Life Sciences Commons^™

In Silico Study Of Newly Synthesized Opioid Analgesics Bound To Three Opioid Receptors, Abdullah Allaoa, Mai Zahran

Publications and Research

Opioids are the most widely used drugs for the treatment of moderate to severe, chronic pain. They achieve antinociception by activation of mu (MOR-1), kappa (KOR-1), and delta (DOR-1) opioid receptors. Natural products found in kratom plant, Mitragyna speciosa, represent diverse chemical groups with opioid activity, providing opportunities to better understand opioid pharmacology. Pharmacology studies show that Mitragynine pseudoindoxyl is a mu agonist/delta antagonist opioid with a signaling bias for G-protein-mediated signaling pathways in vitro and which produced potent antinociception in vivo. Respiratory depression assays along with other behavioral testing also showed that some of the major problems …

Caenorhabditis Elegans Dbl-1/Bmp Regulates Lipid Accumulation Via Interaction With Insulin Signaling, James F. Clark, Michael Meade, Gehan Ranepura, David H. Hall, Cathy Savage-Dunn

Publications and Research

Metabolic homeostasis is coordinately controlled by diverse inputs. Understanding these regulatory networks is vital to combating metabolic disorders. The nematode Caenorhabditis elegans has emerged as a powerful, genetically tractable model system for the discovery of lipid regulatory mechanisms. Here we introduce DBL-1, the C. elegans homolog of bone morphogenetic protein 2/4 (BMP2/4), as a significant regulator of lipid homeostasis. We used neutral lipid staining and a lipid droplet marker to demonstrate that both increases and decreases in DBL-1/BMP signaling result in reduced lipid stores and lipid droplet count. We find that lipid droplet size, however, correlates positively with the level …

Nlrp10 Enhances Cd4+ T-Cell-Mediated Ifnγ Response Via Regulation Of Dendritic Cell-Derived Il-12 Release, Maurizio Vacca, Julia Böhme, Lisa Zambetti, Hanif Javanmard Khameneh, Bhairav S. Paleja, Federica Laudisi, Adrian W. S. Ho, Kurt Neo, Keith Weng Kit Leong, Mardiana Marzuki, Bernett Lee, Michael Poidinger, Laura Santambrogio, Liana Tsenova, Francesca Zolezzi, Gennaro De Libero, Amit Singhal, Alessandra Mortellaro

Publications and Research

NLRP10 is a nucleotide-binding oligomerization domain-like receptor that functions as an intracellular pattern recognition receptor for microbial products. Here, we generated a Nlrp10−/− mouse to delineate the role of NLRP10 in the host immune response and found that Nlrp10−/− dendritic cells (DCs) elicited sub-optimal IFNγ production by antigenspecific CD4+ T cells compared to wild-type (WT) DCs. In response to T-cell encounter, CD40 ligation or Toll-like receptor 9 stimulation, Nlrp10−/− DCs produced low levels of IL-12, due to a substantial decrease in NF-κB activation. Defective IL-12 production was also evident in vivo and affected IFNγ production by CD4+ T cells. Upon …

Early And Late Components Of Eeg Delay Activity Correlate Differently With Scene Working Memory Performance, Timothy M. Ellmore, Kenneth Ng, Chelsea P. Reichert

Publications and Research

Sustained and elevated activity during the working memory delay period has long been considered the primary neural correlate for maintaining information over short time intervals. This idea has recently been reinterpreted in light of findings generated from multiple neural recording modalities and levels of analysis. To further investigate the sustained or transient nature of activity, the temporal-spectral evolution (TSE) of delay period activity was examined in humans with high density EEG during performance of a Sternberg working memory paradigm with a relatively long six second delay and with novel scenes as stimuli. Multiple analyses were conducted using different trial window …

Association Of Body Shape Index (Absi) With Cardio-Metabolic Risk Factors: A Crosssectional Study Of 6081 Caucasian Adults, Simona Bertoli, Alessandro Leone, Nir Y. Krakauer, Giorgio Bedogni, Angelo Vanzulli, Valentino Ippocrates Redaelli, Ramona De Amicis, Laila Vignati, Jesse C. Krakauer, Alberto Battezzati

