Phd

Department of Neurology Faculty Papers

Engaging in cognitive, social, and physical activities may prevent cognitive decline. In a sample of older African Americans with mild cognitive impairment (MCI; N=221), we investigated the cross-sectional relationships between activity levels and participants' demographic, clinical, and neuropsychological characteristics. The average age of participants was 75.4 years (SD, 7.0); 177 (80.1%) were women. Participation in cognitive/social activities was positively associated with education, depression, literacy, mobility, instrumental activities of daily living (IADL), verbal learning, and subcomponents of executive function. A linear regression identified IADLs, education, depression, and verbal learning as independent predictors. Participation in physical activities was positively associated with sex, …


Developmental Transcription Factors In Age-Related Cns Disease: A Phoenix Rising From The Ashes?, Robert White, Meghan Thomas Jan 2016

Developmental Transcription Factors In Age-Related Cns Disease: A Phoenix Rising From The Ashes?, Robert White, Meghan Thomas

Research outputs 2014 to 2021

Few would doubt that understanding the developmental landscape from which a mature neuron is derived is essential to understand its biology. The temporal and spatial position of a cell from the very earliest stages of development predicts the unique combinations of growth factors it will subsequently be exposed to. This combination of factors determines the transcriptional platform set within the cell by its specific combination of transcription factors, who direct the show. This, in turn, determines what cell type it will differentiate into, and what connections it will make. How this developmental platform translates to maintenance of a differentiated neuron …


Association Between Igf2bp2 Polymorphisms And Type 2 Diabetes Mellitus: A Case-Control Study And Meta-Analysis, Ping Rao, Hao Wang, Honghong Fang, Qing Gao, Jie Zhang, Manshu Song, Yong Zhou, Youxin Wang, Wei Wang Jan 2016

Association Between Igf2bp2 Polymorphisms And Type 2 Diabetes Mellitus: A Case-Control Study And Meta-Analysis, Ping Rao, Hao Wang, Honghong Fang, Qing Gao, Jie Zhang, Manshu Song, Yong Zhou, Youxin Wang, Wei Wang

Research outputs 2014 to 2021

Background:

Genome-wide association studies (GWAS) found that IGF2BP2 rs4402960 and rs1470579 polymorphisms were associated with type 2 diabetes mellitus (T2DM) risk. Many studies have replicated this association, but yielded inconsistent results.

Materials and Methods:

A case-control study consisting of 461 T2DM patients and 434 health controls was conducted to detect the genetic susceptibility of IGF2BP2 in a northern Han Chinese population. A meta-analysis was to evaluate the association more precisely in Asians.

Results:

In the case-control study, the carriers of TT genotype at rs4402960 had a higher T2DM risk than the G carriers (TG + GG) (adjusted …


Preparation And Biological Activity Of The Monoclonal Antibody Against The Second Extracellular Loop Of The Angiotensin Ii Type 1 Receptor, Mingming Wei, Chengrui Zhao, Suli Zhang, Li Wang, Huirong Liu, Xin-Liang Ma Jan 2016

Preparation And Biological Activity Of The Monoclonal Antibody Against The Second Extracellular Loop Of The Angiotensin Ii Type 1 Receptor, Mingming Wei, Chengrui Zhao, Suli Zhang, Li Wang, Huirong Liu, Xin-Liang Ma

Department of Medicine Faculty Papers

No abstract provided.


Neurovascular Disorders: Novel Perspectives On Pathogenesis, Diagnosis, And Treatment., David Hasan, Nohra Chalouhi, Md, Aaron S Dumont, Robert M Starke, Pascal Jabbour Md Jan 2016

Neurovascular Disorders: Novel Perspectives On Pathogenesis, Diagnosis, And Treatment., David Hasan, Nohra Chalouhi, Md, Aaron S Dumont, Robert M Starke, Pascal Jabbour Md

Department of Neurosurgery Faculty Papers

No abstract provided.


