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Full-Text Articles in Medicine and Health Sciences

Genomic Patterns Of Malignant Peripheral Nerve Sheath Tumor (Mpnst) Evolution Correlate With Clinical Outcome And Are Detectable In Cell-Free Dna, Isidro Cortes-Ciriano, Dana C Borcherding, Jeffrey J Szymanski, Angela C Hirbe, Et Al. Mar 2023

Genomic Patterns Of Malignant Peripheral Nerve Sheath Tumor (Mpnst) Evolution Correlate With Clinical Outcome And Are Detectable In Cell-Free Dna, Isidro Cortes-Ciriano, Dana C Borcherding, Jeffrey J Szymanski, Angela C Hirbe, Et Al.

2020-Current year OA Pubs

UNLABELLED: Malignant peripheral nerve sheath tumor (MPNST), an aggressive soft-tissue sarcoma, occurs in people with neurofibromatosis type 1 (NF1) and sporadically. Whole-genome and multiregional exome sequencing, transcriptomic, and methylation profiling of 95 tumor samples revealed the order of genomic events in tumor evolution. Following biallelic inactivation of NF1, loss of CDKN2A or TP53 with or without inactivation of polycomb repressive complex 2 (PRC2) leads to extensive somatic copy-number aberrations (SCNA). Distinct pathways of tumor evolution are associated with inactivation of PRC2 genes and H3K27 trimethylation (H3K27me3) status. Tumors with H3K27me3 loss evolve through extensive chromosomal losses followed by whole-genome doubling …


Effect Of Fecal Microbial Transplantation On Clostridioides Difficile Infection: Dysbiosis, Metabolites And Health Related Quality Of Life, Kevin W Garey, Paul Feuerstadt, Erik R Dubberke, Amy Guo, Glenn S Tillotson Mar 2023

Effect Of Fecal Microbial Transplantation On Clostridioides Difficile Infection: Dysbiosis, Metabolites And Health Related Quality Of Life, Kevin W Garey, Paul Feuerstadt, Erik R Dubberke, Amy Guo, Glenn S Tillotson

2020-Current year OA Pubs

No abstract provided.


Cmpk2 Is A Host Restriction Factor That Inhibits Infection Of Multiple Coronaviruses In A Cell-Intrinsic Manner, Mingjun Zhu, Jiahuang Lv, Wei Wang, Rongli Guo, Chunyan Zhong, Avan Antia, Qiru Zeng, Jizong Li, Qingtao Liu, Jinzhu Zhou, Xuejiao Zhu, Baochao Fan, Siyuan Ding, Bin Li Mar 2023

Cmpk2 Is A Host Restriction Factor That Inhibits Infection Of Multiple Coronaviruses In A Cell-Intrinsic Manner, Mingjun Zhu, Jiahuang Lv, Wei Wang, Rongli Guo, Chunyan Zhong, Avan Antia, Qiru Zeng, Jizong Li, Qingtao Liu, Jinzhu Zhou, Xuejiao Zhu, Baochao Fan, Siyuan Ding, Bin Li

2020-Current year OA Pubs

Coronaviruses (CoVs) comprise a group of important human and animal pathogens. Despite extensive research in the past 3 years, the host innate immune defense mechanisms against CoVs remain incompletely understood, limiting the development of effective antivirals and non-antibody-based therapeutics. Here, we performed an integrated transcriptomic analysis of porcine jejunal epithelial cells infected with porcine epidemic diarrhea virus (PEDV) and identified cytidine/uridine monophosphate kinase 2 (CMPK2) as a potential host restriction factor. CMPK2 exhibited modest antiviral activity against PEDV infection in multiple cell types. CMPK2 transcription was regulated by interferon-dependent and interferon regulatory factor 1 (IRF1)-dependent pathways post-PEDV infection. We demonstrated …


An Open Label Randomized Controlled Trial Of Ivermectin Plus Favipiravir-Based Standard Of Care Versus Favipiravir-Based Standard Of Care For Treatment Of Moderate Covid-19 In Thailand, Phahol Sarojvisut, Anucha Apisarnthanarak, Kittiya Jantarathaneewat, Ornnicha Sathitakorn, Thanus Pienthong, Chatchai Mingmalairak, David K. Warren, David J. Weber Mar 2023