Publications and Research

A Body Shape Index (ABSI) was specifically developed as a transformation of waist circumference (WC), statistically independent of BMI to better evaluate the relative contribution of WC to central obesity and clinical outcomes. Previous studies have found ABSI is associated with total mortality and cardiovascular events. However, no study has specifically evaluated the joint contribution of ABSI and BMI to cardio-metabolic outcomes (high triglycerides, low HDL, high fasting glucose and high blood pressure). With this aim, we performed a retrospective study on 6081 Caucasian adults. Subjects underwent a medical interview, anthropometric measurements, blood sampling, measurement of blood pressure, and measurement …

Chloride Intracellular Channel Proteins Respond To Heat Stress In Caenorhabditis Elegans, Jun Liang, Yakov Shaulov, Cathy Savage-Dunn, Stéphane Boissinot, Tasmia Hoque

Publications and Research

Chloride intracellular channel proteins (CLICs) are multi-functional proteins that are expressed in various cell types and differ in their subcellular location. Two CLIC homologs, EXL-1 (excretory canal abnormal like-1) and EXC-4 (excretory canal abnormal± 4), are encoded in the Caenorhabditis elegans genome, providing an excellent model to study the functional diversification of CLIC proteins. EXC-4 functions in excretory canal formation during normal animal development. However, to date, the physiological function of EXL-1 remains largely unknown. In this study, we demonstrate that EXL-1 responds specifically to heat stress and translocates from the cytoplasm to the nucleus in intestinal cells and body …

Maternal Choline Supplementation Alters Fetal Growth Patterns In A Mouse Model Of Placental Insufficiency, Julia H. King, Sze Ting (Cecilia) Kwan, Jian Yan, Kevin C. Klatt, Xinyin Jiang, Mark S. Roberson, Marie A. Caudill

Publications and Research

Impairments in placental development can adversely affect pregnancy outcomes. The bioactive nutrient choline may mitigate some of these impairments, as suggested by data in humans, animals, and human trophoblasts. Herein, we investigated the effects of maternal choline supplementation (MCS) on parameters of fetal growth in a Dlx3+/− (distal-less homeobox 3) mouse model of placental insufficiency. Dlx3+/− female mice were assigned to 1X (control), 2X, or 4X choline intake levels during gestation. Dams were sacrificed at embryonic days E10.5, 12.5, 15.5, and 18.5. At E10.5, placental weight, embryo weight, and placental efficiency were higher in 4X versus 1X choline. Higher concentrations …

Effects Of A Multidisciplinary Weight Loss Intervention In Overweight And Obese Children And Adolescents: 11 Years Of Experience, Chiara Mameli, Jesse C. Krakauer, Nir Y. Krakauer, Alessandra Bosetti, Chiara Matilde Ferrari, Laura Schneider, Barbara Borsani, Sara Arrigoni, Erica Pendezza, Gian Vincenzo Zuccotti

Publications and Research

Aims To evaluate the effects of an outpatient multidisciplinary weight loss intervention in reducing body mass index (BMI) in children and adolescents suffering overweight and obesity, changes in A Body Shape Index (ABSI, waist circumference normalized to height and weight) and Hip Index (HI, normalized hip circumference) during treatment and correlation between the ABSI and HI with change in BMI z score.

Methods We analyze anthropometric data from pediatric patients affected by overweight and obesity aged 2 to 18 years old who entered our multidisciplinary weight loss intervention, which included medical, psychological and nutritional sessions, from January 1st 2006 to …

Transcranial Direct Current Stimulation And Sports Performance, Dylan J. Edwards, Mar Cortes, Susan Wortman-Jutt, David Putrino, Marom Bikson, Gary Thickbroom, Alvaro Pascual-Leone

Publications and Research

No abstract provided.

