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Full-Text Articles in Life Sciences

Trna Anticodon Cleavage By Target-Activated Crispr-Cas13a Effector, Ishita Jain, Matvey Kolesnik, Konstantin Kuznedelov, Leonid Minakhin, Natalia Morozova, Anna Shiriaeva, Alexandr Kirillov, Sofia Medvedeva, Alexei Livenskyi, Laura Kazieva, Kira S Makarova, Eugene V Koonin, Sergei Borukhov, Konstantin Severinov, Ekaterina Semenova Apr 2024

Trna Anticodon Cleavage By Target-Activated Crispr-Cas13a Effector, Ishita Jain, Matvey Kolesnik, Konstantin Kuznedelov, Leonid Minakhin, Natalia Morozova, Anna Shiriaeva, Alexandr Kirillov, Sofia Medvedeva, Alexei Livenskyi, Laura Kazieva, Kira S Makarova, Eugene V Koonin, Sergei Borukhov, Konstantin Severinov, Ekaterina Semenova

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Type VI CRISPR-Cas systems are among the few CRISPR varieties that target exclusively RNA. The CRISPR RNA–guided, sequence-specific binding of target RNAs, such as phage transcripts, activates the type VI effector, Cas13. Once activated, Cas13 causes collateral RNA cleavage, which induces bacterial cell dormancy, thus protecting the host population from the phage spread. We show here that the principal form of collateral RNA degradation elicited by Leptotrichia shahii Cas13a expressed in Escherichia coli cells is the cleavage of anticodons in a subset of transfer RNAs (tRNAs) with uridine-rich anticodons. This tRNA cleavage is accompanied by inhibition of protein synthesis, thus …


Dysexecutive Difficulty And Subtle Everyday Functional Disabilities: The Digital Trail Making Test, David J Libon, Rod Swenson, Sean Tobyne, Ali Jannati, Daniel Schulman, Catherine C Price, Melissa Lamar, Alvaro Pascual-Leone Apr 2024

Dysexecutive Difficulty And Subtle Everyday Functional Disabilities: The Digital Trail Making Test, David J Libon, Rod Swenson, Sean Tobyne, Ali Jannati, Daniel Schulman, Catherine C Price, Melissa Lamar, Alvaro Pascual-Leone

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: Digital neuropsychological tests reliably capture real-time, process-based behavior that traditional paper/pencil tests cannot detect, enabling earlier detection of neurodegenerative illness. We assessed relations between informant-based subtle and mild functional decline and process-based features extracted from the digital Trail Making Test-Part B (dTMT-B).

METHODS: A total of 321 community-dwelling participants (56.0% female) were assessed with the Functional Activities Questionnaire (FAQ) and the dTMT-B. Three FAQ groups were constructed: FAQ = 0 (unimpaired); FAQ = 1-4 (subtle impairment); FAQ = 5-8 (mild impairment).

Results: Compared to the FAQ-unimpaired group, other groups required longer pauses inside target circles (p < 0.050) and produced more total pen strokes to complete the test (p < 0.016). FAQ-subtle participants required more time to complete the entire test (p …


Ursapgx: A New R Package To Annotate Pharmacogenetic Star Alleles Using Phased Whole-Genome Sequencing Data., Gennaro Calendo, Dara Kusic, Josef Madzo, Neda Gharani, Laua Scheinfeldt Mar 2024

Ursapgx: A New R Package To Annotate Pharmacogenetic Star Alleles Using Phased Whole-Genome Sequencing Data., Gennaro Calendo, Dara Kusic, Josef Madzo, Neda Gharani, Laua Scheinfeldt

Cooper Medical School of Rowan University Faculty Scholarship

Long-read sequencing technologies offer new opportunities to generate high-confidence phased whole-genome sequencing data for robust pharmacogenetic annotation. Here, we describe a new user-friendly R package, ursaPGx, designed to accept multi-sample phased whole-genome sequencing data VCF input files and output star allele annotations for pharmacogenes annotated in PharmVar.


