Digital Commons Network^™

Androgen-Regulated Stromal Complement Component 7 (C7) Suppresses Prostate Cancer Growth, Zhicheng Zhou, Deyong Jia, Ohjoon Kwon, Shan Li, Huiyun Sun, Martine P Roudier, Daniel W Lin, Lawrence True, Colm Morrissey, Chad J Creighton, John K Lee, Li Xin

Faculty, Staff and Students Publications

The complement system is a major component of the innate immune system that works through the cytolytic effect of the membrane attack complex (MAC). Complement component 7 (C7) is essential for MAC assembly and its precisely regulated expression level is crucial for the cytolytic activity of MAC. We show that C7 is specifically expressed by the stromal cells in both mouse and human prostates. The expression level of C7 inversely correlates with clinical outcomes in prostate cancer. C7 is positively regulated by androgen signaling in the mouse prostate stromal cells. The androgen receptor directly transcriptionally regulates the mouse and human …

Dental Pulp Stem Cells And Current In Vivo Approaches To Study Dental Pulp Stem Cells In Pulp Injury And Regeneration, Dongwook Yang, Jea Giezl Niedo Solidum, Dongsu Park

Faculty, Staff and Students Publications

Dental pulp stem cells (DPSCs) have garnered significant interest in dental research for their unique characteristics and potential in tooth development and regeneration. While there were many studies to define their stem cell-like characteristics and osteogenic differentiation functions that are considered ideal candidates for regenerating damaged dental pulp tissue, how endogenous DPSCs respond to dental pulp injury and supply new dentin-forming cells has not been extensively investigated in vivo. Here, we review the recent progress in identity, function, and regulation of endogenous DPSCs and their clinical potential for pulp injury and regeneration. In addition, we discuss current advances in new …

Chromatin Architectural Factor Ctcf Is Essential For Progesterone-Dependent Uterine Maturation, Sylvia C Hewitt, Artiom Gruzdev, Cynthia J Willson, San-Pin Wu, John P Lydon, Niels Galjart, Francesco J Demayo

Faculty, Staff and Students Publications

Receptors for estrogen and progesterone frequently interact, via Cohesin/CTCF loop extrusion, at enhancers distal from regulated genes. Loss-of-function CTCF mutation in >20% of human endometrial tumors indicates its importance in uterine homeostasis. To better understand how CTCF-mediated enhancer-gene interactions impact endometrial development and function, the Ctcf gene was selectively deleted in female reproductive tissues of mice. Prepubertal Ctcf

Trim28 Modulates Nuclear Receptor Signaling To Regulate Uterine Function, Rong Li, Tianyuan Wang, Ryan M Marquardt, John P Lydon, San-Pin Wu, Francesco J Demayo

Faculty, Staff and Students Publications

Estrogen and progesterone, acting through their cognate receptors the estrogen receptor α (ERα) and the progesterone receptor (PR) respectively, regulate uterine biology. Using rapid immunoprecipitation and mass spectrometry (RIME) and co-immunoprecipitation, we identified TRIM28 (Tripartite motif containing 28) as a protein which complexes with ERα and PR in the regulation of uterine function. Impairment of TRIM28 expression results in the inability of the uterus to support early pregnancy through altered PR and ERα action in the uterine epithelium and stroma by suppressing PR and ERα chromatin binding. Furthermore, TRIM28 ablation in PR-expressing uterine cells results in the enrichment of a …

Heterogeneity Of The Group B Streptococcal Type Vii Secretion System And Influence On Colonization Of The Female Genital Tract, Brady L Spencer, Alyx M Job, Clare M Robertson, Zainab A Hameed, Camille Serchejian, Caitlin S Wiafe-Kwakye, Jéssica C Mendonça, Morgan A Apolonio, Prescilla E Nagao, Melody N Neely, Natalia Korotkova, Konstantin V Korotkov, Kathryn A Patras, Kelly S Doran