An Open Label Randomized Controlled Trial Of Ivermectin Plus Favipiravir-Based Standard Of Care Versus Favipiravir-Based Standard Of Care For Treatment Of Moderate Covid-19 In Thailand, Phahol Sarojvisut, Anucha Apisarnthanarak, Kittiya Jantarathaneewat, Ornnicha Sathitakorn, Thanus Pienthong, Chatchai Mingmalairak, David K. Warren, David J. Weber

2020-Current year OA Pubs

BACKGROUND: The role of ivermectin in the treatment of moderate coronavirus disease 2019 (COVID-19) is controversial. We performed an open label randomized controlled trial to evaluate the role of ivermectin plus favipiravir-based standard of care versus favipiravir-based standard of care for the treatment of moderate COVID-19 infection.

MATERIALS AND METHODS: An open-label randomized control trial was performed at Thammasat Field Hospital and Thammasat University Hospital from October 1st, 2021 to May 31st, 2022. Patients with moderate COVID-19 infections were randomized to the intervention (ivermectin plus favipiravir-based standard of care) or control group (favipiravir-based standard of care alone). Patients were followed …


Strengthening Implementation Guidelines For Hiv Service Delivery: Considerations For Future Evidence Generation And Synthesis, Ingrid Eshun-Wilson, Nathan Ford, Aaloke Mody, Laura Beres, Sheree Schwartz, Stefan Baral, Elvin H. Geng Mar 2023

Strengthening Implementation Guidelines For Hiv Service Delivery: Considerations For Future Evidence Generation And Synthesis, Ingrid Eshun-Wilson, Nathan Ford, Aaloke Mody, Laura Beres, Sheree Schwartz, Stefan Baral, Elvin H. Geng

2020-Current year OA Pubs

Ingrid Eshun-Wilson and colleagues summarize gaps in primary HIV implementation research methods and reporting, and propose areas for future methodological development.


Cnih3 Deletion Dysregulates Dorsal Hippocampal Transcription Across The Estrous Cycle, Bernard Mulvey, Hannah E. Frye, Tania Lintz, Stuart Fass, Eric Tycksen, Elliot C. Nelson, Jose A. Morón, Joseph D. Dougherty Mar 2023

Cnih3 Deletion Dysregulates Dorsal Hippocampal Transcription Across The Estrous Cycle, Bernard Mulvey, Hannah E. Frye, Tania Lintz, Stuart Fass, Eric Tycksen, Elliot C. Nelson, Jose A. Morón, Joseph D. Dougherty

2020-Current year OA Pubs

In females, the hippocampus, a critical brain region for coordination of learning, memory, and behavior, displays altered physiology and behavioral output across the estrous or menstrual cycle. However, the molecular effectors and cell types underlying these observed cyclic changes have only been partially characterized to date. Recently, profiling of mice null for the AMPA receptor trafficking gene


Molecular Phenotyping Of Single Pancreatic Islet Leader Beta Cells By "Flash-Seq", Pauline Chabosseau, Fiona Yong, Luis F Delgadillo-Silva, Eun Young Lee, Rana Melhem, Shiying Li, Nidhi Gandhi, Jules Wastin, Livia Lopez Noriega, Isabelle Leclerc, Yusuf Ali, Jing W Hughes, Robert Sladek, Aida Martinez-Sanchez, Guy A Rutter Mar 2023

Molecular Phenotyping Of Single Pancreatic Islet Leader Beta Cells By "Flash-Seq", Pauline Chabosseau, Fiona Yong, Luis F Delgadillo-Silva, Eun Young Lee, Rana Melhem, Shiying Li, Nidhi Gandhi, Jules Wastin, Livia Lopez Noriega, Isabelle Leclerc, Yusuf Ali, Jing W Hughes, Robert Sladek, Aida Martinez-Sanchez, Guy A Rutter

2020-Current year OA Pubs

AIMS: Spatially-organized increases in cytosolic Ca

MAIN METHODS: High speed confocal Ca

KEY FINDINGS: Distinct Ca

SIGNIFICANCE: The existence of both a discrete transcriptome and unique localisation implies a role for these features in defining the specialized function of leaders. These data also raise the possibility that localised signalling between delta and leader cells contributes to the initiation and propagation of islet Ca


