Medicine and Health Sciences Commons^™

Atypical Signaling And Functional Desensitization Response Of Mas Receptor To Peptide Ligands, Kalyan C. Tirupula, Russell Desnoyer, Robert C. Speth, Sadashiva S. Karnik

HPD Articles

MAS is a G protein-coupled receptor (GPCR) implicated in multiple physiological processes. Several physiological peptide ligands such as angiotensin-(1-7), angiotensin fragments and neuropeptide FF (NPFF) are reported to act on MAS. Studies of conventional G protein signaling and receptor desensitization upon stimulation of MAS with the peptide ligands are limited so far. Therefore, we systematically analyzed G protein signals activated by the peptide ligands. MAS-selective non-peptide ligands that were previously shown to activate G proteins were used as controls for comparison on a common cell based assay platform. Activation of MAS by the non-peptide agonist (1) increased intracellular calcium and …

Dietary Supplement Labeling: Cognitive Biases, Market Manipulation & Consumer Choice, Michael Mccann

Law Faculty Scholarship

There exists increasing concern that the Dietary Supplements Health and Education Act (DSHEA) has proven ineffective. Much of the concern regards the disparity in legislative treatment between dietary supplements, foods, and pharmaceutical drugs. Namely, while pharmaceutical drugs must undergo years of costly pre-market testing, most supplements, like foods, can immediately enter the market, and only after repeated instances of adverse reactions can the Food and Drug Administration (FDA) remove them. Such a framework appears to belie both consumer expectations and marketing strategies, as supplements tend to be most perceived for their apparent medicinal qualities. This philosophy of waiting for a …

Contraceptive Sabotage, Leah A. Plunkett

Law Faculty Scholarship

This Article responds to the alarm recently sounded by the American College of Obstetricians and Gynecologists over “birth control sabotage”—the “active interference [by one partner] with [the other] partner’s contraceptive methods in an attempt to promote pregnancy.” Currently, sabotage is not a crime, and existing categories of criminal offenses fail to capture the essence of the injury it does to victims. This Article argues that sabotage should be a separate crime—but only when perpetrated against those partners who can and do get pregnant as a result of having sabotaged sex. Using the principle of self-possession—understood as a person’s basic right …

Nudging The Fda, W. Nicholson Price Ii, I. Glenn Cohen

Law Faculty Scholarship

[Excerpt] "The FDA’s regulation of drugs is frequently the subject of policy debate, with arguments falling into two camps. On the one hand, a libertarian view of patients and the health care system holds high the value of consumer choice. Patients should get all the information and the drugs they want; the FDA should do what it can to enforce some basic standards but should otherwise get out of the way. On the other hand, a paternalist view values the FDA’s role as an expert agency standing between patients and a set of potentially dangerous drugs and potentially unscrupulous or …

Making Do In Making Drugs: Innovation Policy And Pharmaceutical Manufacturing, W. Nicholson Price Ii

Law Faculty Scholarship

Despite increasing recalls, contamination events, and shortages, drug companies continue to rely on outdated manufacturing plants and processes. Drug manufacturing’s inefficiency and lack of innovation stand in stark contrast to drug discovery, which is the focus of a calibrated innovation policy that combines patents and FDA regulation. Pharmaceutical manufacturing lags far behind the innovative techniques found in other industries due to high regulatory barriers and ineffective intellectual property incentives. Among other challenges, although manufacturers tend to rely on trade secrecy because of the difficulty in enforcing patents on manufacturing processes, trade secrecy provides limited incentives for innovation. To increase those …

Estimating Population Treatment Effects From A Survey Sub-Sample, Kara E. Rudolph, Ivan Diaz, Michael Rosenblum, Elizabeth A. Stuart

