Medicine and Health Sciences Commons^™

Assessing Blood Oxygen Level–Dependent Signal Variability As A Biomarker Of Brain Injury In Sport-Related Concussion, Evan D. Anderson, Tanveer Talukdar, Grace Goodwin, Valentina Di Pietro, Kamal M. Yakoub, Christopher E. Zwilling, David Davies, Antonio Belli, Aron K. Barbey

Center for Brain, Biology, and Behavior: Faculty Publications

Mild traumatic brain injury is a complex neurological disorder of significant concern among athletes who play contact sports. Athletes who sustain sport-related concussion typically undergo physical examination and neurocognitive evaluation to determine injury severity and return-to-play status. However, traumatic disruption to neurometabolic processes can occur with minimal detectable anatomic pathology or neurocognitive alteration, increasing the risk that athletes may be cleared for return-to-play during a vulnerable period and receive a repetitive injury. This underscores the need for sensitive functional neuroimaging methods to detect altered cerebral physiology in concussed athletes. The present study compared the efficacy of Immediate Post-concussion Assessment and …

Enhanced Cerebroprotection Of Xenon-Loaded Liposomes In Combination With Rtpa Thrombolysis For Embolic Ischemic Stroke, Tao Peng, Keith Booher, Melanie R Moody, Xing Yin, Jaroslaw Aronowski, David D Mcpherson, Sean I Savitz, Hyunggun Kim, Shao-Ling Huang

Faculty, Staff and Student Publications

Xenon (Xe) has shown great potential as a stroke treatment due to its exceptional ability to protect brain tissue without inducing side effects. We have previously developed Xe-loaded liposomes for the ultrasound-activated delivery of Xe into the cerebral region and demonstrated their therapeutic efficacy. At present, the sole FDA-approved thrombolytic agent for stroke treatment is recombinant tissue plasminogen activator (rtPA). In this study, we aimed to investigate the potential of combining Xe-liposomes with an intravenous rtPA treatment in a clinically relevant embolic rat stroke model. We evaluated the combinational effect using an in vitro clot lysis model and an in …

Estrogen-Related Receptor Gamma Gene Therapy Promotes Therapeutic Angiogenesis And Muscle Recovery In Preclinical Model Of Pad, Danesh H Sopariwala, Andrea S Rios, Addison Saley, Ashok Kumar, Vihang A Narkar

Faculty, Staff and Student Publications

Background Peripheral arterial disease and critical limb ischemia are cardiovascular complications associated with vascular insufficiency, oxidative metabolic dysfunction, and myopathy in the limbs. Estrogen-related receptor gamma (ERRγ) has emerged as a dual regulator of paracrine angiogenesis and oxidative metabolism through transgenic mouse studies. Here our objective was to investigate whether postischemic intramuscular targeting of ERRγ via gene therapy promotes ischemic recovery in a preclinical model of peripheral arterial disease/critical limb ischemia. Methods and Results Adeno-associated virus 9 (AAV9)

Spatial Immunoprofiling Of Adenoid Cystic Carcinoma Reveals B7-H4 Is A Therapeutic Target For Aggressive Tumors, Luana Guimaraes Sousa, Daniel J Mcgrail, Felippe Lazar Neto, Kaiyi Li, Mario L Marques-Piubelli, Sammy Ferri-Borgogno, Hui Dai, Yoshitsugu Mitani, Nicole Spardy Burr, Zachary A Cooper, Krista Kinneer, Maria Angelica Cortez, Shiaw-Yih Lin, Diana Bell, Adel El Naggar, Jared Burks, Renata Ferrarotto

Faculty, Staff and Student Publications

PURPOSE: Adenoid cystic carcinoma (ACC) is a heterogeneous malignancy, and no effective systemic therapy exists for metastatic disease. We previously described two prognostic ACC molecular subtypes with distinct therapeutic vulnerabilities, ACC-I and ACC-II. In this study, we explored the ACC tumor microenvironment (TME) using RNA-sequencing and spatial biology to identify potential therapeutic targets.

