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Phosphorylated Iκbα Predicts Poor Prognosis In Activated B-Cell Lymphoma And Its Inhibition With Thymoquinone Induces Apoptosis Via Ros Release, Azhar Hussain, Shahab Uddin, Maqbool Ahmed, Fouad Al-Dayel, Prashant P. Bavi, Khawla S. Al-Kuraya

Centre for Regenerative Medicine & Stem Cell Research

Activated B-cell lymphoma (ABC), one of the three subtypes of Diffuse Large B-cell Lymphoma (DLBCL) has the worst survival rate after upfront chemotherapy and is characterized by constitutively activated NFκB. We therefore studied the role of NFκB In a cohort of clinical DLBCL samples and ABC cell lines. In our clinical tissue microarray cohort of DLBCL samples, p-IκBα was detected in 38.3% of ABC DLBCL and was an independent prognostic marker for poor survival. In vitro, we found that Thymoquinone (TQ), a natural compound isolated from Nigella sativa caused release of ROS in ABC cells. TQ-mediated release of ROS …

Copper Triflate-Mediated Synthesis Of 1,3,5-Triarylpyrazoles In [Bmim][Pf6] Ionic Liquid And Evaluation Of Their Anticancer Activities, V. Kameshwara Rao, Rakesh Tiwari, Bhupender S. Chhikara, Amir Nasrolahi Shirazi, Keykavous Parang, Anil Kumar

Pharmacy Faculty Articles and Research

A simple, efficient, and environment friendly protocol for the synthesis of 1,3,5-triarylpyrazoles and 1,3,5-triarylpyrazolines in [bmim][PF6] ionic liquid mediated by Cu(OTf)2 is described. The reaction protocol gave 1,3,5-triarylpyrazoles in good to high yields (71–84%) via a one-pot addition–cyclocondensation between chalcones and arylhydrazines, and oxidative aromatization without the requirement for an additional oxidizing reagent. The catalyst can be reused for up to four cycles without much loss in the catalytic activity. The pyrazoles (4a–o) and pyrazolines (3a–n) were evaluated for their antiproliferative activity in SK-OV-3, HT-29, and HeLa human cancer cells lines. Among all the compounds, 3b inhibited cell proliferation of …

Molecular Architecture Of The Uncleaved Hiv-1 Envelope Glycoprotein Trimer, Youdong Mao, Luis Castillo-Menendez, Liping Wang, Christopher Gu, Alon Herschhorn, Anik Désormeaux, Andrés Finzi, Shi-Hua Xiang, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

The human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer, a membrane-fusing machine, mediates virus entry into host cells and is the sole virusspecific target for neutralizing antibodies. Binding the receptors, CD4 and CCR5/CXCR4, triggers Env conformational changes from the metastable unliganded state to the fusion-active state. We used cryo-electron microscopy to obtain a 6-Å structure of the membranebound, heavily glycosylated HIV-1 Env trimer in its uncleaved and unliganded state. The spatial organization of secondary structure elements reveals that the unliganded conformations of both gp120 and gp41 subunits differ from those induced by receptor binding. The gp120 trimer association domains, which …

Variations In The Biological Functions Of Hiv-1 Clade C Envelope In A Shiv-Infected Rhesus Macaque During Disease Progression, For Yue Tso, Levon Abrahamyan, Shiu-Lok Hu, Ruth M. Ruprecht, Charles Wood

Nebraska Center for Virology: Faculty Publications

A better understanding of how the biological functions of the HIV-1 envelope (Env) changes during disease progression may aid the design of an efficacious anti-HIV-1 vaccine. Although studies from patient had provided some insights on this issue, the differences in the study cohorts and methodology had make it difficult to reach a consensus of the variations in the HIV-1 Env functions during disease progression. To this end, an animal model that can be infected under controlled environment and reflect the disease course of HIV-1 infection in human will be beneficial. Such an animal model was previously demonstrated by the infection …

Kaposi’S Sarcoma-Associated Herpesvirus Transactivator Rta Induces Cell Cycle Arrest In G0/G1 Phase By Stabilizing And Promoting Nuclear Localization Of P27Kip, Pankaj Kumar, Charles Wood