Faculty, Staff and Students Publications

Type VIIb secretion systems (T7SSb) in Gram-positive bacteria facilitate physiology, interbacterial competition, and/or virulence via EssC ATPase-driven secretion of small ɑ-helical proteins and toxins. Recently, we characterized T7SSb in group B Streptococcus (GBS), a leading cause of infection in newborns and immunocompromised adults. GBS T7SS comprises four subtypes based on variation in the C-terminus of EssC and the repertoire of downstream effectors; however, the intraspecies diversity of GBS T7SS and impact on GBS-host interactions remains unknown. Bioinformatic analysis indicates that GBS T7SS loci encode subtype-specific putative effectors, which have low interspecies and inter-subtype homology but contain similar domains/motifs and therefore …

Effects Of Cathepsin S Inhibition In The Age-Related Dry Eye Phenotype, Jeremias G Galletti, Kaitlin K Scholand, Claudia M Trujillo-Vargas, Wolfgang Haap, Tiago Santos-Ferreira, Christoph Ullmer, Zhiyuan Yu, Cintia S De Paiva

Faculty, Staff and Students Publications

PURPOSE: Aged C57BL/6J (B6) mice have increased levels of cathepsin S, and aged cathepsin S (Ctss-/-) knockout mice are resistant to age-related dry eye. This study investigated the effects of cathepsin S inhibition on age-related dry eye disease.

METHODS: Female B6 mice aged 15.5 to 17 months were randomized to receive a medicated diet formulated by mixing the RO5461111 cathepsin S inhibitor or a standard diet for at least 12 weeks. Cornea mechanosensitivity was measured with a Cochet-Bonnet esthesiometer. Ocular draining lymph nodes and lacrimal glands (LGs) were excised and prepared for histology or assayed by flow cytometry to quantify …

Loss Of Cytochrome P450 (Cyp)1b1 Mitigates Hyperoxia Response In Adult Mouse Lung By Reprogramming Metabolism And Translation, Sandra L Grimm, Rachel E Stading, Matthew J Robertson, Tanmay Gandhi, Chenlian Fu, Weiwu Jiang, Guobin Xia, Krithika Lingappan, Cristian Coarfa, Bhagavatula Moorthy

Faculty, Staff and Students Publications

Oxygen supplementation is life saving for premature infants and for COVID-19 patients but can induce long-term pulmonary injury by triggering inflammation, with xenobiotic-metabolizing CYP enzymes playing a critical role. Murine studies showed that CYP1B1 enhances, while CYP1A1 and CYP1A2 protect from, hyperoxic lung injury. In this study we tested the hypothesis that Cyp1b1-null mice would revert hyperoxia-induced transcriptomic changes observed in WT mice at the transcript and pathway level. Wild type (WT) C57BL/6J and Cyp1b1-null mice aged 8-10 weeks were maintained in room air (21% O

Early Clinical Variables Associated With Refractory Convulsive Status Epilepticus In Children, Katrina Peariso, Ravindra Arya, Tracy Glauser, Nicholas S Abend, Cristina Barcia Aguilar, Marta Amengual-Gual, Anne Anderson, Brian L Appavu, J Nicholas Brenton, Jessica Carpenter, Kevin E Chapman, Justice Clark, William D Gaillard, Marina Gaínza-Lein, Joshua Goldstein, Howard Goodkin, Zachary Grinspan, Rejean M Guerriero, Paul S Horn, Linda Huh, Robert Kahoud, Sarah A Kelley, Eric H Kossoff, Kush Kapur, Yi-Chen Lai, B Oyinkan Marquis, Tiffani Mcdonough, Mohamad A Mikati, Lindsey Morgan, Edward Novotny, Adam P Ostendorf, Eric T Payne, Juan Piantino, James Riviello, Tristan Sands, Carl E Stafstrom, Robert C Tasker, Dmitry Tchapyjnikov, Alejandra Vasquez, Mark S Wainwright, Angus Wilfong, Korwyn Williams, Tobias Loddenkemper

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: The objective of this study was to determine patient-specific factors known proximate to the presentation to emergency care associated with the development of refractory convulsive status epilepticus (RSE) in children.