EXPERIMENTAL DESIGN: Tumor samples from 62 ACC patients with available RNA-sequencing data that had been collected as part of previous studies were stained with a panel of 28 validated metal-tagged antibodies. Imaging mass cytometry (IMC) was performed using the Fluidigm Helios CyTOF instrument and analyzed with Visiopharm …

Compass: Joint Copy Number And Mutation Phylogeny Reconstruction From Amplicon Single-Cell Sequencing Data, Etienne Sollier, Jack Kuipers, Koichi Takahashi, Niko Beerenwinkel, Katharina Jahn

Faculty, Staff and Student Publications

Reconstructing the history of somatic DNA alterations can help understand the evolution of a tumor and predict its resistance to treatment. Single-cell DNA sequencing (scDNAseq) can be used to investigate clonal heterogeneity and to inform phylogeny reconstruction. However, most existing phylogenetic methods for scDNAseq data are designed either for single nucleotide variants (SNVs) or for large copy number alterations (CNAs), or are not applicable to targeted sequencing. Here, we develop COMPASS, a computational method for inferring the joint phylogeny of SNVs and CNAs from targeted scDNAseq data. We evaluate COMPASS on simulated data and apply it to several datasets including …

Impact Of Black Soldier Fly (Hermetia Illucens) Fresh Meal On The Growth Performance, Digestive Enzymes, Hematology, And Intestinal Histology Of Cork Fish (Channa Striata), Boby Muslimin, Danang Yonarta, Eny Heriyati, Helmizuryani Helmizuryani, Meika Puspita Sari, Dewi Apriyanti, Rahmat Kurniawan

Turkish Journal of Veterinary & Animal Sciences

Black Soldier Fly (BSF) is an alternative ingredient for Fish Meal (FM) which is expected to reduce aquaculture operational costs and positively impact fish growth and health. The effect of BSF fresh meal on growth response, digestibility, intestinal hematology, and intestinal histology of cork fish was investigated. The BSF experiment with mixed percentages as treatments, by 20%, 50%, 80%, and 100%, was repeated four times. Furthermore, there were 50 individuals/m3 cork fish with an average weight of 1.6 ± 0.05 g distributed in each treatment. An increase in BSF influences a significant decrease in the Relative Growth Weight (RGW) and …

Evaluation Of Different Stocking Densities On Fattening Performance, Slaughter, Carcass, Meat Quality Characteristics, And Fatty Acid Composition In New Zealand Rabbits, Büşra Yaranoğlu, Mustafa Hi̇lmi̇ Yaranoğlu, Sali̇ha Uysal, Adnan Adi̇l Hi̇şmi̇oğullari

Turkish Journal of Veterinary & Animal Sciences

The aim of the research was to investigate the effects of different stocking densities on fattening performance, slaughter, carcass, meat quality characteristics, and fatty acid composition in New Zealand rabbits raised in cage conditions and also determine the ideal housing frequency so that yields were not adversely affected. In the study, 36 New Zealand rabbits were used. After weaning, the fattening was started and rabbits were put into cages at different stocking densities as 1 rabbit/cage, 2 rabbits/cage, and 3 rabbits/ cage. The live weight of rabbits and feed consumption data were taken every week. At the end of 8 …

Expression Of Hif-1Α, Caspase-3, P53, Hsp70, Hsp90, And Nrf2 In The Canine Spleen With Siderofibrotic Nodules: An Immunohistochemical And Immunofluorescence Perspective On Apoptosis, Ferroptosis, And Oxidative Stress, Ali Babanezhad-Gajouti, Amir Amniattalab

Turkish Journal of Veterinary & Animal Sciences

Splenic siderofibrotic nodules (SFNs) are benign tiny yellow-brownish foci found in dogs. Their pathogenesis is unclear whereas trauma and hemorrhage are assumed to be the possible causative factors. The spleen of 73 Iranian dogs of the mixed breed was examined for possible splenomegaly with SFNs. Ultrasonography, blood biochemistry, pathology, and immunohistochemistry revealed splenomegaly (n = 7), splenomegaly with SFNs (n = 6) and normal spleens (n = 60). There was no significant difference between the prevalence of splenomegaly with SFN among the examined dogs and their age or sex (p > 0.05). Ultrasonography represented a significant increase (p ≤ 0.01) in …

An Evaluation Of Canine Inguinal Hernias Containing The Uterus: Clinical Experience Of Four Cases (2017-2022) And Literature Review, Fi̇rdevs Bi̇nli̇, Fati̇h Büyükbudak, İpek İnan, Volkan Ferahoğlu, Anil Gürkan Aksu, Murat Findik, Serhan Serhat Ay

