Medical Sciences Commons^™

Parenteral Nutrition Additive Shortages: The Short-Term, Long-Term And Potential Epigenetic Implications In Premature And Hospitalized Infants., Corrine K. Hanson, Melissa Thoene, Julie Wagner, Dean Collier, Kassandra Lecci, Ann Anderson-Berry

Journal Articles: Medical Nutrition

Nutrition support practitioners are currently dealing with shortages of parenteral nutrition micronutrients, including multivitamins (MVI), selenium and zinc. A recent survey from the American Society of Enteral and Parenteral Nutrition (ASPEN) indicates that this shortage is having a profound effect on clinical practice. A majority of respondents reported taking some aggressive measures to ration existing supplies. Most premature infants and many infants with congenital anomalies are dependent on parenteral nutrition for the first weeks of life to meet nutritional needs. Because of fragile health and poor reserves, they are uniquely susceptible to this problem. It should be understood that shortages …

New Fusion Transcripts Identified In Normal Karyotype Acute Myeloid Leukemia, Hongxiu Wen, Yongjin Li, Sami N. Malek, Yeong C. Kim, Jia Xu, Pei Xian Chen, Fengxia Xiao, Xin Huang, Xianzheng Zhou, Zhenyu Xuan, Shiva Mankala, Guihua Hou, Janet D. Rowley, Michael Q. Zhang, San Ming Wang

Journal Articles: Genetics, Cell Biology & Anatomy

Genetic aberrations contribute to acute myeloid leukemia (AML). However, half of AML cases do not contain the well-known aberrations detectable mostly by cytogenetic analysis, and these cases are classified as normal karyotype AML. Different outcomes of normal karyotype AML suggest that this subgroup of AML could be genetically heterogeneous. But lack of genetic markers makes it difficult to further study this subgroup of AML. Using paired-end RNAseq method, we performed a transcriptome analysis in 45 AML cases including 29 normal karyotype AML, 8 abnormal karyotype AML and 8 AML without karyotype informaiton. Our study identified 134 fusion transcripts, all of …

Ccpa Regulates Arginine Biosynthesis In Staphylococcus Aureus Through Repression Of Proline Catabolism., Austin S. Nuxoll, Steven M. Halouska, Marat Sadykov, Mark L. Hanke, Kenneth W. Bayles, Tammy Kielian, Robert Powers, Paul D. Fey

Journal Articles: Pathology and Microbiology

Staphylococcus aureus is a leading cause of community-associated and nosocomial infections. Imperative to the success of S. aureus is the ability to adapt and utilize nutrients that are readily available. Genomic sequencing suggests that S. aureus has the genes required for synthesis of all twenty amino acids. However, in vitro experimentation demonstrates that staphylococci have multiple amino acid auxotrophies, including arginine. Although S. aureus possesses the highly conserved anabolic pathway that synthesizes arginine via glutamate, we demonstrate here that inactivation of ccpA facilitates the synthesis of arginine via the urea cycle utilizing proline as a substrate. Mutations within putA, rocD, …

Muc4 And Muc1 Expression In Adenocarcinoma Of The Stomach Correlates With Vessel Invasion And Lymph Node Metastasis: An Immunohistochemical Study Of Early Gastric Cancer., Yukihiro Tamura, Michiyo Higashi, Sho Kitamoto, Seiya Yokoyama, Masahiko Osako, Michiko Horinouchi, Takeshi Shimizu, Mineo Tabata, Surinder K. Batra, Masamichi Goto, Suguru Yonezawa

Journal Articles: Biochemistry & Molecular Biology

We have previously reported that MUC4 expression is a poor prognostic factor in various carcinomas. Our previous study also showed that MUC1 expression in gastric cancers, including the early and advanced stages is a poor prognostic factor. In the present study, the expression profiles of MUC4 and MUC1 were examined by immunohistochemistry (IHC) using two anti-MUC4 monoclonal antibodies (MAbs), 8G7 and 1G8, and anti-MUC1 MAb DF3 in 104 gastrectomy specimens of early gastric adenocarcinoma with submucosal invasion (pT1b2), including 197 histological subtype lesions. Before the IHC study of the human specimens, we evaluated the specificity of the two MAbs by …

