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Vitamin D Status And Its Association With Gradual Decline In Cognitive Function, Yusuf Yeşi̇l, Mehmet Emi̇n Kuyumcu, Özgür Kara, Burçi̇n Halaçli, Sezgi̇n Etgül, Muhammet Cemal Kizilarslanoğlu, Burcu Balam Yavuz, Münevver Özcan, Meltem Gülhan Hali̇l, Eylem Şahi̇n Cankurtaran, Mustafa Cankurtaran, Servet Arioğul

Turkish Journal of Medical Sciences

Background/aim: To compare plasma vitamin D concentrations among patients with normal cognitive function (control group), mild cognitive impairment (MCI), and Alzheimer disease (AD). Materials and methods: In total, 158 patients with AD, 228 patients with MCI, and 603 control subjects were included. Plasma levels of 25-hydroxyvitamin D were measured after comprehensive geriatric assessment and compared among groups. SPSS 15.0 was used for statistical analysis. Results: Mean levels of 25-hydroxyvitamin D were significantly different among the 3 groups of AD patients, MCI patients, and controls (P < 0.001). Post hoc analysis revealed that the levels were significantly lower in the MCI group than the control group (P = 0.002) and significantly lower in the AD group than the control group (P = 0.003). Multivariate analysis showed that age (OR: 1.070, 95% CI: 1.025-1.116, P = 0.002), instrumental activities of daily living score (OR: 0.920, 95% CI: 0.850-0.995, P = 0.037), 25-hydroxyvitamin D level (OR: 0.959, 95% CI: 0.932-0.987, P = 0.004), and diabetes mellitus (OR: 2.476, 95% CI: 1.153-5.319, P = 0.020) were factors independently associated with AD. Conclusion: This study demonstrated that there is a correlation between plasma 25-hydroxyvitamin D levels and cognitive functions.

Is Alzheimer Disease Related To Age-Related Macular Degeneration?, Seden Demi̇rci̇, Ali̇me Güneş, Kadi̇r Demi̇rci̇, Serpi̇l Demi̇rci̇, Levent Tök, Özlem Tök

Turkish Journal of Medical Sciences

Background/aim: To compare the cognitive functions and define the frequency of Alzheimer disease (AD) between participants with and without age-related macular degeneration (AMD). Materials and methods: Fifty-nine patients with late-stage AMD (74.3 ± 7.3 years) and 49 age-, sex-, and education-matched control subjects were compared for the presence of AD according to the guidelines of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA). Detailed neuropsychological tests were performed for all subjects. Results: Neuropsychiatric tests scores were lower in the AMD group than the control group. The frequency of AD …

Effect Of Capparis Spinosa L. On Cognitive Impairment Induced By D-Galactosein Mice Via Inhibition Of Oxidative Stress, Nergi̇z Hacer Turgut, Haki̇ Kara, Emre Arslanbaş, Derya Güli̇z Mert, Bektaş Tepe, Hüseyi̇n Güngör

Turkish Journal of Medical Sciences

Background/aim: To determine the phenolic acid levels and DNA damage protection potential of Capparis spinosa L. seed extract and to investigate the effect of the extract on cognitive impairment and oxidative stress in an Alzheimer disease mice model. Materials and methods: Thirty BALB/c mice divided into 5 groups (control??, D-galactose, D-galactose + C. spinosa 50, D-galactose + C. spinosa 100, D-galactose + C. spinosa 200) were used. Mice were administered an injection of D-galactose (100 mg/kg, subcutaneous) and orally administered C. spinosa (50, 100, or 200 mg/kg) daily for 8 weeks. Results: Syringic acid was detected and the total amount …

Molecular Docking And Ex Vivo And In Vitro Anticholinesterase Activity Studies Ofsalvia Sp. And Highlighted Rosmarinic Acid, Lütfi̇ye Ömür Demi̇rezer, Peri̇han Gürbüz, Emi̇ne Peli̇n Keli̇cen Uğur, Mi̇ne Bodur, Nadi̇re Özenver, Ayşe Uz, Zühal Güvenalp

