Medicine and Health Sciences Commons^™

Cocaine Enhances Hiv-1 Infectivity In Monocyte Derived Dendritic Cells By Suppressing Microrna-155, Jessica Napuri, Sudheesh Pilakka-Kanthikeel, Andrea Raymond, Marisela Agudelo, Adriana Yndart-Arias, Madhavan Nair, Shailendra K. Saxena

HWCOM Faculty Publications

Cocaine and other drugs of abuse increase HIV-induced immunopathogenesis; and neurobiological mechanisms of cocaine addiction implicate a key role for microRNAs (miRNAs), single-stranded non-coding RNAs that regulate gene expression and defend against viruses. In fact, HIV defends against miRNAs by actively suppressing the expression of polycistronic miRNA cluster miRNA-17/92, which encodes miRNAs including miR-20a. IFN-g production by natural killer cells is regulated by miR-155 and this miRNA is also critical to dendritic cell (DC) maturation. However, the impact of cocaine on miR-155 expression and subsequent HIV replication is unknown. We examined the impact of cocaine on two miRNAs, miR-20a and …

The Effects Of Nesting Environment On Neonatal Hypoxic-Ischemic Injury, Laura Grace Rollins

Graduate Masters Theses

Term neonates with hypoxic-ischemic (HI) injury are at risk for devastating neurological sequelae. The objective of this study is to determine if altering the early environment for maternal care-taking impacts the immediate and long-term sequelae of HI offspring. The Rice-Vannucci model was used to induce HI in postnatal day (PND) 7 Long-Evans pups. Litters were assigned to a closed nest (CN) or normal standard housing (SH) condition. Neurobehavioral development, cognitive ability, and stress response were assessed to establish any benefits of the CN condition. Finally, postmortem brain tissue was analyzed for morphometric markers of injury.

Novel And Predominant Pathogen Responsible For The Enterovirus-Associated Encephalitis In Eastern China, Lei Zhang, Jie Yan, David M. Ojcius, Huakun Lv, Ziping Miao, Yin Chen, Yanjun Zhang, Jvying Yan

All Dugoni School of Dentistry Faculty Articles

Enteroviruses (EV) have been increasingly identified as the causative agent for unknown etiological encephalitis in many parts of the world, but the long period surveillance for enterovirus-associated encephalitis (EAE) was not reported in China. From 2002-2012 in Zhejiang, Coxsackieviruses A9, B1, B2, B3, B4, B5; and echoviruses 3, 4, 6, 9, 14, 25, 30 were detected from the unknown etiological encephalitis cases, with coxsackievirus B4 been identified here for the first time. From 2002-2004 and 2010-2012, echovirus 30 was found to be the periodically predominant serotype for in the EAE. The molecular typing results showed that all the EV isolates …

Sphingosine-1-Phosphate-Mediated Mobilization Of Hematopoietic Stem/Progenitor Cells During Intravascular Hemolysis Requires Attenuation Of Sdf-1-Cxcr4 Retention Signaling In Bone Marrow, Kasia Mierzejewska, Yuri M. Klyachkin, Janina Ratajczak, Ahmed Abdel-Latif, Magda Kucia, Mariusz Z. Ratajczak

Saha Cardiovascular Research Center Faculty Publications

Sphingosine-1-phosphate (S1P) is a crucial chemotactic factor in peripheral blood (PB) involved in the mobilization process and egress of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM). Since S1P is present at high levels in erythrocytes, one might assume that, by increasing the plasma S1P level, the hemolysis of red blood cells would induce mobilization of HSPCs. To test this assumption, we induced hemolysis in mice by employing phenylhydrazine (PHZ). We observed that doubling the S1P level in PB from damaged erythrocytes induced only a marginally increased level of mobilization. However, if mice were exposed to PHZ together with the …

Beyond Perceptual Expertise: Revisiting The Neural Substrates Of Expert Object Recognition, Assaf Harel, Dwight J. Kravitz, Chris I. Baker

Psychology Faculty Publications

Real-world expertise provides a valuable opportunity to understand how experience shapes human behavior and neural function. In the visual domain, the study of expert object recognition, such as in car enthusiasts or bird watchers, has produced a large, growing, and often-controversial literature. Here, we synthesize this literature, focusing primarily on results from functional brain imaging, and propose an interactive framework that incorporates the impact of high-level factors, such as attention and conceptual knowledge, in supporting expertise. This framework contrasts with the perceptual view of object expertise that has concentrated largely on stimulus-driven processing in visual cortex. One prominent version of …