Mucin (Muc) Expression During Pancreatic Cancer Progression In Spontaneous Mouse Model: Potential Implications For Diagnosis And Therapy., Satyanarayana Rachagani, María P Torres, Sushil Kumar, Dhanya Haridas, Michael J. Baine, Muzafar A. Macha, Sukhwinder Kaur, Moorthy P. Ponnusamy, Parama Dey, Parthasarathy Seshacharyulu, Sonny L. Johansson, Maneesh Jain, Kay-Uwe Wagner, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Pancreatic cancer (PC) is a lethal malignancy primarily driven by activated Kras mutations and characterized by the deregulation of several genes including mucins. Previous studies on mucins have identified their significant role in both benign and malignant human diseases including PC progression and metastasis. However, the initiation of MUC expression during PC remains unknown because of lack of early stage tumor tissues from PC patients.

METHODS: In the present study, we have evaluated stage specific expression patterns of mucins during mouse PC progression in (Kras(G12D);Pdx1-Cre (KC)) murine PC model from pancreatic intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma (PDAC) …

Expression Of Muc17 Is Regulated By Hif1Α-Mediated Hypoxic Responses And Requires A Methylation-Free Hypoxia Responsible Element In Pancreatic Cancer., Sho Kitamoto, Seiya Yokoyama, Michiyo Higashi, Norishige Yamada, Shyuichiro Matsubara, Sonshin Takao, Surinder K. Batra, Suguru Yonezawa

Journal Articles: Biochemistry & Molecular Biology

MUC17 is a type 1 membrane-bound glycoprotein that is mainly expressed in the digestive tract. Recent studies have demonstrated that the aberrant overexpression of MUC17 is correlated with the malignant potential of pancreatic ductal adenocarcinomas (PDACs); however, the exact regulatory mechanism of MUC17 expression has yet to be identified. Here, we provide the first report of the MUC17 regulatory mechanism under hypoxia, an essential feature of the tumor microenvironment and a driving force of cancer progression. Our data revealed that MUC17 was significantly induced by hypoxic stimulation through a hypoxia-inducible factor 1α (HIF1α)-dependent pathway in some pancreatic cancer cells (e.g., …

Exosome-Mediated Shuttling Of Microrna-29 Regulates Hiv Tat And Morphine-Mediated Neuronal Dysfunction., Guoku Hu, H Yao, A D. Chaudhuri, Sowmya V. Yelamanchili, H Wen, P D. Cheney, Howard S. Fox, Shilpa J. Buch

Journal Articles: Pharmacology & Experimental Neuroscience

Neuronal damage is a hallmark feature of HIV-associated neurological disorders (HANDs). Opiate drug abuse accelerates the incidence and progression of HAND; however, the mechanisms underlying the potentiation of neuropathogenesis by these drugs remain elusive. Opiates such as morphine have been shown to enhance HIV transactivation protein Tat-mediated toxicity in both human neurons and neuroblastoma cells. In the present study, we demonstrate reduced expression of the tropic factor platelet-derived growth factor (PDGF)-B with a concomitant increase in miR-29b in the basal ganglia region of the brains of morphine-dependent simian immunodeficiency virus (SIV)-infected macaques compared with the SIV-infected controls. In vitro relevance …

Mammalian Alteration/Deficiency In Activation 3 (Ada3) Is Essential For Embryonic Development And Cell Cycle Progression., Shakur Mohibi, Channabasavaiah B. Gurumurthy, Alo Nag, Jun Wang, Sameer Mirza, Yousaf Mian, Meghan Quinn, Bryan J. Katafiasz, James D. Eudy, Sanjit Pandey, Chittibabu Guda, Mayumi Naramura, Hamid Band, Vimla Band

Journal Articles: Genetics, Cell Biology & Anatomy

Ada3 protein is an essential component of histone acetyl transferase containing coactivator complexes conserved from yeast to human. We show here that germline deletion of Ada3 in mouse is embryonic lethal, and adenovirus-Cre mediated conditional deletion of Ada3 in Ada3(FL/FL) mouse embryonic fibroblasts leads to a severe proliferation defect which was rescued by ectopic expression of human Ada3. A delay in G(1) to S phase of cell cycle was also seen that was due to accumulation of Cdk inhibitor p27 which was an indirect effect of c-myc gene transcription control by Ada3. We further showed that this defect could be …

Low Levels Of Β-Lactam Antibiotics Induce Extracellular Dna Release And Biofilm Formation In Staphylococcus Aureus., Jeffrey B. Kaplan, Era A. Izano, Prerna Gopal, Michael T. Karwacki, Sangho Kim, Jeffrey L. Bose, Kenneth W. Bayles, Alexander R. Horswill