Turkish Journal of Veterinary & Animal Sciences

The aim of this study is to identify and summarize the evidence and risk factors of canine inguinal hernia containing the uterus (Inguinal Hysterocele; IH) etiology by presenting our clinical experience with a literature review. A total of 18 canine IH cases were evaluated in the study. Of these, four have not yet been published anywhere, two have been published before, and 12 were obtained through a literature review. According to the findings, 81.3% of the cases were small/medium races, 83.3% were ≥5 years old, and 72.7% were multiparous. Totally 83.3% of the cases were chronic and 72.2% of the …

Comparison Of Bacterial Profile And Antibiotic Susceptibility Isolated From Surgical Site After Ventral Midline And Lateral Flank Approaches Of Ovariohysterectomy In Queens And Bitches, Ebru Karakaya Bi̇len, Serpi̇l Kahya Demi̇rbi̇lek, Öznur Yilmaz, Muhammet Ali̇ Karadağ, Havva Aner

Turkish Journal of Veterinary & Animal Sciences

The aim of the study was to identify the bacterial profile and antimicrobial susceptibility from surgical site cultures in queens and bitches undergoing ovariohysterectomy via ventral midline and lateral flank approaches. Healthy 22 queens and 21 bitches were assigned randomly either ventral midline or lateral flank approach for routine ovariohysterectomy. Surgical site samples were collected before the surgery and on the 1$^{st}$, 2$^{nd}$ , and 3 $^{rd}$days after the surgery for microbiological analysis. A total of 70 different strains were isolated from 50 (29%) of 172 samples. In both queens and bitches the total number of bacteria isolated from the …

Stereological Investigation Of Medulla Oblongata Volume In Norduz Sheep, Ozan Ertaş, Gamze Çakmak

Turkish Journal of Veterinary & Animal Sciences

In this study, it was aimed to stereologically examine the medulla oblongata volume of Norduz sheep in the Gürpınar District of Van Province. Upon receiving news from the sections in the Gürpınar region, we went to the region. A total of 12 Norduz sheep skulls, 6 females and 6 males, were received from the Norduz sheep slaughter in the region. After the brains of Norduz sheep were dissected, they were fixed as a whole in formaldehyde for 1 week. Medulla oblongatas were separated from the brain and kept in formaldehyde for 1 week. Tissues obtained by sequential random sampling from …

Determination Of Virulence Genes And Antibiotic Resistance Profiles Of Streptococcus Agalactiae Isolated From Buffalo Milk, Nevi̇n Tuzcu, Hasan Hüseyi̇n Hadi̇mli̇, Beatri̇z Padron

Turkish Journal of Veterinary & Animal Sciences

Mastitis is a contagious disease that causes significant milk loss and serious economic damage in dairy animals. Streptococcus agalactiae causes clinical and subclinical mastitis in animals and infections in humans, especially adults, and newborns. This study aimed to confirm the identification of S. agalactiae isolates by PCR in buffalo milk; to determine the antibiotic resistance and virulence genes by multiplex PCR. The material of this study consisted of 30 (12%) S. agalactiae strains identified by phenotypic, biochemical, and PCR methods (rRNA-16S) from 250 isolates with bacterial growth from milk samples of buffaloes with mastitis. In addition, the Kirby-Bauer disc diffusion …

Effect Of Feeding Frequency On Growth, Fecundity, And Meat Quality Of Abant Trout (Salmo Abanticus Tortonese, 1954) Broodstock, Mehmet Zeki̇ Alkan, Nadi̇r Başçinar

Turkish Journal of Veterinary & Animal Sciences

This study was carried out to investigate the growth data, egg production and changes in the biochemical structure of meat of Abant trout depending on feeding frequency (once a day, twice a day, three times a day, four times a day) in order to contribute to the economy through the private sector. All fish in the groups were planned to be of similar weight at the beginning of the study. Individual fish weights were measured at the beginning of the study, and the average was found to be 224.87 ± 0.69 g. At the end of the study, the weights …