Turkish Journal of Medical Sciences

Background/aim: To evaluate acetylcholinesterase (AChE) inhibitory activity and antioxidant capacity of the major molecule from Salvia sp., rosmarinic acid, as a drug candidate molecule for treatment of Alzheimer disease (AD). Materials and methods: The AChE inhibitory activity of different extracts from Salvia trichoclada, Salvia verticillata, and Salvia fruticosa was determined by the Ellman and isolated guinea pig ileum methods, and the antioxidant capacity was determined with DPPH. The AChE inhibitory activity of the major molecule rosmarinic acid was determined by in silico docking and isolated guinea pig ileum methods. Results: The methanol extract of Salvia trichoclada showed the highest inhibition …

Mirna-Mediated Regulation Of Heat Shock Proteins In Human Ejaculated Spermatozoa, Tang Wenhao, Liu De-Feng, Hong Kai, Zhao Lian-Ming, Mao Jia-Ming, Zhuang Xin-Jie, Ma Lu-Lin, Jiang Hui

Turkish Journal of Medical Sciences

Background/aim: Heat shock proteins (HSPs) are expressed in human spermatozoa and play a role in sperm function. MicroRNAs (miRNAs) regulate gene expression, and the possible involvement of miRNAs in the regulation of HSP gene expression in sperm was investigated in this study. Materials and methods: miRNAs differentially expressed in 8 copies of an oligoasthenozoospermic semen group (OA) were identified by comparison with a normal male semen control group (NC) using microarray technology. Potential targets of HSP proteins among the differentially expressed miRNAs were further investigated. Results: HSP40, HSP60, HSP70, and HSP90 were all found to be expressed in human ejaculated …

Spontaneous Withdrawal In Intermittent Morphine Administration In Rats And Mice: Effect Of Clonidine Coadministration And Sex-Related Differences, Oruc Allahverdi̇yev, Asli Zengi̇n Türkmen, Asi̇ye Nurten, İclal Şehi̇rli̇, Nurhan Engi̇nar

Turkish Journal of Medical Sciences

Background/aim: Treating animals repeatedly with intermittent and increasing morphine doses has been suggested to allow some withdrawal during each dosing interval, which causes repeated stress. The present study aimed to test this hypothesis and assess sex-related differences in withdrawal signs and their suppression by clonidine. Materials and methods: Male and female rats and mice were administered with increasing doses of morphine twice daily at different dosing intervals. Rats were given clonidine in drinking water (5 μg/mL). Spontaneous and naloxone-precipitated withdrawal signs and novelty-induced grooming were evaluated. Results: Male rats and male and female rats displayed manifestations of morphine withdrawal at …

Investigation Of The Protective Effect Of Erdosteine Against Cyclosporine-Inducedinjury In Rat Liver With Histological And Biochemical Methods, Ahmet Nacar, İhsan Karaboğa, Hamza Mali̇k Okuyan, Nebi̇hat Kaplan Sefi̇l, Emel Nacar, Sedat Motor, Seçki̇n Akküçük, Orhan Veli̇ Özkan

Turkish Journal of Medical Sciences

Background/aim: In the present study, the protective effect of erdosteine against cyclosporine-induced injury in rat liver was investigated with histological and biochemical methods. Materials and methods: Thirty-two Wistar albino male rats were randomly divided into 4 groups: control (n = 8), cyclosporine (n = 8, 20 mg kg-1 day-1 i.p.), cyclosporine + erdosteine (n = 8, erdosteine 12 mg kg-1 day-1 orally), and erdosteine (n = 8). At the end of day 12, liver tissues were removed for histological and biochemical analysis. After liver tissues were fixed in 10% buffered neutral formalin, routine histological processes were applied and tissue sections …

Mitochondrial And Neuroprotective Effects Of Phenelzine Related To Scavenging Of Neurotoxic Lipid Peroxidation Products, John Cebak