Journal Articles: Pathology and Microbiology

UNLABELLED: Subminimal inhibitory concentrations of antibiotics have been shown to induce bacterial biofilm formation. Few studies have investigated antibiotic-induced biofilm formation in Staphylococcus aureus, an important human pathogen. Our goal was to measure S. aureus biofilm formation in the presence of low levels of β-lactam antibiotics. Fifteen phylogenetically diverse methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) strains were employed. Methicillin, ampicillin, amoxicillin, and cloxacillin were added to cultures at concentrations ranging from 0× to 1× MIC. Biofilm formation was measured in 96-well microtiter plates using a crystal violet binding assay. Autoaggregation was measured using a visual test tube …

Contribution Of The Staphylococcus Aureus Atl Am And Gl Murein Hydrolase Activities In Cell Division, Autolysis, And Biofilm Formation., Jeffrey L. Bose, Mckenzie K. Lehman, Paul D. Fey, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

The most prominent murein hydrolase of Staphylococcus aureus, AtlA, is a bifunctional enzyme that undergoes proteolytic cleavage to yield two catalytically active proteins, an amidase (AM) and a glucosaminidase (GL). Although the bifunctional nature of AtlA has long been recognized, most studies have focused on the combined functions of this protein in cell wall metabolism and biofilm development. In this study, we generated mutant derivatives of the clinical S. aureus isolate, UAMS-1, in which one or both of the AM and GL domains of AtlA have been deleted. Examination of these strains revealed that each mutant exhibited growth rates comparable …

The Importance Of Amino Acid Composition In Natural Amps: An Evolutional, Structural, And Functional Perspective., Biswajit Mishra, Guangshun Wang

Journal Articles: Pathology and Microbiology

No abstract provided.

Secreted Semaphorin 5a Suppressed Pancreatic Tumour Burden But Increased Metastasis And Endothelial Cell Proliferation., A Sadanandam, S S. Sidhu, S Wullschleger, S Singh, M L. Varney, C-S Yang, A E. Ashour, Surinder K. Batra, Rakesh Singh

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Our earlier reports demonstrated that membrane-bound semaphorin 5A (SEMA5A) is expressed in aggressive pancreatic cancer cells and tumours, and promotes tumour growth and metastasis. In this study, we examine whether (1) pancreatic cancer cells secrete SEMA5A and (2) that secreted SEMA5A modulates certain phenotypes associated with tumour progression, angiogenesis and metastasis through various other molecular factors and signalling proteins.

METHODS AND RESULTS: In this study, we show that human pancreatic cancer cell lines secrete the extracellular domain (ECD) of SEMA5A (SEMA5A-ECD) and overexpression of mouse Sema5A-ECD in Panc1 cells (not expressing SEMA5A; Panc1-Sema5A-ECD; control cells - Panc1-control) significantly increases …

Overexpression Of A Novel Cell Cycle Regulator Ecdysoneless In Breast Cancer: A Marker Of Poor Prognosis In Her2/Neu-Overexpressing Breast Cancer Patients., Xiangshan Zhao, Sameer Mirza, Alaa Alshareeda, Ying Zhang, Channabasavaiah B. Gurumurthy, Aditya Bele, Jun Hyun Kim, Shakur Mohibi, Monica Goswami, Subodh M. Lele, William West, Fang Qiu, Ian O. Ellis, Emad A. Rakha, Andrew R. Green, Hamid Band, Vimla Band

Journal Articles: Genetics, Cell Biology & Anatomy

Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression …

Visualizing Spatiotemporal Dynamics Of Apoptosis After G1 Arrest By Human T Cell Leukemia Virus Type 1 Tax And Insights Into Gene Expression Changes Using Microarray-Based Gene Expression Analysis., Mariluz Araínga, Hironobu Murakami, Yoko Aida

Journal Articles: Pharmacology & Experimental Neuroscience

BACKGROUND: Human T cell leukemia virus type 1 (HTLV-1) Tax is a potent activator of viral and cellular gene expression that interacts with a number of cellular proteins. Many reports show that Tax is capable of regulating cell cycle progression and apoptosis both positively and negatively. However, it still remains to understand why the Tax oncoprotein induces cell cycle arrest and apoptosis, or whether Tax-induced apoptosis is dependent upon its ability to induce G1 arrest. The present study used time-lapse imaging to explore the spatiotemporal patterns of cell cycle dynamics in Tax-expressing HeLa cells containing the fluorescent ubiquitination-based cell cycle …