Nebraska Center for Virology: Faculty Publications

The Kaposi’s sarcoma-associated herpesvirus (KSHV) immediate-early gene, replication, and transcription activator (KRta) is a key viral protein that serves as the master regulator for viral lytic replication. In this study, we investigated the role of K-Rta in cell cycle regulation and found that the expression of K-Rta in doxycycline (Dox)-inducible BJAB cells induced cell cycle arrest in G₀/G₁ phase. Western blot analysis of key cell cycle regulators revealed that K-Rta-mediated cell cycle arrest was associated with a decrease in cyclin A and phosphorylated Rb (pS807/pS811) protein levels, both markers of S phase progression, and an increase in …

Low-Abundance Resistant Mutations In Hiv-1 Subtype C Antiretroviral Therapy-Naïve Individuals As Revealed By Pyrosequencing, Sandra Gonzalez, Damien C. Tully, Clement Gondwe, Charles Wood

Nebraska Center for Virology: Faculty Publications

Given the recent scale-up of antiretroviral therapy (ART) in sub-Saharan Africa, we sought to determine how often and at what levels do drug-resistant mutant variants exist in ART-naïve HIV subtype C infected individuals. Samples from 10 ART-naïve Zambian individuals were subjected to ultra-deep pyrosequencing (UDPS) to characterize the frequency of low-abundance drug resistance mutations in the pol gene. Low-abundance clinically relevant variants were detected for nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) in eight of the ten subjects. Intermediate to high-level resistance was predicted for the majority of NRTIs. Mutations conferring resistance to …

Clade C Hiv-1 Isolates Circulating In Southern Africa Exhibit A Greater Frequency Of Dicysteine Motif-Containing Tat Variants Than Those In Southeast Asia And Cause Increased Neurovirulence, Vasudev R. Rao, Ujjwal Neogi, Joshua S, Talboom, Ligia Padilla, Mustafizur Rahman, Cari Fritz-French, Sandra Gonzalez-Ramirez, Anjali Verma, Charles Wood, Ruth M. Ruprecht, Udaykumar Ranga, Tasnim Azim, Vinayaka R. Prasad

Nebraska Center for Virology: Faculty Publications

Background: HIV-1 Clade C (Subtype C; HIV-1C) is responsible for greater than 50% of infections worldwide. Unlike clade B HIV-1 (Subtype B; HIV-1B), which is known to cause HIV associated dementia (HAD) in approximately 15% to 30% of the infected individuals, HIV-1C has been linked with lower prevalence of HAD (0 to 6%) in India and Ethiopia. However, recent studies report a higher prevalence of HAD in South Africa, Zambia and Botswana, where HIV-1C infections predominate. Therefore, we examined whether Southern African HIV-1C is genetically distinct and investigated its neurovirulence. HIV-1 Tat protein is a viral determinant of neurocognitive dysfunction. …

Global Neuroaids Roundtable, Jeymohan Joseph, Cristian L. Achim, Michael J. Boivin, Bruce J. Brew, David B. Clifford, Deborah A. Colosi, Ronald J. Ellis, Robert K. Heaton, Amadou Gallo-Diop, Igor Grant, Georgette D. Kanmogne, Mahendra Kumar, Scott Letendre, Thomas D. Marcotte, Avindra Nath, Carlos A. Pardo, Robert H. Paul, Lynn Pulliam, Kevin Robertson, Walter Royal Iii, Ned Sacktor, Pasiri Sithinamsuwan, Davey M. Smith, Victor Valcour, Brian Wigdahl, Charles Wood

Nebraska Center for Virology: Faculty Publications

In May 2012, the Division of AIDS Research at the National Institute of Mental Health (NIMH) organized the “Global NeuroAIDS Roundtable” in conjunction with the 11th International Symposium on Neurovirology and the 2012 Conference on HIV in the Nervous System. The meeting was held in New York, NY, USA and brought together NIMH-funded investigators who are currently working on projects related to the neurological complications of AIDS (NeuroAIDS) in Africa, Asia, Eastern Europe, and Latin America in order to provide an opportunity to share their recent findings and discuss the challenges encountered within each country. The major goals of the …