Theses and Dissertations--Neuroscience

Lipid peroxidation is a key contributor to the pathophysiology of traumatic brain injury (TBI). Traditional antioxidant therapies are intended to scavenge the free radicals responsible for either the initiation or propagation of lipid peroxidation (LP). However, targeting free radicals after TBI is difficult as they rapidly react with other cellular macromolecules, and thus has a limited post-injury time window in which they may be intercepted by a radical scavenging agent. In contrast, our laboratory has begun testing an antioxidant approach that scavenges the final stages of LP i.e. formation of carbonyl-containing breakdown products. By scavenging breakdown products such as the …

Tumor-Derived Proteins And Mitochondrial Dysfunction In Lung Cancer-Induced Cachexia, Julie B. Mclean

Theses and Dissertations--Physiology

Lung tumors secrete multiple factors that contribute to cachexia, a severe wasting syndrome that includes loss of muscle mass, weakness, and fatigue. 80% of advanced lung cancer patients experience cachexia, which cannot be reversed by nutritional interventions, diminishes response to and tolerance of cancer treatments, and increases morbidity and mortality. Despite a multitude of clinical trials, there are currently no approved treatments. This deficiency suggests that not all of the factors that contribute to cachexia have been identified.

Cancer is frequently accompanied by an increase in cyclooxygenase-2 (COX-2), a hallmark of inflammation. Clinical trials for COX-2 inhibitors have resulted in …

The Skeletal Muscle Molecular Clock Regulates The Timing Of Substrate Metabolism And The Circadian Expression Of Titin-Cap, Brian A. Hodge

Theses and Dissertations--Physiology

Skeletal muscle is a major contributor to whole-body metabolism as it serves as a depot for both glucose and amino acids, and is a highly metabolically active tissue. An intrinsic molecular clock mechanism exists within skeletal muscle that regulates the timing of physiological processes. A key function of the clock is to regulate the timing of metabolic processes to anticipate time of day changes in environmental conditions. The purpose of this study was to identify metabolic genes that are expressed in a circadian manner and determine if these genes are regulated downstream of the intrinsic molecular clock by assaying gene …

Global-Scale Analysis Of The Dynamic Transcriptional Adaptations Within Skeletal Muscle During Hypertrophic Growth, Tyler Kirby

Theses and Dissertations--Physiology

Skeletal muscle possesses remarkable plasticity in responses to altered mechanical load. An established murine model used to increase mechanical load on a muscle is the surgical removal of the gastrocnemius and soleus muscles, thereby placing a functional overload on the plantaris muscle. As a consequence, there is hypertrophic growth of the plantaris muscle. We used this model to study the molecular mechanisms regulating skeletal muscle hypertrophy.

Aged skeletal muscle demonstrates blunted hypertrophic growth in response to functional overload. We hypothesized that an alteration in gene expression would contribute to the blunted hypertrophic response observed with aging. However, the difference in …

Enhanced Cgmp-Dependent Signaling In Astrocytes: Novel Therapeutic Target In Alzheimer's Disease, Nyema M. Woart

PCOM Biomedical Studies Student Scholarship

Over five million Americans suffer from Alzheimer’s Disease (AD), with an expected 34% increase in the incidence in this disease over the next decade. Unfortunately, there is no cure for AD. Recent studies have indicated that drugs which increase the levels of cyclic guanosine-3’5’-monophosphate (cGMP) may help preserve learning and memory in AD and enhance cognition in the aging brain; however, the mechanism(s) of how cGMP exerts this beneficial effect is unknown. The present findings now suggest that elevation of cGMP in astrocytes depresses inhibitory potassium currents in these cells to stimulate their protective influence on neuronal activity. Cellular currents …

Norepinephrine Circuits In Mediating Stress-Elicited Behavior, Hyungwoo Nam

All ETDs from UAB

Norepinephrine in the central nervous system (CNS) is a key mediator of stress-elicited behavioral and physiological adaptations. However, our understanding of central noradrenergic circuitry that regulates specific stress-elicited adaptations is incomplete. The working model for the studies described in this dissertation is that disruptions of specific noradrenergic circuits are responsible for the manifestation of distinct stress-elicited behaviors. Initially the organization of descending noradrenergic neurons with poly-synaptic collaterals to the adrenal gland and skeletal muscle was defined. These noradrenergic presympathetic-premotor neurons (PSPMNs) were distributed within the ventral locus coeruleus (LC), nucleus subcoeruleus (SubC), and the A7 cell group. Then behavioral characterization …