Ksp1 Is An Autophagic Receptor Protein For The Snx4-Assisted Autophagy Of Ssn2/Med13, Sara E Hanley, Stephen D Willis, Steven J Doyle, Randy Strich, Katrina F Cooper Feb 2024

Ksp1 Is An Autophagic Receptor Protein For The Snx4-Assisted Autophagy Of Ssn2/Med13, Sara E Hanley, Stephen D Willis, Steven J Doyle, Randy Strich, Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Ksp1 is a casein II-like kinase whose activity prevents aberrant macroautophagy/autophagy induction in nutrient-rich conditions in yeast. Here, we describe a kinase-independent role of Ksp1 as a novel autophagic receptor protein for Ssn2/Med13, a known cargo of Snx4-assisted autophagy of transcription factors. In this pathway, a subset of conserved transcriptional regulators, Ssn2/Med13, Rim15, and Msn2, are selectively targeted for vacuolar proteolysis following nitrogen starvation, assisted by the sorting nexin heterodimer Snx4-Atg20. Here we show that phagophores also engulf Ksp1 alongside its cargo for vacuolar proteolysis. Ksp1 directly associates with Atg8 following nitrogen starvation at the interface of an Atg8-family interacting …


Comparing Cognitive Tests And Smartphone-Based Assessment In 2 Us Community-Based Cohorts., Ileana De Anda-Duran, Preeti Sunderaraman, Edward Searls, Shirine Moukaled, Xuanyi Jin, Zachary Popp, Cody Karjadi, Phillip H Hwang, Huitong Ding, Sherral Devine, Ludy C Shih, Spencer Low, Honghuang Lin, Vijaya B Kolachalama, Lydia Bazzano, David J Libon, Rhoda Au Jan 2024

Comparing Cognitive Tests And Smartphone-Based Assessment In 2 Us Community-Based Cohorts., Ileana De Anda-Duran, Preeti Sunderaraman, Edward Searls, Shirine Moukaled, Xuanyi Jin, Zachary Popp, Cody Karjadi, Phillip H Hwang, Huitong Ding, Sherral Devine, Ludy C Shih, Spencer Low, Honghuang Lin, Vijaya B Kolachalama, Lydia Bazzano, David J Libon, Rhoda Au

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: Smartphone-based cognitive assessments have emerged as promising tools, bridging gaps in accessibility and reducing bias in Alzheimer disease and related dementia research. However, their congruence with traditional neuropsychological tests and usefulness in diverse cohorts remain underexplored.

METHODS AND RESULTS: A total of 406 FHS (Framingham Heart Study) and 59 BHS (Bogalusa Heart Study) participants with traditional neuropsychological tests and digital assessments using the Defense Automated Neurocognitive Assessment (DANA) smartphone protocol were included. Regression models investigated associations between DANA task digital measures and a neuropsychological global cognitive

CONCLUSIONS: Our findings demonstrate that smartphone-based cognitive assessments exhibit concurrent validity with a …


Tail-Tape-Fused Virion And Non-Virion Rna Polymerases Of A Thermophilic Virus With An Extremely Long Tail, Anastasiia Chaban, Leonid Minakhin, Ekaterina Goldobina, Brain Bae, Yue Hao, Sergei Borukhov, Leena Putzeys, Maarten Boon, Florian Kabinger, Rob Lavigne, Kira S Makarova, Eugene V Koonin, Satish K Nair, Shunsuke Tagami, Konstantin Severinov, Maria L Sokolova Jan 2024

Tail-Tape-Fused Virion And Non-Virion Rna Polymerases Of A Thermophilic Virus With An Extremely Long Tail, Anastasiia Chaban, Leonid Minakhin, Ekaterina Goldobina, Brain Bae, Yue Hao, Sergei Borukhov, Leena Putzeys, Maarten Boon, Florian Kabinger, Rob Lavigne, Kira S Makarova, Eugene V Koonin, Satish K Nair, Shunsuke Tagami, Konstantin Severinov, Maria L Sokolova

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Thermus thermophilus bacteriophage P23-45 encodes a giant 5,002-residue tail tape measure protein (TMP) that defines the length of its extraordinarily long tail. Here, we show that the N-terminal portion of P23-45 TMP is an unusual RNA polymerase (RNAP) homologous to cellular RNAPs. The TMP-fused virion RNAP transcribes pre-early phage genes, including a gene that encodes another, non-virion RNAP, that transcribes early and some middle phage genes. We report the crystal structures of both P23-45 RNAPs. The non-virion RNAP has a crab-claw-like architecture. By contrast, the virion RNAP adopts a unique flat structure without a clamp. Structure and sequence comparisons of …


Fused In Sarcoma Regulates Glutamate Signaling And Oxidative Stress Response, Chiong-Hee Wong, Abu Rahat, Howard C Chang Jan 2024

Fused In Sarcoma Regulates Glutamate Signaling And Oxidative Stress Response, Chiong-Hee Wong, Abu Rahat, Howard C Chang