Heterogeneity In Platelet Exocytosis, Deepa Jonnalagadda

Theses and Dissertations--Molecular and Cellular Biochemistry

Platelet exocytosis is essential for hemostasis and for many of its sequelae. Platelets release numerous bioactive molecules stored in their granules enabling them to exert a wide range of effects on the vascular microenvironment. Are these granule cargo released thematically in a context-specific pattern or via a stochastic, kinetically-controlled process? My work describes platelet exocytosis using a systematic examination of platelet secretion kinetics. Platelets were stimulated for increasing times with different agonists (i.e. thrombin, PAR1-agonist, PAR4-agonist, and convulxin) and micro-ELISA arrays were used to quantify the release of 28 distinct α-granule cargo molecules. Agonist potency directly correlated with the speed …

Investigating Therapeutic Options For Lafora Disease Using Structural Biology And Translational Methods, Amanda R. Sherwood

Theses and Dissertations--Molecular and Cellular Biochemistry

Lafora disease (LD) is a rare yet invariably fatal form of epilepsy characterized by progressive degeneration of the central nervous and motor systems and accumulation of insoluble glucans within cells. LD results from mutation of either the phosphatase laforin, an enzyme that dephosphorylates cellular glycogen, or the E3 ubiquitin ligase malin, the binding partner of laforin. Currently, there are no therapeutic options for LD, or reported methods by which the specific activity of glucan phosphatases such as laforin can be easily measured. To facilitate our translational studies, we developed an assay with which the glucan phosphatase activity of laforin as …

Food Limitation As A Potentially Emerging Contributor To The Asian Vulture Crisis, Fakhar -I- Abbas, Thomas P. Rooney, Jibran Haider, Afsar Mian

Biological Sciences Faculty Publications

It was believed that the reason for decline in Asian vulture population is the drug, Diclofenac sodium (DFS), used in livestock. Even after declaring the DFS use banned by the government, apparent decrease in the population of vultures was reported. Alternate hypothesis was suggested that food limitation may be a cause of Asian vulture crisis in Pakistan. Very recent shifts in livestock utilization observed in Pakistan may present a significant barrier to vulture recovery. Increased livestock utilization is translated to fewer carcasses. Since 2005, no livestock carcasses were found in 1650 km transect in the habitat of vultures. Carcasses recorded …

Game-Based Curricula In Biology Classes: Multi-Level Assessment Of Science Learning, Troy D. Sadler, William L. Romine, Parker E. Stuart

Biological Sciences Faculty Publications

Video games played on computers, game consoles, tablets and smart phones have become a very popular medium in our society. A growing body of scholarship suggests that video games can support substantial learning (for reviews see Gee, 2007; Honey & Hilton, 2011; Squire, 2011). Research has documented ways in which games engage students deeply in thinking, learning, and collaboration (Gee, 2005). Evidence suggests that games can support development of critical thinking (Squire, 2006), creativity (Annetta, Cheng, & Holmes, 2010), and mastery and application of target concepts (Squire, 2011).

Impairment Of Trkb-Psd-95 Signaling In Angelman Syndrome, Cong Cao, Mengia S. Rioult-Pedotti, Paolo Migani, Crystal J. Yu, Rakesh Tiwari, Keykavous Parang, Mark R. Spaller, Dennis J. Goebel, John Marshall

Pharmacy Faculty Articles and Research

Angelman syndrome (AS) is a neurodevelopment disorder characterized by severe cognitive impairment and a high rate of autism. AS is caused by disrupted neuronal expression of the maternally inherited Ube3A ubiquitin protein ligase, required for the proteasomal degradation of proteins implicated in synaptic plasticity, such as the activity-regulated cytoskeletal-associated protein (Arc/Arg3.1). Mice deficient in maternal Ube3A express elevated levels of Arc in response to synaptic activity, which coincides with severely impaired long-term potentiation (LTP) in the hippocampus and deficits in learning behaviors. In this study, we sought to test whether elevated levels of Arc interfere with brain-derived neurotrophic factor (BDNF) …

Corneal Gene Therapy: Basic Science And Translational Perspective, Rajiv R. Mohan, Jason T. Rodier, Ajay Sharma