METHODS: An observational case-control study was conducted comparing pediatric patients (1 month-21 years) with convulsive SE whose seizures stopped after benzodiazepine (BZD) and a single second-line antiseizure medication (ASM) (responsive established status epilepticus [rESE]) with patients requiring more than a BZD and a single second-line ASM to stop their seizures (RSE). These subpopulations were obtained from the pediatric Status Epilepticus Research Group study cohort. We explored clinical …

Robotic Nerve Surgery: Brachial Plexus, Matthew J Parham, Samuel H Cole, Nicholas H Yim, William C Pederson

Faculty, Staff and Students Publications

Management of closed brachial plexus injuries has traditionally favored conservative approaches with lengthy intervals between initial injury and surgical reconstruction. The complex anatomy of this region often requires large incisions with extensive dissection. Recently, the use of robotic systems in plastic and reconstructive surgery has been increasing, and robot-assisted brachial plexus reconstruction is a novel application that is currently being explored. Current literature describing this application is primarily comprised of feasibility studies using animal and cadaver models, and literature describing use in human subjects is limited. Advantages demonstrated by these early studies include the reduction of physiologic tremor, 3D visualization …

Cerebellar Dysfunction As A Source Of Dystonic Phenotypes In Mice, Amanda M Brown, Meike E Van Der Heijden, H A Jinnah, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

There is now a substantial amount of compelling evidence demonstrating that the cerebellum may be a central locus in dystonia pathogenesis. Studies using spontaneous genetic mutations in rats and mice, engineered genetic alleles in mice, shRNA knockdown in mice, and conditional genetic silencing of fast neurotransmission in mice have all uncovered a common set of behavioral and electrophysiological defects that point to cerebellar cortical and cerebellar nuclei dysfunction as a source of dystonic phenotypes. Here, we revisit the Ptf1aCre/+;Vglut2flox/flox mutant mouse to define fundamental phenotypes and measures that are valuable for testing the cellular, circuit, and …

Sculpting Astrocyte Diversity Through Circuits And Transcription, Yi-Ting Cheng, Junsung Woo, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes are the most abundant glial cell in the central nervous system and occupy a wide range of roles that are essential for brain function. Over the past few years, evidence has emerged that astrocytes exhibit cellular and molecular heterogeneity, raising the possibility that subsets of astrocytes are functionally distinct and that transcriptional mechanisms are involved in encoding this prospective diversity. In this review, we focus on three emerging areas of astrocyte biology: region-specific circuit regulation, molecular diversity, and transcriptional regulation. This review highlights our nascent understanding of how molecular diversity is converted to functional diversity of astrocytes through the …

Why Animal Experiments Are Still Indispensable In Bone Research: A Statement By The European Calcified Tissue Society, Merle Stein, Florent Elefteriou, Björn Busse, Imke Ak Fiedler, Ronald Young Kwon, Eric Farrell, Mubashir Ahmad, Anita Ignatius, Liam Grover, Liesbet Geris, Jan Tuckermann

Faculty, Staff and Students Publications

Major achievements in bone research have always relied on animal models and in vitro systems derived from patient and animal material. However, the use of animals in research has drawn intense ethical debate and the complete abolition of animal experimentation is demanded by fractions of the population. This phenomenon is enhanced by the reproducibility crisis in science and the advance of in vitro and in silico techniques. 3D culture, organ-on-a-chip, and computer models have improved enormously over the last years. Nevertheless, the overall complexity of bone tissue-cross talk and the systemic and local regulation of bone physiology can often only …

Prdm16 Deletion Is Associated With Sex-Dependent Cardiomyopathy And Cardiac Mortality: A Translational, Multi-Institutional Cohort Study, Ryan J Kramer, Amir Nima Fatahian, Alice Chan, Jeffery Mortenson, Jennifer Osher, Bo Sun, Lauren E Parker, Michael B Rosamilia, Kyra B Potter, Kaila Moore, Sage L Atkins, Jill A Rosenfeld, Alona Birjiniuk, Edward Jones, Taylor S Howard, Jeffrey J Kim, Daryl A Scott, Seema Lalani, Omid M T Rouzbehani, Samantha Kaplan, Marissa A Hathaway, Jennifer L Cohen, S Yukiko Asaki, Hugo R Martinez, Sihem Boudina, Andrew P Landstrom