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Mutations in fused in sarcoma (fust-1) are linked to ALS. However, how these ALS causative mutations alter physiological processes and lead to the onset of ALS remains largely unknown. By obtaining humanized fust-1 ALS mutations via CRISPR-CAS9, we generated a C. elegans ALS model. Homozygous fust-1 ALS mutant and fust-1 deletion animals are viable in C. elegans. This allows us to better characterize the molecular mechanisms of fust-1-dependent responses. We found FUST-1 plays a role in regulating superoxide dismutase, glutamate signaling, and oxidative stress. FUST-1 suppresses SOD-1 and VGLUT/EAT-4 in the nervous system. FUST-1 also regulates synaptic AMPA-type glutamate receptor …


Nucleus Accumbens Core Single Cell Ensembles Bidirectionally Respond To Experienced Versus Observed Aversive Events, Oyku Dinckol, Noah Harris Wenger, Jennifer E Zachry, Munir Gunes Kutlu Dec 2023

Nucleus Accumbens Core Single Cell Ensembles Bidirectionally Respond To Experienced Versus Observed Aversive Events, Oyku Dinckol, Noah Harris Wenger, Jennifer E Zachry, Munir Gunes Kutlu

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Fear learning is a critical feature of survival skills among mammals. In rodents, fear learning manifests itself through direct experience of the aversive event or social transmission of aversive stimuli such as observing and acting on conspecifics' distress. The neuronal network underlying the social transmission of information largely overlaps with the brain regions that mediate behavioral responses to aversive and rewarding stimuli. In this study, we recorded single cell activity patterns of nucleus accumbens (NAc) core neurons using in vivo optical imaging of calcium transients via miniature scopes. This cutting-edge imaging methodology not only allows us to record activity patterns …


Effects Of Dimerization On The Deacylase Activities Of Human Sirt2., Jie Yang, Nathan I Nicely, Brian P Weiser Dec 2023

Effects Of Dimerization On The Deacylase Activities Of Human Sirt2., Jie Yang, Nathan I Nicely, Brian P Weiser

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Human sirtuin isoform 2 (SIRT2) is an NAD+-dependent enzyme that functions as a lysine deacetylase and defatty-acylase. Here, we report that SIRT2 readily dimerizes in solution and in cells and that dimerization affects its ability to remove different acyl modifications from substrates. Dimerization of recombinant SIRT2 was revealed with analytical size exclusion chromatography and chemical cross-linking. Dimerized SIRT2 dissociates into monomers upon binding long fatty acylated substrates (decanoyl-, dodecanoyl-, and myristoyl-lysine). However, we did not observe dissociation of dimeric SIRT2 in the presence of acetyl-lysine. Analysis of X-ray crystal structures led us to discover a SIRT2 double mutant (Q142A/E340A) that …


Neutralizing Antibodies Against Ebv Gp42 Show Potent In Vivo Protection And Define Novel Epitopes, Qian Wu, Ling Zhong, Dongmei Wei, Wanlin Zhang, Junping Hong, Yinfeng Kang, Kaiyun Chen, Yang Huang, Qingbing Zheng, Miao Xu, Mu-Sheng Zeng, Yi-Xin Zeng, Ningshao Xia, Qinjian Zhao, Claude Krummenacher, Yixin Chen, Xiao Zhang Dec 2023

Neutralizing Antibodies Against Ebv Gp42 Show Potent In Vivo Protection And Define Novel Epitopes, Qian Wu, Ling Zhong, Dongmei Wei, Wanlin Zhang, Junping Hong, Yinfeng Kang, Kaiyun Chen, Yang Huang, Qingbing Zheng, Miao Xu, Mu-Sheng Zeng, Yi-Xin Zeng, Ningshao Xia, Qinjian Zhao, Claude Krummenacher, Yixin Chen, Xiao Zhang

Faculty Scholarship for the College of Science & Mathematics

Epstein-Barr virus (EBV) is the first reported human oncogenic virus and infects more than 95% of the human population worldwide. EBV latent infection in B lymphocytes is essential for viral persistence. Glycoprotein gp42 is an indispensable member of the triggering complex for EBV entry into B cells. The C-type lectin domain (CTLD) of gp42 plays a key role in receptor binding and is the major target of neutralizing antibodies. Here, we isolated two rabbit antibodies, 1A7 and 6G7, targeting gp42 CTLD with potent neutralizing activity against B cell infection. Antibody 6G7 efficiently protects humanized mice from lethal EBV challenge and …


Editorial: Sex Differences In The Neurobiology Of Drug Relapse Vulnerability, Daniel F Manvich, Jessica A Loweth, Wendy J Lynch, Jayme R Mcreynolds Sep 2023

Editorial: Sex Differences In The Neurobiology Of Drug Relapse Vulnerability, Daniel F Manvich, Jessica A Loweth, Wendy J Lynch, Jayme R Mcreynolds

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

No abstract provided.


