Life Sciences Commons^™

Intracellular Delivery Of Nanoparticles And Dnas By Ir9 Cell-Penetrating Peptides, Betty Revon Liu, Ji-Sing Liou, Yue-Wern Huang, Robert Aronstam, Han-Jung Lee

Biological Sciences Faculty Research & Creative Works

Cell-penetrating peptides (CPPs) comprised of basic amino residues are able to cross cytoplasmic membranes and are able to deliver biologically active molecules inside cells. However, CPP/cargo entrapment in endosome limits biomedical utility as cargoes are destroyed in the acidic environment. In this study, we demonstrate protein transduction of a novel CPP comprised of an INF7 fusion peptide and nona-arginine (designated IR9). IR9 noncovalently interacts with quantum dots (QDs) and DNAs to form stable IR9/QD and IR9/DNA complexes which are capable of entering human A549 cells. Zeta-potentials were a better predictor of transduction efficiency than gel shift analysis, emphasizing the importance …

Chemically Diverse Microtubule Stabilizing Agents Initiate Distinct Mitotic Defects And Dysregulated Expression Of Key Mitotic Kinases., Cristina C. Rohena, Jiangnan Peng, Tyler A. Johnson, Phillip Crews, Susan L. Mooberry

Natural Sciences and Mathematics | Faculty Scholarship

Microtubule stabilizers are some of the most successful drugs used in the treatment of adult solid tumors and yet the molecular events responsible for their antimitotic actions are not well defined. The mitotic events initiated by three structurally and biologically diverse microtubule stabilizers; taccalonolide AJ, laulimalide/fijianolide B and paclitaxel were studied. These microtubule stabilizers cause the formation of aberrant, but structurally distinct mitotic spindles leading to the hypothesis that they differentially affect mitotic signaling. Each microtubule stabilizer initiated different patterns of expression of key mitotic signaling proteins. Taccalonolide AJ causes centrosome separation and disjunction failure to a much greater extent …

Side Chain Requirements For Affinity And Specificity In D5, An Hiv-1 Antibody Derived From The Vh1-69 Germline Segment, Alex Stewart, Joseph S. Harrison, Lauren K. Regula, Jonathan R. Lai

College of the Pacific Faculty Articles

BACKGROUND: Analysis of factors contributing to high affinity antibody-protein interactions provides insight into natural antibody evolution, and guides the design of antibodies with new or enhanced function. We previously studied the interaction between antibody D5 and its target, a designed protein based on HIV-1 gp41 known as 5-Helix, as a model system [Da Silva, G. F.; Harrison, J. S.; Lai, J. R., Biochemistry, 2010, 49, 5464-5472]. Antibody D5 represents an interesting case study because it is derived from the VH1-69 germline segment; this germline segment is characterized by a hydrophobic second heavy chain complementarity determining region (HCDR2) that constitutes the …

Humans And Dolphins: An Exploration Of Anthropocentrism In Applied Environmental Ethics, Thomas I. White

Management Faculty Works

This article argues that one of the reasons that the unethical character of much human-dolphin contact is not more apparent to ethicists is that discussion of central issues has been colored with unintentional species bias. This article points out weaknesses in the traditional approach to discussing topics that bear on the question of whether dolphins have moral standing. It demonstrates that discussions of the cognitive abilities of dolphins by Steven Wise and Alasdair MacIntyre are unintentionally but fundamentally anthropocentric-largely because the authors are not familiar with enough of the scientific literature about dolphins to draw the conclusions that they do.

Fuzzy Complex Formation Between The Intrinsically Disordered Prothymosin Α And The Kelch Domain Of Keap1 Involved In The Oxidative Stress Response., Halema Khan, Elio A Cino, Anne Brickenden, Jingsong Fan, Daiwen Yang, Wing-Yiu Choy

Biochemistry Publications

Kelch-like ECH-associated protein 1 (Keap1) is an inhibitor of nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription factor for cytoprotective gene activation in the oxidative stress response. Under unstressed conditions, Keap1 interacts with Nrf2 in the cytoplasm via its Kelch domain and suppresses the transcriptional activity of Nrf2. During oxidative stress, Nrf2 is released from Keap1 and is translocated into the nucleus, where it interacts with the small Maf protein to initiate gene transcription. Prothymosin α (ProTα), an intrinsically disordered protein, also interacts with the Kelch domain of Keap1 and mediates the import of Keap1 into the nucleus …