Faculty, Staff and Students Publications

BACKGROUND: 1p36 deletion syndrome can predispose to pediatric-onset cardiomyopathy. Deletion breakpoints are variable and may delete the transcription factor

METHODS: This retrospective cohort included subjects with 1p36 deletion syndrome from 4 hospitals. Prevalence of cardiomyopathy and freedom from death, cardiac transplantation, or ventricular assist device were analyzed. A systematic review cohort was derived for further analysis. A cardiac-specific

RESULTS: The retrospective cohort included 71 patients. Among individuals with

CONCLUSIONS:

Inhibition Of Microsomal Prostaglandin E2 Synthase Reduces Collagen Deposition In Melanoma Tumors And May Improve Immunotherapy Efficacy By Reducing T-Cell Exhaustion, Yasunari Fukuda, Sun-Hee Kim, Matias A Bustos, Sung-Nam Cho, Jason Roszik, Jared K Burks, Hong Kim, Dave S B Hoon, Elizabeth A Grimm, Suhendan Ekmekcioglu

Faculty, Staff and Student Publications

The arachidonic acid pathway participates in immunosuppression in various types of cancer. Our previous observation detailed that microsomal prostaglandin E2 synthase 1 (mPGES-1), an enzyme downstream of cyclooxygenase 2 (COX-2), limited antitumor immunity in melanoma; in addition, genetic depletion of mPGES-1 specifically enhanced immune checkpoint blockade therapy. The current study set out to distinguish the roles of mPGES-1 from those of COX-2 in tumor immunity and determine the potential of mPGES-1 inhibitors for reinforcing immunotherapy in melanoma. Genetic deletion of mPGES-1 showed different profiles of prostaglandin metabolites from that of COX-2 deletion. In our syngeneic mouse model, mPGES-1-deficient cells exhibited …

Potential Toxic Elements And Their Carcinogenic And Non-Carcinogenic Risk Assessment In Some Commercially Important Fish Species From A Ramsar Site, Mohammad Belal Hossain, Md Moudud Ahmed, Yeasmin Nahar Jolly, As-Ad Ujjaman Nur, Salma Sultana, Shirin Akter, Jimmy Yu, Bilal Ahamad Paray, Takaomi Arai

Faculty, Staff and Student Publications

Potentially toxic elements (PTEs) such as Hg, As, and Pb have become concentrated in the aquatic ecosystem as a result of increased human activities. However, these substances frequently have synergistic or antagonistic effects on the human body or other animals. As a result, there are concerns world-wide that commercially available food products, especially fish, may be contaminated with hazardous elements. In this study, samples of four selected fishes, Gutum (Lepidocephalichthys guntea), Baim (Macrognathus pancalus), Baila (Glossogobius giuris), Meni (Nandus nandus) were analyzed from one of the largest freshwater wetlands (designed as a …

The Role Of Fas Receptor Methylation In Osteosarcoma Metastasis, Jiayi M Sun, Wing-Yuk Chow, Gufeng Xu, M John Hicks, Manjula Nakka, Jianhe Shen, Patrick Kwok Shing Ng, Aaron M Taylor, Alexander Yu, Jason E Farrar, Donald A Barkauskas, Richard Gorlick, Jaime M Guidry Auvil, Daniela Gerhard, Paul Meltzer, Rudy Guerra, Tsz-Kwong Man, Ching C Lau, On Behalf Of The Target Osteosarcoma Consortium

Faculty, Staff and Students Publications

Osteosarcoma is the most frequent primary malignant bone tumor with an annual incidence of about 400 cases in the United States. Osteosarcoma primarily metastasizes to the lungs, where FAS ligand (FASL) is constitutively expressed. The interaction of FASL and its cell surface receptor, FAS, triggers apoptosis in normal cells; however, this function is altered in cancer cells. DNA methylation has previously been explored as a mechanism for altering FAS expression, but no variability was identified in the CpG island (CGI) overlapping the promoter. Analysis of an expanded region, including CGI shores and shelves, revealed high variability in the methylation of …