Johns Hopkins University, Dept. of Biostatistics Working Papers

We consider the problem of estimating an average treatment effect for a target population from a survey sub-sample. Our motivating example is generalizing a treatment effect estimated in a sub-sample of the National Comorbidity Survey Replication Adolescent Supplement to the population of U.S. adolescents. To address this problem, we evaluate easy-to-implement methods that account for both non-random treatment assignment and a non-random two-stage selection mechanism. We compare the performance of a Horvitz-Thompson estimator using inverse probability weighting (IPW) and two double robust estimators in a variety of scenarios. We demonstrate that the two double robust estimators generally outperform IPW in …

Asking The Questions And The Importance Of Saying No, Kristine Lund

Luther Faculty Publications

Sermon on Matthew 21:23-32.

Assessing 2 D-Dimer Age-Adjustment Strategies To Optimize Computed Tomographic Use In Ed Evaluation Of Pulmonary Embolism, A. Gupta, A. S. Raja, I. K. Ip, R. Khorasani

Journal Articles

STUDY OBJECTIVE: Validate the sensitivity and specificity of 2 age adjustment strategies for d-dimer values in identifying patients at risk for pulmonary embolism (PE) compared with traditional D-dimer cutoff value (500 ng/mL) to decrease inappropriate computed tomography pulmonary angiography (CTPA) use. METHODS: This institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study included all adult emergency department patients evaluated for PE over a 32-month period (1/1/11-8/30/13). Only patients undergoing CTPA and D-dimer testing were included. We used a validated natural language processing algorithm to parse CTPA radiology reports and determine the presence of acute PE. Outcome measures were …

Incidence And Predictors Of Acute Psychological Distress And Dissociation After Motor Vehicle Collision: A Cross-Sectional Study, G. C. Lewis, T. F. Platts-Mills, I. Liberzon, E. Bair, R. Swor, N. Rathlev, D. Lee, R. Domeier, P. Hendry, S. A. Mclean, +2 Additional Authors

Journal Articles

Objective: We examined the incidence and predictors of peritraumatic distress and dissociation after one of the most common forms of civilian trauma exposure: motor vehicle collision (MVC). Method: In this study, patients presenting to the emergency department after MVCs who were without serious injury and discharged to home after evaluation (n = 935) completed an emergency department interview evaluating sociodemographic, collision-related, and psychological characteristics. Results: The incidence and predictors of distress (Peritraumatic Distress Inventory score 23) and dissociation (Michigan Critical Events Perception Scale score >3) were assessed. Distress was present in 355 of 935 patients (38%), and dissociation was present …

Incidence And Predictors Of Neck And Widespread Pain After Motor Vehicle Collision Among Us Litigants And Nonlitigants, S. A. Mclean, J. C. Ulirsch, G. D. Slade, A. C. Soward, R. A. Swor, D. A. Peak, J. S. Jones, N. K. Rathlev, D. C. Lee, E. Bair, +3 Additional Authors

Journal Articles

Debate continues regarding the influence of litigation on pain outcomes after motor vehicle collision (MVC). In this study we enrolled European Americans presenting to the emergency department (ED) in the hours after MVC (n = 948). Six weeks later, participants were interviewed regarding pain symptoms and asked about their participation in MVC-related litigation. The incidence and predictors of neck pain and widespread pain 6 weeks after MVC were compared among those engaged in litigation (litigants) and those not engaged in litigation (nonlitigants). Among the 859 of 948 (91%) participants completing 6-week follow-up, 711 of 849 (83%) were nonlitigants. Compared to …

B Cells Populating The Multiple Sclerosis Brain Mature In The Draining Cervical Lymph Nodes, J. N. Stern, G. Yaari, J. A. Vander Heiden, G. Church, W. F. Donahue, R. Q. Hintzen, A. J. Huttner, J. D. Laman, R. M. Nagra, K. C. O’Connor, +7 Additional Authors