The Association Between Environmental Cadmium Exposure And All-Cause Mortality And Cardiovascular Disease In A Cohort Of Elderly Western Australian Women, Kane Deering

Theses : Honours

Introduction: Recent research suggests an association between environmental cadmium exposure and increased risk of, and death from, cardiovascular disease, the number one cause of mortality in Australia and worldwide. However, the research to date is neither comprehensive nor have there been any studies conducted on an Australian population. This study identified whether increasing concentrations of urinary cadmium in elderly West Australian women was associated with an increased odds of incidence of, and deaths from CVD, as well as all-cause mortality.

Method: Cadmium excretion was measured in urine samples collected at baseline (1998) from 1359 women from Perth who …

Tumor Necrosis Factor Alpha Converting Enzyme Inhibition During Acute Colitis In Mice: A Regional Analysis, Brian Maddox

Graduate Theses/Dissertations

Tumor Necrosis Factor-a Converting Enzyme (TACE) induces active TNFa and may contribute to the development of colitis in humans. I hypothesized that pharmacological blockade of TNFa production would improve colitis scoring through decreased expression of inflammatory biomarkers. Acute colitis was induced in wild type BALB/c mice using 5% dextran sulfate sodium (DSS) in drinking water for 7 days. TACE inhibition was accomplished through twice daily intraperitoneal injection of DPC- 333 (10mg/kg; BSM Inc.) To determine the effects of TACE blockade during colitis, the following experimental groups (n=6-7/group) were tested: 1) vehicle; 2) DPC-333; 3) 5% DSS and vehicle; and 4) …

Unstable Ventilatory Control During Sleep After High Spinal Cord Injury: The Contribution Of Chemosensitivity And Hypoventilation, Amy Therese Bascom

Wayne State University Dissertations

ABSTRACT

UNSTABLE VENTILATORY CONTROL DURING SLEEP AFTER HIGH SPINAL CORD INJURY: THE CONTRIBUTION OF CHEMOSENSITIVITY AND HYPOVENTILATION

by

Amy T. Bascom

May 2015

Advisor: Dr. Harry G. Goshgarian

Major: Anatomy and Cell Biology

Degree: Doctor of Philosophy

A high prevalence of sleep-disordered breathing (SDB) after spinal cord injury (SCI) has been reported in the literature; however, the underlying mechanisms are not well understood. My studies had 2 aims: 1) to determine the effect of the withdrawal of the wakefulness drive to breathe on the degree of hypoventilation in SCI patients and able-bodied controls and 2) to determine the response of …

Investigation Of Whether Sedentary And Physically Active Conditions Lead To Altered Gabaergic Signaling In The Rvlm, Maryetta Donna Dombrowski

Wayne State University Dissertations

Investigation of whether sedentary and physically active conditions lead to altered GABAergic signaling in the RVLM

MD Dombrowski, and PJ Mueller

Department of Physiology, Wayne State University, School of Medicine, Detroit, MI

A sedentary lifestyle is a major risk for cardiovascular disease. Cardiovascular disease has been associated with elevated basal sympathetic nerve activity. The rostral ventrolateral medulla is a bilateral brainstem region that is an important for the control of resting and reflex control of sympathetic nerve activity and blood pressure. The activity of these neurons in this region is tonically inhibited by the neurotransmitter γ-butyric amino acid (GABA). Interestingly, …

A Cgh Array Study In Nonsyndromic (Primary) Autism Patients: Deletions On16p13.11, 16p11.2, 1q21.1, 2q21.1q21.2, And 8p23.1, Kudret Esen Gümüşlü, Hakan Savli, Deni̇z Sünnetçi̇, Naci̇ Çi̇ne, Bülent Kara, Seda Eren Keski̇n, Rami̇s Ufuk Akkoyunlu