Association Of Delirium And Depression With Respiratory And Outcome Measures In Covid-19 Inpatients, Alessio Simonetti, Cristina Pais, Vezio Savoia, Maria Camilla Cipriani, Matteo Tosato, Delfina Janiri, Evelina Bernardi, Ottavia Marianna Ferrara, Stella Margoni, Georgios D Kotzalidis, Daniela Chieffo, Massimo Fantoni, Rosa Liperoti, Francesco Landi, Roberto Bernabei, Gabriele Sani

Faculty, Staff and Students Publications

Delirium (DEL) and depression (DEP) may impair the course and severity of acute respiratory illness. The impact of such syndromes on respiratory and outcome parameters in inpatients with COVID-19 needs clarification. To clarify the relationship between DEL and DEP and respiratory outcome measures, we enrolled 100 inpatients from COVID-19 units of the Fondazione Policlinico Universitario Agostino Gemelli IRCCS of Rome. Participants were divided into those with DEL, DEP, or absence of either delirium or depression (CONT). Delirium severity was assessed with the Neelson and Champagne Confusion Scale (NEECHAM). Psychopathology was assessed with the Hamilton Rating Scale for Depression (HAM-D), the …

Phosphorylated Nuclear Dicer1 Promotes Open Chromatin State And Lineage Plasticity Of At2 Tumor Cells In Lung Adenocarcinomas, Raisa A Reyes-Castro, Shin-Yu Chen, Jacob Seemann, Samrat T Kundu, Don L Gibbons, Swathi Arur

Faculty, Staff and Student Publications

KRAS/ERK pathway phosphorylates DICER1, causing its nuclear translocation, and phosphomimetic Dicer1 contributes to tumorigenesis in mice. Mechanisms through which phospho-DICER1 regulates tumor progression remain undefined. While DICER1 canonically regulates microRNAs (miRNA) and epithelial-to-mesenchymal transition (EMT), we found that phosphorylated nuclear DICER1 (phospho-nuclear DICER1) promotes late-stage tumor progression in mice with oncogenic Kras, independent of miRNAs and EMT. Instead, we observe that the murine AT2 tumor cells exhibit altered chromatin compaction, and cells from disorganized advanced tumors, but not localized tumors, express gastric genes. Collectively, this results in subpopulations of tumor cells transitioning from a restricted alveolar to a broader …

Loss Of Metabolic Fitness Drives Tumor Resistance After Car-Nk Cell Therapy And Can Be Overcome By Cytokine Engineering, Li Li, Vakul Mohanty, Jinzhuang Dou, Yuefan Huang, Pinaki P Banerjee, Qi Miao, Jens G Lohr, Tushara Vijaykumar, Julia Frede, Birgit Knoechel, Luis Muniz-Feliciano, Tamara J Laskowski, Shaoheng Liang, Judy S Moyes, Vandana Nandivada, Rafet Basar, Mecit Kaplan, May Daher, Enli Liu, Ye Li, Sunil Acharya, Paul Lin, Mayra Shanley, Hind Rafei, David Marin, Stephan Mielke, Richard E Champlin, Elizabeth J Shpall, Ken Chen, Katayoun Rezvani

Faculty, Staff and Student Publications

Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells is promising, with early-phase clinical studies showing encouraging responses. However, the transcriptional signatures that control the fate of CAR-NK cells after infusion and factors that influence tumor control remain poorly understood. We performed single-cell RNA sequencing and mass cytometry to study the heterogeneity of CAR-NK cells and their in vivo evolution after adoptive transfer, from the phase of tumor control to relapse. Using a preclinical model of noncurative lymphoma and samples from a responder and a nonresponder patient treated with CAR19/IL-15 NK cells, we observed the emergence of NK cell …

Perspectives In Melanoma: Meeting Report From The Melanoma Bridge (December 1st–3rd, 2022-Naples, Italy), Paolo A Ascierto, Sanjiv S Agarwala, Allison Betof Warner, Marc S Ernstoff, Bernard A Fox, Thomas F Gajewski, Jérôme Galon, Claus Garbe, Brian R Gastman, Jeffrey E Gershenwald, Pawel Kalinski, Michelle Krogsgaard, Rom S Leidner, Roger S Lo, Alexander M Menzies, Olivier Michielin, Poulikos I Poulikakos, Jeffrey S Weber, Corrado Caracò, Iman Osman, Igor Puzanov, Magdalena Thurin