Journal Articles

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by autoimmune-mediated demyelination and neurodegeneration. The CNS of patients with MS harbors expanded clones of antigen-experienced B cells that reside in distinct compartments including the meninges, cerebrospinal fluid (CSF), and parenchyma. It is not understood whether this immune infiltrate initiates its development in the CNS or in peripheral tissues. B cells in the CSF can exchange with those in peripheral blood, implying that CNS B cells may have access to lymphoid tissue that may be the specific compartment(s) in which CNS-resident B cells encounter antigen and …

Transcriptional Diversity Of Long-Term Glioblastoma Survivors, N. K. Gerber, A. Goenka, S. Turcan, M. Reyngold, V. Makarov, K. Kannan, K. Beal, C. W. Brennan, J. T. Huse, T. A. Chan, +3 Additional Authors

Journal Articles

BACKGROUND: Glioblastoma (GBM) is a highly aggressive type of glioma with poor prognosis. However, a small number of patients live much longer than the median survival. A better understanding of these long-term survivors (LTSs) may provide important insight into the biology of GBM. METHODS: We identified 7 patients with GBM, treated at Memorial Sloan-Kettering Cancer Center (MSKCC), with survival >48 months. We characterized the transcriptome of each patient and determined rates of MGMT promoter methylation and IDH1 and IDH2 mutational status. We identified LTSs in 2 independent cohorts (The Cancer Genome Atlas [TCGA] and NCI Repository for Molecular Brain Neoplasia …

Defining Internal Target Volume Using Positron Emission Tomography For Radiation Therapy Planning Of Moving Lung Tumors, A. C. Riegel, M. K. Bucci, O. R. Mawlawi, M. Ahmad, D. Luo, A. Chandler, T. S. Pan

Journal Articles

Substantial disagreement exists over appropriate PET segmentation techniques for non-small cell lung cancer. Currently, no segmentation algorithm explicitly considers tumor motion in determining tumor borders. We developed an automatic PET segmentation model as a function of target volume, motion extent, and source-to-background ratio (the VMSBR model). The purpose of this work was to apply the VMSBR model and six other segmentation algorithms to a sample of lung tumors. PET and 4D CT were performed in the same imaging session for 23 patients (24 tumors) for radiation therapy planning. Internal target volumes (ITVs) were autosegmented on maximum intensity projection (MIP) of …

Substance Use In Clinical High Risk For Psychosis: A Review Of The Literature, J. Addington, N. Case, M. M. Saleem, A. M. Auther, B. A. Cornblatt, K. S. Cadenhead

Journal Articles

AimIn the literature, there is evidence suggesting an association between substance use and psychosis. However, little is known about substance use in those who may be in the pre-psychotic phase, that is, those who are putatively prodromal are considered to be at clinical high risk (CHR) of developing psychosis. MethodsWe conducted a review of publications measuring patterns and rates of substance use in CHR for psychosis individuals and the effects on the transition to psychosis. ResultsOf 5527 potentially relevant research papers, 10 met inclusion criteria of CHR subjects and specifically mentioned substance use in the sample. The results of these …

The Subjective Experience Of Youths At Clinically High Risk Of Psychosis: A Qualitative Study, S. Ben-David, M. L. Birnbaum, M. E. Eilenberg, J. E. Devylder, K. E. Gill, J. Schienle, N. Azimov, E. P. Lukens, L. Davidson, C. M. Corcoran

Journal Articles

Objective: Understanding the experience of individuals across stages of schizophrenia is important for development of services to promote recovery. As yet, little is known about the experience of individuals who exhibit prodromal symptoms of schizophrenia. Methods: Audiotaped interviews were conducted with 27 participants of diverse racial-ethnic backgrounds who were at clinically high risk of psychosis (15 males and 12 females; mean age 21). Phenomenological qualitative research techniques of coding, consensus, and comparison were used. Results: Emergent themes differed by gender. Themes for males were feeling abnormal or "broken," focus on going " crazy," fantasy and escapism, and alienation and despair, …

