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Full-Text Articles in Medicine and Health Sciences

A Conformation Variant Of P53 Combined With Machine Learning Identifies Alzheimer Disease In Preclinical And Prodromal Stages, Giulia Abate, Marika Vezzoli, Letizia Polito, Antonio Guaita, Diego Albani, Moira Marizzoni, Emirena Garrafa, Alessandra Marengoni, Gianluigi Forloni, Giovanni B. Frisoni, Jeffrey L. Cummings, Maurizio Memo, Daniela Uberti Dec 2020

A Conformation Variant Of P53 Combined With Machine Learning Identifies Alzheimer Disease In Preclinical And Prodromal Stages, Giulia Abate, Marika Vezzoli, Letizia Polito, Antonio Guaita, Diego Albani, Moira Marizzoni, Emirena Garrafa, Alessandra Marengoni, Gianluigi Forloni, Giovanni B. Frisoni, Jeffrey L. Cummings, Maurizio Memo, Daniela Uberti

School of Medicine Faculty Publications

© 2020 by the authors. Li-censee MDPI, Basel, Switzerland. Early diagnosis of Alzheimer’s disease (AD) is a crucial starting point in disease man-agement. Blood-based biomarkers could represent a considerable advantage in providing AD-risk information in primary care settings. Here, we report new data for a relatively unknown blood-based biomarker that holds promise for AD diagnosis. We evaluate a p53-misfolding conformation rec-ognized by the antibody 2D3A8, also named Unfolded p53 (U-p532D3A8+), in 375 plasma samples derived from InveCe.Ab and PharmaCog/E-ADNI longitudinal studies. A machine learning approach is used to combine U-p532D3A8+ plasma levels with Mini-Mental State Examination (MMSE) and apolipoprotein E …


Locating Specific Acupoints Large Intestine 4 (Li4) And Large Intestine 6 (Li6) In Cadavers Using Anthropometric And Cun Measurement Systems, Gregory P. Casey Nov 2020

Locating Specific Acupoints Large Intestine 4 (Li4) And Large Intestine 6 (Li6) In Cadavers Using Anthropometric And Cun Measurement Systems, Gregory P. Casey

School of Medicine Faculty Publications

Background: Anthropometric and anatomical Chinese inch measurement (CUN) systems are useful in understanding the location of acupoints; however, locating acupoints is challenging. Objectives: The study aimed to locate LI4 and LI6, to measure differences and similarities in body dimensions based on sex using anthropometric and CUN systems, and to observe the relationship between f-cun and b-cun. Methods: 25 forearms and hands from 16 embalmed cadavers had body dimensions measured using anthropometric and CUN systems. LI4 and LI6 were located using a combination of both systems. Data were compiled and calculated to observe any variation in means and ranges. Statistical analysis …


Effect Of High-Dose Vs Standard-Dose Vitamin D Supplementation On Body Composition Among Patients With Advanced Or Metastatic Colorectal Cancer: A Randomized Trial, Justin C. Brown, Michael H. Rosenthal, Chao Ma, Sui Zhang, Halla S. Nimeiri, Nadine J. Mccleary, Thomas A. Abrams, Matthew B. Yurgelun, James M. Cleary, Douglas A. Rubinson, Deborah Schrag, Andrea J. Bullock, Jill Allen, Dan Zuckerman, Emily Chan, Jennifer A. Chan, Brian Wolpin, Michael Constantine Nov 2020

Effect Of High-Dose Vs Standard-Dose Vitamin D Supplementation On Body Composition Among Patients With Advanced Or Metastatic Colorectal Cancer: A Randomized Trial, Justin C. Brown, Michael H. Rosenthal, Chao Ma, Sui Zhang, Halla S. Nimeiri, Nadine J. Mccleary, Thomas A. Abrams, Matthew B. Yurgelun, James M. Cleary, Douglas A. Rubinson, Deborah Schrag, Andrea J. Bullock, Jill Allen, Dan Zuckerman, Emily Chan, Jennifer A. Chan, Brian Wolpin, Michael Constantine