Faculty, Staff and Student Publications

Outcomes for patients with melanoma have improved over the past decade with the clinical development and approval of immunotherapies targeting immune checkpoint receptors such as programmed death-1 (PD-1), programmed death ligand 1 (PD-L1) or cytotoxic T lymphocyte antigen-4 (CTLA-4). Combinations of these checkpoint therapies with other agents are now being explored to improve outcomes and enhance benefit-risk profiles of treatment. Alternative inhibitory receptors have been identified that may be targeted for anti-tumor immune therapy, such as lymphocyte-activation gene-3 (LAG-3), as have several potential target oncogenes for molecularly targeted therapy, such as tyrosine kinase inhibitors. Unfortunately, many patients still progress and …

Nanoparticle-Mediated Therapy With Mir-198 Sensitizes Pancreatic Cancer To Gemcitabine Treatment Through Downregulation Of Vcp-Mediated Autophagy, Christian Marin-Muller, Dali Li, Jian-Ming Lü, Zhengdong Liang, Osvaldo Vega-Martínez, Sue E Crawford, Mary K Estes, William E Fisher, Changyi Chen, Qizhi Yao

Faculty, Staff and Students Publications

Pancreatic ductal adenocarcinoma (PDAC) remains an extremely aggressive disease characterized by rapidly acquired multi-drug resistance, including to first-line chemotherapeutic agent gemcitabine. Autophagy is a process that is often exploited by cancer and is one of several intrinsic factors associated with resistance to gemcitabine. We have previously found that miR-198 acts as a tumor suppressor in PDAC through the targeting of factors including Valosin-containing protein (VCP). VCP has been reported to play an important role in autophagic flux. In this study, we investigated whether the repression of VCP through miR-198 administration disrupts the autophagy process and sensitizes PDAC cells to gemcitabine …

Tp53 Induced Glycolysis And Apoptosis Regulator And Monocarboxylate Transporter 4 Drive Metabolic Reprogramming With C-Myc And Nfkb Activation In Breast Cancer, Megan E. Roche, Ying-Hui Ko, Marina Domingo-Vidal, Zhao Lin, Diana Whitaker-Menezes, Ruth C. Birbe, Madalina Tuluc, Balázs Győrffy, Jaime Caro, Nancy J. Philp, Ramon Bartrons, Ubaldo Martinez-Outshoorn

Department of Medical Oncology Faculty Papers

Breast cancer is composed of metabolically coupled cellular compartments with upregulation of TP53 Induced Glycolysis and Apoptosis Regulator (TIGAR) in carcinoma cells and loss of caveolin 1 (CAV1) with upregulation of monocarboxylate transporter 4 (MCT4) in fibroblasts. The mechanisms that drive metabolic coupling are poorly characterized. The effects of TIGAR on fibroblast CAV1 and MCT4 expression and breast cancer aggressiveness was studied using coculture and conditioned media systems and in-vivo. Also, the role of cytokines in promoting tumor metabolic coupling via MCT4 on cancer aggressiveness was studied. TIGAR downregulation in breast carcinoma cells reduces tumor growth. TIGAR overexpression in carcinoma …

A Phase Ii Clinical Trial Of Pembrolizumab Efficacy And Safety In Advanced Renal Medullary Carcinoma, Chijioke Nze, Pavlos Msaouel, Mohamed H Derbala, Bettzy Stephen, Abdulrahman Abonofal, Funda Meric-Bernstam, Nizar M Tannir, Aung Naing

Faculty, Staff and Student Publications

Background: Renal medullary carcinoma (RMC) is one of most aggressive renal cell carcinomas and novel therapeutic strategies are therefore needed. Recent comprehensive molecular and immune profiling of RMC tissues revealed a highly inflamed phenotype, suggesting the potential therapeutic role for immune checkpoint therapies. We present the first prospective evaluation of an immune checkpoint inhibitor in a cohort of patients with RMC.

