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Glutaminase mediated glutamate neurotoxicity by HIV-1 infected macrophage

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Glutaminase mediated glutamate neurotoxicity by HIV-1 infect...

Mental health problems due to community violence exposure in a small urban setting

第十五届国际药理学大会

作者： Erdmann Nathan Herek Shelley Lopez Alicia Takashi Tsukamoto Ferraris Dana unmc unmc unmc MGI Pharma. MGI Pharma.

＜正＞ Mononuclear phagocyte （MP, macrophages and microglia） dysfunction is thought to play a significant role in the pathogenesis of neurodegenerative disorders including HIV - 1 - associated dementia （HAD）. Glutamate is known to be elevated in HAD, and previous studies have reported HIV - 1 - infected human monocyte derived macrophage （MDM） increase the production of glutamate in a glutamine dependent manner. The enzyme glutaminase converts glutamine to glutamate in an energy free reaction. In this report, we demonstrate that HIV- 1 infected MDM condition media （MCM） induces neurotoxicity. Three glutaminase inhibitors and one control designed by MGI Pharma were blindly tested, with glutamate production measured by reverse - phase high performance liquid chromatography （RP-HPLC）.Two of the GPI inhibitors nearly abrogated the increased production of glutamate by HIV - infected MDM when delivered at micromolar concentrations （19560 and 14256）;the inhibitors did not directly affect cell viability or alter the progression of HIV infection. Glutaminase its and specific inhibitors may be important as a potential target for therapy in HIV - 1 mediated neuronal injury during HAD.

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Family Medicine and Community Health 2017年第3期5卷 170-178页

作者： Faraz Ahmad Jim Medder Jenenne Geske Jannette Taylor Ruth Margalit Mental health problems due to community violence exposure in a small urban setting unmc Dept.of Family Medicine 983075 Nebraska Medical CenterOmahaNE 68198-3075USA unmc College of Medicine 985520 Nebraska Medical CenterOmahaNE 68198-5520USA Creighton University School of Law2500 California PlazaOmahaNE 68178USA unmc College of Public Health 984355 Medical CenterOmahaNE 68198-4355USA

Objective:Studies conducted in large metropolitan inner-city communities with high violent crime rates have demonstrated an association between exposure to violence and mental health problems;therefore the purpose of this study was to determine if similar trends exist in smaller inner-city communities with substantially lower violent crime ***:One hundred twenty-six children and young adults living in inner-city Omaha,Nebraska,were screened for posttraumatic stress disorder(PTSD),depression,and anxiety symptoms and assessed for community violence exposure(CVE).Pearson’s correlation and analysis of variance were used to determine the relationship between PTSD,depression,and anxiety symptoms and ***:A statistically significant relationship was found between CVE and PTSD and anxiety symptoms among participants despite their having lower rates of exposure to violent events in com-parison with other *** association was found between violence and depression ***,the presence of anxiety and depression,as well as increased age of participants,was associated with higher rates of PTSD ***:We recommend that health care providers in smaller cities,where the effects of violent crime may be underestimated or overlooked,be informed of the existence of this pub-lic health problem within their community and that they screen at-risk patients for mental health problems.

关键词： Community violence inner city posttraumatic stress disorder depression anxiety

Sexually Transmitted Infections among African-American Population of the Midwest United States

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Advances in Infectious Diseases 2014年第1期4卷 49-57页

作者： K. M. Islam Robin High Veenu Minhas Ruth Margalit Department of Biostatistics UNMC Omaha USA Department of Epidemiology UNMC Omaha USA Department of Health Promotion Social & Behavioral Health UNMC Omaha USA Nebraska Center for Virology University of Nebraska-Lincoln Lincoln USA

Background: Sexually transmitted infections (STIs) such as chlamydia and gonorrhea are commonly reported infections in the United States. Greater Omaha has had continually higher reported rates of chlamydia and gonorrhea for more than a decade compared to the rest of the state rates. Minority and young adults have been disproportionately affected. Purpose: The objectives of our study were to estimate the prevalence and to identify risk factors for chlamydia and gonorrhea among young adults. Methods: We conducted a cross-sectional survey with 310 young adults aged 19 -25 years between June 2011 and June 2012. The study collected socio-demographic, behavioral and other risk factors for STIs utilizing a pre-design standardized questionnaire. Gonorrhea and chlamydia status of the participants were established by testing urine samples using PCR-based diagnostic technique. Descriptive and multivariable regression analyses were used to examine risk factors for STIs. Results: About 12.6% survey participants had at least one STI test positive. Lower education was associated with STIs but was not statistically significant (Odd Ratio for no schooling was 8.24, 95% CI 0.93 -72.86, Odd Ratio for high school education was 2.05, 95% CI 0.25 -16.63 compared to associate or college level education). No other predictors were associated with STIs. The average age of the first sexual intercourse was lower, and the number of sexual partners was higher compared to their national counterparts. Conclusion: We found a higher percentage of STI-positive individuals compared to previously reported county-level estimates. Education was the single and most important predictor of positive STI status.

