Medicine and Health Sciences Commons^™

Efficient Method For Transfer Of Microinjected Eggs To Mouse Ampulla For Generating Transgenic Mice, Guang Wen, Jin Di, Qian Li, Jianling Chen, Ling Jin, Cheng Wang, Sanqing Xu

Publications and Research

Background: The new method described here is highly efficient in transferring microinjected mouse eggs (MEs) through the bursa membrane of a surrogate mother mouse to the ampulla of the oviduct without damaging the blood vessels on the bursa membrane.

Results: This method causes no loss of blood, and it produces newborn pups/founders from approximately 70% of the transferred MEs, because only a small hole is made on the blood vessel–free area of the bursa membrane and ampulla of the surrogate mother mouse. The infundibulum remains intact. The small hole on the bursa membrane/ ampulla may already heal up before the …

Temporary Nerve Block At Selected Digits Revealed Hand Motor Deficits In Grasping Tasks, Aude Cateron, Kerry Mcpartlan, Christina Gioeli, Emily Reid, Matt Turturro, Barry Hahn, Cynthia Benson, Wei Zhang

Publications and Research

Peripheral sensory feedback plays a crucial role in ensuring correct motor execution throughout hand grasp control. Previous studies utilized local anesthesia to deprive somatosensory feedback in the digits or hand, observations included sensorimotor deficits at both corticospinal and peripheral levels. However, the questions of how the disturbed and intact sensory input integrate and interact with each other to assist the motor program execution, and whether the motor coordination based on motor output variability between affected and non-affected elements (e.g., digits) becomes interfered by the local sensory deficiency, have not been answered. The current study aims to investigate the effect of …

Direct Current-Induced Calcium Trafficking In Different Neuronal Preparations, Andrzej Wieraszko, Zaghloul Ahmed

Publications and Research

The influence of direct current (DC) stimulation on radioactive calcium trafficking in sciatic nerve in vivo and in vitro, spinal cord, and synaptosomes was investigated. The exposure to DC enhanced calcium redistribution in all of these preparations. The effect was dependent on the strength of the stimulation and extended beyond the phase of exposure to DC. The DC-induced increase in calcium sequestration by synaptosomes was significantly reduced by cobalt and rupture of synaptosomes by osmotic shock. Although both anodal and cathodal currents were effective, the experiments with two electrodes of different areas revealed that cathodal stimulation exerted stronger effect. The …

Fhf2 Gene Deletion Causes Temperature-Sensitive Cardiac Conduction Failure, David S. Park, Akshay Shekhar, Christopher Marra, Xianming Lin, Carolina Vasquez, Sergio Solinas, Kevin Kelley, Gregory Morley, Mitchell Goldfarb, Glenn I. Fishman

Publications and Research

Fever is a highly conserved systemic response to infection dating back over 600 million years. Although conferring a survival benefit, fever can negatively impact the function of excitable tissues, such as the heart, producing cardiac arrhythmias. Here we show that mice lacking fibroblast growth factor homologous factor 2 (FHF2) have normal cardiac rhythm at baseline, but increasing core body temperature by as little as 3 C causes coved-type STelevations and progressive conduction failure that is fully reversible upon return to normothermia. FHF2-deficient cardiomyocytes generate action potentials upon current injection at 25 C but are unexcitable at 40 C. The absence …

Association Of A Pai-1 Gene Polymorphism And Early Life Infections With Asthma Risk, Exacerbations, And Reduced Lung Function, Seong H. Cho, Jin-Young Min, Dong Young Kim, Sam S. Oh, Dara R. Torgerson, Maria Pino-Yanes, Donglei Hu, Saunak Sen, Scott Huntsman, Celeste Eng, Harold J. Farber, William Rodriguez-Cintron, Jose R. Rodriguez-Santana, Denise Serebrisky, Shannon M. Thyne, Luisa N. Borrell, L. Keoki Williams, William Dupont, Max A. Seibold, Esteban G. Burchard, Pedro C. Avila, Rajesh Kumar

Publications and Research

Background Plasminogen activator inhibitor-1 (PAI-1) is induced in airways by virus and may mediate asthmatic airway remodeling. We sought to evaluate if genetic variants and early life lower respiratory infections jointly affect asthma risk.

Methods We included Latino children, adolescents, and young adults aged 8–21 years (1736 subjects with physician-diagnosed asthma and 1747 healthy controls) from five U.S. centers and Puerto Rico after excluding subjects with incomplete clinical or genetic data. We evaluated the independent and joint effects of a PAI-1 gain of function polymorphism and bronchiolitis / Respiratory Syncytial Virus (RSV) or other lower respiratory infections (LRI) within the …

Statistical Learning In Specific Language Impairment And Autism Spectrum Disorder: A Meta-Analysis, Rita Obeid, Patricia J. Brooks, Kasey L. Powers, Kristen Gillespie-Lynch, Jarrad A. G. Lum

Publications and Research

Impairments in statistical learning might be a common deficit among individuals with Specific Language Impairment (SLI) and Autism Spectrum Disorder (ASD). Using metaanalysis, we examined statistical learning in SLI (14 studies, 15 comparisons) and ASD (13 studies, 20 comparisons) to evaluate this hypothesis. Effect sizes were examined as a function of diagnosis across multiple statistical learning tasks (Serial Reaction Time, Contextual Cueing, Artificial Grammar Learning, Speech Stream, Observational Learning, and Probabilistic Classification). Individuals with SLI showed deficits in statistical learning relative to age-matched controls. In contrast, statistical learning was intact in individuals with ASD relative to controls. Effect sizes did …