Inflammatory Cytokine Gene Expression In Mesenteric Adipose Tissue During Acute Experimental Colitis, William Conan Mustain, Marlene E. Starr, Joseph Daniel Valentino, Donald A. Cohen, Daiki Okamura, Chi Wang, B. Mark Evers, Hiroshi Saito

Markey Cancer Center Faculty Publications

BACKGROUND: Production of inflammatory cytokines by mesenteric adipose tissue (MAT) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Animal models of colitis have demonstrated inflammatory changes within MAT, but it is unclear if these changes occur in isolation or as part of a systemic adipose tissue response. It is also unknown what cell types are responsible for cytokine production within MAT. The present study was designed to determine whether cytokine production by MAT during experimental colitis is depot-specific, and also to identify the source of cytokine production within MAT.

METHODS: Experimental colitis was induced in 6-month-old C57BL/6 …

The Toxoplasma Gondii Cyst Wall Protein Cst1 Is Critical For Cyst Wall Integrity And Promotes Bradyzoite Persistence, Tadakimi Tomita, David J. Bzik, Yan Fen Ma, Barbara A. Fox

Dartmouth Scholarship

Toxoplasma gondii infects up to one third of the world's population. A key to the success of T. gondii as a parasite is its ability to persist for the life of its host as bradyzoites within tissue cysts. The glycosylated cyst wall is the key structural feature that facilitates persistence and oral transmission of this parasite. Because most of the antibodies and reagents that recognize the cyst wall recognize carbohydrates, identification of the components of the cyst wall has been technically challenging. We have identified CST1 (TGME49_064660) as a 250 kDa SRS (SAG1 related sequence) domain protein with a large …

Table Of Contents, Michele Harmon

Journal of the South Carolina Academy of Science

No abstract provided.

A Mechanism Linking Id2-Tgfβ Crosstalk To Reversible Adaptive Plasticity In Neuroblastoma, Lina Chakrabarti, Bi-Dar Wang, Norman H. Lee, Anthony D. Sandler

Pharmacology and Physiology Faculty Publications

The ability of high-risk neuroblastoma to survive unfavorable growth conditions and multimodal therapy has produced an elusive childhood cancer with remarkably poor prognosis. A novel phenomenon enabling neuroblastoma to survive selection pressure is its capacity for reversible adaptive plasticity. This plasticity allows cells to transition between highly proliferative anchorage dependent (AD) and slow growing, anoikis-resistant anchorage independent (AI) phenotypes. Both phenotypes are present in established mouse and human tumors. The differential gene expression profile of the two cellular phenotypes in the mouse Neuro2a cell line delineated pathways of proliferation in AD cells or tyrosine kinase activation/ apoptosis inhibition in AI …

Septins Of Platyhelminths: Identification, Phylogeny, Expression And Localization Among Developmental Stages Of Schistosoma Mansoni, Ana E. Zeraik, Gabriel Rinaldi, Victoria H. Mann, Anastas Popratiloff, Ana P.U. Araujo, Ricardo Demarco, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Septins are a family of eukaryotic GTP binding proteins conserved from yeasts to humans. Originally identified in mutants of budding yeast, septins participate in diverse cellular functions including cytokinesis, organization of actin networks, cell polarity, vesicle trafficking and many others. Septins assemble into heteroligomers to form filaments and rings. Here, four septins of Schistosoma mansoni are described, which appear to be conserved within the phylum Platyhelminthes. These orthologues were related to the SEPT5, SEPT10 and SEPT7 septins of humans, and hence we have termed the schistosome septins SmSEPT5, SmSEPT10, SmSEPT7.1 and SmSEPT7.2. Septin transcripts were detected throughout the developmental cycle …

Differential Effects Of Endocannabinoid Catabolic Inhibitors On Opioid Withdrawal In Mice, Thomas Gamage