关键词： Sexually Transmitted Infections STIs Chlamydia Gonorrhea African-American Survey

Design of nanocarriers for efficient cellular uptake and endosomal release of small molecule and nucleic acid drugs： learning from virus

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Frontiers of Chemical Science and Engineering 2014年第4期8卷 387-404页

作者： Vaibhav Mundra4 Ram I. Mahato Department of Pharmaceutical Sciences University of Nebraska Medical Center (UNMC) Omaha NE 68198-6025 USA

There are many challenges in developing efficient and target specific delivery systems of small molecule and nucleic acid drugs. Cell membrane presents one of the major barriers for the penetration of hydrophilic macromolecules across the plasma membrane. Nanocar- riers have been designed to enhance their cellular uptake via endocytosis but following their cellular uptake, endosomal escape is the rate limiting step which restricts the value associated with the enhanced uptake by nanocarriers. Viruses are an excellent model for efficient cytosolic delivery by nanocarriers. Viruses exploit intra- cellular cues to release the genome to cytosol. In this review, we first discuss different endocytic uptake path- ways and endosomal escape mechanisms. We then summarize the existing tools for studying the intracellular trafficking of nanocarriers. Finally, we highlight the important design elements of recent virus-based nanocar- tiers for efficient cellular uptake and endosomal escape.

关键词： nanocarrier cellular uptake endosomal release nucleic acid drug

Evaluating the Quality of Malaria-Related Health Information in the Nigerian Internet Context

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Advances in Infectious Diseases 2014年第1期4卷 42-48页

作者： Trout Kate Puricelli Perin Douglas Davy Timothy Ashish Joshi K. M. Islam Boys Town Omaha USA Center for Global Health and Development College of Public Health (CoPH) University of Nebraska Medical Center (UNMC) OmahaUSA Department of Epidemiology CoPH UNMC Omaha USA

Background: Patients and public are increasingly relying on Internet for health information. Health care providers are using internet for dissemination of health information. However, health information available on internet is not well regulated, and information quality varies greatly. Malaria is the leading cause of death and disease in many developing countries and has serious health burden around the world. The Internet could become a major resource for malaria education and information in Africa. This may potentially save millions of lives. The purpose of this study is to evaluate the quality of malaria health and treatment information available on the internet provided by the Nigerian context. Methods: Two key terms (malaria & treatment) were entered into three search engines: Google, Yahoo! and Bing. In order to retrieve articles as if the searches were conducted in Nigeria, the Local Area Network (LAN) settings were changed to a Nigerian proxy server, with a local Internet Protocol address. Three raters evaluated the quality of information using the DISCERN [9] instrument criteria. Kendall’s concordance coefficient (W) was calculated to determine the level of agreement among the three raters. Results: Thirty-eight websites evaluated, and the highest inter-rater average score was attributed to the *** website, followed by Wikipedia web site and Malaria Site. The “Home Remedies for You” website received the lowest score. Most evaluated websites were .com domains. The highest average score was given to .*** domains while .int had the lowest score. Conclusions: Improving the quality of malaria-related health information could lead to empowering communities, engaging and assisting them to strengthen their health and social information sharing and support.

关键词： Malaria Nigeria Health Information Internet

PROTEIN SERINE/THREONINE PHOSPHATASES IN OCULAR DEVELOPMENT AND DISEASES.

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PROTEIN SERINE/THREONINE PHOSPHATASES IN OCULAR DEVELOPMENT ...

Construction of RNA nanotubes

第十八届国际眼科研究大会

作者： David W..Li Department of Biochemistry ＆ Molecular Biology College of MedicineUNMCOmahaNE 68198USA

＜正＞Reversible protein phosphorylation is a fundamental regulatory mechanism in all biological *** senne/threunine phosphatases-1（PP-1）and-2A（PP-2A） accounts for 90% serine/threunine phosphatase activity in eukaryote cells and play distinct roles in regulating multiple cellular processes and *** recent studies have

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Nano Research 2019年第8期12卷 1952-1958页

作者： Hui Li Shaoying Wang Zhouxiang Ji Congcong Xu Lyudmila S. Shlyakhtenko Peixuan Guo Center for RNA Nanobiotechnology and Nanomedicine Division of Pharmaceutics and Pharmaceutical ChemistryCollege of Pharmacy/Department of Physiology & Cell BiologyCollege of Medicine/Dorothy M. Davis Heart and Lung Research Institute and James Comprehensive Cancer CenterThe Ohio State UniversityColumbusOH43210USA unmc Nanoimaging Core Facility Department of Pharmaceutical SciencesCollege of Pharmacy University of Nebraska Medical CenterOmahaNE68182USA Present address: University of California San FranciscoCA94158USA Present address: P&Z Biological Technology NewarkNJ07103USA