Self-Supervised Deep Clustering Of Single-Cell Rna-Seq Data To Hierarchically Detect Rare Cell Populations., Tianyuan Lei, Ruoyu Chen, Shaoqiang Zhang, Yong Chen Sep 2023

Self-Supervised Deep Clustering Of Single-Cell Rna-Seq Data To Hierarchically Detect Rare Cell Populations., Tianyuan Lei, Ruoyu Chen, Shaoqiang Zhang, Yong Chen

Faculty Scholarship for the College of Science & Mathematics

Single-cell RNA sequencing (scRNA-seq) is a widely used technique for characterizing individual cells and studying gene expression at the single-cell level. Clustering plays a vital role in grouping similar cells together for various downstream analyses. However, the high sparsity and dimensionality of large scRNA-seq data pose challenges to clustering performance. Although several deep learning-based clustering algorithms have been proposed, most existing clustering methods have limitations in capturing the precise distribution types of the data or fully utilizing the relationships between cells, leaving a considerable scope for improving the clustering performance, particularly in detecting rare cell populations from large scRNA-seq data. …


Bisphenol-A And Phthalate Metabolism In Children With Neurodevelopmental Disorders, T Peter Stein, Margaret D Schluter, Robert A Steer, Xue Ming Sep 2023

Bisphenol-A And Phthalate Metabolism In Children With Neurodevelopmental Disorders, T Peter Stein, Margaret D Schluter, Robert A Steer, Xue Ming

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

BACKGROUND: The etiology of autism spectrum (ASD) and Attention Deficit/Hyperactivity (ADHD) disorders are multifactorial. Epidemiological studies have shown associations with environmental pollutants, such as plasticizers. This study focused on two of these compounds, the Bisphenol-A (BPA) and Diethylhexyl Phthalate (DEHP). The major pathway for BPA and DEHP excretion is via glucuronidation. Glucuronidation makes insoluble substances more water-soluble allowing for their subsequent elimination in urine.

HYPOTHESIS: Detoxification of these two plasticizers is compromised in children with ASD and ADHD. Consequently, their tissues are more exposed to these two plasticizers.

METHODS: We measured the efficiency of glucuronidation in three groups of children, …


Sctiger: A Deep-Learning Method For Inferring Gene Regulatory Networks From Case Versus Control Scrna-Seq Datasets., Madison Dautle, Shaoqiang Zhang, Yong Chen Aug 2023

Sctiger: A Deep-Learning Method For Inferring Gene Regulatory Networks From Case Versus Control Scrna-Seq Datasets., Madison Dautle, Shaoqiang Zhang, Yong Chen

Faculty Scholarship for the College of Science & Mathematics

Inferring gene regulatory networks (GRNs) from single-cell RNA-seq (scRNA-seq) data is an important computational question to find regulatory mechanisms involved in fundamental cellular processes. Although many computational methods have been designed to predict GRNs from scRNA-seq data, they usually have high false positive rates and none infer GRNs by directly using the paired datasets of case-versus-control experiments. Here we present a novel deep-learning-based method, named scTIGER, for GRN detection by using the co-differential relationships of gene expression profiles in paired scRNA-seq datasets. scTIGER employs cell-type-based pseudotiming, an attention-based convolutional neural network method and permutation-based significance testing for inferring GRNs among …


Profiling And Verifying The Substrates Of E3 Ubiquitin Ligase Rsp5 In Yeast Cells, Shuai Fang, Geng Chen, Yiyang Wang, Rakhee Ganti, Tatiana A Chernova, Li Zhou, Savannah E Jacobs, Duc Duong, Hiroaki Kiyokawa, Yury O Chernoff, Ming Li, Natalia Shcherbik, Bo Zhao, Jun Yin Aug 2023

Profiling And Verifying The Substrates Of E3 Ubiquitin Ligase Rsp5 In Yeast Cells, Shuai Fang, Geng Chen, Yiyang Wang, Rakhee Ganti, Tatiana A Chernova, Li Zhou, Savannah E Jacobs, Duc Duong, Hiroaki Kiyokawa, Yury O Chernoff, Ming Li, Natalia Shcherbik, Bo Zhao, Jun Yin

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Yeast is an essential model organism for studying protein ubiquitination pathways; however, identifying the direct substrates of E3 in the cell presents a challenge. Here, we present a protocol for using the orthogonal ubiquitin transfer (OUT) cascade to profile the substrate specificity of yeast E3 Rsp5. We describe steps for OUT profiling, proteomics analysis, in vitro and in cell ubiquitination, and stability assay. The protocol can be adapted for identifying and verifying the ubiquitination targets of other E3s in yeast. For complete details on the use and execution of this protocol, please refer to Wang et al.