Effectiveness Of Lurasidone In Schizophrenia Or Schizoaffective Patients Switched From Other Antipsychotics: A 6-Month, Open-Label, Extension Study, L. Citrome, P. J. Weiden, J. P. Mcevoy, C. U. Correll, J. Cucchiaro, J. Hsu, A. Loebel

Journal Articles

Objective. To evaluate the long-term safety and tolerability of lurasidone in schizophrenia and schizoaffective disorder patients switched to lurasidone. Method. Patients in this multicenter, 6-month open-label, flexible-dose, extension study had completed a core 6-week randomized trial in which clinically stable, but symptomatic, outpatients with schizophrenia or schizoaffective disorder were switched to lurasidone. Patients started the extension study on treatment with the same dose of lurasidone taken at study endpoint of the 6-week core study; following this, lurasidone was flexibly dosed (40-120 mg/day), if clinically indicated, starting on Day 7 of the extension study. The primary safety endpoints were the proportion …

Neural Activation During Response Inhibition In Adult Attention-Deficit/Hyperactivity Disorder: Preliminary Findings On The Effects Of Medication And Symptom Severity, E. Congdon, L. L. Altshuler, J. A. Mumford, K. H. Karlsgodt, F. W. Sabb, J. Ventura, E. D. London, T. D. Cannon, R. M. Bilder, R. A. Poldrack, +1 Additional Author

Journal Articles

Studies of adults with attention-deficit/hyperactivity disorder (ADHD) have suggested that they have deficient response inhibition, but findings concerning the neural correlates of inhibition in this patient population are inconsistent. We used the Stop Signal task and functional magnetic resonance imaging (fMRI) to compare neural activation associated with response inhibition between adults with ADHD (N=35) and healthy comparison subjects (N=62), and in follow-up tests to examine the effect of current medication use and symptom severity. There were no differences in Stop Signal task performance or neural activation between ADHD and control participants. Among the ADHD participants, however, significant differences were associated …

Effects Of Aripiprazole Once-Monthly On Domains Of Personal And Social Performance: Results From 2 Multicenter, Randomized, Double-Blind Studies, W. W. Fleischhacker, R. A. Baker, A. Eramo, R. Sanchez, L. F. Tsai, T. Peters-Strickland, P. P. Perry, R. D. Mcquade, B. R. Johnson, W. H. Carson, J. M. Kane

Journal Articles

Objective: To assess the effects of maintenance therapy with aripiprazole once-monthly 400 mg on personal and social functioning. Methods: Data were analyzed from 2 randomized, double-blind trials of patients with schizophrenia requiring chronic antipsychotic treatment. One study was a 52-week trial of aripiprazole once-monthly 400 mg versus placebo; the other was a 38-week trial of aripiprazole once-monthly 400 mg, oral aripiprazole (10-30 mg daily), and aripiprazole once-monthly 50 mg (subtherapeutic dose to test assay sensitivity). Functioning was assessed using the Personal and Social Performance (PSP) scale, comprising 4 domain subscales. Results: In the 52-week study, 403 patients stabilized on aripiprazole …

Predicting Risky Choices From Brain Activity Patterns, S. M. Helfinstein, T. Schonberg, E. Congdon, K. H. Karlsgodt, J. A. Mumford, F. W. Sabb, T. D. Cannon, E. D. London, R. M. Bilder, R. A. Poldrack

Journal Articles

Previous research has implicated a large network of brain regions in the processing of risk during decision making. However, it has not yet been determined if activity in these regions is predictive of choices on future risky decisions. Here, we examined functional MRI data from a large sample of healthy subjects performing a naturalistic risk-taking task and used a classification analysis approach to predict whether individuals would choose risky or safe options on upcoming trials. We were able to predict choice category successfully in 71.8% of cases. Searchlight analysis revealed a network of brain regions where activity patterns were reliably …