Polycations. 23. Antimicrobial Surfaces For Prevention Of Pathogen Transmission, Robert Engel, Karin Melkonian, Jay Ho, Jaime Lee Iolani Rizzo

Publications and Research

The continued evolution of bacterial and fungal species poses a significant difficulty for the treatment of disease of microbial origin. Given this situation, the prevention of transmission of such microbial diseases becomes of increasing importance. Efforts of this laboratory have been directed toward the destruction of microbial species on environmental surfaces as a prophylaxis toward infection, and we herein report on the efficacy of a system that demonstrates activity against both Gram-positive and Gram-negative bacteria, as well as fungi. We report specifically herein on the use of fabric materials so activated for the destruction of these microbial species, useful for …

Toward Repurposing Metformin As A Precision Anti-Cancer Therapy Using Structural Systems Pharmacology, Thomas Hart, Shihab Dider, Weiwei Han, Hua Xu, Zhongming Zhao, Lei Xie

Publications and Research

Metformin, a drug prescribed to treat type-2 diabetes, exhibits anti-cancer effects in a portion of patients, but the direct molecular and genetic interactions leading to this pleiotropic effect have not yet been fully explored. To repurpose metformin as a precision anti-cancer therapy, we have developed a novel structural systems pharmacology approach to elucidate metformin’s molecular basis and genetic biomarkers of action. We integrated structural proteome-scale drug target identification with network biology analysis by combining structural genomic, functional genomic, and interactomic data. Through searching the human structural proteome, we identified twenty putative metformin binding targets and their interaction models. We experimentally …

Adjunctive Phosphodiesterase-4 Inhibitor Therapy Improves Antibiotic Response To Pulmonary Tuberculosis In A Rabbit Model, Selvakumar Subbian, Liana Tsenova, Jennifer Holloway, Blas Peixoto, Paul O'Brien, Veronique Dartois, Vikram Khetani, Jerome B. Zeldis, Gilla Kaplan

Publications and Research

Objectives: Adjunctive host-directed therapy is emerging as a new potential approach to improve the outcome of conventional antimicrobial treatment for tuberculosis (TB).We tested the ability of a phosphodiesterase-4 inhibitor (PDE4i) CC-11050, co-administered with the first-line anti-TB drug isoniazid (INH), to accelerate bacillary killing and reduce chronic inflammation in the lungs of rabbits with experimental Mycobacterium tuberculosis (Mtb) infection.

Methods: A rabbit model of pulmonary TB that recapitulates the pathologic manifestations seen in humans was used. Rabbits were infected with virulent Mtb by aerosol exposure and treated for eight weeks with INH with orwithout CC-11050, starting at fourweeks post infection. The …

Non-Nad-Like Poly(Adp-Ribose) Polymerase-1 Inhibitors Effectively Eliminate Cancer In Vivo, Colin Thomas, Yingbiao Ji, Niraj Lodhi, Elena Kotova, Aaron Dan Pinnola, Konstantin Golovine, Peter Makhov, Kate Pechenkina, Vladimir Kolenko, Alexei V. Tulin

Publications and Research

The clinical potential of PARP-1 inhibitors has been recognized N10 years ago, prompting intensive research on their pharmacological application in several branches of medicine, particularly in oncology. However, natural or acquired resistance of tumors to known PARP-1 inhibitors poses a serious problemfor their clinical implementation. Present study aims to reignite clinical interest to PARP-1 inhibitors by introducing a new method of identifying highly potent inhibitors and presenting the largest known collection of structurally diverse inhibitors. The majority of PARP-1 inhibitors known to date have been developed as NAD competitors. NAD is utilized by many enzymes other than PARP-1, resulting in …

Re: "Job Strain And The Cortisol Diurnal Cycle In Mesa: Accounting For Between- And Within-Day Variability, Irvin Sam Schonfeld, Renzo Bianchi

Publications and Research

Rudolph et al. (2016) examined the association between job strain and cortisol profile. Several potential confounders were considered, including sociodemographic characteristics, income-wealth index, financial strain, physical health, physical activity, and medication use. No relationship between job strain and the cortisol awakening response was observed. We have 4 comments on the methods used in the study. First, although the authors related the modifications in cortisol profiles to job strain, they did not assess and statistically control for a number of nonoccupational strain factors (e.g., family- or couple-related chronic stress). Second, depressive symptoms and disorders were not considered in the study. Depression …

Modulation Of Gamma And Alpha Spinal Motor Neurons Activity By Trans-Spinal Direct Current Stimulation: Effects On Reflexive Actions And Locomotor Activity, Zaghloul Ahmed

Publications and Research

Spontaneous and evoked spinal activities interact to set the characteristics of emergent motor responses. Gamma motor neurons have feedforward and feedback functions in motor control, which are crucial for transforming motor commands into action. Meanwhile, the intrinsic excitability and functional connectivity of alpha motor neurons determine the accuracy of actions. In this study, we investigated the effects of trans-spinal direct current stimulation (tsDCS) on spontaneous and cortically evoked activity of well-isolated single units of gamma and alpha motor neurons in mice. We also investigated the effects of tsDCS on reflexive and locomotor actions. In general, motor neurons showed increased responses …