Theses and Dissertations

The effects of cannabinoids in reducing somatic signs of opioid withdrawal have been known for some time. In morphine dependent rodents, opioid withdrawal following precipitation with the mu opioid antagonist naloxone elicits robust withdrawal behaviors including jumps, paw flutters, head shakes, diarrhea and weight loss. Delta-9-tetrahydrocannabinol has been shown to reduce this opioid withdrawal in mice via activation of the cannabinoid type-1 (CB1) receptor and recently it has been shown that inhibition of the catabolic enzymes for endocannabinoids also reduce somatic signs of opioid withdrawal. Specifically, inhibition the enzyme fatty acid amide hydrolase (FAAH), the catabolic enzyme for the endocannabinoid …

Dose Dependent Effects Of Caffeine On Cognitive Performance And Neuronal Activation, Stephan Albrecht, Helen Morris, Michelle Vieyra

Journal of the South Carolina Academy of Science

Many students assume that the more caffeine you drink, the better your cognitive performance. Over-consumption of caffeine has many negative effects, so if there are no dose related cognitive benefits to large amounts of caffeine, then college students should limit their intake. This study looked at whether ingesting a medium dose (200 mg) versus a lower dose (100 mg) of caffeine improved short term memory as measured by Flanker and n-back tests, compared to a control group. In addition, we looked at whether larger doses of caffeine produced a difference in neuronal activation during these tests as measured by functional …

Fourier Analysis Of Phase Resetting Curves Of Neural Oscillators, Robert A. Raidt, Sorinel A. Oprisan

Journal of the South Carolina Academy of Science

We investigated the impact of changes in biologically relevant control parameters, such as the shape of an external perturbation or the conductance values of an individual model neuron, on the shape of the phase resetting curve (PRC) of that neuron. For that purpose, PRCs were generated for groups of Morris-Lecar (ML) model neurons with different conductance values but similar firing periods (within 0.005ms) using external rectangular, triangular, or trapezoidal perturbations of varying areas. These PRCs were numerically described and analyzed as a series of coefficient values using a Fourier Discrete Sine Transform (DST). We found that changes in the shape …

Divergent Antibody Subclass And Specificity Profiles But Not Protective Hla-B Alleles Are Associated With Variable Antibody Effector Function Among Hiv-1 Controllers, Jennifer I. Lai, Anna F. Licht, Anne-Sophie Dugast, Todd Suscovich, Ickwon Choi, Chris Bailey-Kellogg, Galit Alter, Margaret E. Ackerman

Dartmouth Scholarship

Understanding the coordination between humoral and cellular immune responses may be the key to developing protective vaccines, and because genetic studies of long-term HIV-1 nonprogressors have associated specific HLA-B alleles with spontaneous control of viral replication, this subject group presents an opportunity to investigate relationships between arms of the adaptive immune system. Given evidence suggesting that cellular immunity may play a role in viral suppression, we sought to determine whether and how the humoral immune response might vary among controllers. Significantly, Fc-mediated antibody effector functions have likewise been associated with durable viral control. In this study, we compared the effector …

A Pil1–Sle1–Syj1–Tax4 Functional Pathway Links Eisosomes With Pi(4,5)P2 Regulation, Ruth Kabeche, Assen Roguev, Nevan J. Krogan, James B. Moseley

Dartmouth Scholarship

Stable compartments of the plasma membrane promote a wide range of cellular functions. In yeast cells, cytosolic structures called eisosomes generate prominent cortical invaginations of unknown function. Through a series of genetic screens in fission yeast, we found that the eisosome proteins Pil1 and Sle1 function with the synaptojanin-like lipid phosphatase Syj1 and its ligand Tax4. This genetic pathway connects eisosome function with the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] in cells. Defects in PI(4,5)P2 regulation led to eisosome defects, and we found that the core eisosome protein Pil1 can bind to and tubulate liposomes containing PI(4,5)P2. Mutations in components of …

Hypoxia/Aglycemia-Induced Endothelial Barrier Dysfunction And Tight Junction Protein Downregulation Can Be Ameliorated By Citicoline, Xiaotang Ma, Huiting Zhang, Qunwen Pan, Yuhui Zhao, Ji Chen, Yanfang Chen