Naegleria Fowleri Meningoencephalitis Associated With Public Water Supply, Pakistan, 2014, Najia Ghanchi, Erum Khan, Azam Khan, Wali Muhammad, Faisal Riaz Malik, Afia Zafar Jan 2016

Naegleria Fowleri Meningoencephalitis Associated With Public Water Supply, Pakistan, 2014, Najia Ghanchi, Erum Khan, Azam Khan, Wali Muhammad, Faisal Riaz Malik, Afia Zafar

Department of Pathology and Laboratory Medicine

No abstract provided.


Editorial: Biology Of Cognitive Aging: Model Systems, Technologies, And Beyond, Shin Murakami Jan 2016

Editorial: Biology Of Cognitive Aging: Model Systems, Technologies, And Beyond, Shin Murakami

Faculty Publications & Research of the TUC College of Osteopathic Medicine

The author provides an introduction to a research issue of Frontiers in Genetics on models and techniques related to age-related memory impairment.


Activation Of Signal Transduction Pathways During Hepatic Oncogenesis, W Chung, M Kim, S De La Monte, L Longato, R Carlson, B L. Slagle, X Dong, J R. Wands Jan 2016

Activation Of Signal Transduction Pathways During Hepatic Oncogenesis, W Chung, M Kim, S De La Monte, L Longato, R Carlson, B L. Slagle, X Dong, J R. Wands

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Understanding the molecular pathogenesis of hepatocellular carcinoma (HCC) is essential to identify therapeutic targets. A hepatitis B virus (HBV) related double transgenic murine model was developed. METHODS: Liver specific expression of HBV X protein (HBx) and insulin receptor substrate 1 (IRS1) was achieved and transgenic mice were followed from birth to age 21 months. Liver and tumor tissue were assessed for histologic changes as well as activation of signal transduction pathways by qRT-PCR and multiplex ELISA protein assays. RESULTS: Overexpression of HBx and IRS1 stimulates liver cell proliferation in the double transgenic mice. Only the male mice …


Rapamycin Rescues Vascular, Metabolic And Learning Deficits In Apolipoprotein E4 Transgenic Mice With Pre-Symptomatic Alzheimer’S Disease, Ai-Ling Lin, Jordan B. Jahrling, Wei Zhang, Nicholas Derosa, Vikas Bakshi, Peter Romero, Veronica Galvan, Arlan Richardson Dec 2015

Rapamycin Rescues Vascular, Metabolic And Learning Deficits In Apolipoprotein E4 Transgenic Mice With Pre-Symptomatic Alzheimer’S Disease, Ai-Ling Lin, Jordan B. Jahrling, Wei Zhang, Nicholas Derosa, Vikas Bakshi, Peter Romero, Veronica Galvan, Arlan Richardson

Sanders-Brown Center on Aging Faculty Publications

Apolipoprotein E ɛ4 allele is a common susceptibility gene for late-onset Alzheimer's disease. Brain vascular and metabolic deficits can occur in cognitively normal apolipoprotein E ɛ4 carriers decades before the onset of Alzheimer's disease. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of Alzheimer's disease-like symptoms in pre-symptomatic Apolipoprotein E ɛ4 transgenic mice. Using in vivo, multimodal neuroimaging, we found that apolipoprotein E ɛ4 mice treated with rapamycin had restored cerebral blood flow, blood–brain barrier integrity and glucose metabolism, compared …


Atp-Site Binding Inhibitor Effectively Targets Mtorc1 And Mtorc2 Complexes In Glioblastoma, Jayson Neil, Craig Shannon, Avinash Mohan, Dimitri Laurent, Raj Murali, Meena Jhanwar-Uniyal Dec 2015

Atp-Site Binding Inhibitor Effectively Targets Mtorc1 And Mtorc2 Complexes In Glioblastoma, Jayson Neil, Craig Shannon, Avinash Mohan, Dimitri Laurent, Raj Murali, Meena Jhanwar-Uniyal