In Vitro Antimicrobial And Antibiofilm-Forming Activities Of Origanum Munzurense Plant Extract On Some Foodborne Gram-Negative Bacteria, Hali̇l Yalçin, Esra Zeybek, Oktay Özkan, Asim Kart

Turkish Journal of Veterinary & Animal Sciences

lants are an important source for the discovery of antimicrobial formulations due to the many biologically active components they contain. In this study, in vitro antimicrobial and antibiofilm forming activities of ethanolic extract of Origanum munzurense were investigated against some strains of foodborne pathogenic bacteria. To investigate the antimicrobial activity, the minimal inhibitory concentration values against the selected bacteria and antibiofilm-forming activity were tested with the liquid microdilution method and microplate method, respectively. MICs of Origanum munzurense extract against the bacteria tested are 32 mg/mL for Escherichia coli O157: H7 ATCC 35150, 32 mg/mL for Escherichia coli O157: H7 ATCC …

The First Data Of A Newly Recorded Native Goat Genotype Called Manavlı In Türkiye: Growth Traits Of Kids, Aykut Asim Akbaş, Mustafa Saatci, Özkan Elmaz, Can Meti̇n Yazici

Turkish Journal of Veterinary & Animal Sciences

This study aimed to define growth traits of kids named Manavlı goat from six flocks under the breeder?s conditions in Denizli Province. The average birth weights of the kids were 3.63 kg, 4.28 kg, 3.85 kg, 4.11 kg, 3.83 kg, and 3.64 kg for the six flocks, respectively. The average live weights of male and female kids on 60th, 90th, and 150th day of age were 16.50 kg, 22.35 kg, and 34.82 kg and 15.33 kg, 20.14 kg, and 32.06 kg, respectively (p < 0.05). While the average live weights of single kids on 60th, 90th were 16.70 kg and 21.96 kg, the values for twins were 15.13 kg and 21.03 kg, respectively (p < 0.05). Body measurements of male kids such as height at withers, rump height, rump width, body length, heart girth, head length, ear length, tail length, and front and back wrist girth were measured as 70.26 cm, 70.21 cm, 16.23 cm, 66.80 cm, 70.11 cm, 19.51 cm, 22.16 cm, 18.59 cm, 11.85 cm, and 11.57 cm, respectively, on the 150th day of age. This study is the first research related to growth traits of Manavlı kids, for which no features have been reported to date. It was thought that the results obtained will help to characterise the Manavlı goat and will provide a database for the following studies.

Prolonged Cytopenia Following Cd19 Car T Cell Therapy Is Linked With Bone Marrow Infiltration Of Clonally Expanded Ifnγ-Expressing Cd8 T Cells, Paolo Strati, Xubin Li, Qing Deng, Mario L Marques-Piubelli, Jared Henderson, Grace Watson, Laurel Deaton, Taylor Cain, Haopeng Yang, Vida Ravanmehr, Luis E Fayad, Swaminathan P Iyer, Loretta J Nastoupil, Frederick B Hagemeister, Edwin R Parra, Neeraj Saini, Koichi Takahashi, Nathan H Fowler, Jason R Westin, Raphael E Steiner, Ranjit Nair, Christopher R Flowers, Linghua Wang, Sairah Ahmed, Gheath Al-Atrash, Francisco Vega, Sattva S Neelapu, Michael R Green

Faculty, Staff and Student Publications

Autologous anti-CD19 chimeric antigen receptor T cell (CAR T) therapy is highly effective in relapsed/refractory large B cell lymphoma (rrLBCL) but is associated with toxicities that delay recovery. While the biological mechanisms of cytokine release syndrome and neurotoxicity have been investigated, the pathophysiology is poorly understood for prolonged cytopenia, defined as grade ≥3 cytopenia lasting beyond 30 days after CAR T infusion. We performed single-cell RNA sequencing of bone marrow samples from healthy donors and rrLBCL patients with or without prolonged cytopenia and identified significantly increased frequencies of clonally expanded CX3CR1hi cytotoxic T cells, expressing high interferon (IFN)-γ and cytokine …