Pharmacology and Toxicology Faculty Publications

This study explores the effect of citicoline on the permeability and expression of tight junction proteins (TJPs) in endothelial cells under hypoxia/aglycemia conditions. Hypoxia or oxygen and glucose deprivation (OGD) was utilized to induce endothelial barrier breakdown model on human umbilical vein endothelial cells (HUVECs) and mouse brain microvascular endothelial cells (bEnd.3s). The effect of citicoline on endothelial barrier breakdown models was determined at either low or high concentrations. FITC-Dextran flux was used to examine the endothelial permeability. The expression of TJPs was measured by immunofluorescence, Real-time PCR and Western Blot methods. Results showed that hypoxia or OGD increased the …

Impact Of Oxidative Stress On Female Fertility., Tasha Harris

Undergraduate Honors Theses

This study examined nutritional status and fecundity of women and was approved for patient enrollment by the ETSU Institutional Review Board (IRB). Once enrolled, participants filled out two food frequency questionnaires (FFQ, fruit/vegetable intake, fat intake), self-reported anthropometric data, and had one 5 mL vacutainer of whole blood (EDTA) collected for measures of oxidative stress (OS), coenzyme Q10 level, and fatty acid profile of the red blood cell (RBC) membrane. Participants were either designated to the case group (13 women experiencing fertility problems and an anti-mullerian hormone level of 1 ng/ml or less (AMH, <1 ng/mL)) or the control group (13 women experiencing normal ovulation cycles and no evidence of polycystic disease). This study hypothesized that the case group would have poorer plasma antioxidant status, consume more dietary saturated fat and have lower levels of omega-3 and higher levels of omega-6 fatty acids in the RBC membrane. Results showed that case participants had significantly higher body mass index (BMI) when graduating from high school, BMI upon enrollment in the study, and trended to gain more weight since high school. Antioxidant status of the plasma tended to be higher for the case group. This result was surprising as case participants consumed significantly fewer servings of fruits and vegetables (sources of antioxidants) than control subjects. FFQ results indicated that case participants consumed significantly higher amounts of total fat (g), saturated fat (g), unsaturated fat (g), and their diets had a higher dietary fat percent. No significant differences were noted in the individual fatty acids isolated from the RBC membrane or in calculated ratios of fatty acid between case and control groups. The fatty acid profile from RBC membranes are in agreement with self-reported fat intake from FFQ data and may provide a rationale for no differences observed between the two groups.

Biochemical Assay Optimization And Computational Screening Efforts To Identify Potential Luxs Inhibitors, Keeshia Q. Wang

Master's Theses

Quorum sensing (QS) is a process of coordination of bacterial gene expression in response to cell population. System two QS is regulated by the small signaling molecule autoinducer-2 (AI-2) and is implicated in the infectious behaviors of various bacterial species. AI-2 is biosynthesized from S-ribosylhomocysteine (SRH) by the enzyme LuxS and induces interspecies cell-to-cell communication. Inhibition of LuxS would therefore inhibit interspecies QS. Herein, a search for novel molecular species that will competitively bind with SRH in the LuxS binding site is performed in silico. Computational screening results are then validated in vitro using an optimized LuxS inhibition …

Interactions Of Peptide Triazole Thiols With Env Gp120 Induce Irreversible Breakdown And Inactivation Of Hiv-1 Virions, Arangassery Bastian, Mark Contarino, Lauren D. Bailey, Rachna Aneja, Diogo Rodrigo Magalhaes Moreira, Kevin Freedman, Karyn Mcfadden, Caitlin Duffy, Ali Emileh

Dartmouth Scholarship

Background: We examined the underlying mechanism of action of the peptide triazole thiol, KR13 that has been shown previously to specifically bind gp120, block cell receptor site interactions and potently inhibit HIV-1 infectivity.

Results: KR13, the sulfhydryl blocked KR13b and its parent non-sulfhydryl peptide triazole, HNG156, induced gp120 shedding but only KR13 induced p24 capsid protein release. The resulting virion post virolysis had an altered morphology, contained no gp120, but retained gp41 that bound to neutralizing gp41 antibodies. Remarkably, HIV-1 p24 release by KR13 was inhibited by enfuvirtide, which blocks formation of the gp41 6-helix bundle during membrane fusion, while …

Development Of A Translational Animal Model Of Sepsis, Nathaniel E. Hayward

Electronic Thesis and Dissertation Repository

Sepsis is an excessive inflammatory response to infection that leads to multiple organ failure. The high mortality rates in the intensive care unit have remained stagnant, which can be attributed to the disconnect between the bench and the bedside. There is a global need for an animal model of sepsis that is more relevant to the clinical scenario. We developed an in vivo rat model of sepsis, with a high level of instrumentation, to monitor macrovascular and microvascular changes over the course of a feces-induced peritonitis (FIP) .