Zika Virus-Like Particle (Vlp) Based Vaccine, Héléne Boigard, Alexandra Alimova, George R. Martin, Al Katz, Paul Gottlieb, Jose M. Galarza

Publications and Research

The newly emerged mosquito-borne Zika virus poses a major public challenge due to its ability to cause significant birth defects and neurological disorders. The impact of sexual transmission is unclear but raises further concerns about virus dissemination. No specific treatment or vaccine is currently available, thus the development of a safe and effective vaccine is paramount. Here we describe a novel strategy to assemble Zika virus-like particles (VLPs) by co-expressing the structural (CprME) and non-structural (NS2B/NS3) proteins, and demonstrate their effectiveness as vaccines. VLPs are produced in a suspension culture of mammalian cells and self-assembled into particles closely resembling Zika …

How Income And Food Prices Influence Global Dietary Intakes By Age And Sex: Evidence From 164 Countries, Andrew Muhammad, Anna D'Souza, Birgit Meade, Renata Micha, Dariush Mozaffarian

Publications and Research

Background While income and prices are key drivers of dietary choices, how their influence varies by food category, nation, and demographics is not well established. Based on intake data for 164 countries and 11 food categories, we examined how income and food prices relate to food intake globally, including by world region, age, and sex.

Methods We used 2010 intake data from the Global Dietary Database, the first database of consumption estimates for major food categories by country, age, and sex. We combined these data with national per capita GDP and food price data. We estimated intake responsiveness to income …

Stability Of Synthetic Cathinones In Oral Fluid Samples, Briana Miller, Jiyoung Kim, Marta Concheiro

Publications and Research

Synthetic cathinones are new stimulant drugs derived from cathinone that have been sold as “legal highs” worldwide. These compounds can elicit powerful effects such as delusions, hallucinations as well as other potentially dangerous behavior. New analogs with varying effects and potencies are constantly introduced in the market to evade legislation, and they are not detected by routine screening and confirmation methods. Oral fluid is an alternative matrix of increasing interest in forensic toxicology. Its collection is non-invasive and easily supervised, and positive drug findings typically reflect recent drug exposure. The focus of this research was to develop a method for …

Unique Synergistic Formulation Of Curcumin, Epicatechin Gallate And Resveratrol, Tricurin, Suppresses Hpv E6, Eliminates Hpv+ Cancer Cells, And Inhibits Tumor Progression, Sumit Mukherjee, Priya Ranjan Debata, Rahman Hussaini, Kaushiki Chatterjee, Juliet N. E. Baidoo, Samay Sampat, Anita Szerszen, Joseph P. Navarra, Jimmie Fata, Elena Severinova, Probal Banerjee, Mario R. Castellanos

Publications and Research

Curcumin (from curry) (C) is highly potent against cervical cancer cells (CCC), but poor bioavailability has limited its clinical use. Similar natural polyphenols resveratrol (from grapes) (R), and epicatechin gallate (from green tea) (E) also display activity against CCC. By treating CCC (HeLa) with C, E, or R, or combinations of these compounds, we computed combination indices and observed a strong synergism among C, E, and R at the unique molar ratio 4:1:12.5. This combination, named as TriCurin, rapidly down regulated HPV18 E6 and NF-kB expression while concomitantly inducing the tumor suppressor protein p53 in HeLa cells. In the mouse …

Mirnas Associated With Prostate Cancer Risk And Progression, Hung N. Luu, Hui-Yi Lin, Karina Dalsgaard Sorensen, Olorunseun O. Ogunwobi, Nagi Kumar, Ganna Chornokur, Catherine Phelan, Dominique Jones, Lacreis Kidd, Jyotsna Batra, Kosj Yamoah, Anders Berglund, Robert J. Rounbehler, Mihi Yang, Sang Haak Lee, Nahyeon Kang, Seung Joon Kim, Jong Y. Park, Giuliano Di Pietro