Indoor Airborne Microbiome And Endotoxin: Meteorological Events And Occupant Characteristics Are Important Determinants, Hesham Amin, Tina Šantl-Temkiv, Christine Cramer, Kai Finster, Francisco Gomez Real, Thorarinn Gislason, Mathias Holm, Christer Janson, Nils Oskar Jögi, Rain Jogi, Andrei Malinovschi, Ian P G Marshall, Lars Modig, Dan Norbäck, Rajesh Shigdel, Torben Sigsgaard, Cecilie Svanes, Hulda Thorarinsdottir, Inge M Wouters, Vivi Schlünssen, Randi J Bertelsen

Faculty, Staff and Student Publications

Airborne bacteria and endotoxin may affect asthma and allergies. However, there is limited understanding of the environmental determinants that influence them. This study investigated the airborne microbiomes in the homes of 1038 participants from five cities in Northern Europe: Aarhus, Bergen, Reykjavik, Tartu, and Uppsala. Airborne dust particles were sampled with electrostatic dust fall collectors (EDCs) from the participants’ bedrooms. The dust washed from the EDCs’ clothes was used to extract DNA and endotoxin. The DNA extracts were used for quantitative polymerase chain (qPCR) measurement and 16S rRNA gene sequencing, while endotoxin was measured using the kinetic chromogenic limulus amoebocyte …

Enigma Chek2gether Project: A Comprehensive Study Identifies Functionally Impaired Chek2 Germline Missense Variants Associated With Increased Breast Cancer Risk, Lenka Stolarova, Petra Kleiblova, Petra Zemankova, Barbora Stastna, Marketa Janatova, Jana Soukupova, Maria Isabel Achatz, Christine Ambrosone, Paraskevi Apostolou, Banu K Arun, Paul Auer, Mollie Barnard, Birgitte Bertelsen, Biobank Japan, Marinus J Blok, Nicholas Boddicker, Joan Brunet, Elizabeth S Burnside, Mariarosaria Calvello, Ian Campbell, Sock Hoai Chan, Fei Chen, Jian Bang Chiang, Anna Coppa, Laura Cortesi, Ana Crujeiras-González, Consortium Czecanca, Kim De Leeneer, Robin De Putter, Allison Depersia, Lisa Devereux, Susan Domchek, Anna Efremidis, Christoph Engel, Corinna Ernst, D Gareth R Evans, Lidia Feliubadaló, Florentia Fostira, Olivia Fuentes-Ríos, Encarna B Gómez-García, Sara González, Christopher Haiman, Thomas Van Overeem Hansen, Jan Hauke, James Hodge, Chunling Hu, Hongyan Huang, Nur Diana Binte Ishak, Yusuke Iwasaki, Irene Konstantopoulou, Peter Kraft, James Lacey, Conxi Lázaro, Na Li, Weng Khong Lim, Sara Lindstrom, Adriana Lori, Elana Martinez, Alexandra Martins, Koichi Matsuda, Giuseppe Matullo, Simone Mcinerny, Kyriaki Michailidou, Marco Montagna, Alvaro N A Monteiro, Luigi Mori, Katherine Nathanson, Susan L Neuhausen, Heli Nevanlinna, Janet E Olson, Julie Palmer, Barbara Pasini, Alpa Patel, Maria Piane, Bruce Poppe, Paolo Radice, Alessandra Renieri, Nicoletta Resta, Marcy E Richardson, Toon Rosseel, Kathryn J Ruddy, Marta Santamariña, Elizabeth Santana Dos Santos, Lauren Teras, Amanda E Toland, Amy Trentham-Dietz, Celine M Vachon, Alexander E Volk, Nana Weber-Lassalle, Jeffrey N Weitzel, Lisa Wiesmuller, Stacey Winham, Siddhartha Yadav, Drakoulis Yannoukakos, Song Yao, Valentina Zampiga, Magnus Zethoven, Ze Wen Zhang, Tomas Zima, Amanda B Spurdle, Ana Vega, Maria Rossing, Jesús Del Valle, Arcangela De Nicolo, Eric Hahnen, Kathleen B M Claes, Joanne Ngeow, Yukihide Momozawa, Paul A James, Fergus J Couch, Libor Macurek, Zdenek Kleibl

Faculty, Staff and Student Publications

PURPOSE: Germline pathogenic variants in CHEK2 confer moderately elevated breast cancer risk (odds ratio, OR ∼ 2.5), qualifying carriers for enhanced breast cancer screening. Besides pathogenic variants, dozens of missense CHEK2 variants of uncertain significance (VUS) have been identified, hampering the clinical utility of germline genetic testing (GGT).