Mucosal And Systemic Neutralizing Antibodies To Norovirus Induced In Infant Mice Orally Inoculated With Recombinant Rotaviruses, Takahiro Kawagishi, Liliana Sánchez-Tacuba, Ningguo Feng, Veronica P Costantini, Ming Tan, Xi Jiang, Kim Y Green, Jan Vinjé, Siyuan Ding, Harry B Greenberg Feb 2023

Mucosal And Systemic Neutralizing Antibodies To Norovirus Induced In Infant Mice Orally Inoculated With Recombinant Rotaviruses, Takahiro Kawagishi, Liliana Sánchez-Tacuba, Ningguo Feng, Veronica P Costantini, Ming Tan, Xi Jiang, Kim Y Green, Jan Vinjé, Siyuan Ding, Harry B Greenberg

2020-Current year OA Pubs

Rotaviruses (RVs) preferentially replicate in the small intestine and frequently cause severe diarrheal disease, and the following enteric infection generally induces variable levels of protective systemic and mucosal immune responses in humans and other animals. Rhesus rotavirus (RRV) is a simian RV that was previously used as a human RV vaccine and has been extensively studied in mice. Although RRV replicates poorly in the suckling mouse intestine, infection induces a robust and protective antibody response. The recent availability of plasmid only-based RV reverse genetics systems has enabled the generation of recombinant RVs expressing foreign proteins. However, recombinant RVs have not …


Single Cell Preparations Of Mycobacterium Tuberculosis Damage The Mycobacterial Envelope And Disrupt Macrophage Interactions, Ekansh Mittal, Andrew T Roth, Anushree Seth, Srikanth Singamaneni, Wandy Beatty, Jennifer A Philips Feb 2023

Single Cell Preparations Of Mycobacterium Tuberculosis Damage The Mycobacterial Envelope And Disrupt Macrophage Interactions, Ekansh Mittal, Andrew T Roth, Anushree Seth, Srikanth Singamaneni, Wandy Beatty, Jennifer A Philips

2020-Current year OA Pubs

For decades, investigators have studied the interaction of


Virology Under The Microscope-A Call For Rational Discourse, Felicia Goodrum, Carolina Lopez, Sean Whelan, Et Al. Feb 2023

Virology Under The Microscope-A Call For Rational Discourse, Felicia Goodrum, Carolina Lopez, Sean Whelan, Et Al.

2020-Current year OA Pubs

Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns - conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled …


Apical Secretory Glycoprotein Complex Contributes To Cell Attachment And Entry By Cryptosporidium Parvum, Marianna E. Akey, Rui Xu, Soumya Ravindran, Lisa Funkhouser-Jones, L. David Sibley Feb 2023

Apical Secretory Glycoprotein Complex Contributes To Cell Attachment And Entry By Cryptosporidium Parvum, Marianna E. Akey, Rui Xu, Soumya Ravindran, Lisa Funkhouser-Jones, L. David Sibley

2020-Current year OA Pubs

Cryptosporidium parvum is an enteric pathogen that invades epithelial cells in the intestine, where it resides at the apical surface in a unique epicellular location. Compared with those of related apicomplexan parasites, the processes of host cell attachment and invasion by C. parvum are poorly understood. The streamlined C. parvum genome contains numerous mucin-like glycoproteins, several of which have previously been shown to mediate cell attachment, although the majority are unstudied. Here, we identified the antigens recognized by monoclonal antibody (MAb) 1A5, which stains the apical end of sporozoites and mature merozoites. Immunoprecipitation with MAb 1A5 followed by mass spectrometry …


The Er Protein Translocation Channel Subunit Sbh1 Controls Virulence Of Cryptococcus Neoformans, Felipe H. Santiago-Tirado, Thomas Hurtaux, Jennifer Geddes-Mcalister, Duy Nguyen, Volkhard Helms, Tamara L Doering, Karin Römisch Feb 2023

The Er Protein Translocation Channel Subunit Sbh1 Controls Virulence Of Cryptococcus Neoformans, Felipe H. Santiago-Tirado, Thomas Hurtaux, Jennifer Geddes-Mcalister, Duy Nguyen, Volkhard Helms, Tamara L Doering, Karin Römisch

2020-Current year OA Pubs

The fungal pathogen Cryptococcus neoformans is distinguished by a cell-wall-anchored polysaccharide capsule that is critical for virulence. Biogenesis of both cell wall and capsule relies on the secretory pathway. Protein secretion begins with polypeptide translocation across the endoplasmic reticulum (ER) membrane through a highly conserved channel formed by three proteins: Sec61, Sbh1, and Sss1. Sbh1, the most divergent, contains multiple phosphorylation sites, which may allow it to regulate entry into the secretory pathway in a species- and protein-specific manner. Absence of