Publications and Research

Prostate cancer is the most common malignancy among men in the US. Though considerable improvement in the diagnosis of prostate cancer has been achieved in the past decade, predicting disease outcome remains a major clinical challenge. Recent expression profiling studies in prostate cancer suggest microRNAs (miRNAs) may serve as potential biomarkers for prostate cancer risk and disease progression. miRNAs comprise a large family of about 22-nucleotide-long non-protein coding RNAs, regulate gene expression post-transcriptionally and participate in the regulation of numerous cellular processes. In this review, we discuss the current status of miRNA in studies evaluating the disease progression of prostate …

Vestibular Activation Habituates The Vasovagal Response In The Rat, Bernard Cohen, Giorgio P. Martinelli, Yongqing Xiang, Theodore Raphan, Sergei B. Yakushin

Publications and Research

Vasovagal syncope is a significant medical problem without effective therapy, postulated to be related to a collapse of baroreflex function. While some studies have shown that repeated static tilts can block vasovagal syncope, this was not found in other studies. Using anesthetized, male Long–Evans rats that were highly susceptible to generation of vasovagal responses, we found that repeated activation of the vestibulosympathetic reflex (VSR) with ±2 and ±3 mA, 0.025 Hz sinusoidal galvanic vestibular stimulation (sGVS) caused incremental changes in blood pressure (BP) and heart rate (HR) that blocked further generation of vasovagal responses. Initially, BP and HR fell ≈20–50 …

Beta Oscillatory Changes And Retention Of Motor Skills During Practice In Healthy Subjects And In Patients With Parkinson’S Disease, Aaron B. Nelson, Clara Moisello, Jing Lin, Priya Panday, Serena Ricci, Andrea Canessa, Alessandro Di Rocco, Angelo Quartarone, Giuseppe Frazzitta, Ioannis U. Isaias, Giulio Tononi, Chiara Cirelli, M. Felice Ghilardi

Publications and Research

Recently we found that modulation depth of beta power during movement increases with practice over sensory-motor areas in normal subjects but not in patients with Parkinson’s disease (PD). As such changesmight reflect use-dependentmodifications, we concluded that reduction of beta enhancement in PD represents saturation of cortical plasticity. A few questions remained open: What is the relation between these EEG changes and retention of motor skills? Would a second task exposure restore beta modulation enhancement in PD? Do practice-induced increases of beta modulation occur within each block? We thus recorded EEG in patients with PD and age-matched controls in two consecutive …

Ecological Correlations Of Dietary Food Intake And Mental Health Disorders, Jordan Hoerr, Joshua Fogel, Benjamin Van Voorhees

Publications and Research

This paper examines the ecological association of dietary food intake with mental health outcomes on the group level across countries. Published data from the World Mental Health Survey were used to compare lifetime prevalence of four categories of mental health disorders (anxiety disorders, mood disorders, impulse control disorders, and substance use disorders) with a country’s fish/seafood and sugar/sweetener supply quantity using the Spearman rank correlation. Data were compared for 17 countries across the world. Sugar and sweetener supply quantity was significantly and positively associated with anxiety disorders (rho = 0.75, p = 0.001), mood disorders (rho = 0.75, p = …

Gait Changes In A Line Of Mice Artificially Selected For Longer Limbs, Leah M. Sparrow, Emily Pellattt, Sabrina S. Yu, David A. Raichlen, Herman Pontzer, Campbell Rolian

Publications and Research

In legged terrestrial locomotion, the duration of stance phase, i.e., when limbs are in contact with the substrate, is positively correlated with limb length, and negatively correlated with the metabolic cost of transport. These relationships are well documented at the interspecific level, across a broad range of body sizes and travel speeds. However, such relationships are harder to evaluate within species (i.e., where natural selection operates), largely for practical reasons, including low population variance in limb length, and the presence of confounding factors such as body mass, or training. Here, we compared spatiotemporal kinematics of gait in Longshanks, a long-legged …

Nourishing Nycha: Food Policy As A Tool For Improving The Well-Being Of New York City’S Public Housing Residents, Nevin Cohen, Nicholas Freudenberg, Craig Willingham

Publications and Research

This policy brief examines food environments in New York City public housing. It looks at the food public housing residents buy, prepare and eat and the role food plays in the health, environment and economy of the city’s NYCHA population. Our goal is to contribute new insights into how NYCHA can use food policy and programs to improve the well-being of its residents and make New York City healthier, more self-sufficient, safer and more sustainable.