School of Medicine Faculty Publications

Skeletal muscle and adipose tissue express the vitamin D receptor and may be a mechanism through which vitamin D supplementation slows cancer progression and reduces cancer death. In this exploratory analysis of a double-blind, multicenter, randomized phase II clinical trial, 105 patients with advanced or metastatic colorectal cancer who were receiving chemotherapy were randomized to either high-dose vitamin D3 (4000 IU) or standard-dose (400 IU) vitamin D3. Body composition was measured with abdominal computed tomography at enrollment (baseline) and after cycle 8 of chemotherapy (16 weeks). As compared with standard-dose vitamin D3, high-dose vitamin D3 did not significantly change body …


Corticotropin-Releasing Factor Infusion In The Bed Nucleus Of The Stria Terminalis Of Lactating Mice Alters Maternal Care And Induces Behavioural Phenotypes In Offspring, Kerstin Camile Creutzberg, Érika Kestering-Ferreira, Thiago Wendt Viola, Luis Eduardo Wearick-Silva, Rodrigo Orso, Bernardo Aguzzoli Heberle, Lucas Albrechet-Souza, Rosa Maria Martins De Almeida, Rodrigo Grassi-Oliveira Nov 2020

Corticotropin-Releasing Factor Infusion In The Bed Nucleus Of The Stria Terminalis Of Lactating Mice Alters Maternal Care And Induces Behavioural Phenotypes In Offspring, Kerstin Camile Creutzberg, Érika Kestering-Ferreira, Thiago Wendt Viola, Luis Eduardo Wearick-Silva, Rodrigo Orso, Bernardo Aguzzoli Heberle, Lucas Albrechet-Souza, Rosa Maria Martins De Almeida, Rodrigo Grassi-Oliveira

School of Medicine Faculty Publications

The peripartum period is accompanied by numerous physiological and behavioural adaptations organised by the maternal brain. These changes are essential for adequate expression of maternal behaviour, thereby ensuring proper development of the offspring. The corticotropin-releasing factor (CRF) plays a key role in a variety of behaviours accompanying stress, anxiety, and depression. There is also evidence that CRF contributes to maladaptations during the peripartum period. We investigated the effects of CRF in the bed nucleus of the stria terminalis (BNST) of lactating mice during maternal care and analysed locomotor activity and anxiety-like behaviour in the offspring. The BNST has been implicated …


Role Of Interleukin-1 Family Members And Signaling Pathways In Kshv Pathogenesis, Lindsey Barrett, Jungang Chen, Lu Dai, Karlie Plaisance-Bonstaff, Luis Del Valle, Zhiqiang Qin Oct 2020

Role Of Interleukin-1 Family Members And Signaling Pathways In Kshv Pathogenesis, Lindsey Barrett, Jungang Chen, Lu Dai, Karlie Plaisance-Bonstaff, Luis Del Valle, Zhiqiang Qin

School of Medicine Faculty Publications

No abstract provided.


Bioavailability And Spatial Distribution Of Fatty Acids In The Rat Retina After Dietary Omega-3 Supplementation, Elisa Vidal, Bokkyoo Jun, William C. Gordon, Marie Annick Maire, Lucy Martine, Stéphane Grégoire, Spiro Khoury, Stephanie Cabaret, Olivier Berdeaux, Niyazi Acar, Lionel Bretillon, Nicolas G. Bazan Oct 2020

Bioavailability And Spatial Distribution Of Fatty Acids In The Rat Retina After Dietary Omega-3 Supplementation, Elisa Vidal, Bokkyoo Jun, William C. Gordon, Marie Annick Maire, Lucy Martine, Stéphane Grégoire, Spiro Khoury, Stephanie Cabaret, Olivier Berdeaux, Niyazi Acar, Lionel Bretillon, Nicolas G. Bazan

School of Medicine Faculty Publications

Spatial changes of FAs in the retina in response to different dietary n-3 formulations have never been explored, although a diet rich in EPA and DHA is recommended to protect the retina against the effects of aging. In this study, Wistar rats were fed for 8 weeks with balanced diet including either EPA-containing phospholipids (PLs), EPA-containing TGs, DHA-containing PLs, or DHA-containing TGs. Qualitative changes in FA composition of plasma, erythrocytes, and retina were evaluated by gas chromatography-flame ionization detector. Following the different dietary intakes, changes to the quantity and spatial organization of PC and PE species in retina were determined …


Microrna-Based Biomarkers In Alzheimer’S Disease (Ad), Yuhai Zhao, Vivian Jaber, Peter N. Alexandrov, Andrea Vergallo, Simone Lista, Harald Hampel, Walter J. Lukiw Oct 2020