Modeling Biphasic, Non-Sigmoidal Dose-Response Relationships: Comparison Of Brain- Cousens And Cedergreen Models For A Biochemical Dataset, Venkat D. Abbaraju, Tamaraty L. Robinson, Brian P. Weiser Aug 2023

Modeling Biphasic, Non-Sigmoidal Dose-Response Relationships: Comparison Of Brain- Cousens And Cedergreen Models For A Biochemical Dataset, Venkat D. Abbaraju, Tamaraty L. Robinson, Brian P. Weiser

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Biphasic, non-sigmoidal dose-response relationships are frequently observed in biochemistry and pharmacology, but they are not always analyzed with appropriate statistical methods. Here, we examine curve fitting methods for “hormetic” dose-response relationships where low and high doses of an effector produce opposite responses. We provide the full dataset used for modeling, and we provide the code for analyzing the dataset in SAS using two established mathematical models of hormesis, the Brain-Cousens model and the Cedergreen model. We show how to obtain and interpret curve parameters such as the ED50 that arise from modeling, and we discuss how curve parameters might change …


Effects Of Sex And Estrous Cycle On Intravenous Oxycodone Self-Administration And The Reinstatement Of Oxycodone-Seeking Behavior In Rats, Nicole M. Hinds, Ireneusz D. Wojtas, Corinne A. Gallagher, Claire M. Corbett, Daniel F. Manvich Jul 2023

Effects Of Sex And Estrous Cycle On Intravenous Oxycodone Self-Administration And The Reinstatement Of Oxycodone-Seeking Behavior In Rats, Nicole M. Hinds, Ireneusz D. Wojtas, Corinne A. Gallagher, Claire M. Corbett, Daniel F. Manvich

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

The increasing misuse of both prescription and illicit opioids has culminated in a national healthcare crisis in the United States. Oxycodone is among the most widely prescribed and misused opioid pain relievers and has been associated with a high risk for transition to compulsive opioid use. Here, we sought to examine potential sex differences and estrous cycle-dependent effects on the reinforcing efficacy of oxycodone, as well as on stress-induced or cue-induced oxycodone-seeking behavior, using intravenous (IV) oxycodone self-administration and reinstatement procedures. In experiment 1, adult male and female Long-Evans rats were trained to self-administer 0.03 mg/kg/inf oxycodone according to a …


Invited Review: Adrenocortical Function In Avian And Non-Avian Reptiles: Insights From Dispersed Adrenocortical Cells., Rocco V. Carsia, Patrick J. Mcilroy, Henry B John-Alder Jul 2023

Invited Review: Adrenocortical Function In Avian And Non-Avian Reptiles: Insights From Dispersed Adrenocortical Cells., Rocco V. Carsia, Patrick J. Mcilroy, Henry B John-Alder

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Herein we review our work involving dispersed adrenocortical cells from several lizard species: the Eastern Fence Lizard (Sceloporus undulatus), Yarrow's Spiny Lizard (Sceloporus jarrovii), Striped Plateau Lizard (Sceloporus virgatus) and the Yucatán Banded Gecko (Coleonyx elegans). Early work demonstrated changes in steroidogenic function of adrenocortical cells derived from adult S. undulatus associated with seasonal interactions with sex. However, new information suggests that both sexes operate within the same steroidogenic budget over season. The observed sex effect was further explored in orchiectomized and ovariectomized lizards, some supported with exogenous testosterone. Overall, a suppressive effect of testosterone was evident, especially in cells …


Voluntary Wheel Running Promotes Resilience To The Behavioral Effects Of Unpredictable Chronic Mild Stress In Male And Female Mice., Elias Elias, Ariel Y Zhang, Abigail G White, Matthew J Pyle, Melissa T Manners May 2023

Voluntary Wheel Running Promotes Resilience To The Behavioral Effects Of Unpredictable Chronic Mild Stress In Male And Female Mice., Elias Elias, Ariel Y Zhang, Abigail G White, Matthew J Pyle, Melissa T Manners