In addition, early fluid resuscitation of septic patients is associated with better …

Use Of Irf-3 And/Or Irf-7 Knockout Mice To Study Viral Pathogenesis: Lessons From A Murine Retrovirus-Induced Aids Model, Megan A. O'Connor, William R. Green

Dartmouth Scholarship

Interferon regulatory factor (IRF) regulation of the type I interferon response has not been extensively explored in murine retroviral infections. IRF-3(-/-) and select IRF-3/7(-/-) mice were resistant to LP-BM5-induced pathogenesis. However, further analyses strongly suggested that resistance could be attributed to strain 129-specific contamination of the known retrovirus resistance gene Fv1. Therefore, caution should be taken when interpreting phenotypes observed in these knockout mice, as strain 129-derived genetic polymorphisms may explain observed differences.

Defects In Synapse Structure And Function Precede Motor Neuron Degeneration In Drosophila Models Of Fus-Related Als., Mohammad Shahidullah, Sylvain J Le Marchand, Hong Fei, Jiaming Zhang, Udai Bhan Pandey, Matthew B. Dalva, Piera Pasinelli, Irwin B. Levitan

Department of Neuroscience Faculty Papers

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that leads invariably to fatal paralysis associated with motor neuron degeneration and muscular atrophy. One gene associated with ALS encodes the DNA/RNA-binding protein Fused in Sarcoma (FUS). There now exist two Drosophila models of ALS. In one, human FUS with ALS-causing mutations is expressed in fly motor neurons; in the other, the gene cabeza (caz), the fly homolog of FUS, is ablated. These FUS-ALS flies exhibit larval locomotor defects indicative of neuromuscular dysfunction and early death. The locus and site of initiation of this neuromuscular dysfunction remain unclear. We show here …

Investigating The Effects Of Custom Made Orthotics On Brain Forms: A Pilot Study, Lindsay Carey

Electronic Thesis and Dissertation Repository

OBJECTIVES: To determine (1) the feasibility of this novel approach and technique of recording brain activity, wirelessly and continuously, during human gait, and (2) if custom made orthotics will alter the brain activity patterns recorded. METHODS: Gait trials were performed on 16 participants walking with and without orthotic devices in their shoes while simultaneously collecting EEG data through the Emotiv wireless neuroheadset. RESULTS: The Emotiv neuroheadset was capable of detecting changes in brain activity between the two gait trials. The differences in brain activity identified between conditions were not statistically significant. CONCLUSION: The findings suggest the Emotiv EEG device is …

Ceramic Scaffolds Produced By Computer-Assisted 3d Printing And Sintering: Characterization And Biocompatibility Investigations, Patrick Warnke, Hermann Seitz, Stephan Becker, Sureshan Sivananthan, Eugene Sherry, Qin Liu, Jorge Wiltfang, Timothy Douglas

Qin Liu

Hydroxyapatite (HAP) and tricalcium phosphate (TCP) are two very common ceramic materials for bone replacement. However, in general HAP and TCP scaffolds are not tailored to the exact dimensions of the defect site and are mainly used as granules or beads. Some scaffolds are available as ordinary blocks, but cannot be customized for individual perfect fit. Using computer-assisted 3D printing, an emerging rapid prototyping technique, individual three-dimensional ceramic scaffolds can be built up from TCP or HAP powder layer by layer with subsequent sintering. These scaffolds have precise dimensions and highly defined and regular internal characteristics such as pore size. …

The Primordium Of A Biological Joint Replacement: Coupling Of Two Stem Cell Pathways In Biphasic Ultrasound Compressed Gel Niches, Mariea Brady, Sureshan Sivananthan, Vivek Mudera, Qin Liu, Joerg Wiltfang, Patrick Warnke

Qin Liu

The impaired temporomandibular joint might be the first to benefit from applied tissue engineering techniques because it is small and tissue growth in larger amounts is challenging. Bone and cartilage require different competing environmental conditions to be cultivated in vitro. But coupling both the osteogenic and cartilaginous pathways of mesenchymal stem cell differentiation in homeostasis will be a key essential to grow osteochondral constructs or even the first biological joint replacement in the future.