EXPERIMENTAL DESIGN: We collected 460 CHEK2 missense VUS identified by the ENIGMA consortium in 15 countries. Their functional characterization was performed using CHEK2-complementation assays quantifying KAP1 phosphorylation and CHK2 autophosphorylation in human RPE1-CHEK2-knockout cells. Concordant results in both functional assays were used to categorize CHEK2 VUS from 12 ENIGMA case-control datasets, including …

Targeting Bcl2 Overcomes Resistance And Augments Response To Aurora Kinase B Inhibition By Azd2811 In Small Cell Lung Cancer, Kavya Ramkumar, Azusa Tanimoto, Carminia M Della Corte, C Allison Stewart, Qi Wang, Li Shen, Robert J Cardnell, Jing Wang, Urszula M Polanska, Courtney Andersen, Jamal Saeh, J Elizabeth Pease, Jon Travers, Giulia Fabbri, Carl M Gay, Jelena Urosevic, Lauren A Byers

Faculty, Staff and Student Publications

PURPOSE: Therapeutic resistance to frontline therapy develops rapidly in small cell lung cancer (SCLC). Treatment options are also limited by the lack of targetable driver mutations. Therefore, there is an unmet need for developing better therapeutic strategies and biomarkers of response. Aurora kinase B (AURKB) inhibition exploits an inherent genomic vulnerability in SCLC and is a promising therapeutic approach. Here, we identify biomarkers of response and develop rational combinations with AURKB inhibition to improve treatment efficacy.

EXPERIMENTAL DESIGN: Selective AURKB inhibitor AZD2811 was profiled in a large panel of SCLC cell lines (n = 57) and patient-derived xenograft (PDX) models. …

Loss Of Syncrip Unleashes Apobec-Driven Mutagenesis, Tumor Heterogeneity, And Ar-Targeted Therapy Resistance In Prostate Cancer, Xiaoling Li, Yunguan Wang, Su Deng, Guanghui Zhu, Choushi Wang, Nickolas A Johnson, Zeda Zhang, Carla Rodriguez Tirado, Yaru Xu, Lauren A Metang, Julisa Gonzalez, Atreyi Mukherji, Jianfeng Ye, Yuqiu Yang, Wei Peng, Yitao Tang, Mia Hofstad, Zhiqun Xie, Heewon Yoon, Liping Chen, Xihui Liu, Sujun Chen, Hong Zhu, Douglas Strand, Han Liang, Ganesh Raj, Housheng Hansen He, Joshua T Mendell, Bo Li, Tao Wang, Ping Mu

Faculty, Staff and Student Publications

Tumor mutational burden and heterogeneity has been suggested to fuel resistance to many targeted therapies. The cytosine deaminase APOBEC proteins have been implicated in the mutational signatures of more than 70% of human cancers. However, the mechanism underlying how cancer cells hijack the APOBEC mediated mutagenesis machinery to promote tumor heterogeneity, and thereby foster therapy resistance remains unclear. We identify SYNCRIP as an endogenous molecular brake which suppresses APOBEC-driven mutagenesis in prostate cancer (PCa). Overactivated APOBEC3B, in SYNCRIP-deficient PCa cells, is a key mutator, representing the molecular source of driver mutations in some frequently mutated genes in PCa, including FOXA1, …

Bacteroides Uniformis-Induced Perturbations In Colonic Microbiota And Bile Acid Levels Inhibit Th17 Differentiation And Ameliorate Colitis Developments, Yiting Yan, Yu Lei, Ying Qu, Zhen Fan, Ting Zhang, Yangbin Xu, Qian Du, Daniel Brugger, Yulin Chen, Ke Zhang, Enping Zhang

Faculty, Staff and Student Publications

Inflammatory bowel disease (IBD) is associated with gut dysbiosis and can lead to colitis-associated malignancies. Bacteroides uniformis (Bu) regulates animal intestinal homeostasis; however, the mechanism by which it alleviates colitis in mice remains unknown. We investigated the effects of B. uniformis JCM5828 and its metabolites on female C57BL/6J mice with dextran sulfate sodium salt (DSS) induced colitis. Treatment with Bu considerably alleviated colitis progression and restored the mechanical and immune barrier protein expression. Additionally, Bu increased the abundance of the symbiotic bacteria Bifidobacterium and Lactobacillus vaginalis while decreasing that of pathogenic Escherichia-Shigella, and modulated intestinal bile acid metabolism. Bu largely …