Faculty Scholarship for the College of Science & Mathematics

Besides significant benefits to physical health, exercise promotes mental health, reduces symptoms of mental illness, and enhances psychological development. Exercise can offset the impact of chronic stress, which is a major precursor to the development of mental disorders. The effects of exercise on chronic stress-induced behaviors are contradictory in preclinical studies, primarily due to the lack of data and sex-specific investigations. We sought to evaluate the effects of exercise on chronic stress-induced behavioral changes in both male and female mice. Mice were subjected to an Unpredictable Chronic Mild Stress (UCMS) paradigm with accessibility to running wheels for 2 h daily. …


The Mindful Athlete Program, Joanne Bullard, Sojung Kim Mar 2023

The Mindful Athlete Program, Joanne Bullard, Sojung Kim

Rita & Larry Salva School of Nursing and Health Professions Faculty Scholarship

According to the spring 2020 NCAA Well-Being Study, collegiate student-athletes reported experiencing mental health concerns due to the impact of the COVID-19 pandemic. The data indicated that student-athletes were experiencing mental health concerns 150%-250% higher than historically reported (NCAA, 2020). These concerns were prevalent among all divisions. For Division III student-athletes, mental health concerns experienced during the COVID-19 pandemic included “feeling overwhelmed by all they had to do, sleep difficulties, feeling mentally exhausted, feeling very lonely, feeling a sense of loss, and feeling very lonely and sad” (NCAA, 2020). This study indicated desired resources of Division III student-athletes included elements …


Anterior And Posterior Tongue Regions And Taste Papillae: Distinct Roles And Regulatory Mechanisms With An Emphasis On Hedgehog Signaling And Antagonism., Archana Kumari, Charlotte M. Mistretta Mar 2023

Anterior And Posterior Tongue Regions And Taste Papillae: Distinct Roles And Regulatory Mechanisms With An Emphasis On Hedgehog Signaling And Antagonism., Archana Kumari, Charlotte M. Mistretta

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Sensory receptors across the entire tongue are engaged during eating. However, the tongue has distinctive regions with taste (fungiform and circumvallate) and non-taste (filiform) organs that are composed of specialized epithelia, connective tissues, and innervation. The tissue regions and papillae are adapted in form and function for taste and somatosensation associated with eating. It follows that homeostasis and regeneration of distinctive papillae and taste buds with particular functional roles require tailored molecular pathways. Nonetheless, in the chemosensory field, generalizations are often made between mechanisms that regulate anterior tongue fungiform and posterior circumvallate taste papillae, without a clear distinction that highlights …


Mglu5 Inhibition In The Basolateral Amygdala Prevents Estrous Cycle-Dependent Changes In Cue-Induced Cocaine Seeking, Claire M. Corbett, Emily N. D. Miller, Jessica A. Loweth Mar 2023

Mglu5 Inhibition In The Basolateral Amygdala Prevents Estrous Cycle-Dependent Changes In Cue-Induced Cocaine Seeking, Claire M. Corbett, Emily N. D. Miller, Jessica A. Loweth

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Drug associated cues are a common relapse trigger for individuals recovering from cocaine use disorder. Sex and ovarian hormones influence patterns of cocaine use and relapse vulnerability, with studies indicating that females show increased cue-induced craving and relapse vulnerability compared to males. In a rodent model of cocaine craving and relapse vulnerability, cue-induced cocaine seeking behavior following weeks of withdrawal from extended-access cocaine self-administration is higher in females in the estrus stage of the reproductive (estrous) cycle (Estrus Females) compared to both Males and females in all other stages (Non-Estrus Females). However, the neuronal substrates and cellular mechanisms underlying these …


Dpc29 Promotes Post-Initiation Mitochondrial Translation In Saccharomyces Cerevisiae, Kyle A. Hubble, Michael F. Henry Feb 2023

Dpc29 Promotes Post-Initiation Mitochondrial Translation In Saccharomyces Cerevisiae, Kyle A. Hubble, Michael F. Henry

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Mitochondrial ribosomes synthesize essential components of the oxidative phosphorylation (OXPHOS) system in a tightly regulated process. In the yeast Saccharomyces cerevisiae, mitochondrial mRNAs require specific translational activators, which orchestrate protein synthesis by recognition of their target gene's 5'-untranslated region (UTR). Most of these yeast genes lack orthologues in mammals, and only one such gene-specific translational activator has been proposed in humans-TACO1. The mechanism by which TACO1 acts is unclear because mammalian mitochondrial mRNAs do not have significant 5'-UTRs, and therefore must promote translation by alternative mechanisms. In this study, we examined the role of the TACO1 orthologue in yeast. We …