Microrna-Based Biomarkers In Alzheimer’S Disease (Ad), Yuhai Zhao, Vivian Jaber, Peter N. Alexandrov, Andrea Vergallo, Simone Lista, Harald Hampel, Walter J. Lukiw

School of Medicine Faculty Publications

Alzheimer’s disease (AD) is a multifactorial, age-related neurological disease characterized by complex pathophysiological dynamics taking place at multiple biological levels, including molecular, genetic, epigenetic, cellular and large-scale brain networks. These alterations account for multiple pathophysiological mechanisms such as brain protein accumulation, neuroinflammatory/neuro-immune processes, synaptic dysfunction, and neurodegeneration that eventually lead to cognitive and behavioral decline. Alterations in microRNA (miRNA) signaling have been implicated in the epigenetics and molecular genetics of all neurobiological processes associated with AD pathophysiology. These changes encompass altered miRNA abundance, speciation and complexity in anatomical regions of the CNS targeted by the disease, including modified miRNA expression …


Chain-Selective Isotopic Labeling Of The Heterodimeric Type Iii Secretion Chaperone, Scc4:Scc1, Reveals The Total Structural Rearrangement Of The Chlamydia Trachomatis Bi-Functional Protein, Scc4, Thilini O. Ukwaththage, Samantha M. Keane, Li Shen, Megan A. Macnaughtan Oct 2020

Chain-Selective Isotopic Labeling Of The Heterodimeric Type Iii Secretion Chaperone, Scc4:Scc1, Reveals The Total Structural Rearrangement Of The Chlamydia Trachomatis Bi-Functional Protein, Scc4, Thilini O. Ukwaththage, Samantha M. Keane, Li Shen, Megan A. Macnaughtan

School of Medicine Faculty Publications

Scc4 is an unusual bi-functional protein from Chlamydia trachomatis (CT) that functions as a type III secretion system (T3SS) chaperone and an RNA polymerase (RNAP)-binding protein. Both functions require interactions with protein partners during specific stages of the CT developmental cycle. As a T3SS chaperone, Scc4 binds Scc1 during the late stage of development to form a heterodimer complex, which chaperones the essential virulence effector, CopN. During the early-middle stage of development, Scc4 regulates T3SS gene expression by binding the σ66-containing RNAP holoenzyme. In order to study the structure and association mechanism of the Scc4:Scc1 T3SS chaperone complex using nuclear …


Actinic Granuloma Responding To Doxycycline, George M. Jeha, Kathryn Olivier Luckett, Lauren Kole Oct 2020

Actinic Granuloma Responding To Doxycycline, George M. Jeha, Kathryn Olivier Luckett, Lauren Kole

School of Medicine Faculty Publications

No abstract provided.


Constitutive Genetic Deletion Of Hcn1 Increases Alcohol Preference During Adolescence, Michael C. Salling, Neil L. Harrison Oct 2020

Constitutive Genetic Deletion Of Hcn1 Increases Alcohol Preference During Adolescence, Michael C. Salling, Neil L. Harrison

School of Medicine Faculty Publications

The hyperpolarization-activated cyclic nucleotide-gated channel (HCN), which underlies the hyperpolarization-activated cation current (Ih), has diverse roles in regulating neuronal excitability across cell types and brain regions. Recently, HCN channels have been implicated in preclinical models of substance abuse including alcohol. In the prefrontal cortex of rodents, HCN expression and Ih magnitude are developmentally regulated during adolescence and may be vulnerable to alcohol’s effects. In mice, binge alcohol consumption during the adolescent period results in a sustained reduction in Ih that coincides with increased alcohol consumption in adulthood, yet the direct role HCN channels have on alcohol consumption are unknown. Here, …


Characterization Of The 5′-Flanking Region Of The Human And Mouse Chac1 Genes, Yuki Nomura, Charity F. Sylvester, Lisa O. Nguyen, Mahmoud Kandeel, Yoko Hirata, Imran N. Mungrue, Kentaro Oh-Hashi Oct 2020

Characterization Of The 5′-Flanking Region Of The Human And Mouse Chac1 Genes, Yuki Nomura, Charity F. Sylvester, Lisa O. Nguyen, Mahmoud Kandeel, Yoko Hirata, Imran N. Mungrue, Kentaro Oh-Hashi