Experimental And Natural Warming Elevates Mercury Concentrations In Estuarine Fish, Jennifer A. Dijkstra, Kate L. Buckman, Darren Ward, David W. Evans, Michele Dionne, Celia Y. Chen

Dartmouth Scholarship

Marine food webs are the most important link between the global contaminant, methylmercury (MeHg), and human exposure through consumption of seafood. Warming temperatures may increase human exposure to MeHg, a potent neurotoxin, by increasing MeHg production as well as bioaccumulation and trophic transfer through marine food webs. Studies of the effects of temperature on MeHg bioaccumulation are rare and no study has specifically related temperature to MeHg fate by linking laboratory experiments with natural field manipulations in coastal ecosystems. We performed laboratory and field experiments on MeHg accumulation under varying temperature regimes using the killifish, Fundulus heteroclitus. Temperature treatments …

Excitatory Amino Acids Display Compartmental Disparity Between Plasma And Synovial Fluid In Clinical Arthropathies, Terry A. Mcnearney, Karin N. Westlund

Physiology Faculty Publications

BACKGROUND: Previous studies have demonstrated elevated levels of excitatory amino acids (EAA) glutamate (Glu) and aspartate (Asp) in the synovial fluid (SF) of patients with active arthritis. The source of SF EAA concentrations are thought in large part to be secondary to passive diffusion from the plasma across synovial membranes and less so, reflective of local synovial pathology.

OBJECTIVE: This descriptive report assesses the hypothesis that the SF EAA levels reflect inflammatory processes of the joint and are not dependent on plasma levels.

METHODS: Simultaneously drawn plasma and SF samples were obtained from 14 recently deceased cadavers and 10 patients …

Detection And Quantification Of Methylation In Dna Using Solid-State Nanopores., Jiwook Shim, Gwendolyn I Humphreys, Bala Murali Venkatesan, Jan Marie Munz, Xueqing Zou, Chaitanya Sathe, Klaus Schulten, Farhad Kosari, Ann M Nardulli, George Vasmatzis, Rashid Bashir

Faculty Scholarship for the College of Science & Mathematics

Epigenetic modifications in eukaryotic genomes occur primarily in the form of 5-methylcytosine (5 mC). These modifications are heavily involved in transcriptional repression, gene regulation, development and the progression of diseases including cancer. We report a new single-molecule assay for the detection of DNA methylation using solid-state nanopores. Methylation is detected by selectively labeling methylation sites with MBD1 (MBD-1x) proteins, the complex inducing a 3 fold increase in ionic blockage current relative to unmethylated DNA. Furthermore, the discrimination of methylated and unmethylated DNA is demonstrated in the presence of only a single bound protein, thereby giving a resolution of a single …

Implicitly Priming The Social Brain: Failure To Find Neural Effects, Katherine E. Powers, Todd F. Heatherton

Dartmouth Scholarship

Humans have a fundamental need for social relationships. Rejection from social groups is especially detrimental, rendering the ability to detect threats to social relationships and respond in adaptive ways critical. Indeed, previous research has shown that experiencing social rejection alters the processing of subsequent social cues in a variety of socially affiliative and avoidant ways. Because social perception and cognition occurs spontaneously and automatically, detecting threats to social relationships may occur without conscious awareness or control. Here, we investigated the automaticity of social threat detection by examining how implicit primes affect neural responses to social stimuli. However, despite using a …

Pyrvinium Pamoate Changes Alternative Splicing Of The Serotonin Receptor 2c By Influencing Its Rna Structure, Manli Shen, Stanislav Bellaousov, Michael Hiller, Pierre De La Grange, Trevor O. Creamer, Orit Malina, Ruth Sperling, David H. Mathews, Peter Stoilov, Stefan Stamm

Molecular and Cellular Biochemistry Faculty Publications

The serotonin receptor 2C plays a central role in mood and appetite control. It undergoes pre-mRNA editing as well as alternative splicing. The RNA editing suggests that the pre-mRNA forms a stable secondary structure in vivo. To identify substances that promote alternative exons inclusion, we set up a high-throughput screen and identified pyrvinium pamoate as a drug-promoting exon inclusion without editing. Circular dichroism spectroscopy indicates that pyrvinium pamoate binds directly to the pre-mRNA and changes its structure. SHAPE (selective 2'-hydroxyl acylation analysed by primer extension) assays show that part of the regulated 5'-splice site forms intramolecular base pairs that …