Plasmid Diversity And Phylogenetic Consistency In The Lyme Disease Agent Borrelia Burgdorferi, Sherwood R. Casjens, Eddie B. Gilcrease, Marija Vujadinovic, Emmanuel F. Mongodin, Benjamin J. Luft, Steven E. Schutzer, Claire M. Fraser, Wei-Gang Qiu

Publications and Research

Background: Bacteria from the genus Borrelia are known to harbor numerous linear and circular plasmids. We report here a comparative analysis of the nucleotide sequences of 236 plasmids present in fourteen independent isolates of the Lyme disease agent B. burgdorferi.

Results: We have sequenced the genomes of 14 B. burgdorferi sensu stricto isolates that carry a total of 236 plasmids. These individual isolates carry between seven and 23 plasmids. Their chromosomes, the cp26 and cp32 circular plasmids, as well as the lp54 linear plasmid, are quite evolutionarily stable; however, the remaining plasmids have undergone numerous non-homologous and often duplicative recombination …

Quantifying Cerebral Contributions To Pain Beyond Nociception, Choong-Wan Woo, Liane Schmidt, Anjali Krishnan, Marieke Jempa, Mathieu Roy, Martin A. Lindquist, Lauren Y. Atlas, Tor D. Wager

Publications and Research

Cerebral processes contribute to pain beyond the level of nociceptive input and mediate psychological and behavioural influences. However, cerebral contributions beyond nociception are not yet well characterized, leading to a predominant focus on nociception when studying pain and developing interventions. Here we use functional magnetic resonance imaging combined with machine learning to develop a multivariate pattern signature—termed the stimulus intensity independent pain signature-1 (SIIPS1)—that predicts pain above and beyond nociceptive input in four training data sets (Studies 1–4, N¼137). The SIIPS1 includes patterns of activity in nucleus accumbens, lateral prefrontal and parahippocampal cortices, and other regions. In cross-validated analyses of …

A Novel Microrna-1207-3p/Fndc1/Fn1/Ar Regulatory Pathway In Prostate Cancer, Dibash K. Das, Olorunseun O. Ogunwobi

Publications and Research

Prostate cancer (PCa) is the second most common cause of cancer-specific deaths in the U.S. Unfortunately, the underlying molecular mechanisms for its development and progression remain unclear. Studies have established that microRNAs (miRNAs) are dysregulated in PCa. The intron-derived microRNA-1207-3p (miR-1207-3p) is encoded at the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, miR-1207-3p in PCa had not previously been investigated. Therefore, we explored if miR-1207-3p plays any regulatory role in PCa. We discovered that miR-1207-3p is significantly underexpressed in PCa cell lines in comparison to normal prostate epithelial cells, and …

Protein Calorie Malnutrition, Nutritional Intervention And Personalized Cancer Care, Anju Gangadharan, Sung-Eun Choi, Ahmed Hassan, Nehad M. Ayoub, Gina Durante, Sakshi Balwani, Young Hee Kim, Andrew Pecora, Andre Goy, K. Stephen Suh

Publications and Research

Cancer patients often experience weight loss caused by protein calorie malnutrition (PCM) during the course of the disease or treatment. PCM is expressed as severe if the patient has two or more of the following characteristics: obvious significant muscle wasting, loss of subcutaneous fat; nutritional intake of <50% of recommended intake for 2 weeks or more; bedridden or otherwise significantly reduced functional capacity; weight loss of >2% in 1 week, 5% in 1 month, or 7.5% in 3 months. Cancer anorexiacachexia syndrome (CACS) is a multifactorial condition of advanced PCM associated with underlying illness (in this case cancer) and is characterized by loss of muscle with or without loss of fat mass. Cachexia is defined as weight loss of …