School of Medicine Faculty Publications

The Unfolded Protein Response pathway is a conserved signaling mechanism having important roles in cellular physiology and is perturbed accompanying disease. We previously identified the novel UPR target gene CHAC1, a direct target of ATF4, downstream of PERK-EIF2A and activated by the UPR pathway. CHAC1 enzyme directs catalysis of γ-linked glutamate bonds within specific molecular targets. CHAC1 is the first enzyme characterized that can catalyze intracellular glutathione degradation in eukaryotes, having implications for regulation of oxidative stress. DDIT3 (CHOP) is a terminal UPR transcription factor, regulated by ATF4 and an output promoting cell death signaling. Herein we examine the relationship …


Ace2 Mouse Models: A Toolbox For Cardiovascular And Pulmonary Research, Hongpeng Jia, Xinping Yue, Eric Lazartigues Oct 2020

Ace2 Mouse Models: A Toolbox For Cardiovascular And Pulmonary Research, Hongpeng Jia, Xinping Yue, Eric Lazartigues

School of Medicine Faculty Publications

Angiotensin-converting enzyme 2 (ACE2) has been identified as the host entry receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the COVID-19 pandemic. ACE2 is a regulatory enzyme of the renin-angiotensin system and has protective functions in many cardiovascular, pulmonary and metabolic diseases. This review summarizes available murine models with systemic or organ-specific deletion of ACE2, or with overexpression of murine or human ACE2. The purpose of this review is to provide researchers with the genetic tools available for further understanding of ACE2 biology and for the investigation of ACE2 in the pathogenesis and treatment of COVID-19.


Age Based Evaluation Of Nut Aspiration Risk., Jill N D'Souza, Taher S Valika, Bharat Bhushan, Jonathan B Ida Oct 2020

Age Based Evaluation Of Nut Aspiration Risk., Jill N D'Souza, Taher S Valika, Bharat Bhushan, Jonathan B Ida

School of Medicine Faculty Publications

Objective: To identify an age at which initiation of whole nut into the pediatric diet could be considered safe, by evaluating the age distribution of children undergoing bronchoscopy with removal of nut or seed material from the airway. Method: A retrospective chart review over a ten-year period identifying children age 0–18 that have undergone bronchoscopy with retrieval of airway foreign bodies. A statistical analysis of demographic data was carried out to identify age distribution of aspiration events. Results: Sixty-four cases of foreign body aspiration were identified, of which 43 (67%) were of organic origin, specifically nuts. A Fisher's exact test …


A Hyperpigmented Plaque In A Female Patient, Harel G. Schwartzberg, Alexandra Bourgeois, Amber Souers, Jeremy Atkinson, Pamela Martin Sep 2020

A Hyperpigmented Plaque In A Female Patient, Harel G. Schwartzberg, Alexandra Bourgeois, Amber Souers, Jeremy Atkinson, Pamela Martin

School of Medicine Faculty Publications

No abstract provided.


Intratumoral Translocation Positive Heterogeneity In Pediatric Alveolar Rhabdomyosarcoma Tumors Correlates To Patient Survival Prognosis, Katrina Gleditsch, Jorge Peñas, Danielle Mercer, Ayesha Umrigar, James Briscoe, Matthew Stark, Fern Tsien, Andrew D. Hollenbach Sep 2020

Intratumoral Translocation Positive Heterogeneity In Pediatric Alveolar Rhabdomyosarcoma Tumors Correlates To Patient Survival Prognosis, Katrina Gleditsch, Jorge Peñas, Danielle Mercer, Ayesha Umrigar, James Briscoe, Matthew Stark, Fern Tsien, Andrew D. Hollenbach

School of Medicine Faculty Publications

Alveolar rhabdomyosarcoma (ARMS) is characterized by one of three translocation states: t(2;13) (q35;q14) producing PAX3-FOXO1, t(1;13) (p36;q14) producing PAX7-FOXO1, or translocation-negative. Tumors with t(2;13) are associated with greater disease severity and mortality than t(1;13) positive or translocation negative patients. Consistent with this fact, previous work concluded that a molecular analysis of RMS translocation status is essential for the accurate determination of prognosis and diagnosis. However, despite this knowledge, most diagnoses rely on histology and in some cases utilize fluorescence in situ hybridization (FISH) probes unable to differentiate between translocation products. Along these same lines, diagnostic RT-PCR analysis, which can differentiate …