Surgical Management Of Ascending Aortic Aneurysm And Its Complications, S. Sran, M. Sran, N. Ferguson, A. N. Makaryus

Journal Articles

Ascending aortic aneurysms involving the proximal aortic arch, arising anywhere from the aortic valve to the innominate artery, represent various problems in which open surgery is generally required. Surgical options include excision of the aortic pathology or wrapping the aneurysm shell with an aortic Dacron graft. Intervention using the latter method can lead to extravasation of blood along the suture lines resulting in continuous bleeding within the periprosthetic space. The Cabrol technique was developed as a method for decompression of postoperative leaks by the formation of a conduit system from the periprosthetic space to the right atrium. The coronary ostia …

Diagnosis Of Abnormal Biliary Copper Excretion By Positron Emission Tomography With Targeting Of (64)Copper-Asialofetuin Complex In Lec Rat Model Of Wilson's Disease, R. Bahde, S. Kapoor, K. K. Bhargava, C. J. Palestro, S. Gupta

Journal Articles

Identification by molecular imaging of key processes in handling of transition state metals, such as copper (Cu), will be of considerable clinical value. For instance, the ability to diagnose Wilson's disease with molecular imaging by identifying copper excretion in an ATP7B-dependent manner will be very significant. To develop highly effective diagnostic approaches, we hypothesized that targeting of radiocopper via the asialoglycoprotein receptor will be appropriate for positron emission tomography, and examined this approach in a rat model of Wilson's disease. After complexing (64)Cu to asialofetuin we studied handling of this complex compared with (64)Cu in healthy LEA rats and diseased …

Ct Perfusion For Detection Of Delayed Cerebral Ischemia In Aneurysmal Subarachnoid Hemorrhage: A Systematic Review And Meta-Analysis, D. I. A. Mir, A. Gupta, A. Dunning, L. Puchi, C. L. Robinson, H. A. B. Epstein, P. C. Sanelli

Journal Articles

BACKGROUND AND PURPOSE: Delayed cerebral ischemia is a significant cause of morbidity and mortality after aneurysmal SAH, leading to poor outcomes. The purpose of this study was to evaluate the usefulness of CTP in determining delayed cerebral ischemia in patients with aneurysmal SAH. MATERIALS AND METHODS: We conducted a systematic review evaluating studies that assessed CTP in patients with aneurysmal SAH for determining delayed cerebral ischemia. Studies using any of the following definitions of delayed cerebral ischemia were included in the systematic review: 1) new onset of clinical deterioration, 2) cerebral infarction identified on follow-up CT or MR imaging, and …

Nuclear Medicine And The Failed Joint Replacement: Past, Present, And Future, C. J. Palestro

Journal Articles

Soon after the introduction of the modern prosthetic joint, it was recognized that radionuclide imaging provides useful information about these devices. The bone scan was used extensively to identify causes of prosthetic joint failure. It became apparent, however, that although sensitive, regardless of how the images were analyzed or how it was performed, the test was not specific and could not distinguish among the causes of prosthetic failure. Advances in anatomic imaging, notably cross sectional modalities, have facilitated the diagnosis of many, if not most, causes of prosthetic failure, with the important exception of infection. This has led to a …

Attenuating The Systemic Inflammatory Response To Adult Cardiopulmonary Bypass: A Critical Review Of The Evidence Base, R. Clive Landis, J. R. Brown, D. Fitzgerald, D. S. Likosky, L. Shore-Lesserson, R. A. Baker, J. W. Hammon

Journal Articles

A wide range of pharmacological, surgical, and mechanical pump approaches have been studied to attenuate the systemic inflammatory response to cardiopulmonary bypass, yet no systematically based review exists to cover the scope of anti-inflammatory interventions deployed. We therefore conducted an evidence-based review to capture "self-identified" anti-inflammatory interventions among adult cardiopulmonary bypass procedures. To be included, trials had to measure at least one inflammatory mediator and one clinical outcome, specified in the "Outcomes 2010" consensus statement. Ninety-eight papers satisfied inclusion criteria and formed the basis of the review. The review identified 33 different interventions and approaches to attenuate the systemic inflammatory …