Zika Virus Spreads Through Infection Of Lymph Node-Resident Macrophages, Glennys V Reynoso, Autumn C Holmes, Yael Alippe, Michael S Diamond, Et Al. Feb 2023

Zika Virus Spreads Through Infection Of Lymph Node-Resident Macrophages, Glennys V Reynoso, Autumn C Holmes, Yael Alippe, Michael S Diamond, Et Al.

2020-Current year OA Pubs

To disseminate through the body, Zika virus (ZIKV) is thought to exploit the mobility of myeloid cells, in particular monocytes and dendritic cells. However, the timing and mechanisms underlying shuttling of the virus by immune cells remains unclear. To understand the early steps in ZIKV transit from the skin, at different time points, we spatially mapped ZIKV infection in lymph nodes (LNs), an intermediary site en route to the blood. Contrary to prevailing hypotheses, migratory immune cells are not required for the virus to reach the LNs or blood. Instead, ZIKV rapidly infects a subset of sessile CD169


Network Analysis Of Large-Scale Immgen And Tabula Muris Datasets Highlights Metabolic Diversity Of Tissue Mononuclear Phagocytes, Anastasiia Gainullina, Denis A Mogilenko, Li-Hao Huang, Ki-Wook Kim, Karen Krchma, Jun Wu, Geetika Bajpai, Peter Wang, Kyunghee Choi, Kory Lavine, Gwendalyn J Randolph, Alexey Sergushichev, Maxim N Artyomov, Et Al. Feb 2023

Network Analysis Of Large-Scale Immgen And Tabula Muris Datasets Highlights Metabolic Diversity Of Tissue Mononuclear Phagocytes, Anastasiia Gainullina, Denis A Mogilenko, Li-Hao Huang, Ki-Wook Kim, Karen Krchma, Jun Wu, Geetika Bajpai, Peter Wang, Kyunghee Choi, Kory Lavine, Gwendalyn J Randolph, Alexey Sergushichev, Maxim N Artyomov, Et Al.

2020-Current year OA Pubs

The diversity of mononuclear phagocyte (MNP) subpopulations across tissues is one of the key physiological characteristics of the immune system. Here, we focus on understanding the metabolic variability of MNPs through metabolic network analysis applied to three large-scale transcriptional datasets: we introduce (1) an ImmGen MNP open-source dataset of 337 samples across 26 tissues; (2) a myeloid subset of ImmGen Phase I dataset (202 MNP samples); and (3) a myeloid mouse single-cell RNA sequencing (scRNA-seq) dataset (51,364 cells) assembled based on Tabula Muris Senis. To analyze such large-scale datasets, we develop a network-based computational approach, genes and metabolites (GAM) clustering, …


A Fetal Tumor Suppressor Axis Abrogates Mll-Fusion-Driven Acute Myeloid Leukemia, Mohamed Eldeeb, Ouyang Yuan, Nicola Guzzi, Phuong Cao Thi Ngoc, Anna Konturek-Ciesla, Trine A Kristiansen, Sowndarya Muthukumar, Jeffrey Magee, Cristian Bellodi, Joan Yuan, David Bryder Feb 2023

A Fetal Tumor Suppressor Axis Abrogates Mll-Fusion-Driven Acute Myeloid Leukemia, Mohamed Eldeeb, Ouyang Yuan, Nicola Guzzi, Phuong Cao Thi Ngoc, Anna Konturek-Ciesla, Trine A Kristiansen, Sowndarya Muthukumar, Jeffrey Magee, Cristian Bellodi, Joan Yuan, David Bryder

2020-Current year OA Pubs

MLL-rearrangements (MLL-r) are recurrent genetic events in acute myeloid leukemia (AML) and frequently associate with poor prognosis. In infants, MLL-r can be sufficient to drive transformation. However, despite the prenatal origin of MLL-r in these patients, congenital leukemia is very rare with transformation usually occurring postnatally. The influence of prenatal signals on leukemogenesis, such as those mediated by the fetal-specific protein LIN28B, remains controversial. Here, using a dual-transgenic mouse model that co-expresses MLL-ENL and LIN28B, we investigate the impact of LIN28B on AML. LIN28B impedes the progression of MLL-r AML through compromised leukemia-initiating cell activity and suppression of MYB signaling. …