Immune-Related Gene Expression And Cytokine Secretion Is Reduced Among African American Colon Cancer Patients, Jenny Paredes, Jovanny Zabaleta, Jone Garai, Ping Ji, Sayed Imtiaz, Marzia Spagnardi, Joussette Alvarado, Li Li, Mubarak Akadri, Kaylene Barrera, Maria Munoz-Sagastibelza, Raavi Gupta, Mohamed Alshal, Maksim Agaronov, Henry Talus, Xuefeng Wang, John M. Carethers, Jennie L. Williams, Laura A. Martello Sep 2020

Immune-Related Gene Expression And Cytokine Secretion Is Reduced Among African American Colon Cancer Patients, Jenny Paredes, Jovanny Zabaleta, Jone Garai, Ping Ji, Sayed Imtiaz, Marzia Spagnardi, Joussette Alvarado, Li Li, Mubarak Akadri, Kaylene Barrera, Maria Munoz-Sagastibelza, Raavi Gupta, Mohamed Alshal, Maksim Agaronov, Henry Talus, Xuefeng Wang, John M. Carethers, Jennie L. Williams, Laura A. Martello

School of Medicine Faculty Publications

Background: Colorectal cancer is the third most deadly cancer among African Americans (AA). When compared to Caucasian Americans (CA), AA present with more advanced disease and lower survival rates. Here, we investigated if differences in tumor immunology could be contributive to disparities observed between these populations. Methods: We examined gene expression of tumor and non-tumor adjacent tissues from AA and CA by whole transcriptome sequencing, and generated scores for immune cell populations by NanoString. In addition, we utilized “The Cancer Genome Atlas” (TCGA) database from AA and CA as a validation cohort. Finally, we measured the secretion of cytokines characteristic …


Predicting Amyloid Burden To Accelerate Recruitment Of Secondary Prevention Clinical Trials, O. Langford, R. Raman, R. A. Sperling, J. Cummings, C.-K. Sun, G. Jimenez-Maggiora, P. S. Aisen, M. C. Donohue, Trc-Pad Investigators Aug 2020

Predicting Amyloid Burden To Accelerate Recruitment Of Secondary Prevention Clinical Trials, O. Langford, R. Raman, R. A. Sperling, J. Cummings, C.-K. Sun, G. Jimenez-Maggiora, P. S. Aisen, M. C. Donohue, Trc-Pad Investigators

School of Medicine Faculty Publications

Background: Screening to identify individuals with elevated brain amyloid (Aβ+) for clinical trials in Preclinical Alzheimer’s Disease (PAD), such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s disease (A4) trial, is slow and costly. The Trial-Ready Cohort in Preclinical/Prodromal Alzheimer’s Disease (TRC-PAD) aims to accelerate and reduce costs of AD trial recruitment by maintaining a web-based registry of potential trial participants, and using predictive algorithms to assess their likelihood of suitability for PAD trials. Objectives: Here we describe how algorithms used to predict amyloid burden within TRC-PAD project were derived using screening data from the A4 trial. Design: We apply machine …


Direct Delivery Of Antisense Oligonucleotides To The Middle And Inner Ear Improves Hearing And Balance In Usher Mice, Jennifer J. Lentz, Bifeng Pan, Abhilash Ponnath, Christopher M. Tran, Carl Nist-Lund, Alice Galvin, Hannah Goldberg, Katelyn N. Robillard, Francine M. Jodelka, Hamilton E. Farris, Jun Huang, Tianwen Chen, Hong Zhu, Wu Zhou, Frank Rigo, Michelle L. Hastings, Gwenaëlle S.G. Géléoc Aug 2020

Direct Delivery Of Antisense Oligonucleotides To The Middle And Inner Ear Improves Hearing And Balance In Usher Mice, Jennifer J. Lentz, Bifeng Pan, Abhilash Ponnath, Christopher M. Tran, Carl Nist-Lund, Alice Galvin, Hannah Goldberg, Katelyn N. Robillard, Francine M. Jodelka, Hamilton E. Farris, Jun Huang, Tianwen Chen, Hong Zhu, Wu Zhou, Frank Rigo, Michelle L. Hastings, Gwenaëlle S.G. Géléoc