NYMC Faculty Publications

The PI3K-AKT-mTOR signaling axis is central to the transformed phenotype of glioblastoma (GBM) cells, due to frequent loss of tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10). The mechanistic target of rapamycin (mTOR) kinase is present in two cellular multi-protein complexes, mTORC1 and mTORC2, which have distinct subunit composition, substrates and mechanisms of action. Targeting the mTOR protein is a promising strategy for GBM therapy. However, neither of these complexes is fully inhibited by the allosteric inhibitor of mTOR, rapamycin or its analogs. Herein, we provide evidence that the combined inhibition of mTORC1/2, using the ATP-competitive binding …


Rnai-Mediated Control Of Aflatoxins In Peanut: Method To Analyze Mycotoxin Production And Transgene Expression In The Peanut/Aspergillus Pathosystem, Renee S. Arias, Phat M. Dang, Victor S. Sobolev Dec 2015

Rnai-Mediated Control Of Aflatoxins In Peanut: Method To Analyze Mycotoxin Production And Transgene Expression In The Peanut/Aspergillus Pathosystem, Renee S. Arias, Phat M. Dang, Victor S. Sobolev

United States Department of Agriculture-Agricultural Research Service / University of Nebraska-Lincoln: Faculty Publications

The Food and Agriculture Organization of the United Nations estimates that 25% of the food crops in the world are contaminated with aflatoxins. That represents 100 million tons of food being destroyed or diverted to non-human consumption each year. Aflatoxins are powerful carcinogens normally accumulated by the fungi Aspergillus flavus and A. parasiticus in cereals, nuts, root crops and other agricultural products. Silencing of five aflatoxin-synthesis genes by RNA interference (RNAi) in peanut plants was used to control aflatoxin accumulation following inoculation with A. flavus. Previously, no method existed to analyze the effectiveness of RNAi in individual peanut transgenic events, …


Dysregulation Of The Haem-Haemopexin Axis Is Associated With Severe Malaria In A Case-Control Study Of Ugandan Children., Robyn E Elphinstone, Frank Riley, Tian Lin, Sarah Higgins, Aggrey Dhabangi, Charles Musoke, Christine Cserti-Gazdewich, Raymond F. Regan, H Shaw Warren, Kevin C Kain Dec 2015

Dysregulation Of The Haem-Haemopexin Axis Is Associated With Severe Malaria In A Case-Control Study Of Ugandan Children., Robyn E Elphinstone, Frank Riley, Tian Lin, Sarah Higgins, Aggrey Dhabangi, Charles Musoke, Christine Cserti-Gazdewich, Raymond F. Regan, H Shaw Warren, Kevin C Kain

Department of Medicine Faculty Papers

BACKGROUND: Malaria is associated with haemolysis and the release of plasma haem. Plasma haem can cause endothelial injury and organ dysfunction, and is normally scavenged by haemopexin to limit toxicity. It was hypothesized that dysregulation of the haem-haemopexin pathway contributes to severe and fatal malaria infections.

METHODS: Plasma levels of haemin (oxidized haem), haemopexin, haptoglobin, and haemoglobin were quantified in a case-control study of Ugandan children with Plasmodium falciparum malaria. Levels at presentation were compared in children with uncomplicated malaria (UM; n = 29), severe malarial anaemia (SMA; n = 27) or cerebral malaria (CM; n = 31), and evaluated …


Cyclin D1 Silencing Suppresses Tumorigenicity, Impairs Dna Double Strand Break Repair And Thus Radiosensitizes Androgenindependent Prostate Cancer Cells To Dna Damage., F Marampon, G L Gravina, Xiaoming Ju, A Vetuschi, R Sferra, Mathew C Casimiro, S Pompili, C Festuccia, A Colapietro, E Gaudio, E Di Cesare, V Tombolini, Richard Pestell Dec 2015

Cyclin D1 Silencing Suppresses Tumorigenicity, Impairs Dna Double Strand Break Repair And Thus Radiosensitizes Androgenindependent Prostate Cancer Cells To Dna Damage., F Marampon, G L Gravina, Xiaoming Ju, A Vetuschi, R Sferra, Mathew C Casimiro, S Pompili, C Festuccia, A Colapietro, E Gaudio, E Di Cesare, V Tombolini, Richard Pestell

