Life Sciences Commons^™

Can Unconventional Immunomodulatory Agents Help Alleviate Covid-19 Symptoms And Severity?, Stephen W. Mamber, Steven Krakowka, Jeffrey L. Osborn, Lloyd Saberski, Ryan G. Rhodes, Albert E. Dahlberg, Sunthorn Pond-Tor, Kara Fitzgerald, Neal Wright, Sarah Beseme, John Mcmichael

Biology Faculty Publications

Severe acute respiratory syndrome coronavirus 2 (SARS coronavirus 2, or SARS-CoV-2) is the cause of the respiratory infection known as COVID-19. From an immunopathological standpoint, coronaviruses such as SARS-CoV-2 induce increased levels of a variety of T-helper 1 (Th1) and inflammatory cytokines and chemokines, including interleukin-1 (IL-1), IL-6, CCL2 protein, and CXCL10 protein. In the absence of proven antiviral agents or an effective vaccine, substances with immunomodulatory activity may be able to inhibit inflammatory and Th1 cytokines and/or yield an anti-inflammatory and/or Th2 immune response to counteract COVID-19 symptoms and severity. This report briefly describes the following four unconventional but …

Morphogenetic Defects Underlie Superior Coloboma, A Newly Identified Closure Disorder Of The Dorsal Eye, Jennifer C. Hocking, Jakub K. Famulski, Kevin H. Yoon, Sonya A. Widen, Cassidy S. Bernstein, Sophie Koch, Omri Weiss, Forge Canada Consortium, Canada, Seema Agarwala, Adi Inbal, Ordan J. Lehmann, Andrew J. Waskiewicz

Biology Faculty Publications

The eye primordium arises as a lateral outgrowth of the forebrain, with a transient fissure on the inferior side of the optic cup providing an entry point for developing blood vessels. Incomplete closure of the inferior ocular fissure results in coloboma, a disease characterized by gaps in the inferior eye and recognized as a significant cause of pediatric blindness. Here, we identify eight patients with defects in tissues of the superior eye, a congenital disorder that we term superior coloboma. The embryonic origin of superior coloboma could not be explained by conventional models of eye development, leading us to …

Molecular Analyses Of Circadian Gene Variants Reveal Sex-Dependent Links Between Depression And Clocks, S-Q Shi, M. J. White, H. M. Borsetti, Julie S. Pendergast, A. Hida, C. M. Ciarleglio, P. A. De Verteuil, A. G. Cadar, C. Cala, D. G. Mcmahon, R. C. Shelton, S. M. Williams, C. H. Johnson

Biology Faculty Publications

An extensive literature links circadian irregularities and/or sleep abnormalities to mood disorders. Despite the strong genetic component underlying many mood disorders, however, previous genetic associations between circadian clock gene variants and major depressive disorder (MDD) have been weak. We applied a combined molecular/functional and genetic association approach to circadian gene polymorphisms in sex-stratified populations of control subjects and case subjects suffering from MDD. This approach identified significant sex-dependent associations of common variants of the circadian clock genes hClock, hPer3 and hNpas2 with major depression and demonstrated functional effects of these polymorphisms on the expression or activity of the hCLOCK …

Human Gut Bacteria Are Sensitive To Melatonin And Express Endogenous Circadian Rhythmicity, Jiffin K. Paulose, John M. Wright, Akruti G. Patel, Vincent M. Cassone

Biology Faculty Publications

Circadian rhythms are fundamental properties of most eukaryotes, but evidence of biological clocks that drive these rhythms in prokaryotes has been restricted to Cyanobacteria. In vertebrates, the gastrointestinal system expresses circadian patterns of gene expression, motility and secretion in vivo and in vitro, and recent studies suggest that the enteric microbiome is regulated by the host’s circadian clock. However, it is not clear how the host’s clock regulates the microbiome. Here, we demonstrate at least one species of commensal bacterium from the human gastrointestinal system, Enterobacter aerogenes, is sensitive to the neurohormone melatonin, which is secreted into the …

The Sea Lamprey Meiotic Map Improves Resolution Of Ancient Vertebrate Genome Duplications, Jeramiah James Smith, Melissa C. Keinath

Biology Faculty Publications

It is generally accepted that many genes present in vertebrate genomes owe their origin to two whole-genome duplications that occurred deep in the ancestry of the vertebrate lineage. However, details regarding the timing and outcome of these duplications are not well resolved. We present high-density meiotic and comparative genomic maps for the sea lamprey (Petromyzon marinus), a representative of an ancient lineage that diverged from all other vertebrates ~550 million years ago. Linkage analyses yielded a total of 95 linkage groups, similar to the estimated number of germline chromosomes (1n ~ 99), spanning a total of 5570.25 cM. …

A Hunter Virus That Targets Both Infected Cells And Hiv Free Virions: Implications For Therapy, Cody Greer, Gisela García-Ramos