Nanotubes are miniature materials with significant potential applications in nanotechnological, medical, biological and material sciences. The quest for manufacturing methods of nano-mechanical modules is in progress. For example, the application of carbon nanotubes has been extensively investigated due to the precise width control, but the precise length control remains challenging. Here we report two approaches for the one-pot self-assembly of RNA nanotubes. For the first approach, six RNA strands were used to assemble the nanotube by forming a 11 nm long hollow channel with the inner diameter of 1.7 nm and the outside diameter of 6.3 nm. For the second approach, six RNA strands were designed to hybridize with their neighboring strands by complementary base pairing and formed a nanotube with a six-helix hollow channel similar to the nanotube assembled by the first approach. The fabricated RNA nanotubes were characterized by gel electrophoresis and atomic force microscopy (AFM), confirming the formation of nanotube-shaped RNA nanostructures. Cholesterol molecules were introduced into RNA nanotubes to facilitate their incorporation into lipid bilayer. Incubation of RNA nanotube complex with the free-standing lipid bilayer membrane under applied voltage led to discrete current signatures. Addition of peptides into the sensing chamber revealed discrete steps of current blockage. Polyarginine peptides with different lengths can be detected by current signatures, suggesting that the RNA-cholesterol complex holds the promise of achieving single molecule sensing of peptides.

关键词： RNA nanotechnology peptide sensing RNA nanotube nanobiotechnology

Therapeutic implications of SARS-CoV-2 dysregulation of the gutbrain-lung axis

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World Journal of Gastroenterology 2021年第29期27卷 4763-4783页

作者： Samuel D Johnson Omalla A Olwenyi Namita Bhyravbhatla Michellie Thurman Kabita Pandey Elizabeth A Klug Morgan Johnston Shetty Ravi Dyavar Arpan Acharya Anthony T Podany Courtney V Fletcher Mahesh Mohan Kamal Singh Siddappa N Byrareddy Department of Pathology and Microbiology University of Nebraska Medical CenterOmahaNE 68198United States Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical CenterOmahaNE 68198United States Antiviral Pharmacology Laboratory University of Nebraska Medical Center(UNMC)Center for Drug DiscoveryOmahaNE 68198United States Southwest National Primate Research Center Texas Biomedical Research InstituteSan AntonioTX 78227United States Department of Molecular Microbiology and Immunology and Bond Life Sciences Center University of MissouriColumbiaMO 65212United States Department of Genetics Cell Biology and AnatomyUniversity of Nebraska Medical CenterOmahaNE 68198United States Department of Biochemistry and Molecular Biology University of Nebraska Medical CenterOmahaNE 68198United States

The emergence and rapid spread of novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused over 180 million confirmed cases resulting in over 4 million deaths worldwide with no clear end in sight for the coronavirus disease 19(COVID-19)*** SARS-CoV-2 exposed individuals experience mild to moderate symptoms,including fever,cough,fatigue,and loss of smell and ***,many individuals develop pneumonia,acute respiratory distress syndrome,septic shock,and multiorgan *** addition to these primarily respiratory symptoms,SARS-CoV-2 can also infiltrate the central nervous system,which may damage the blood-brain barrier and the neuron's *** inflammation and neurodegeneration in the brain stem can further prevent efferent signaling to cranial nerves,leading to the loss of anti-inflammatory signaling and normal respiratory and gastrointestinal ***,SARS-CoV-2 can infect enterocytes resulting in gut damage followed by microbial dysbiosis and translocation of bacteria and their byproducts across the damaged epithelial *** a result,this exacerbates pro-inflammatory responses both locally and systemically,resulting in impaired clinical *** evidence has highlighted the complex interactions that mutually modulate respiratory,neurological,and gastrointestinal *** this review,we discuss the ways SARS-CoV-2 potentially disrupts the gut-brain-lung *** further highlight targeting specific responses to SARS-CoV-2 for the development of novel,urgently needed therapeutic ***,we propose a prospective related to the individuals from Low-and Middle-Income ***,the underlying propensity for heightened gut damage/microbial translocation is likely to result in worse clinical outcomes during this COVID-19 pandemic.

关键词： SARS-CoV-2 Gut Microbiome Lungs Brain Therapeutics

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Alcohol and liver

World Journal of Gastroenterology 2009年第10期15卷 1162-1162页

作者： Natalia A Osna Department of Internal Medicine University of Nebraska Medical Center Liver Study Unit R151 VA Medical Center 4101 Woolworth Ave Omaha NE 68105 United States. nosna@unmc.edu

Liver is a primary site of ethanol metabolism, which makes this organ susceptible to alcohol-induced damage. Alcoholic liver disease （ALD） has many manifestations and complicated pathogenesis. In this Topic Highlight, we included the key reviews that characterize new findings about the mechanisms of ALD development and might be of strong interest for clinicians and researchers involved in liver alcohol studies.

关键词： Gastroenterology