Leveraging Practice-Based Research Networks To Accelerate Implementation And Diffusion Of Chronic Kidney Disease Guidelines In Primary Care Practices: A Prospective Cohort Study, James W. Mold, Cheryl B. Aspy, Paul D. Smith, Therese M. Zink, Lyndee Knox, Paula Darby Lipman, Margot Krauss, D. Robert Harris, Chester Fox, Leif I. Solberg, Rachel Cohen

Family Medicine Faculty Publications

Background

Four practice-based research networks (PBRNs) participated in a study to determine whether networks could increase dissemination, implementation, and diffusion of evidence-based treatment guidelines for chronic kidney disease by leveraging early adopter practices.

Methods

Motivated practices from four PBRNs received baseline and periodic performance feedback, academic detailing, and weekly practice facilitation for 6 months during wave I of the study. Each wave I practice then recruited two additional practices (wave II), which received performance feedback and academic detailing and participated in monthly local learning collaboratives led by the wave I clinicians. They received only monthly practice facilitation. The primary outcomes …

Smoking And Major Depressive Disorder In Chinese Women, Qiang He, Lei Yang, Shenxun Shi, Jingfang Gao, Ming Tao, Kerang Zhang, Chengge Gao, Lijun Yang, Kan Li, Jianguo Shi, Gang Wang, Lanfen Liu, Jinbei Zhang, Bo Du, Guoqing Jiang, Jianhua Shen, Zhen Zhang, Wei Liang, Jing Sun, Jian Hu, Tiebang Liu, Xueyi Wang, Guodong Miao, Huaqing Meng, Yi Li, Chunmei Hu, Yi Li, Guoping Huang, Gongying Li, Baowei Ha, Hong Deng, Qiyi Mei, Hui Zhong, Shugui Gao, Hong Sang, Yutang Zhang, Xiang Fang, Fengyu Yu, Donglin Yang, Tieqiao Liu, Yunchun Chen, Xiaohong Hong, Wenyuan Wu, Guibing Chen, Min Cai, Yan Song, Jiyang Pan, Jicheng Dong, Runde Pan, Wei Zhang, Zhenming Shen, Zhengrong Liu, Danhua Gu, Xiaoping Wang, Ying Liu, Xiaojuan Liu, Qiwen Zhang, Yihan Li, Yiping Chen, Kenneth S. Kendler, Xumei Wang, Youhui Li, Jonathan Flint

Psychiatry Publications

Objective

To investigate the risk factors that contribute to smoking in female patients with major depressive disorder (MDD) and the clinical features in depressed smokers.

Methods

We examined the smoking status and clinical features in 6120 Han Chinese women with MDD (DSM-IV) between 30 and 60 years of age across China. Logistic regression was used to determine the association between clinical features of MDD and smoking status and between risk factors for MDD and smoking status.

Results

Among the recurrent MDD patients there were 216(3.6%) current smokers, 117 (2.0%) former smokers and 333(5.6%) lifetime smokers. Lifetime smokers had a slightly …