Pharmacy Faculty Articles and Research

Corneal blindness is the third leading cause of blindness worldwide. Gene therapy is an emerging technology for corneal blindness due to the accessibility and immune-privileged nature of the cornea, ease of vector administration and visual monitoring, and ability to perform frequent noninvasive corneal assessment. Vision restoration by gene therapy is contingent upon vector and mode of therapeutic gene introduction into targeted cells/tissues. Numerous efficacious vectors, delivery techniques, and approaches have evolved in last decade for developing gene-based interventions for corneal diseases. Maximizing the potential benefits of gene therapy requires efficient and sustained therapeutic gene expression in target cells, low toxicity, …

Historical Remedies Versus Current Pathogens : Laboratory Investigation Of The Efficacy Of Traditional Herbal Remedies Against Present-Day Common Causes Of Bacterial Pneumonia, Eibhlin Mccarthy

Theses

Despite the medical advances of recent years, pneumonia is still a common disease in Ireland, accounting for approximately 7% of deaths in this country'. While national databases such as those run by CIDR and SARI ensure that incidences of systemic and notifiable infections such as tuberculosis are recorded, there are currently no available statistics on commonplace respiratory isolates within Ireland. This study analysed the available data on bacterial pathogens isolated from respiratory samples at a 355 bed Irish hospital over a one year period. Seasonal variations and resistance patterns were noted. The most frequently isolated pathogens were Staphylococcus aureus (27%), …

Sleep Duration And Breast Cancer Phenotype, Ali Khawaja, Santosh Rao, Li Li, Cheryl L. Thompson

Medical College Documents

Emerging evidence suggests that short sleep is associated with an increased risk of cancer; however, little has been done to study the role of sleep on tumor characteristics. In this study, we evaluated the relationship between sleep duration and tumor phenotype in 972 breast cancer patients. Sleep duration was inversely associated with tumor grade (univariate P = 0.032), particularly in postmenopausal women (univariate P = 0.018). This association did not reach statistical significance after adjustments for age, race, body mass index, hormone replacement therapy use, alcohol consumption, smoking, and physical activity in the entire study sample (P = 0.052), but …

Bmp7 Gene Transfer Via Gold Nanoparticles Into Stroma Inhibits Corneal Fibrosis In Vivo, Ashish Tandon, Ajay Sharma, Jason T. Rodier, Alexander M. Klibanov, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

This study examined the effects of BMP7 gene transfer on corneal wound healing and fibrosis inhibition in vivo using a rabbit model. Corneal haze in rabbits was produced with the excimer laser performing -9 diopters photorefractive keratectomy. BMP7 gene was introduced into rabbit keratocytes by polyethylimine-conjugated gold nanoparticles (PEI2- GNPs) transfection solution single 5-minute topical application on the eye. Corneal haze and ocular health in live animals was gauged with stereo- and slit-lamp biomicroscopy. The levels of fibrosis [a-smooth muscle actin (aSMA), F-actin and fibronectin], immune reaction (CD11b and F4/80), keratocyte apoptosis (TUNEL), calcification (alizarin red, vonKossa and osteocalcin), and …

Systems Biology Of The Functional And Dysfunctional Endothelium, Jennifer Frueh, Nataly Maimari, Takayuki Homma, Sandra M. Bovens, Ryan M. Pedrigi, Leila Towhidi, Rob Krams

Department of Mechanical and Materials Engineering: Faculty Publications

This review provides an overview of the effect of blood flow on endothelial cell (EC) signalling pathways, applying microarray technologies to cultured cells, and in vivo studies of normal and atherosclerotic animals. It is found that in cultured ECs, 5–10% of genes are up- or down-regulated in response to fluid flow, whereas only 3–6% of genes are regulated by varying levels of fluid flow. Of all genes, 90%are regulated by the steady part of fluid flow and 10% by pulsatile components. The associated gene profiles show high variability from experiment to experiment depending on experimental conditions, and importantly, the bioinformatical …

Multifactorial Modulation Of The Blood-Brain Barrier: Relationship To Stroke, Bei Zhang

Theses and Dissertations--Nutritional Sciences

The blood-brain barrier (BBB) is a dynamic interface, mainly consisting of highly specialized brain microvascular endothelial cells (BMECs) that segregate the central nervous system (CNS) from the peripheral circulation. Impairment of the BBB, due to disruption of tight junction (TJ) proteins and inflammatory responses, may initiate and/or contribute to the progress of CNS disorders, including stroke. Stroke is the second leading cause of death worldwide. It has been shown that aging and environmental pollutants can induce brain endothelium dysfunction, and are considered as risk factors for stroke.