Serine/Threonine Acetylation Of Tgfbeta-Activated Kinase (Tak1) By Yersinia Pestis Yopj Inhibits Innate Immune Signaling, Nicholas Paul Paquette, Joseph E. Conlon, Charles R. Sweet, Florentina Rus, Lindsay Wilson, Andrea J. Pereira, Charles V. Rosadini, Nadege Goutagny, Alexander N. R. Weber, William S. Lane, Scott A. Shaffer, Stephanie Maniatis, Katherine A. Fitzgerald, Lynda M. Stuart, Neal S. Silverman

Katherine A. Fitzgerald

The Gram-negative bacteria Yersinia pestis, causative agent of plague, is extremely virulent. One mechanism contributing to Y. pestis virulence is the presence of a type-three secretion system, which injects effector proteins, Yops, directly into immune cells of the infected host. One of these Yop proteins, YopJ, is proapoptotic and inhibits mammalian NF-kappaB and MAP-kinase signal transduction pathways. Although the molecular mechanism remained elusive for some time, recent work has shown that YopJ acts as a serine/threonine acetyl-transferase targeting MAP2 kinases. Using Drosophila as a model system, we find that YopJ inhibits one innate immune NF-kappaB signaling pathway (IMD) but not …

Serine/Threonine Acetylation Of Tgfbeta-Activated Kinase (Tak1) By Yersinia Pestis Yopj Inhibits Innate Immune Signaling, Nicholas Paul Paquette, Joseph E. Conlon, Charles R. Sweet, Florentina Rus, Lindsay Wilson, Andrea J. Pereira, Charles V. Rosadini, Nadege Goutagny, Alexander N. R. Weber, William S. Lane, Scott A. Shaffer, Stephanie Maniatis, Katherine A. Fitzgerald, Lynda M. Stuart, Neal S. Silverman

Neal Silverman

The Gram-negative bacteria Yersinia pestis, causative agent of plague, is extremely virulent. One mechanism contributing to Y. pestis virulence is the presence of a type-three secretion system, which injects effector proteins, Yops, directly into immune cells of the infected host. One of these Yop proteins, YopJ, is proapoptotic and inhibits mammalian NF-kappaB and MAP-kinase signal transduction pathways. Although the molecular mechanism remained elusive for some time, recent work has shown that YopJ acts as a serine/threonine acetyl-transferase targeting MAP2 kinases. Using Drosophila as a model system, we find that YopJ inhibits one innate immune NF-kappaB signaling pathway (IMD) but not …

Initial Multicenter Experience With Double Nucleoside Therapy For Human Immunodeficiency Virus Infection During Pregnancy, Neal S. Silverman, D. Heather Watts, Joseph Hitti, D. M. Money, E. Livingston, J. Axelrod, J. M. Ernest, Douglas Robbins, M. M. Divito

Neal Silverman

OBJECTIVE: To study maternal and neonatal effects of combination nucleoside analog therapy administered to human immunodeficiency virus (HIV)-infected pregnant women for maternal indications. METHODS: A multicenter, prospective observational study was undertaken at six perinatal centers in the United States and Canada that supported regional referral programs for the treatment of HIV-infected pregnant women. Demographic, laboratory, and pregnancy outcome data were collected for 39 women whose antiretroviral treatment regimens were expanded to include more than one nucleoside analog for maternal indications. The 40 newborns were monitored at pediatric referral centers through at least three months of age to ascertain their HIV …

Honokiol Blocks Store Operated Calcium Entry In Cho Cells Expressing The M3 Muscarinic Receptor: Honokiol And Muscarinic Signaling, Hsiu-Jen Wang, Alexis Martin, Po-Kuan Chao, Rhett A. Reichard, Adam L. Martin, Yue-Wern Huang, Ming-Huan Chan, Robert Aronstam

Biological Sciences Faculty Research & Creative Works

Background: Honokiol, a cell-permeable phenolic compound derived from the bark of magnolia trees and present in Asian herbal teas, has a unique array of pharmacological actions, including the inhibition of multiple autonomic responses. We determined the effects of honokiol on calcium signaling underlying transmission mediated by human M3 muscarinic receptors expressed in Chinese hamster ovary (CHO) cells. Receptor binding was determined in radiolabelled ligand binding assays; changes in intracellular calcium concentrations were determined using a fura-2 ratiometric imaging protocol; cytotoxicity was determined using a dye reduction assay.