Differential Effects Of Interleukin-17 Receptor Signaling On Innate And Adaptive Immunity During Central Nervous System Bacterial Infection., Debbie Vidlak, Tammy Kielian

Journal Articles: Pathology and Microbiology

Although IL-17A (commonly referred to as IL-17) has been implicated in the pathogenesis of central nervous system (CNS) autoimmune disease, its role during CNS bacterial infections remains unclear. To evaluate the broader impact of IL-17 family members in the context of CNS infection, we utilized IL-17 receptor (IL-17R) knockout (KO) mice that lack the ability to respond to IL-17, IL-17F and IL-17E (IL-25). In this article, we demonstrate that IL-17R signaling regulates bacterial clearance as well as natural killer T (NKT) cell and gamma-delta (γδ) T cell infiltrates during Staphylococcus aureus-induced brain abscess formation. Specifically, when compared with wild-type (WT) …

Perk-Dependent Repression Of Mir-106b-25 Cluster Is Required For Er Stress-Induced Apoptosis., S. Gupta, D. E. Read, A. Deepti, K. Cawley, A. Gupta, D. Oommen, T. Verfaillie, S. Matus, Mary A. Smith, Justin L. Mott, P. Agostinis, C. Hetz, A. Samali

Journal Articles: Biochemistry & Molecular Biology

Activation of the unfolded protein response sensor PKR-like endoplasmic reticulum kinase (Perk) attenuates endoplasmic reticulum (ER) stress levels. Conversantly, if the damage is too severe and ER function cannot be restored, this signaling branch triggers apoptosis. Bcl-2 homology 3-only family member Bim is essential for ER stress-induced apoptosis. However, the regulatory mechanisms controlling Bim activation under ER stress conditions are not well understood. Here, we show that downregulation of the miR-106b-25 cluster contributes to ER stress-induced apoptosis and the upregulation of Bim. Hypericin-mediated photo-oxidative ER damage induced Perk-dependent cell death and led to a significant decrease in the levels of …

Frecuencia De Leptospira Spp En Porcinos De Crianza Tecnificada Y De Traspatio Beneficiados En Dos Mataderos De Lima, Luis Anampa V., Hermelinda Rivera G., Nestor Falcon P., Mariluz Araínga, Mercy Ramirez V.

Journal Articles: Pharmacology & Experimental Neuroscience

The objective of this study was to determine the frequency of antibodies against Leptospira spp in pigs reared in five well-managed farms (n = 163) and from 11 backyard breeding (n = 133) owners in the valley Lima, Peru. Blood samples (n=296) were collected in two slaughterhouses for antibody detection against eight serovars of Leptospira by microaglutination test. The 85.8 ± 3.9% (254/296) of samples had antibodies against one or more serovars of Leptospira. . The 89.6 ± 4.7% (146/163) and 82.1 ± 6.5% (108/133) of samples from well-managed farms and from backyard breeding pigs showed antibodies against Leptospira spp. …

Deciphering Mechanisms Of Staphylococcal Biofilm Evasion Of Host Immunity., Mark L. Hanke, Tammy Kielian

Journal Articles: Pathology and Microbiology

Biofilms are adherent communities of bacteria contained within a complex matrix. Although host immune responses to planktonic staphylococcal species have been relatively well-characterized, less is known regarding immunity to staphylococcal biofilms and how they modulate anti-bacterial effector mechanisms when organized in this protective milieu. Previously, staphylococcal biofilms were thought to escape immune recognition on the basis of their chronic and indolent nature. Instead, we have proposed that staphylococcal biofilms skew the host immune response away from a proinflammatory bactericidal phenotype toward an anti-inflammatory, pro-fibrotic response that favors bacterial persistence. This possibility is supported by recent studies from our laboratory using …

Nicotine, Ifn-Γ And Retinoic Acid Mediated Induction Of Muc4 In Pancreatic Cancer Requires E2f1 And Stat-1 Transcription Factors And Utilize Different Signaling Cascades., Sateesh Kunigal, Moorthy P. Ponnusamy, Navneet Momi, Surinder K. Batra, Srikumar P. Chellappan