Biology Faculty Publications

The design of 'hunter' viruses aimed at destroying human immunodeficiency virus (HIV) infected cells is an active area of research that has produced promising results in vitro. Hunters are designed to target exposed viral envelope proteins in the membranes of infected cells, but there is evidence that the hunter may also target envelope proteins of free HIV, inducing virus-virus fusion. In order to predict the effects of this fusion on therapy outcomes and determine whether fusion ability is advantageous for hunter virus design, we have constructed a model to account for the possibility of hunter-HIV fusion. The study was based …

Variable Effect Of Co-Infection On The Hiv Infectivity: Within-Host Dynamics And Epidemiological Significance, Diego F. Cuadros, Gisela García-Ramos

Biology Faculty Publications

BACKGROUND: Recent studies have implicated viral characteristics in accounting for the variation in the HIV set-point viral load (spVL) observed among individuals. These studies have suggested that the spVL might be a heritable factor. The spVL, however, is not in an absolute equilibrium state; it is frequently perturbed by immune activations generated by co-infections, resulting in a significant amplification of the HIV viral load (VL). Here, we postulated that if the HIV replication capacity were an important determinant of the spVL, it would also determine the effect of co-infection on the VL. Then, we hypothesized that viral factors contribute to …

No Evidence Of Association Between Hiv-1 And Malaria In Populations With Low Hiv-1 Prevalence, Diego F. Cuadros, Adam J. Branscum, Gisela García-Ramos

Biology Faculty Publications

BACKGROUND: The geographic overlap between HIV-1 and malaria has generated much interest in their potential interactions. A variety of studies have evidenced a complex HIV-malaria interaction within individuals and populations that may have dramatic effects, but the causes and implications of this co-infection at the population level are still unclear. In a previous publication, we showed that the prevalence of malaria caused by the parasite Plasmodium falciparum is associated with HIV infection in eastern sub-Saharan Africa. To complement our knowledge of the HIV-malaria co-infection, the objective of this work was to assess the relationship between malaria and HIV prevalence in …

Effect Of Variable Transmission Rate On The Dynamics Of Hiv In Sub-Saharan Africa, Diego F. Cuadros, Phillip H. Crowley, Ben Augustine, Sarah L. Stewart, Gisela García-Ramos

Biology Faculty Publications

BACKGROUND: The cause of the high HIV prevalence in sub-Saharan Africa is incompletely understood, with heterosexual penile-vaginal transmission proposed as the main mechanism. Heterosexual HIV transmission has been estimated to have a very low probability; but effects of cofactors that vary in space and time may substantially alter this pattern.

METHODS: To test the effect of individual variation in the HIV infectiousness generated by co-infection, we developed and analyzed a mathematical sexual network model that simulates the behavioral components of a population from Malawi, as well as the dynamics of HIV and the co-infection effect caused by other infectious diseases, …

Origin Of Amphibian And Avian Chromosomes By Fission, Fusion, And Retention Of Ancestral Chromosomes, Stephen R. Voss, D. Kevin Kump, Srikrishna Putta, Nathan Pauly, Anna Reynolds, Rema J. Henry, Saritha Basa, John A. Walker, Jeramiah J. Smith

Biology Faculty Publications

Amphibian genomes differ greatly in DNA content and chromosome size, morphology, and number. Investigations of this diversity are needed to identify mechanisms that have shaped the evolution of vertebrate genomes. We used comparative mapping to investigate the organization of genes in the Mexican axolotl (Ambystoma mexicanum), a species that presents relatively few chromosomes (n = 14) and a gigantic genome (>20 pg/N). We show extensive conservation of synteny between Ambystoma, chicken, and human, and a positive correlation between the length of conserved segments and genome size. Ambystoma segments are estimated to be four to 51 times longer than homologous …

Meditation Acutely Improves Psychomotor Vigilance, And May Decrease Sleep Need, Prashant Kaul, Jason Passafiume, Craig R. Sargent, Bruce F. O'Hara

Biology Faculty Publications

BACKGROUND: A number of benefits from meditation have been claimed by those who practice various traditions, but few have been well tested in scientifically controlled studies. Among these claims are improved performance and decreased sleep need. Therefore, in these studies we assess whether meditation leads to an immediate performance improvement on a well validated psychomotor vigilance task (PVT), and second, whether longer bouts of meditation may alter sleep need.

METHODS: The primary study assessed PVT reaction times before and after 40 minute periods of mediation, nap, or a control activity using a within subject cross-over design. This study utilized novice …

Genic Regions Of A Large Salamander Genome Contain Long Introns And Novel Genes, Jeramiah J. Smith, Srikrishna Putta, Wei Zhu, Gerald M. Pao, Inder M. Verma, Tony Hunter, Susan V. Bryant, David M. Gardiner, Timothy T. Harkins, S. Randal Voss

Biology Faculty Publications

BACKGROUND: The basis of genome size variation remains an outstanding question because DNA sequence data are lacking for organisms with large genomes. Sixteen BAC clones from the Mexican axolotl (Ambystoma mexicanum: c-value = 32 x 10(9) bp) were isolated and sequenced to characterize the structure of genic regions.