School of Medicine Faculty Publications

Usher syndrome is a syndromic form of hereditary hearing impairment that includes sensorineural hearing loss and delayed-onset retinitis pigmentosa (RP). Type 1 Usher syndrome (USH1) is characterized by congenital profound sensorineural hearing impairment and vestibular areflexia, with adolescent-onset RP. Systemic treatment with antisense oligonucleotides (ASOs) targeting the human USH1C c.216G>A splicing mutation in a knockin mouse model of USH1 restores hearing and balance. Herein, we explore the effect of delivering ASOs locally to the ear to treat hearing and vestibular dysfunction associated with Usher syndrome. Three localized delivery strategies were investigated in USH1C mice: inner ear injection, trans-tympanic membrane …


Stem Crisis Teaching: Curriculum Design With E-Learning Tools, Sonya E. Van Nuland, Elissa Hall, Natalie R. Langley Jul 2020

Stem Crisis Teaching: Curriculum Design With E-Learning Tools, Sonya E. Van Nuland, Elissa Hall, Natalie R. Langley

School of Medicine Faculty Publications

The COVID-19 pandemic and subsequent social distancing protocols have accelerated the shift to online teaching across the globe. In Science, Technology, Engineering, and Mathematics (STEM) programs this means a shift from face-to-face laboratory instruction to self-directed learning with e-learning tools. Unfortunately, selecting and integrating an e-learning tool into a curriculum can be daunting. This article highlights key questions and practical suggestions instructors should consider in choosing the most effective option for their course and learners.


Endocrine Significance Of Sars-Cov-2'S Reliance On Ace2, Eric Lazartigues, Mirza Muhammad Fahd Qadir, Franck Mauvais-Jarvis Jul 2020

Endocrine Significance Of Sars-Cov-2'S Reliance On Ace2, Eric Lazartigues, Mirza Muhammad Fahd Qadir, Franck Mauvais-Jarvis

School of Medicine Faculty Publications

The current COVID-19 pandemic is the most disruptive event in the past 50 years, with a global impact on health care and world economies. It is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a coronavirus that uses angiotensin-converting enzyme 2 (ACE2) as an entry point to the cells. ACE2 is a transmembrane carboxypeptidase and member of the renin-angiotensin system. This mini-review summarizes the main findings regarding ACE2 expression and function in endocrine tissues. We discuss rapidly evolving knowledge on the potential role of ACE2 and SARS coronaviruses in endocrinology and the development of diabetes mellitus, hypogonadism, and pituitary and …


Efficacy Of A Novel Mitochondrial-Derived Peptide In A Porcine Model Of Myocardial Ischemia/Reperfusion Injury, Thomas E. Sharp, Zhenwei Gong, Amy Scarborough, Eric S. Goetzman, Murtuza J. Ali, Pablo Spaletra, David J. Lefer, Radhika H. Muzumdar, Traci T. Goodchild Jul 2020

Efficacy Of A Novel Mitochondrial-Derived Peptide In A Porcine Model Of Myocardial Ischemia/Reperfusion Injury, Thomas E. Sharp, Zhenwei Gong, Amy Scarborough, Eric S. Goetzman, Murtuza J. Ali, Pablo Spaletra, David J. Lefer, Radhika H. Muzumdar, Traci T. Goodchild

School of Medicine Faculty Publications

With the complexities that surround myocardial ischemia/reperfusion (MI/R) injury, therapies adjunctive to reperfusion that elicit beneficial pleiotropic effects and do not overlap with standard of care are necessary. This study found that the mitochondrial-derived peptide S14G-humanin (HNG) (2 mg/kg), an analogue of humanin, reduced infarct size in a large animal model of MI/R. However, when ischemic time was increased, the infarct-sparing effects were abolished with the same dose of HNG. Thus, although the 60-min MI/R study showed that HNG cardioprotection translates beyond small animal models, further studies are needed to optimize HNG therapy for longer, more patient-relevant periods of cardiac …


Pancreatic Stromal Gremlin 1 Expression During Pancreatic Tumorigenesis, Joy M. Davis, Binglu Cheng, Madeline M. Drake, Qiang Yu, Baibing Yang, Jing Li, Chunhui Liu, Mamoun Younes, Xiurong Zhao, Jennifer M. Bailey, Qiang Shen, Tien C. Ko, Yanna Cao May 2020