Deficiency of telomerase is highly linked with aging-associated vascular diseases. Evidence indicates that …

Coplanar Pcb-Induced Inflammation And Dietary Interventions, Katryn Elizabeth Eske

Theses and Dissertations--Nutritional Sciences

Diseases, such as cardiovascular disease (CVD), are linked to chronic low levels of inflammation. This inflamed state is the product of risk factors including exposure to environmental pollutants, such as polychlorinated biphenyls (PCBs), which are correlated with increased risk for CVD and diabetes. In response to this health risk, our research addresses the mechanisms by which coplanar PCBs elicit an inflammatory response and the mitigation of PCB-induced inflammation through dietary intervention using docosahexaenoic acid (DHA), an omega-3 lipid. Investigators from the University of Kentucky Engineering Department are developing remediation technologies that detoxify PCBs through dechlorination. We studied the cellular toxicity …

Novel Insights Into The Function And Regulation Of Group X Secretory Phospholipase A2, Joseph D. Layne Jr

Theses and Dissertations--Nutritional Sciences

Group X secretory phospholipase A₂ (GX sPLA₂) hydrolyzes membrane phospholipids producing free fatty acids and lysophospholipids. Previous studies from our lab suggest that mice with targeted deletion of GX sPLA₂ (GX KO) have increased age-related weight gain due to an increase in overall adiposity. Paradoxically, this increased adiposity is associated with improved age-related glucose intolerance. GX KO mice also demonstrate a reduced inflammatory response to lipopolysaccharide injection. In vitro studies indicate this phenotype may be attributable to blunted macrophage mediated inflammatory responses. Given the role of macrophages in promoting adipose tissue (AT) inflammation and metabolic dysfunction …

Protective Effect Of Vardenafil On Ischemia–Reperfusion Injury In Rat Ovary, Hati̇ce Baş, Özlem Kara, Mustafa Kara, Di̇lek Pandir

Turkish Journal of Medical Sciences

To investigate the effect of vardenafil on ischemia–reperfusion (I/R) injury in rat ovary. Materials and methods: A total of 21 Wistar rats were divided into 3 groups. In group 1, ovary torsion was not performed and no drug was administered. In group 2, 1 h of ischemia and 2 h of reperfusion were performed and no drug was given. In group 3, 1 h of ischemia and 2 h of reperfusion were performed and 1 mg/kg vardenafil was administered after 30 min of ischemia. Right ovaries were surgically removed in all groups. Malondialdehyde (MDA) levels and activities of superoxide dismutase …

Helicobacter Pylori Infection And Relationship With Gastric Epithelial Cell Proliferation And Apoptosis, Zühal Güci̇n, Tuğba Çakmak, Ni̇zametti̇n Bayyurt, Bari̇k Sali̇h

Turkish Journal of Medical Sciences

To evaluate the effects of Helicobacter pylori on cell proliferation and apoptosis in gastric cancer (GC) both at tumoral and nontumoral sites and in gastritis. Materials and methods: Biopsies from 96 patients (gastric cancer = 52, gastritis = 44) were examined immunohistochemically and histopathologically. Results: In H. pylori-positive GC patients the average proliferative index (PI) in tumor and nontumor sites was 40.7% and 24.8%, while in H. pylori-negative patients it was 32.9% and 17.8%, respectively. The PI was significantly higher in the tumor than in the nontumor sites, regardless of H. pylori infection. Cell proliferation was also significantly associated with …

Aβ Alters The Dna Methylation Status Of Cell-Fate Genes In An Alzheimer’S Disease Model, Gary D. Isaacs, Noor Taher, Courtney Mckenzie, Rebecca Garrett, Matthew Baker, Nena Fox

Faculty Publications and Presentations

Alzheimer’s disease (AD) is characterized by neurofibrillary tangles and extracellular amyloid-β plaques (Aβ). Despite ongoing research, some ambiguity remains surrounding the role of Aβ in the pathogenesis of this neurodegenerative disease. While several studies have focused on the mutations associated with AD, our understanding of the epigenetic contributions to the disease remains less clear. To that end, we determined the changes in DNA methylation in differentiated human neurons with and without Aβ treatment. We isolated the DNA from neurons treated with Aβ or vehicle, and digested the two samples with either a methylation-sensitive (HpaII) or a methylation-insensitive (MspI) restriction endonuclease. …