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: The membrane-bound mucins are thought to play an important biological role in cell-cell and cell-matrix interactions, in cell signaling and in modulating biological properties of cancer cell. MUC4, a transmembrane mucin is overexpressed in pancreatic tumors, while remaining undetectable in the normal pancreas, thus indicating a potential role in pancreatic cancer pathogenesis. The molecular mechanisms involved in the regulation of MUC4 gene are not yet fully understood. Smoking is strongly correlated with pancreatic cancer and in the present study; we elucidate the molecular mechanisms by which nicotine as well as agents like retinoic acid (RA) and interferon-γ (IFN-γ) induce …

Il-1ri (Interleukin-1 Receptor Type I) Signalling Is Essential For Host Defence And Hemichannel Activity During Acute Central Nervous System Bacterial Infection., Juan Xiong, Maria Burkovetskaya, Nikolay Karpuk, Tammy Kielian

Journal Articles: Pathology and Microbiology

Staphylococcus aureus is a common aetiological agent of bacterial brain abscesses. We have previously established that a considerable IL-1 (interleukin-1) response is elicited immediately following S. aureus infection, where the cytokine can exert pleiotropic effects on glial activation and blood-brain barrier permeability. To assess the combined actions of IL-1α and IL-1β during CNS (central nervous system) infection, host defence responses were evaluated in IL-1RI (IL-1 receptor type I) KO (knockout) animals. IL-1RI KO mice were exquisitely sensitive to intracerebral S. aureus infection, as demonstrated by enhanced mortality rates and bacterial burdens within the first 24 h following pathogen exposure compared …

Retinoids Regulate The Formation And Degradation Of Gap Junctions In Androgen-Responsive Human Prostate Cancer Cells., Linda Kelsey, Parul Katoch, Kristen E. Johnson, Surinder K. Batra, Parmender P. Mehta

Journal Articles: Biochemistry & Molecular Biology

The retinoids, the natural or synthetic derivatives of Vitamin A (retinol), are essential for the normal development of prostate and have been shown to modulate prostate cancer progression in vivo as well as to modulate growth of several prostate cancer cell lines. 9-cis-retinoic acid and all-trans-retinoic acid are the two most important metabolites of retinol. Gap junctions, formed of proteins called connexins, are ensembles of intercellular channels that permit the exchange of small growth regulatory molecules between adjoining cells. Gap junctional communication is instrumental in the control of cell growth. We examined the effect of 9-cis-retinoic acid and all-trans retinoic …

Identification Of Bovine Leukemia Virus Tax Function Associated With Host Cell Transcription, Signaling, Stress Response And Immune Response Pathway By Microarray-Based Gene Expression Analysis., Mariluz Araínga, Eri Takeda, Yoko Aida

Journal Articles: Pharmacology & Experimental Neuroscience

BACKGROUND: Bovine leukemia virus (BLV) is associated with enzootic bovine leukosis and is closely related to human T-cell leukemia virus type I. The Tax protein of BLV is a transcriptional activator of viral replication and a key contributor to oncogenic potential. We previously identified interesting mutant forms of Tax with elevated (TaxD247G) or reduced (TaxS240P) transactivation effects on BLV replication and propagation. However, the effects of these mutations on functions other than transcriptional activation are unknown. In this study, to identify genes that play a role in the cascade of signal events regulated by wild-type and mutant Tax proteins, we …

Pathobiological Implications Of The Expression Of Egfr, Pakt, Nf-Κb And Mic-1 In Prostate Cancer Stem Cells And Their Progenies., Murielle Mimeault, Sonny L. Johansson, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

The progression of prostate cancers (PCs) to locally invasive, androgen-independent and metastatic disease states is generally associated with treatment resistance and disease relapse. The present study was undertaken to establish the possibility of using a combination of specific oncogenic products, including epidermal growth factor receptor (EGFR), pAkt, nuclear factor-kappaB (NF-κB) and macrophage inhibitory cytokine-1 (MIC-1) as biomarkers and therapeutic targets for optimizing the management of patients with localized PC at earlier disease stages. The immunohistochemical and immunofluorescence data have revealed that the expression levels of EGFR, Ser(473)-pAkt, NF-κB p65 and MIC-1 proteins were significantly enhanced in the same subset of …