Pancreatic Stromal Gremlin 1 Expression During Pancreatic Tumorigenesis, Joy M. Davis, Binglu Cheng, Madeline M. Drake, Qiang Yu, Baibing Yang, Jing Li, Chunhui Liu, Mamoun Younes, Xiurong Zhao, Jennifer M. Bailey, Qiang Shen, Tien C. Ko, Yanna Cao

School of Medicine Faculty Publications

Chronic pancreatitis (CP) is a major risk factor of pancreatic ductal adenocarcinoma (PDAC). How CP promotes pancreatic oncogenesis remains unclear. A characteristic feature of PDAC is its prominent desmoplasia in the tumor microenvironment, composed of activated fibroblasts and macrophages. Macrophages can be characterized as M1 or M2, with tumor-inhibiting or -promoting functions, respectively. We reported that Gremlin 1 (GREM1), a key pro-fibrogenic factor, is upregulated in the stroma of CP. The current study aimed to investigate the expression of GREM1 and correlation between GREM1 and macrophages within the pancreas during chronic inflammation and the development of PDAC. By mRNA in …


Photoactivatable Cre Recombinase 3.0 For In Vivo Mouse Applications, Kumi Morikawa, Kazuhiro Furuhashi, Carmen De Sena-Tomas, Alvaro L. Garcia-Garcia, Ramsey Bekdash, Alison D. Klein, Nicholas Gallerani, Hannah E. Yamamoto, Seon Hye E. Park, Grant S. Collins, Fuun Kawano, Moritoshi Sato, Chyuan Sheng Lin, Kimara L. Targoff, Edmund Au, Michael C. Salling, Masayuki Yazawa May 2020

Photoactivatable Cre Recombinase 3.0 For In Vivo Mouse Applications, Kumi Morikawa, Kazuhiro Furuhashi, Carmen De Sena-Tomas, Alvaro L. Garcia-Garcia, Ramsey Bekdash, Alison D. Klein, Nicholas Gallerani, Hannah E. Yamamoto, Seon Hye E. Park, Grant S. Collins, Fuun Kawano, Moritoshi Sato, Chyuan Sheng Lin, Kimara L. Targoff, Edmund Au, Michael C. Salling, Masayuki Yazawa

School of Medicine Faculty Publications

Optogenetic genome engineering tools enable spatiotemporal control of gene expression and provide new insight into biological function. Here, we report the new version of genetically encoded photoactivatable (PA) Cre recombinase, PA-Cre 3.0. To improve PA-Cre technology, we compare light-dimerization tools and optimize for mammalian expression using a CAG promoter, Magnets, and 2A self-cleaving peptide. To prevent background recombination caused by the high sequence similarity in the dimerization domains, we modify the codons for mouse gene targeting and viral production. Overall, these modifications significantly reduce dark leak activity and improve blue-light induction developing our new version, PA-Cre 3.0. As a resource, …


Novel Rvd6 Stereoisomer Induces Corneal Nerve Regeneration And Wound Healing Post-Injury By Modulating Trigeminal Transcriptomic Signature, Thang L. Pham, Azucena H. Kakazu, Jiucheng He, Bokkyoo Jun, Nicolas G. Bazan, Haydee E.P. Bazan Mar 2020

Novel Rvd6 Stereoisomer Induces Corneal Nerve Regeneration And Wound Healing Post-Injury By Modulating Trigeminal Transcriptomic Signature, Thang L. Pham, Azucena H. Kakazu, Jiucheng He, Bokkyoo Jun, Nicolas G. Bazan, Haydee E.P. Bazan

School of Medicine Faculty Publications

The high-density corneal innervation plays a pivotal role in sustaining the integrity of the ocular surface. We have previously demonstrated that pigment epithelium-derived factor (PEDF) plus docosahexaenoic acid (DHA) promotes corneal nerve regeneration; here, we report the mechanism involved and the discovery of a stereospecific Resolvin D6-isomer (RvD6si) that drives the process. RvD6si promotes corneal wound healing and functional recovery by restoring corneal innervation after injury. RvD6si applied to the eye surface elicits a specific transcriptome signature in the trigeminal ganglion (TG) that includes Rictor, the rapamycin-insensitive complex-2 of mTOR (mTORC2), and genes involved in axon growth, whereas genes related …