Results: Honokiol had a potent (EC50 ≈ 5 μmol/l) inhibitory effect on store …

Decoupling Of Stretch Reflex And Background Muscle Activity During Anticipatory Postural Adjustments In Humans, Siddharth Vedula, Robert Kearney, Ross Wagner, Paul Stapley

Dr Paul J Stapley

We studied the evolution of stretch reXexes in relation to background electromyographic (EMG) activity in the soleus muscle preceding the onset of voluntary arm raise movements. Our objective was to investigate if changes in reXex EMG and muscle activity occur simultaneously and are similarly scaled in amplitude. Ten human subjects stood with each foot on pedals able to exert short dorsiXexor pulses during stance. Subjects were asked to product consistent voluntary arm raise movements to a target upon a visual cue. In ¼ of trials, no pulse perturbations were given, but in the remaining ¾’s of all trials pulses were …

Independent Control Of Limb Force Underlies Stability During Voluntary Head Movements In Standing Humans, Paul Stapley, Alicia Hilderley, Julia Leonard

Dr Paul J Stapley

Postural stability during voluntary head movements is maintained through the integration of vestibular and neck afferent inputs. These inputs combine to accurately estimate trunk position in space, relative to a turning head. In animals, a loss of vestibular information leads to an active destabilization of balance as neck afferent information is interpreted as a movement of the trunk under a stable head (Stapley et al. 2006).

Postural Adjustments For Online Corrections Of Arm Movements In Standing Humans, Julia Leonard, Valeriya Gritsenko, Ryan Ouckama, Paul Stapley

Dr Paul J Stapley

The aim of this study was to investigate how humans correct ongoing arm movements while standing. Specifically, we sought to understand whether the postural adjustments in the legs required for online corrections of arm movements are predictive or rely on feedback from the moving limb. To answer this question we measured online corrections in arm and leg muscles during pointing movements while standing. Nine health right-handed subjects reached with their dominant arm to a visual target in front of them and aligned with their midline. In some trials, the position of the target would switch from the central target to …

Reflex Changes Associated With Anticipatory Postural Adjustments Preceding Voluntary Arm Movements In Standing Humans, Siddharth Vedula, Paul J. Stapley, Robert E. Kearney

Dr Paul J Stapley

Dynamic changes in human stability, such as those induced by upper body movements, are preceded by anticipatory postural adjustments (APAs) in the rest of the body. We measured the excitability of the stretch reflex of the triceps-surae muscle group during APAs associated with unilateral right arm raises in standing humans. Our results demonstrate that reflex excitability and underlying muscle activity are linked during the APA period, but that they differ in their relative timing. This supports the idea that reflexes are controlled independently of muscle activation.

Tree Climbing And Human Evolution, Vivek V. Venkataraman, Thomas S. Kraft, Nathaniel J. Dominy

Dartmouth Scholarship

Paleoanthropologists have long argued—often contentiously—about the climbing abilities of early hominins and whether a foot adapted to terrestrial bipedalism constrained regular access to trees. However, some modern humans climb tall trees routinely in pursuit of honey, fruit, and game, often without the aid of tools or support systems. Mortality and morbidity associated with facultative arboreality is expected to favor behaviors and anatomies that facilitate safe and efficient climbing. Here we show that Twa hunter–gatherers use extraordinary ankle dorsiflexion (>45°) during climbing, similar to the degree observed in wild chimpanzees. Although we did not detect a skeletal signature of dorsiflexion …

Community Outreach And Engagement To Prepare For Household Recruitment Of National Children's Study Participants In A Rural Setting, Nancy L. Fahrenwald, Betty Wey, Ann Martin, Bonny L. Specker

Ethel Austin Martin Program Publications

CONTEXT: The National Children's Study (NCS) is a longitudinal study of environmental influences on children's health. Recruitment of a representative birth cohort that will be followed until 21 years of age requires unique approaches across the nationwide study communities.
PURPOSE: To describe community outreach and engagement in preparation for household recruitment of women of childbearing age at a rural-classified NCS location that includes 4 adjacent Northern Plains counties spanning 2,500 square miles.
METHODS: Outreach and engagement methods focused on rural community characteristics. The team established an advisory council, conducted outreach meetings with agencies and groups, participated in local events, and …