Novel Signposts On The Road From Natural Sources To Pharmaceutical Applications: A Combinative Approach Between Lc-Dad-Ms And Offline Lc-Nmr For The Biochemical Characterization Of Two Hypericum Species (H. Montbretii And H. Origanifolium), Stefania Sut, Stefano Dall'acqua, Gokhan Zengin, Ismail Senkardes, Abdullahi Ibrahim Uba, Abdelhakim Bouyahya, Abdurrahman Aktumsek Feb 2023

Novel Signposts On The Road From Natural Sources To Pharmaceutical Applications: A Combinative Approach Between Lc-Dad-Ms And Offline Lc-Nmr For The Biochemical Characterization Of Two Hypericum Species (H. Montbretii And H. Origanifolium), Stefania Sut, Stefano Dall'acqua, Gokhan Zengin, Ismail Senkardes, Abdullahi Ibrahim Uba, Abdelhakim Bouyahya, Abdurrahman Aktumsek

Faculty Scholarship for the College of Science & Mathematics

The members of the genus Hypericum have great potential to develop functional uses in nutraceutical and pharmaceutical applications. With this in mind, we aimed to determine the chemical profiling and biological properties of different extracts (ethyl acetate, methanol and water) from two Hypericum species (H. montbretii and H. origanifolium). We combined two approaches (LC-DAD-MS and LC-NMR) to identify and quantify chemical compounds of the extracts. Antioxidant properties (free radical quenching, reducing power and metal chelating) and enzyme inhibitory effects (cholinesterase, tyrosinase, amylase and glucosidase) were determined as biological properties. The tested extracts were rich in caffeic acid derivatives and flavonoids, …


A Conserved Mechanism For Hormesis In Molecular Systems, Sharon N. Greenwood, Regina G. Belz, Brian P. Weiser Jul 2022

A Conserved Mechanism For Hormesis In Molecular Systems, Sharon N. Greenwood, Regina G. Belz, Brian P. Weiser

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Hormesis refers to dose-response phenomena where low dose treatments elicit a response that is opposite the response observed at higher doses. Hormetic dose-response relationships have been observed throughout all of biology, but the underlying determinants of many reported hormetic dose-responses have not been identified. In this report, we describe a conserved mechanism for hormesis on the molecular level where low dose treatments enhance a response that becomes reduced at higher doses. The hormetic mechanism relies on the ability of protein homo-multimers to simultaneously interact with a substrate and a competitor on different subunits at low doses of competitor. In this …


Mechanism Of Translation Inhibition By Type Ii Gnat Toxin Atat2, Stepan V Ovchinnikov, Dmitry Bikmetov, Alexei Livenskyi, Marina Serebryakova, Brendan Wilcox, Kyle Mangano, Dmitrii I Shiriaev, Ilya A Osterman, Petr V Sergiev, Sergei Borukhov, Nora Vazquez-Laslop, Alexander S Mankin, Konstantin Severinov, Svetlana Dubiley Sep 2020

Mechanism Of Translation Inhibition By Type Ii Gnat Toxin Atat2, Stepan V Ovchinnikov, Dmitry Bikmetov, Alexei Livenskyi, Marina Serebryakova, Brendan Wilcox, Kyle Mangano, Dmitrii I Shiriaev, Ilya A Osterman, Petr V Sergiev, Sergei Borukhov, Nora Vazquez-Laslop, Alexander S Mankin, Konstantin Severinov, Svetlana Dubiley

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Type II toxin-antitoxins systems are widespread in prokaryotic genomes. Typically, they comprise two proteins, a toxin, and an antitoxin, encoded by adjacent genes and forming a complex in which the enzymatic activity of the toxin is inhibited. Under stress conditions, the antitoxin is degraded liberating the active toxin. Though thousands of various toxin-antitoxins pairs have been predicted bioinformatically, only a handful has been thoroughly characterized. Here, we describe the AtaT2 toxin from a toxin-antitoxin system from Escherichia coli O157:H7. We show that AtaT2 is the first GNAT (Gcn5-related N-acetyltransferase) toxin that specifically targets charged glycyl tRNA. In vivo, the AtaT2 …


Deficiency Of Complement Component C1q Prevents Cerebrovascular Damage And White Matter Loss In A Mouse Model Of Chronic Obesity., Leah C Graham, Heidi E Kocalis, Ileana Soto Reyes, Gareth R Howell May 2020