Methods: A cohort of patients with locally advanced or metastatic RMC was treated with pembrolizumab 200 mg intravenously every 21 days in a phase II basket trial (ClinicalTrials.gov: NCT02721732). Responses were assessed by irRECIST. Tumor tissues were evaluated …

A Review On Anatomical And Surgical Importance Of Mammary Gland, Sneha Jm Sneha Jm Dr, Pushpa Nb Dr, Vidya Cs Dr, Manjappa M Dr

Digital Journal of Clinical Medicine

ABSTRACT

The mammary gland is an exocrine gland present in female mammals responsible for the production and secretion of milk during the process of lactation. It is mainly composed by epithelial cells and adipocytes. The features that make mammary gland unique are 1) its highly plastic properties displayed during pregnancy, lactation and involution (all steps belonging to the lactation cycle) and 2) its requirement to grow in close association with adipocytes which are absolutely necessary to ensure mammary gland development at puberty and remodelling during the lactation cycle. (Georgia colleluori, Jessica perugini, Giorgio barbatelli, and saverio cintr (2021).

Conclusion

The …

Gender Differences In A Mouse Model Of Hepatocellular Carcinoma Revealed Using Multi-Modal Imaging, Brian J Engel, Vincenzo Paolillo, Md Nasir Uddin, Kristyn A Gonzales, Kathryn M Mcginnis, Margie N Sutton, Madhavi Patnana, Brian J Grindel, Gregory J Gores, David Piwnica-Worms, Laura Beretta, Federica Pisaneschi, Seth T Gammon, Steven W Millward

Faculty, Staff and Student Publications

The worldwide incidence of hepatocellular carcinoma (HCC) continues to rise, in part due to poor diet, limited exercise, and alcohol abuse. Numerous studies have suggested that the loss or mutation of PTEN plays a critical role in HCC tumorigenesis through the activation of the PI3K/Akt signaling axis. The homozygous knockout of PTEN in the livers of mice results in the accumulation of fat (steatosis), inflammation, fibrosis, and eventually progression to HCC. This phenotype bears a striking similarity to non-alcoholic steatohepatitis (NASH) which is thought to occupy an intermediate stage between non-alcoholic fatty liver disease (NAFLD), fibrosis, and HCC. The molecular …

Tissue-Specific Features Of The T Cell Repertoire After Allogeneic Hematopoietic Cell Transplantation In Human And Mouse, Susan Dewolf, Yuval Elhanati, Katherine Nichols, Nicholas R Waters, Chi L Nguyen, John B Slingerland, Natasia Rodriguez, Olga Lyudovyk, Paul A Giardina, Anastasia I Kousa, Hana Andrlová, Nick Ceglia, Teng Fei, Rajya Kappagantula, Yanyun Li, Nathan Aleynick, Priscilla Baez, Rajmohan Murali, Akimasa Hayashi, Nicole Lee, Brianna Gipson, Madhumitha Rangesa, Zoe Katsamakis, Anqi Dai, Amanda G Blouin, Maria Arcila, Ignas Masilionis, Ronan Chaligne, Doris M Ponce, Heather J Landau, Ioannis Politikos, Roni Tamari, Alan M Hanash, Robert R Jenq, Sergio A Giralt, Kate A Markey, Yanming Zhang, Miguel-Angel Perales, Nicholas D Socci, Benjamin D Greenbaum, Christine A Iacobuzio-Donahue, Travis J Hollmann, Marcel R M Van Den Brink, Jonathan U Peled

Faculty, Staff and Student Publications

T cells are the central drivers of many inflammatory diseases, but the repertoire of tissue-resident T cells at sites of pathology in human organs remains poorly understood. We examined the site-specificity of T cell receptor (TCR) repertoires across tissues (5 to 18 tissues per patient) in prospectively collected autopsies of patients with and without graft-versus-host disease (GVHD), a potentially lethal tissue-targeting complication of allogeneic hematopoietic cell transplantation, and in mouse models of GVHD. Anatomic similarity between tissues was a key determinant of TCR repertoire composition within patients, independent of disease or transplant status. The T cells recovered from peripheral blood …