Molecular Staging Of Node Negative Patients With Colorectal Cancer., Terry Hyslop, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Metastatic disease is the principle cause of death from colorectal cancer. In that context, the most significant indicator of overall survival and therapeutic response to adjuvant chemotherapy is the presence of metastatic tumor cells in regional lymph nodes. Although histopathologic analysis of lymph nodes is central to all colorectal cancer staging paradigms, its prognostic and predictive value is limited. Indeed, about 30% of patients with histopathology-negative lymph nodes (pN0) die from metastatic disease, reflected by microscopic lymph node metastases that are overlooked by standard techniques. These unrecognized tumor cells are especially important when considering racial disparities in outcomes in colorectal …

Discovering Protein Functions And Career Goals: The Suppressor Sike, Rebekah Rifareal

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Discovering IMSD was accidental. I was having a routine advising appointment and discussing future careers when the topic surfaced. At the time, I had no clue about what I wanted to do, so my advisor suggested that I explore research and encouraged me to apply for the program.

Examining The Relationship Between Particulate Matter, Nitrogen Oxide, Carbon Oxides, Sulfur Dioxide And Hypertension In Urban Areas In India: A Review, Hiren Kolli

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

While blood pressure may be decreasing around the world, it has been on the rise in India (Kounteya, 2012). According to the World Health Organization, the average blood pressure went down by 2.7mm Hg among women globally, while increasing by 2.4mm Hg in India. In men, blood pressure decreased by 2.3mm Hg globally in the past three decades but increased by 2.2mm Hg in India (Kounteya, 2012). Almost three-quarters of people with hypertension live in developing countries with limited health resources where there is very low awareness of hypertension, and India is one of these countries. Hypertension is the leading …

Two Coiled-Coil Domains Of Chlamydia Trachomatis Inca Affect Membrane Fusion Events During Infection., Erik Ronzone, Fabienne Paumet

Department of Microbiology and Immunology Faculty Papers

Chlamydia trachomatis replicates in a parasitophorous membrane-bound compartment called an inclusion. The inclusions corrupt host vesicle trafficking networks to avoid the degradative endolysosomal pathway but promote fusion with each other in order to sustain higher bacterial loads in a process known as homotypic fusion. The Chlamydia protein IncA (Inclusion protein A) appears to play central roles in both these processes as it participates to homotypic fusion and inhibits endocytic SNARE-mediated membrane fusion. How IncA selectively inhibits or activates membrane fusion remains poorly understood. In this study, we analyzed the spatial and molecular determinants of IncA's fusogenic and inhibitory functions. Using …

Toward A Network Model Of Mhc Class Ii-Restricted Antigen Processing., Michael A Miller, Asha Purnima V Ganesan, Laurence C. Eisenlohr

Department of Microbiology and Immunology Faculty Papers

The standard model of Major Histocompatibility Complex class II (MHCII)-restricted antigen processing depicts a straightforward, linear pathway: internalized antigens are converted into peptides that load in a chaperone dependent manner onto nascent MHCII in the late endosome, the complexes subsequently trafficking to the cell surface for recognition by CD4(+) T cells (TCD4+). Several variations on this theme, both moderate and radical, have come to light but these alternatives have remained peripheral, the conventional pathway generally presumed to be the primary driver of TCD4+ responses. Here we continue to press for the conceptual repositioning of these alternatives toward the center while …

The Effects Of Hydrostatic Pressure On Early Endothelial Tubulogenic Processes, Ryan M. Underwood

Theses and Dissertations--Biomedical Engineering

The effects of mechanical forces on endothelial cell function and behavior are well documented, but have not been fully characterized. Specifically, fluid pressure has been shown to elicit physical and chemical responses known to be involved in the initiation and progression of endothelial cell-mediated vascularization. Central to the process of vascularization is the formation of tube-like structures. This process—tubulogenesis—is essential to both the physiological and pathological growth of tissues. Given the known effects of pressure on endothelial cells and its ubiquitous presence in the vasculature, we investigated pressure as a magnitude-dependent parameter for the regulation of endothelial tubulogenic activity. To …