The aim of this study was to test a single source biomaterial and a single source cell type to engineer a biphasic osteochondral construct in vitro …

Novel Ceramic Bone Replacement Material Ceraball® Seeded With Human Mesenchymal Stem Cells, Timothy Douglas, Qin Liu, Andreas Humpe, Jörg Wiltfang, Sureshan Sivananthan, Patrick Warnke

Qin Liu

Objectives: Hydroxyapatite (HA) and tricalcium phosphate (TCP) are two very common ceramic materials for bone replacement. A recently developed material for bone replacement is CeraBall®, which is a mixed HA-TCP scaffold available as porous spherical scaffolds of diameter 4 and 6 mm. Before their use as bone replacement materials in vivo, in vitro testing of these scaffolds is necessary. The goal of this study was to characterise 4 and 6 mm CeraBall® scaffolds in vitro with a view to their future use as bone replacement materials. Materials and methods: The proliferation of human mesenchymal stromal cells (hMSCs) seeded on CeraBall® …

Primordium Of An Artificial Bruch's Membrane Made Of Nanofibers For Engineering Of Retinal Pigment Epithelium Cell Monolayers, Patrick Warnke, Mohammad Alamein, Stuart Skabo, Sebastien Stephens, Robert Bourke, Peter Heiner, Qin Liu

Qin Liu

Transplanted Retinal Pigment Epithelium(RPE) cells hold promise for treatment of Age-related Macular Degeneration(AMD) and Stargardt Disease(SD), but it is conceivable that the degenerated host Bruch's membrane(BM) as a natural substrate for RPE might not optimally support transplanted cell survival with correct cellular organization. We fabricated novel ultrathin 3-dimensional(3D) nanofibrous membranes from Collagen type I and poly(lactic-co-glycolic acid) (PLGA) by an advanced clinical-grade needle-free-electrospinning process. The nanofibrillar 3D networks highly mimicked the fibrillar architecture of the native inner collagenous layer of human BM. Human RPE cells grown on our nanofibrous membranes bore striking resemblance to native human RPE. They exhibited a …

Effects Of A Power-Line Frequency Magnetic Field On Human Cognitive Processing, Michael Corbacio

Electronic Thesis and Dissertation Repository

Extremely low frequency (ELF, < 300 Hz) magnetic fields (MFs) have been reported to modulate human cognitive performance. However, little research has investigated MF exposures comparable to the highest levels experienced in some occupations. This research evaluated the impact of a 60 Hz, 3 mT MF on human cognitive performance. Ninety-nine participants completed the double-blind protocol performing a selection of psychometric tests under two consecutive MF exposure conditions (exposure vs. no exposure). A significant interaction effect on a working memory test (digit span forward - F=5.21, p

Intermittent Hypoxia Alters Metabolic And Cardiovascular Neural Pathways, Jason Michael Moreau

Electronic Thesis and Dissertation Repository

Intermittent hypoxia (IH) is a major pathophysiological manifestation of obstructive sleep apnea (OSA). Previous studies have implicated IH in mediating many pathophysiological outcomes associated with OSA. Only few studies have examined IH-induced alterations to central signaling pathways important in cardiovascular and metabolic phenotypes associated with OSA. This thesis employed a rodent model of IH to examine changes to molecular neural pathways associated with metabolic and cardiovascular pathophysiological outcomes of OSA. Acute IH induces a specific negative body energy balance phenotype. This is concomitant to a reduction in body weight and food intake, with an elevation in food conversion efficiency. Increased …

Impact Of Noise On Molecular Network Inference, Radhakrishnan Nagarajan, Marco Scutari

Biostatistics Faculty Publications

Molecular entities work in concert as a system and mediate phenotypic outcomes and disease states. There has been recent interest in modelling the associations between molecular entities from their observed expression profiles as networks using a battery of algorithms. These networks have proven to be useful abstractions of the underlying pathways and signalling mechanisms. Noise is ubiquitous in molecular data and can have a pronounced effect on the inferred network. Noise can be an outcome of several factors including: inherent stochastic mechanisms at the molecular level, variation in the abundance of molecules, heterogeneity, sensitivity of the biological assay or measurement …