Costly Information And The Evolution Of Self-Organization In A Small, Complex Economy., James A. Wilson

James Wilson

tThe core idea of evolution is that order in living systems emerges from a simple process of variation and selection. In biological systems we usually understand the source of variation as best described by the mechanisms of genetics. If human social systems are evolutionary systems, however, it would seem the variation that most explains the sources of change in these systems, occurs not from a genetic mechanism, but from individual learning. We use an evolutionary computational methodology to explore the way individual learning and adaptation lead to the evolution of persistent, self-organized social and economic activity. The basic idea behind …

Alginate Lyase Exhibits Catalysis-Independent Biofilm Dispersion And Antibiotic Synergy, John W. Lamppa, Karl E. Griswold

Dartmouth Scholarship

More than 2 decades of study support the hypothesis that alginate lyases are promising therapeutic candidates for treating mucoid Pseudomonas aeruginosa infections. In particular, the enzymes' ability to degrade alginate, a key component of mucoid biofilm matrix, has been the presumed mechanism by which they disrupt biofilms and enhance antibiotic efficacy. The systematic studies reported here show that, in an in vitro model, alginate lyase dispersion of P. aeruginosa biofilms and enzyme synergy

Force Generation By Kinesin And Myosin Cytoskeletal Motor Proteins, F. Jon Kull, Sharyn A. Endow

Dartmouth Scholarship

Kinesins and myosins hydrolyze ATP, producing force that drives spindle assembly, vesicle transport and muscle contraction. How do motors do this? Here we discuss mechanisms of motor force transduction, based on their mechanochemical cycles and conformational changes observed in crystal structures. Distortion or twisting of the central β-sheet - proposed to trigger actin-induced Pi and ADP release by myosin, and microtubule-induced ADP release by kinesins - is shown in a movie depicting the transition between myosin ATP-like and nucleotide-free states. Structural changes in the switch I region form a tube that governs ATP hydrolysis and Pi release by the motors, …

A Physical Sciences Network Characterization Of Non-Tumorigenic And Metastatic Cells, Abigail Hielscher, D. Wirtz, Et Al.

PCOM Scholarly Papers

To investigate the transition from non-cancerous to metastatic from a physical sciences perspective, the Physical Sciences-Oncology Centers (PS-OC) Network performed molecular and biophysical comparative studies of the non-tumorigenic MCF-10A and metastatic MDA-MB-231 breast epithelial cell lines, commonly used as models of cancer metastasis. Experiments were performed in 20 laboratories from 12 PS-OCs. Each laboratory was supplied with identical aliquots and common reagents and culture protocols. Analyses of these measurements revealed dramatic differences in their mechanics, migration, adhesion, oxygen response, and proteomic profiles. Model-based multi-omics approaches identified key differences between these cells' regulatory networks involved in morphology and survival. These results …

Predicting Barriers To Primary Care For Patients With Disabilities: A Mixed Methods Study Of Practice Administrators, Jennifer Renee Pharr, Michelle Chino

Environmental & Occupational Health Faculty Publications

Background. People with disabilities continue to be identified as a group who experience disparate health/health care. They are less likely to engage in some health care services. Structural barriers are often identified as one of the reasons for the underutilization of some health care services by people with disabilities. However, to date no study has been conducted to understand why structural barriers persist twenty years after the Americans with Disabilities Act (ADA) became law.

Objectives. We examined the relationship between primary care practice administrators’ knowledge of the ADA and the number of accessibility barriers that patients with mobility disabilities might …

Delivering Genetic Education And Genetic Counseling For Rare Diseases In Rural Brazil, A.X. Acosta, K Abe-Sandes, R Giugliani, Alan H. Bittles

Research outputs 2013

Brazil is the largest country in Latin America, with an ethnically diverse, Portuguese-speaking and predominantly Roman Catholic population of some 194 million. Universal health care is provided under the Federal Unified Health System (Sistema Único de Saúde) but, as in many other middle and low income countries, access to medical genetics services is limited in rural and remote regions of the country. Since there is no formally recognized Genetic Counseling profession, genetic counseling is provided by physicians, trained either in medical genetics or a related clinical discipline. A comprehensive medical genetics program has been established in Monte Santo, an inland …