Turkish Journal of Medical Sciences

Background/aim: To detect specific molecular changes of DNA level in primary autism patients by using whole genome CGH array technology. Materials and methods: A cohort of 35 primary autism patients received clinical genetic testing by using an oligonucleotide-based CGH array platform to test for submicroscopic genomic deletions and duplications. Fluorescent in situ hybridization was performed in seven patients for confirmation of the results. Results: We found 16p13.11 deletion in thirteen patients, 16p11.2 deletion in twelve patients, 1q21.1 deletion in ten patients, 2q21.1q21.2 deletion in eight patients, and 8p23.1 deletion in seven patients. Conclusion: Our study indicates that genes in 16p13.11, …

Relationship Among Mif, Mcp-1, Viral Loads, And Hbs Ag Levelsin Chronic Hepatitis B Patients, Hayati̇ Güneş, Rafet Mete, Murat Aydin, Bi̇rol Topçu, Mustafa Oran, Mustafa Doğan, Oğuzhan Yildirim, İlknur Erdem, Aynur Eren Topkaya, Ahmet Gürel

Turkish Journal of Medical Sciences

Background/aim: To determine whether macrophage migration inhibitory factor (MIF) and monocyte chemoattractant protein-1 (MCP-1) levels in patients with hepatitis B (HB) are different than in normal individuals and whether the HB surface antigen (HBs Ag) level and viral load are correlated with each other and with the two aforementioned parameters. Materials and methods: Sera were obtained from 52 chronic active HB (CAHB) patients and 33 healthy controls, and their MIF and MCP-1 levels were measured. Statistical analyses were performed. A value of P < 0.05 was considered statistically significant. Results: The MIF and MCP-1 values of the control group were increased compared to those of the CAHB group. The MIF and MCP-1 levels were negatively correlated with HBs Ag levels and viral loads. The MIF and MCP-1 levels were positively correlated. The HBs Ag levels and the log10 of the viral loads were positively correlated. Conclusion: We conclude that the negative correlation of MIF and MCP-1 with viral load and HBs Ag levels may be due to T-cell deficiency, antinuclear antibody seropositivity, and/or inhibition of chemokine ligand 2 receptors by viral antigens. More studies with a greater number of subjects are needed to evaluate the potential role of MIF and MCP in CAHB.

Visual And Brainstem Auditory Evoked Potentials In Infants Withsevere Vitamin B12 Deficiency, Ni̇hat Demi̇r, Ahmet Koç, Mahmut Abuhandan, Mustafa Çalik, Akin İşcan

Turkish Journal of Medical Sciences

Background/aim: Vitamin B12 plays an important role in the development of mental, motor, cognitive, and social functions via its role in DNA synthesis and nerve myelination. Its deficiency in infants might cause neuromotor retardation as well as megaloblastic anemia. The objective of this study was to investigate the effects of infantile vitamin B12 deficiency on evoked brain potentials and determine whether improvement could be obtained with vitamin B12 replacement at appropriate dosages. Materials and methods: Thirty patients with vitamin B12 deficiency and 30 age-matched healthy controls were included in the study. Hematological parameters, visual evoked potentials, and brainstem auditory evoked …

De Novo Assembly Of The Chimpanzee Transcriptome From Nextgen Mrna Sequences, Mnirnal D. Maudhoo, Jacob D. Madison, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Common chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) are the species most closely related to humans. For this reason, it is especially important to have complete and accurate chimpanzee nucleotide and protein sequences to understand how humans evolved their unique capabilities. We provide transcriptome data from four untransformed cell types derived from the reference Pan troglodytes, "Clint", to better annotate the chimpanzee genome and provide empirical validation for proposed gene models of this important species.

FINDINGS: RNA was extracted from primary cells cultured from four tissues: skin, adipose stroma, vascular smooth muscle and skeletal muscle. These four RNA samples …

The Effect Of Statins On Il-33 Mediated Mast Cell Function, Marcela Taruselli

Theses and Dissertations

This study demonstrates original findings of statin effects on IL-33 stimulated mast cells. Statins are a class of drugs used to lower cholesterol production by targeting HMG CoA reductase. These commonly prescribed drugs have been shown to be immunomodulatory. In this study, we have found that pretreatment with statins has a variety of effects on IL-33 stimulated mast cells. Atorvastatin suppresses TNF and IL-6 production, while fluvastatin significantly enhances release of these proinflammatory cytokines in BMMCs. Although they have differing effects on cytokine production, both statins lowered ST2 expression on the cell surface, decreased cell viability, and enhanced expression of …