Mir-25 Targets Tnf-Related Apoptosis Inducing Ligand (Trail) Death Receptor-4 And Promotes Apoptosis Resistance In Cholangiocarcinoma., Nataliya Razumilava, Steve F. Bronk, Rory L. Smoot, Christian D. Fingas, Nathan W. Werneburg, Lewis R. Roberts, Justin L. Mott

Journal Articles: Biochemistry & Molecular Biology

It has been established that microRNA expression and function contribute to phenotypic features of malignant cells, including resistance to apoptosis. Although targets and functional roles for a number of microRNAs have been described in cholangiocarcinoma, many additional microRNAs dysregulated in this tumor have not been assigned functional roles. In this study, we identify elevated miR-25 expression in malignant cholangiocarcinoma cell lines as well as patient samples. In cultured cells, treatment with the Smoothened inhibitor, cyclopamine, reduced miR-25 expression, suggesting Hedgehog signaling stimulates miR-25 production. Functionally, miR-25 was shown to protect cells against TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Correspondingly, antagonism of …

Limitations Of The Rhesus Macaque Draft Genome Assembly And Annotation, Xiongfei Zhang, Joel Goodsell, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

Finished genome sequences and assemblies are available for only a few vertebrates. Thus, investigators studying many species must rely on draft genomes. Using the rhesus macaque as an example, we document the effects of sequencing errors, gaps in sequence and misassemblies on one automated gene model pipeline, Gnomon. The combination of draft genome with automated gene finding software can result in spurious sequences. We estimate that approximately 50% of the rhesus gene models are missing, incomplete or incorrect. The problems identified in this work likely apply to all draft vertebrate genomes annotated with any automated gene model pipeline and thus …

Seroprevalencia De Pestivirus De Rumiantes En Ovinos Reproductores De Una Empresa De La Sierra Central Del Perú, Nathalie A. Llancares, Hermelinda G. Rivera, Mariluz Araínga, Nestor Falcon P.

Journal Articles: Pharmacology & Experimental Neuroscience

The aim of the present study was to determine the prevalence of Bovine Viral Diarrhea Virus (BVDV) and Border Disease virus (BDV) in breeding sheep from a large cooperative farm in the Central highlands of Peru. Blood samples from apparently healthy sheep of 4 years old, both sexes (female = 165; male = 165) were collected for antibodies detection against BVDV and BDV using the virus neutralization test. The 2.1 ± 1.5% (7/330) and 28.5 ± 4.9% (94/330) of breeding sheep had antibodies against BVDV and BDV respectively, with antibodies titers of 1:2 and 1:16. There was significant association between …

Interferon-Α Regulates Glutaminase 1 Promoter Through Stat1 Phosphorylation: Relevance To Hiv-1 Associated Neurocognitive Disorders., Lixia Zhao, Yunlong Huang, Changhai Tian, Lynn Taylor, Norman Curthoys, Yi Wang, Hamilton Vernon, Jialin C. Zheng

Journal Articles: Pharmacology & Experimental Neuroscience

HIV-1 associated neurocognitive disorders (HAND) develop during progressive HIV-1 infection and affect up to 50% of infected individuals. Activated microglia and macrophages are critical cell populations that are involved in the pathogenesis of HAND, which is specifically related to the production and release of various soluble neurotoxic factors including glutamate. In the central nervous system (CNS), glutamate is typically derived from glutamine by mitochondrial enzyme glutaminase. Our previous study has shown that glutaminase is upregulated in HIV-1 infected monocyte-derived-macrophages (MDM) and microglia. However, how HIV-1 leads to glutaminase upregulation, or how glutaminase expression is regulated in general, remains unclear. In …

Myd88-Dependent Signaling Influences Fibrosis And Alternative Macrophage Activation During Staphylococcus Aureus Biofilm Infection., Mark L. Hanke, Amanda Angle, Tammy Kielian

Journal Articles: Pathology and Microbiology

Bacterial biofilms represent a significant therapeutic challenge based on their ability to evade host immune and antibiotic-mediated clearance. Recent studies have implicated IL-1β in biofilm containment, whereas Toll-like receptors (TLRs) had no effect. This is intriguing, since both the IL-1 receptor (IL-1R) and most TLRs impinge on MyD88-dependent signaling pathways, yet the role of this key adaptor in modulating the host response to biofilm growth is unknown. Therefore, we examined the course of S. aureus catheter-associated biofilm infection in MyD88 knockout (KO) mice. MyD88 KO animals displayed significantly increased bacterial burdens on catheters and surrounding tissues during early infection, which …