When Phased Without Water: Biophysics Of Cellular Desiccation, From Biomolecules To Condensates, Paulette Sofia Romero-Perez, Yanniv Dorone, Eduardo Flores, Shahar Sukenik, Steven Boeynaems

Faculty, Staff and Students Publications

The molecular machinery that enables life has evolved in water, yet many of the organisms around us are able to survive even extreme desiccation. Especially remarkable are single-cell and sedentary organisms that rely on specialized biomolecular machinery to survive in environments that are routinely subjected to a near-complete lack of water. In this review, we zoom in on the molecular level of what is happening in the cellular environment under water stress. We cover the various mechanisms by which biochemical components of the cell can dysfunction in dehydrated cells and detail the different strategies that organisms have evolved to eliminate …

Harnessing Autoimmunity With Dominant Self-Peptide: Modulating The Sustainability Of Tissue-Preferential Antigen-Specific Tregs By Governing The Binding Stability Via Peptide Flanking Residues, Youwei Lin, Shun Sakuraba, Chandirasegaran Massilamany, Jayagopala Reddy, Yoshimasa Tanaka, Sachiko Miyake, Takashi Yamamura

School of Veterinary and Biomedical Sciences: Faculty Publications

Sensitization to self-peptides induces various immunological responses, from autoimmunity to tumor immunity, depending on the peptide sequence; however, the underlying mechanisms remain unclear, and thus, curative therapeutic options considering immunity balance are limited. Herein, two overlapping dominant peptides of myelin proteolipid protein, PLP136-150 and PLP139-151, which induce different forms of experimental autoimmune encephalomyelitis (EAE), monophasic and relapsing EAE, respectively, were investigated. Mice with monophasic EAE exhibited highly resistant to EAE re-induction with any encephalitogenic peptides, whereas mice with relapsing EAE were susceptible, and progressed, to EAE re-induction. This resistance to relapse and reinduction in monophasic EAE mice was associated with …

Agrp Neurons Are Not Indispensable For Body Weight Maintenance In Adult Mice, Jing Cai, Jing Chen, Joshua Ortiz-Guzman, Jessica Huang, Benjamin R Arenkiel, Yuchen Wang, Yan Zhang, Yuyan Shi, Qingchun Tong, Cheng Zhan

Faculty, Staff and Student Publications

In addition to their role in promoting feeding and obesity development, hypothalamic arcuate agouti-related protein/neuropeptide Y (AgRP/NPY) neurons are widely perceived to be indispensable for maintaining normal feeding and body weight in adults, and consistently, acute inhibition of AgRP neurons is known to reduce short-term food intake. Here, we adopted complementary methods to achieve nearly complete ablation of arcuate AgRP/NPY neurons in adult mice and report that lesioning arcuate AgRP/NPY neurons in adult mice causes no apparent alterations in ad libitum feeding or body weight. Consistent with previous studies, loss of AgRP/NPY neurons blunts fasting refeeding. Thus, our studies show …

Mediation Of Bmi On 25-Hydroxyvitamin D Levels In U.S. Adults With Sugar-Sweetened Beverages Consumption, Wei Ting Lin, Gabrielle V. Gonzalez, Yu Hsiang Kao, Hui Yi Lin, Mirandy S. Li, David W. Seal, Chien Hung Lee, Chih Yang Hu, Lei Shih Chen, Tung Sung Tseng

School of Public Health Faculty Publications

Body mass index (BMI) as well as sugar-sweetened beverages (SSB) has been suggested to independently decrease 25-hydroxyvitamin D (25(OH)D). However, the relationship between SSB, BMI, and 25(OH)D is uncertain. This study aimed to investigate the potential mediating role of BMI in the association between SSB intake and 25(OH)D. A total of 4505 representative U.S. adults aged above 20 years and without liver conditions were selected from the 2013–2014 NHANES. All analyses were performed under survey modules with appropriate sampling weights. The prevalence of 25(OH)D insufficiency and deficiency was 37.8% and 24.1% in U.S. adults, respectively. Compared with non-SSB consumers, an …