Rhabdovirus-Based Vaccine Platforms Against Henipaviruses., Drishya Kurup, Christoph Wirblich, Heinz Feldmann, Andrea Marzi, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

UNLABELLED: The emerging zoonotic pathogens Hendra virus (HeV) and Nipah virus (NiV) are in the genus Henipavirus in the family Paramyxoviridae. HeV and NiV infections can be highly fatal to humans and livestock. The goal of this study was to develop candidate vaccines against henipaviruses utilizing two well-established rhabdoviral vaccine vector platforms, recombinant rabies virus (RABV) and recombinant vesicular stomatitis virus (VSV), expressing either the codon-optimized or the wild-type (wt) HeV glycoprotein (G) gene. The RABV vector expressing the codon-optimized HeV G showed a 2- to 3-fold increase in incorporation compared to the RABV vector expressing wt HeV G. There …

Characterization Of Cd8+ T Cell Differentiation Following Sivδnef Vaccination By Transcription Factor Expression Profiling, James M. Billingsley, Premeela A. Rajakumar, Michelle A. Connole, Nadine C. Salisch, Sama Adnan, Yury V. Kuzmichev, Henoch S. Hong, R. Keith Reeves, Hyung-Joo Kang, Wenjun Li, Qingsheng Li, Ashley T. Haase, R. Paul Johnson

Nebraska Center for Virology: Faculty Publications

The onset of protective immunity against pathogenic SIV challenge in SIVΔnef-vaccinated macaques is delayed for 15-20 weeks, a process that is related to qualitative changes in CD8⁺ T cell responses induced by SIVΔnef. As a novel approach to characterize cell differentiation following vaccination, we used multi-target qPCR to measure transcription factor expression in naïve and memory subsets of CD8+⁺ T cells, and in SIV-specific CD8⁺ T cells obtained from SIVΔnef-vaccinated or wild type SIVmac239-infected macaques. Unsupervised clustering of expression profiles organized naïve and memory CD8⁺ T cells into groups concordant with cell surface phenotype. Transcription factor …

Escherichia Coli Surface Display Of Single-Chain Antibody Vrc01 Against Hiv-1 Infection, Lin-Xu Wang, Michael Mellon, Dane Bowder, Meghan Quinn, Danielle Shea, Charles Wood, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus type 1 (HIV-1) transmission and infection occur mainly via the mucosal surfaces. The commensal bacteria residing in these surfaces can potentially be employed as a vehicle for delivering inhibitors to prevent HIV-1 infection. In this study, we have employed a bacteria-based strategy to display a broadly neutralizing antibody VRC01, which could potentially be used to prevent HIV-1 infection. The VRC01 antibody mimics CD4-binding to gp120 and has broadly neutralization activities against HIV-1. We have designed a construct that can express the fusion peptide of the scFv-VRC01 antibody together with the autotransporter β-barrel domain of IgAP gene from …

The Hippo/Yap Pathway Interacts With Egfr Signaling And Hpv Oncoproteins To Regulate Cervical Cancer Progression, Chunbo He, Dagan Mao, Guohua Hua, Xiangmin Lv, Xingcheng Chen, Peter C. Angeletti, Jixin Dong, Steven W. Remmenga, Kerry J. Rodabaugh, Jin Zhou, Paul F. Lambert, Peixin Yang, John S. Davis, Cheng Wang

Nebraska Center for Virology: Faculty Publications

The Hippo signaling pathway controls organ size and tumorigenesis

through a kinase cascade that inactivates Yes-associated

protein (YAP). Here, we show that YAP plays a central role in

controlling the progression of cervical cancer. Our results suggest

that YAP expression is associated with a poor prognosis for cervical

cancer. TGF-α and amphiregulin (AREG), via EGFR, inhibit the Hippo

signaling pathway and activate YAP to induce cervical cancer cell

proliferation and migration. Activated YAP allows for up-regulation

of TGF-α, AREG, and EGFR, forming a positive signaling loop to

drive cervical cancer cell proliferation. HPV E6 protein, a major

etiological molecule of …

Single-Dose Cpg Immunization Protects Against A Heterosubtypic Challenge And Generates Antigen-Specific Memory T Cells, Alexander J. Vogel, Deborah M. Brown