RESULTS: Annotation of genes within BACs showed that axolotl introns are on average 10x longer than orthologous vertebrate introns and they are predicted to contain more functional elements, including miRNAs and snoRNAs. Loci were discovered within BACs for two novel EST transcripts that are differentially expressed during spinal cord regeneration and skin …

Recent Advances In Basic Neurosciences And Brain Disease: From Synapses To Behavior, Guo-Qiang Bi, Vadim Bolshakov, Guojun Bu, Catherine M. Cahill, Zhou-Feng Chen, Graham L. Collingridge, Robin L. Cooper, Jens R. Coorssen, Alaa El-Husseini, Vasco Galhardo, Wen-Biao Gan, Jianguo Gu, Kazuhide Inoue, John Isaac, Koichi Iwata, Zhengping Jia, Bong-Kiun Kaang, Mikito Kawamata, Satoshi Kida, Eric Klann, Tatsuro Kohno, Min Li, Xiao-Jiang Li, John F. Macdonald, Karim Nader, Peter V. Nguyen, Uhtaek Oh, Ke Ren, John C. Roder, Michael W. Salter, Weihong Song, Shuzo Sugita, Shao-Jun Tang, Yuanxiang Tao, Yu Tian Wang, Newton Woo, Melanie A. Woodin, Zhen Yan, Megumu Yoshimura, Ming Xu, Zao C. Xu, Xia Zhang, Mei Zhen, Min Zhuo

Biology Faculty Publications

Understanding basic neuronal mechanisms hold the hope for future treatment of brain disease. The 1st international conference on synapse, memory, drug addiction and pain was held in beautiful downtown Toronto, Canada on August 21-23, 2006. Unlike other traditional conferences, this new meeting focused on three major aims: (1) to promote new and cutting edge research in neuroscience; (2) to encourage international information exchange and scientific collaborations; and (3) to provide a platform for active scientists to discuss new findings. Up to 64 investigators presented their recent discoveries, from basic synaptic mechanisms to genes related to human brain disease. This meeting …

Gene Order Data From A Model Amphibian (Ambystoma): New Perspectives On Vertebrate Genome Structure And Evolution, Jeramiah J. Smith, S. Randal Voss

Biology Faculty Publications

BACKGROUND: Because amphibians arise from a branch of the vertebrate evolutionary tree that is juxtaposed between fishes and amniotes, they provide important comparative perspective for reconstructing character changes that have occurred during vertebrate evolution. Here, we report the first comparative study of vertebrate genome structure that includes a representative amphibian. We used 491 transcribed sequences from a salamander (Ambystoma) genetic map and whole genome assemblies for human, mouse, rat, dog, chicken, zebrafish, and the freshwater pufferfish Tetraodon nigroviridis to compare gene orders and rearrangement rates.

RESULTS: Ambystoma has experienced a rate of genome rearrangement that is substantially lower than mammalian …

From Biomedicine To Natural History Research: Est Resources For Ambystomatid Aalamanders, Srikrishna Putta, Jeramiah J. Smith, John A. Walker, Mathieu Rondet, David W. Weisrock, James Monaghan, Amy K. Samuels, D. Kevin Kump, David C. King, Nicholas J. Maness, Bianca Habermann, Elly Tanaka, Susan V. Bryant, David M. Gardiner, David M. Parichy, S. Randal Voss

Biology Faculty Publications

BACKGROUND: Establishing genomic resources for closely related species will provide comparative insights that are crucial for understanding diversity and variability at multiple levels of biological organization. We developed ESTs for Mexican axolotl (Ambystoma mexicanum) and Eastern tiger salamander (A. tigrinum tigrinum), species with deep and diverse research histories.

RESULTS: Approximately 40,000 quality cDNA sequences were isolated for these species from various tissues, including regenerating limb and tail. These sequences and an existing set of 16,030 cDNA sequences for A. mexicanum were processed to yield 35,413 and 20,599 high quality ESTs for A. mexicanum and A. t. tigrinum, respectively. Because the …

Is Hp1 An Rna Detector That Functions Both In Repression And Activation?, Rebecca Kellum

Biology Faculty Publications

Heterochromatin is defined as regions of compact chromatin that persist throughout the cell cycle (Heitz, 1928). The earliest cytological observations of heterochromatin were followed by ribonucleotide labeling experiments that showed it to be transcriptionally inert relative to the more typical euchromatic regions that decondense during interphase. Genetic studies of rearrangements that place euchromatic genes next to blocks of heterochromatin also pointed out the repressive nature of heterochromatin (Grigliatti, 1991; and references therein). The discovery of the heterochromatin-enriched protein heterochromatin protein 1 (HP1) by Elgin and co-workers in the mid-1980s suggested that the distinct cytological features of this chromatin may be …