Evolution Of Immune And Stromal Cell States And Ecotypes During Gastric Adenocarcinoma Progression, Ruiping Wang, Shumei Song, Jiangjiang Qin, Katsuhiro Yoshimura, Fuduan Peng, Yanshuo Chu, Yuan Li, Yibo Fan, Jiankang Jin, Minghao Dang, Enyu Dai, Guangsheng Pei, Guangchun Han, Dapeng Hao, Yating Li, Deyali Chatterjee, Kazuto Harada, Melissa Pool Pizzi, Ailing W Scott, Ghia Tatlonghari, Xinmiao Yan, Zhiyuan Xu, Can Hu, Shaowei Mo, Namita Shanbhag, Yang Lu, Matheus Sewastjanow-Silva, Ahmed Adel Fouad Abdelhakeem, Guang Peng, Samir M Hanash, George A Calin, Cassian Yee, Pawel Mazur, Autumn N Marsden, Andrew Futreal, Zhenning Wang, Xiangdong Cheng, Jaffer A Ajani, Linghua Wang

Faculty, Staff and Student Publications

Understanding tumor microenvironment (TME) reprogramming in gastric adenocarcinoma (GAC) progression may uncover novel therapeutic targets. Here, we performed single-cell profiling of precancerous lesions, localized and metastatic GACs, identifying alterations in TME cell states and compositions as GAC progresses. Abundant IgA+ plasma cells exist in the premalignant microenvironment, whereas immunosuppressive myeloid and stromal subsets dominate late-stage GACs. We identified six TME ecotypes (EC1–6). EC1 is exclusive to blood, while EC4, EC5, and EC2 are highly enriched in uninvolved tissues, premalignant lesions, and metastases, respectively. EC3 and EC6, two distinct ecotypes in primary GACs, associate with histopathological and genomic characteristics, and prognosis. …

Immunological Monitoring In Hepatitis C Virus Controlled Human Infection Model, Naglaa H Shoukry, Andrea L Cox, Christopher M Walker

Faculty, Staff and Student Publications

Controlled human infection model trials for hepatitis C virus represent an important opportunity to identify correlates of protective immunity against a well-characterized inoculum of hepatitis C virus and how such responses are modified by vaccination. In this article, we discuss the approach to immunological monitoring during such trials, including a set of recommendations for optimal sampling schedule and preferred immunological assays to examine the different arms of the immune response. We recommend that this approach be adapted to different trial designs. Finally, we discuss how these studies can provide surrogate predictors of the success of candidate vaccines.

The Directional Effect Of Target Position On Spatial Selective Auditory Attention, Heesung Park

Dissertations, 2020-current

Spatial selective auditory attention plays a crucial role in listening in a mixture of competing speech sounds. Previous neuroimaging studies have reported alpha band neural activity modulated by auditory attention, along with the alpha lateralization corresponding to attentional focus. A greater cortical representation of the attended speech envelope compared to the ignored speech envelope was also found, a phenomenon known as 'neural speech tracking’. However, little is known about the neural activities when attentional focus is directed on speech sounds from behind the listener, even though understanding speech from behind is a common and essential aspect of daily life. The …

Characterizing Cancer Metabolism From Bulk And Single-Cell Rna-Seq Data Using Metaflux, Yuefan Huang, Vakul Mohanty, Merve Dede, Kyle Tsai, May Daher, Li Li, Katayoun Rezvani, Ken Chen

Faculty, Staff and Student Publications

Cells often alter metabolic strategies under nutrient-deprived conditions to support their survival and growth. Characterizing metabolic reprogramming in the tumor microenvironment (TME) is of emerging importance in cancer research and patient care. However, recent technologies only measure a subset of metabolites and cannot provide in situ measurements. Computational methods such as flux balance analysis (FBA) have been developed to estimate metabolic flux from bulk RNA-seq data and can potentially be extended to single-cell RNA-seq (scRNA-seq) data. However, it is unclear how reliable current methods are, particularly in TME characterization. Here, we present a computational framework METAFlux (METAbolic Flux balance analysis) …