Department of Cancer Biology Faculty Papers

Patients with hormone-resistant prostate cancer (PCa) have higher biochemical failure rates following radiation therapy (RT). Cyclin D1 deregulated expression in PCa is associated with a more aggressive disease: however its role in radioresistance has not been determined. Cyclin D1 levels in the androgen-independent PC3 and 22Rv1 PCa cells were stably inhibited by infecting with cyclin D1-shRNA. Tumorigenicity and radiosensitivity were investigated using in vitro and in vivo experimental assays. Cyclin D1 silencing interfered with PCa oncogenic phenotype by inducing growth arrest in the G1 phase of cell cycle and reducing soft agar colony formation, migration, invasion in vitro and tumor …


Emergency Care Of Traumatic Brain Injuries In Pakistan: A Multicenter Study, Junaid Ahmad Bhatti, Kent Stevens, Muhammad Umer Mir, Adnan Ali Hyder, Junaid Razzak Dec 2015

Emergency Care Of Traumatic Brain Injuries In Pakistan: A Multicenter Study, Junaid Ahmad Bhatti, Kent Stevens, Muhammad Umer Mir, Adnan Ali Hyder, Junaid Razzak

Department of Emergency Medicine

Background:

This study assessed factors associated with emergency care outcomes and out-of-pocket treatment costs in traumatic brain injury (TBI) patients in Pakistan.

Methods:

Data on TBI patients were extracted from a four-month surveillance study conducted in the emergency departments (ED) of seven large teaching hospitals. Emergency care access to physicians and imaging facilities were compared with respect to ED outcomes (discharged, admitted or dead). Out-of-pocket treatment costs (in United States dollars [USD]) were compared among different patient strata.

Results:

ED outcomes were available for 1,787 TBI patients. Of them, most were males (79%), aged <25 years (46%) and arrived by ambulances (32%). Nurses or paramedical staff saw almost all patients (95%). Physicians with practice privileges (medical officers, residents or consultants) saw about half (55%) of them. Computerized tomography (CT) scans were performed in two of five patients (40%). Of all, 26% (n = 460) were admitted and 3% died (n = 52). Emergency care factors significantly associated with being admitted or died were arriving by ambulance (adjusted odds ratio [aOR] = 2.37, 95% confidence interval (CI) [95%CI] = 1.78-3.16); seen by medical officer/residents (aOR = 2.11; 95%CI = 1.49-2.99); and had CT scan (aOR = 2.93; 95%CI = 2.25-3.83). Out-of-pocket treatment costs at the ED were reported in 803 patients. Average costs were USD 8, (standard deviation [SD] = 23). Costs were twice as high in those arriving in ambulances (USD 20, SD = 49) or who underwent CT scans (USD 16, SD = 37).

Conclusion:

TBI patients' access to ambulance …


Genetic Modification Of Human Mesenchymal Stem Cells Helps To Reduce Adiposity And Improve Glucose Tolerance In An Obese Diabetic Mouse Model., Sabyasachi Sen, Cleyton C Domingues, Carol Rouphael, Cyril Chou, Chul Kim, Nagendra Yadava Dec 2015

Genetic Modification Of Human Mesenchymal Stem Cells Helps To Reduce Adiposity And Improve Glucose Tolerance In An Obese Diabetic Mouse Model., Sabyasachi Sen, Cleyton C Domingues, Carol Rouphael, Cyril Chou, Chul Kim, Nagendra Yadava

Medicine Faculty Publications

INTRODUCTION: Human mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into fat, muscle, bone and cartilage cells. Exposure of subcutaneous abdominal adipose tissue derived AD-MSCs to high glucose (HG) leads to superoxide accumulation and up-regulation of inflammatory molecules. Our aim was to inquire how HG exposure affects MSCs differentiation and whether the mechanism is reversible.

METHODS: We exposed human adipose tissue derived MSCs to HG (25 mM) and compared it to normal glucose (NG, 5.5 mM) exposed cells at 7, 10 and 14 days. We examined mitochondrial superoxide accumulation (Mitosox-Red), cellular oxygen consumption rate (OCR, Seahorse) and gene …