Deficiency Of Complement Component C1q Prevents Cerebrovascular Damage And White Matter Loss In A Mouse Model Of Chronic Obesity., Leah C Graham, Heidi E Kocalis, Ileana Soto Reyes, Gareth R Howell

Faculty Scholarship for the College of Science & Mathematics

Age-related cognitive decline and many dementias involve complex interactions of both genetic and environmental risk factors. Recent evidence has demonstrated a strong association of obesity with the development of dementia. Furthermore, white matter damage is found in obese subjects and mouse models of obesity. Here, we found that components of the complement cascade, including complement component 1qa (C1QA) and C3 are increased in the brain of Western diet (WD)-fed obese mice, particularly in white matter regions. To functionally test the role of the complement cascade in obesity-induced brain pathology, female and male mice deficient in C1QA, an essential molecule in …


Histidine-Triad Hydrolases Provide Resistance To Peptide-Nucleotide Antibiotics., Eldar Yagmurov, Darya Tsibulskaya, Alexey Livenskyi, Marina Serebryakova, Yury I Wolf, Sergei Borukhov, Konstantin Severinov, Svetlana Dubiley Apr 2020

Histidine-Triad Hydrolases Provide Resistance To Peptide-Nucleotide Antibiotics., Eldar Yagmurov, Darya Tsibulskaya, Alexey Livenskyi, Marina Serebryakova, Yury I Wolf, Sergei Borukhov, Konstantin Severinov, Svetlana Dubiley

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

The Escherichia coli microcin C (McC) and related compounds are potent Trojan horse peptide-nucleotide antibiotics. The peptide part facilitates transport into sensitive cells. Inside the cell, the peptide part is degraded by nonspecific peptidases releasing an aspartamide-adenylate containing a phosphoramide bond. This nonhydrolyzable compound inhibits aspartyl-tRNA synthetase. In addition to the efficient export of McC outside the producing cells, special mechanisms have evolved to avoid self-toxicity caused by the degradation of the peptide part inside the producers. Here, we report that histidine-triad (HIT) hydrolases encoded in biosynthetic clusters of some McC homologs or by standalone genes confer resistance to McC-like …


Metabolomic Response Of Equine Skeletal Muscle To Acute Fatiguing Exercise And Training., Dylan J. Klein, Kenneth H Mckeever, Emily T Mirek, Tracy G Anthony Feb 2020

Metabolomic Response Of Equine Skeletal Muscle To Acute Fatiguing Exercise And Training., Dylan J. Klein, Kenneth H Mckeever, Emily T Mirek, Tracy G Anthony

Faculty Scholarship for the College of Science & Mathematics

The athletic horse, despite being over 50% muscle mass, remains understudied with regard to the effects of exercise and training on skeletal muscle metabolism. To begin to address this knowledge gap, we employed an untargeted metabolomics approach to characterize the exercise-induced and fitness-related changes in the skeletal muscle of eight unconditioned Standardbred horses (four male, four female) before and after a 12-week training period. Before training, unconditioned horses showed a high degree of individual variation in the skeletal muscle metabolome, resulting in very few differences basally and at 3 and 24 h after acute fatiguing exercise. Training did not alter …


Bone-Loading Physical Activity And Alcohol Intake But Not Bmi Affect Areal Bone Mineral Density In Young College-Aged Korean Women: A Cross-Sectional Study., Dong Jun Sung, Harshvardhan Singh, Seung-Bum Oh, Sojung Kim Dec 2019

Bone-Loading Physical Activity And Alcohol Intake But Not Bmi Affect Areal Bone Mineral Density In Young College-Aged Korean Women: A Cross-Sectional Study., Dong Jun Sung, Harshvardhan Singh, Seung-Bum Oh, Sojung Kim

Faculty Scholarship for the College of Science & Mathematics

The purpose of this cross-sectional study was to determine the differences in areal bone mineral density (aBMD) based on alcohol consumption behaviors, bone-loading history as assessed by a bone-specific physical activity questionnaire (BPAQ), and the body mass index (BMI). College-aged female students (N = 112) were recruited from the universities in Seoul and Gyeonggi province, South Korea. The aBMD of the lumbar spine and non-dominant side of the proximal femur (total hip, TH; femoral neck, FN; femoral trochanter, FT) were measured using dual energy X-ray absorptiometry (DXA). Alcohol consumption was determined by the frequency and amount of alcohol intake during …