Lvpt: Lazy Velocity Pseudotime Inference Method, Shuainan Mao, Jiajia Liu, Weiling Zhao, Xiaobo Zhou

Faculty, Staff and Student Publications

The emergence of RNA velocity has enriched our understanding of the dynamic transcriptional landscape within individual cells. In light of this breakthrough, we embarked on integrating RNA velocity with cellular pseudotime inference, aiming to improve the prediction of cell orders along biological trajectories beyond existing methods. Here, we developed LVPT, a novel method for pseudotime and trajectory inference. LVPT introduces a lazy probability to indicate the probability that the cell stays in the original state and calculates the transition matrix based on RNA velocity to provide the probability and direction of cell differentiation. LVPT shows better and comparable performance of …

Mutation-Induced Changes In The Stability, B-Cell Epitope, And Antigenicity Of The Sars-Cov-2 Variant Spike Protein: A Comparative Computational Stud, Nira Meirita Wijayanti, Muhammad Hermawan Widyananda, Lailil Muflikhah, Nashi Widodo

Karbala International Journal of Modern Science

The spike (S) protein is a major antigenicity site that targets neutralizing antibodies and drugs. The growing number of S protein mutations has become a severe problem for developing effective vaccines. Here, we investigated four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that were the most infectious and widespread during the COVID-19 pandemic to determine the trends and patterns of mutation-induced changes in the stability, B-cell epitope, and antigenicity of the SARS-CoV-2 S protein. The data showed that the Beta and Gamma variants had three mutations on the receptor-binding domain (RBD), which is the specific site on the S …

The Devil You Know And The Devil You Don’T: Current Status And Challenges Of Bovine Tuberculosis Eradication In The United States, Daniel J. O'Brien, Tyler C. Thacker, Liliana C.M. Salvador, Anthony G. Duffiney, Suelee Robbe‑Austerman, Mark S. Camacho, Jason E. Lombard, Mitchell V. Palmer

United States Department of Agriculture Wildlife Services: Staff Publications

Having entered into its second century, the eradication program for bovine tuberculosis (bTB, caused by Mycobacterium bovis) in the United States of America occupies a position both enviable and daunting. Excepting four counties in Michigan comprising only 6109 km2 (0.06% of US land area) classified as Modified Accredited, as of April 2022 the entire country was considered Accredited Free of bTB by the US Department of Agriculture for cattle and bison. On the surface, the now well-described circumstances of endemic bTB in Michigan, where white-tailed deer (Odocoileus virginianus) serve as a free-ranging wildlife maintenance host, may appear to be …

Exploiting Vulnerabilities In The Ras-Rac Signaling Pathway For The Selective Targeting Of Pancreatic Cancer Cells, Neha Chaudhary

Theses & Dissertations

Deregulation of the KRas (Kirsten rat sarcoma virus) GTPase is one of the early hallmarks of Pancreatic Cancer (PC). The most common genetic alteration found in PC are mutations in the KRas protein that block its ability to hydrolyze GTP to GDP and resulting in higher levels of GTP-bound KRas, its active form. Pancreatic tumors driven by oncogenic mutants of KRas tend to be addicted to the oncogene, to the extent that its repression leads to the induction of cell death. This addiction to the KRAS oncogene makes the KRas protein an ideal target for cancer therapy. However, the globular …

The Co-Oncogenic Function Of Ecdysoneless Protein With Erbb2 In Mammary Epithelial Cells, Benjamin B. Kennedy

Theses & Dissertations

The Ecdysoneless (ECD) protein is highly evolutionarily conserved and ubiquitously expressed across human tissues. ECD has established roles in cell cycle regulation, embryogenesis, cell survival, and RNA biogenesis. ECD mRNA and protein are overexpressed in breast cancer, and its overexpression correlates with poor patient survival, especially in ErbB2/HER2-positive breast cancer. This thesis work investigates the co-oncogenic role of ECD in ErbB2-driven oncogenesis using immortalized mammary epithelial cells. Here, we show that ECD and ErbB2 overexpression in immortalized human mammary epithelial cells increases cancer traits, such as invasion, migration, and anchorage independent growth. Significantly, ECD+ErbB2 co-overexpression further enhanced all oncogenic traits. …