Identification, Validation, And Targeting Of The Mutant P53- Parp-Mcm Chromatin Axis In Triple Negative Breast Cancer, Wei-Gang Qiu, Alla Polotskaia, Gu Xiao, Lia Di, Yuhan Zhao, Wenwei Hu, John Philip, Ronald C. Hendrickson, Jill Bargonetti

Publications and Research

Over 80% of triple negative breast cancers express mutant p53. Mutant p53 often gains oncogenic function suggesting that triple negative breast cancers may be driven by p53 protein type. To determine the chromatin targets of this gain-of-function mutant p53 we used inducible knockdown of endogenous gain-of-function mtp53 in MDA-MB-468 cells in conjunction with stable isotope labeling with amino acids in cell culture and subcellular fractionation. We sequenced over 70,000 total peptides for each corresponding reciprocal data set and were able to identify 3010 unique cytoplasmic fraction proteins and 3403 unique chromatin fraction proteins. The present proteomics experiment corroborated our previous …

Cerebellar Tdcs: A Novel Approach To Augment Language Treatment Post-Stroke, Rajani Sebastian, Sadhvi Saxena, Kyrana Tsapkini, Andreia V. Faria, Charltien Long, Amy Wright, Cameron Davis, Donna C. Tippett, Antonios P. Mourdoukoutas, Marom Bikson, Pablo Celnik, Argye E. Hillis

Publications and Research

People with post-stroke aphasia may have some degree of chronic deficit for which current rehabilitative treatments are variably effective. Accumulating evidence suggests that transcranial direct current stimulation (tDCS) may be useful for enhancing the effects of behavioral aphasia treatment. However, it remains unclear which brain regions should be stimulated to optimize effects on language recovery. Here, we report on the therapeutic potential of right cerebellar tDCS in augmenting language recovery in SMY, who sustained bilateral MCA infarct resulting in aphasia and anarthria. We investigated the effects of 15 sessions of anodal cerebellar tDCS coupled with spelling therapy using a randomized, …

Polyphenols Content And Antioxidant Activity Of Artemisia Sieversiana Willd. In Western Pamir, Gulazor Miravalova, Sh. Kurbonbekova, Sh. Satorov, Akobir Mirzorahimov, Dovudsho Navruzshoev, Vyacheslav Dushenkov, M. Vakhidova

Publications and Research

Polyphenols content and antioxidant activity in Artemisia sieversiana Willd. were investigated in relation to the altitude of the plant growth in the Western Pamir region. Antioxidant activity generally correlated with the polyphenols content. However, no significant association was found between an altitude of the sample collection and polyphenols content or antioxidant activity.

Burnout And The Hypothalamic-Pituitary-Thyroid Axis: A Methodological Comment, Renzo Bianchi, Irvin Sam Schonfeld, Eric Laurent

Publications and Research

Because (a) burnout overlaps with depression and (b) depression has been associated with altered functioning of the hypothalamic-pituitary-thyroid axis changes in the activity of the HPT axis can be expected in burnout. Most probably, Guo et al.’s (2017) results are flawed by a severe form of the “healthy worker effect.”

Biological Research On Burnout-Depression Overlap: Long-Standing Limitations And On-Going Reflections, Renzo Bianchi, Irvin Sam Schonfeld, Eric Laurent

Publications and Research

In this commentary, we discuss seldom-noticed methodological problems affecting biological research on burnout and depression and make recommendations to overcome the limitations of past studies conducted in this area. First, we suggest that identified subtypes of depression (e.g., depression with melancholic features and depression with atypical features) should be taken into account in future biological research on burnout and depression, given that different subtypes of depression have been associated with distinct autonomic and neuroendocrine profiles. Second, we underline that research on burnout-depression overlap is made difficult by the absence of a consensual conceptualization and operationalization of burnout. In order to …