Associations Of Educational Attainment, Occupation, Social Class And Major Depressive Disorder Among Han Chinese Women, Jianguo Shi, Yan Zhang, Feihu Liu, Yajuan Li, Junhui Wang, Jonathan Flint, Jingfang Gao, Youhui Li, Ming Tao, Kerang Zhang, Xumei Wang, Chengge Gao, Lijun Yang, Kan Li, Shenxun Shi, Gang Wang, Lanfen Liu, Jinbei Zhang, Bo Du, Guoqing Jiang, Jianhua Shen, Zhen Zhang, Wei Liang, Jing Sun, Jian Hu, Tiebang Liu, Xueyi Wang, Guodong Miao, Huaqing Meng, Yi Li, Chunmei Hu, Yi Li, Guoping Huang, Gongying Li, Baowei Ha, Hong Deng, Qiyi Mei, Hui Zhong, Shugui Gao, Hong Sang, Yutang Zhang, Xiang Fang, Fengyu Yu, Donglin Yang, Tieqiao Liu, Yunchun Chen, Xiaohong Hong, Wenyuan Wu, Guibing Chen, Min Cai, Yan Song, Jiyang Pan, Jicheng Dong, Runde Pan, Wei Zhang, Zhenming Shen, Zhengrong Liu, Danhua Gu, Xiaoping Wang, Xiaojuan Liu, Qiwen Zhang, Yihan Li, Yiping Chen, Kenneth S. Kendler

Psychiatry Publications

Background

The prevalence of major depressive disorder (MDD) is higher in those with low levels of educational attainment, the unemployed and those with low social status. However the extent to which these factors cause MDD is unclear. Most of the available data comes from studies in developed countries, and these findings may not extrapolate to developing countries. Examining the relationship between MDD and socio economic status in China is likely to add to the debate because of the radical economic and social changes occurring in China over the last 30 years.

Principal findings

We report results from 3,639 Chinese women …

Medical Literary Messenger (Vol. 1, No. 2, Spring 2014)

Medical Literary Messenger

Ether / Anne Leitch -- Pharmacy and Fotography / Lulú De Panbehchi -- Had Mariam Been Watching Through a Crack in the Door / Natalie Sterrett -- Teachings from a 15-year-old “drug seeker” / Larry Istrail -- Annie O’Malley / Mary Ellen Olbrisch -- cartoon / David James Bromley -- YCCOM: You Can Count on Me / Colleen Gallagher -- Clock Clock Clock / Rita Ciresi -- On the Advantages of Not Being Totally Present / Charles F. Opalak -- illustration / Adrienne Robin Enriquez -- The E-mail / Olivia M. McGuire -- Lamentation: Phillip Seymour Hoffman / Mary Ellen …

Intuitive, But Not Simple: Including Explicit Water Molecules In Protein-Protein Docking Simulations Improves Model Quality, Hardik I. Parikh, Glen E. Kellogg

Medicinal Chemistry Publications

Characterizing the nature of interaction between proteins that have not been experimentally co-crystallized requires a computational docking approach that can successfully predict the spatial conformation adopted in the complex. In this work, the Hydropathic INTeractions (HINT) force field model was used for scoring docked models in a data set of 30 high-resolution crystallographically characterized “dry” protein-protein complexes, and was shown to reliably identify native-like models. However, most current protein-protein docking algorithms fail to explicitly account for water molecules involved in bridging interactions that mediate and stabilize the association of the protein partners, so we used HINT to illuminate the physical …

Comprehensive Analysis Of Human Cytomegalovirus Microrna Expression During Lytic And Quiescent Infection, Zhang-Zhou Shen, Xing Pan, Ling-Feng Miao, Han-Qing Ye, Stéphane Chavanas, Christian Davrinche, Michael Mcvoy, Min-Hua Luo

Pediatrics Publications

Background

Human cytomegalovirus (HCMV) encodes microRNAs (miRNAs) that function as post-transcriptional regulators of gene expression during lytic infection in permissive cells. Some miRNAs have been shown to suppress virus replication, which could help HCMV to establish or maintain latent infection. However, HCMV miRNA expression has not been comprehensively examined and compared using cell culture systems representing permissive (lytic) and semi-permissive vs. non-permissive (latent-like) infection.

Methods

Viral miRNAs levels and expression kinetics during HCMV infection were determined by miRNA-specific stem-loop RT-PCR. HCMV infected THP-1 (non-permissive), differentiated THP-1 (d-THP-1, semi-permissive) and human embryo lung fibroblasts (HELs, fully-permissive) were examined. The impact of …