Nebraska Center for Virology: Faculty Publications

Despite extensive research, influenza A virus (IAV) remains a major cause of morbidity, mortality, and healthcare expenditure. Emerging pandemics from highly pathogenic IAV strains, such as H5N1 and pandemic H1N1, highlight the need for universal, crossprotective vaccines. Current vaccine formulations generate strain-specific neutralizing antibodies primarily against the outer coat proteins, hemagglutinin and neuraminidase. In contrast to these highly mutable proteins, internal proteins of IAV are more conserved and are a favorable target for developing vaccines that induce strong T cell responses in addition to humoral immunity. Here, we found that intranasal administration with a single dose of CpG and inactivated …

Long-Acting Parenteral Combination Antiretroviral Loaded Nano-Drug Delivery System To Treat Chronic Hiv-1 Infection: A Humanized Mouse Model Study, Subhra Mandal, Guobin Kang, Pavan Kumar Prathipati, Wenjin Fan, Qingsheng Li, Christopher J. Destache

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus (HIV) patients are often diagnosed in the chronic stage of HIV/AIDS. Combination antiretroviral therapy (cART) has improved quality of life for HIV-infected patients. Present study describes a novel long-acting parenteral formulation of combination antiretroviral (cARV) loaded nano-drugs for treating chronic HIV-1 (cHIV) in a humanized-BLT (hu-BLT) mice model. The cARV (elvitegravir + tenofovir alafenamide + emtricitabine; EVG + TAF + FTC) drugs (mimicking marketed Genvoy® one-pill for HIV-treatment) were encapsulated in poly (lactic-co-glycolic acid) nanoparticles (NPs). To establish cHIV, hu-BLT mice were intravaginally challenged with HIV-1 and maintained for 15 weeks. Plasma viral load (pVL) was monitored …

Mutations In The 5’ Ntr And The Non-Structural Protein 3a Of The Coxsackievirus B3 Selectively Attenuate Myocarditogenicity, Chandirasegaran Massilamany, Arunakumar Gangaplara, Rakesh H. Basavalingappa, Rajkumar A. Rajasekaran, Hiep Vu, Jean-Jack Riethoven, David Steffen, Asit K. Pattnaik, Jay Reddy

School of Veterinary and Biomedical Sciences: Faculty Publications

The 5’ non-translated region (NTR) is an important molecular determinant that controls replication and virulence of coxsackievirus B (CVB)3. Previous studies have reported many nucleotide (nt) sequence differences in the Nancy strain of the virus, including changes in the 5’ NTR with varying degrees of disease severity. In our studies of CVB3-induced myocarditis, we sought to generate an infectious clone of the virus for routine in vivo experimentation. By determining the viral nt sequence, we identified three new nt substitutions in the clone that differed from the parental virus strain: C97U in the 5’ NTR; a silent mutation, A4327G, in …

Confocal Fluorescence Microscopy: An Ultra-Sensitive Tool Used To Evaluate Intracellular Antiretroviral Nano-Drug Delivery In Hela Cells, Subhra Mandal, You Zhou, Annemarie Shibata, Christopher J. Destache

School of Veterinary and Biomedical Sciences: Faculty Publications

In the last decade, confocal fluorescence microscopy has emerged as an ultra-sensitive tool for real-time study of nanoparticles (NPs) fate at the cellular-level. According to WHO 2007 report, Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) is still one of the world’s major health threats by claiming approximately 7,000 new infections daily worldwide. Although combination antiretroviral drugs (cARV) therapy has improved the life-expectancy of HIV-infected patients, routine use of high doses of cARVhas serious health consequences and requires complete adherence to the regimen for success. Thus, our research goal is to fabricate long-acting novel cARV loaded poly(lactide-co-glycolic acid) (PLGA) nanoparticles (cARV-NPs) as …