An Independent Audit Of The Australian Food Industry's Voluntary Front-Of-Pack Nutrition Labelling Scheme For Energy-Dense Nutrition-Poor Foods, Owen B. Carter, Brennen W. Mills, Tina Phan, Elanie Lloyd

Research outputs 2013

Background/Objective: Since 2006, the Australian food industry has promoted its front-of-pack (FOP) food labelling system-the Daily Intake Guide (DIG)-as a success story of industry self-regulation. With over 4000 products already voluntary featuring the DIG, the industry argues that government regulation of FOP nutrition labelling is simply unnecessary. However, no independent audit of the industry's self-regulation has ever been undertaken and we present the first such Australian data. Subjects/Methods: Energy-dense nutrient-poor (EDNP) snacks were audited at nine Australian supermarkets, including biscuits, candy, ice creams, chocolates, crisps, sports drinks, energy drinks, flavoured milks, sweetened juices and soft drinks. In these categories nutrition …

Association Of Iron Depletion With Menstruation And Dietary Intake Indices In Pubertal Girls: The Healthy Growth Study, George Moschonis, Dimitrios Papandreou, Christina Mavrogianni, Angeliki Giannopoulou, Louisa Damianidi, Pavlos Malindretos, Christos Lionis, George P. Chrousos, Yannis Manios

All Works

The aim of the present study was to investigate the associations of iron depletion (ID) with menstrual blood losses, lifestyle, and dietary habits, in pubertal girls. The study sample comprised 1222 girls aged 9-13 years old. Biochemical, anthropometrical, dietary, clinical, and physical activity data were collected. Out of 274 adolescent girls with menses, 33.5% were found to be iron depleted (defined as serum ferritin < 12 g/L) compared to 15.9% out of 948 girls without menses. Iron-depleted girls without menses were found to have lower consumption of poultry (P = 0.017) and higher consumption of fruits (P = 0.044) and fast food (P = 0.041) compared to their peers having normal iron status. Multivariate logistic regression analysis showed that girls with menses were 2.57 (95% CI: 1.37, 4.81) times more likely of being iron depleted compared to girls with no menses. Iron depletion was found to be associated with high calcium intake, high consumption of fast foods, and low consumption of poultry and fruits. Menses was the only factor that was found to significantly increase the likelihood of ID in these girls. More future research is probably needed in order to better understand the role of diet and menses in iron depletion. © 2013 George Moschonis et al.

Identifying Requirements For The Invasion Of A Tick Species And Tick-Borne Pathogen Through Ticksim, Holly Gaff, Robyn Nadolny

Biological Sciences Faculty Publications

Ticks and tick-borne diseases have been on the move throughout the United State over the past twenty years. We use an agent-based model, TICKSIM, to identify the key parameters that determine the success of invasion of the tick and if that is successful, the success of the tick-borne pathogen. We find that if an area has competent hosts, an initial population of ten ticks is predicted to always establish a new population. The establishment of the tick-borne pathogen depends on three parameters: the initial prevalence in the ten founding ticks, the probability that a tick infects the longer-lived hosts and …

Persistence Of Episomal Hiv-1 Infection Intermediates In Patients On Highly Active Anti-Retroviral Therapy, Mark Sharkey, Ian Teo, Thomas Greenough, Natalia Sharova, Katherine Luzuriaga, John Sullivan, R. Bucy, Leondios Kostrikis, Ashley Haase, Claire Veryard, Raul Davaro, Sarah Cheeseman, Jennifer Daly, Carol Bova, Richard Ellison, Brian Mady, Kwan Lai, Graeme Moyle, Mark Nelson, Brian Gazzard, Sunil Shaunak, Mario Stevenson

Associate Professor Mark Nelson

Treatment of HIV-1-infected individuals with a combination of anti-retroviral agents results in sustained suppression of HIV-1 replication, as evidenced by a reduction in plasma viral RNA to levels below the limit of detection of available assays. However, even in patients whose plasma viral RNA levels have been suppressed to below detectable levels for up to 30 months, replication-competent virus can routinely be recovered from patient peripheral blood mononuclear cells and from semen. A reservoir of latently infected cells established early in infection may be involved in the maintenance of viral persistence despite highly active anti-retroviral therapy. However, whether virus replication …