Engineering A Modular 44ti/44sc Generator: Eluate Evaluation In Preclinical Models And Estimation Of Human Radiation Dosimetry, Nadia Benabdallah, Hanwen Zhang, Ryan Unnerstall, Amanda Fears, Lucy Summer, Michael Fassbender, Buck E Rodgers, Diane Abou, Valery Radchenko, Daniel L J Thorek Feb 2023

Engineering A Modular 44ti/44sc Generator: Eluate Evaluation In Preclinical Models And Estimation Of Human Radiation Dosimetry, Nadia Benabdallah, Hanwen Zhang, Ryan Unnerstall, Amanda Fears, Lucy Summer, Michael Fassbender, Buck E Rodgers, Diane Abou, Valery Radchenko, Daniel L J Thorek

2020-Current year OA Pubs

BACKGROUND:

METHODS:

RESULTS:

CONCLUSIONS: A clinical-scale


Long-Term Intensive Endurance Exercise Training Is Associated To Reduced Markers Of Cellular Senescence In The Colon Mucosa Of Older Adults, Marco Demaria, Beatrice Bertozzi, Nicola Veronese, Francesco Spelta, Edda Cava, Valeria Tosti, Laura Piccio, Dayna S Early, Luigi Fontana Feb 2023

Long-Term Intensive Endurance Exercise Training Is Associated To Reduced Markers Of Cellular Senescence In The Colon Mucosa Of Older Adults, Marco Demaria, Beatrice Bertozzi, Nicola Veronese, Francesco Spelta, Edda Cava, Valeria Tosti, Laura Piccio, Dayna S Early, Luigi Fontana

2020-Current year OA Pubs

Regular endurance exercise training is an effective intervention for the maintenance of metabolic health and the prevention of many age-associated chronic diseases. Several metabolic and inflammatory factors are involved in the health-promoting effects of exercise training, but regulatory mechanisms remain poorly understood. Cellular senescence-a state of irreversible growth arrest-is considered a basic mechanism of aging. Senescent cells accumulate over time and promote a variety of age-related pathologies from neurodegenerative disorders to cancer. Whether long-term intensive exercise training affect the accumulation of age-associated cellular senescence is still unclear. Here, we show that the classical senescence markers p16 and IL-6 were markedly …


Orthodenticle Homeobox 2 Is Transported To Lysosomes By Nuclear Budding Vesicles, Jun Woo Park, Eun Jung Lee, Eunyoung Moon, Hong-Lim Kim, In-Beom Kim, Didier Hodzic, Namsuk Kim, Hee-Seok Kweon, Jin Woo Kim Feb 2023

Orthodenticle Homeobox 2 Is Transported To Lysosomes By Nuclear Budding Vesicles, Jun Woo Park, Eun Jung Lee, Eunyoung Moon, Hong-Lim Kim, In-Beom Kim, Didier Hodzic, Namsuk Kim, Hee-Seok Kweon, Jin Woo Kim

2020-Current year OA Pubs

Transcription factors (TFs) are transported from the cytoplasm to the nucleus and disappear from the nucleus after they regulate gene expression. Here, we discover an unconventional nuclear export of the TF, orthodenticle homeobox 2 (OTX2), in nuclear budding vesicles, which transport OTX2 to the lysosome. We further find that torsin1a (Tor1a) is responsible for scission of the inner nuclear vesicle, which captures OTX2 using the LINC complex. Consistent with this, in cells expressing an ATPase-inactive Tor1aΔE mutant and the LINC (linker of nucleoskeleton and cytoskeleton) breaker KASH2, OTX2 accumulated and formed aggregates in the nucleus. Consequently, in the mice expressing …


Care Of Bullet-Related Injuries: A Cross-Sectional Study Of Instructions And Prescriptions Provided On Discharge From The Emergency Department, Jane M. Hayes, L J. Punch, Kristen L. Mueller Feb 2023

Care Of Bullet-Related Injuries: A Cross-Sectional Study Of Instructions And Prescriptions Provided On Discharge From The Emergency Department, Jane M. Hayes, L J. Punch, Kristen L. Mueller

2020-Current year OA Pubs

INTRODUCTION: There are more than 80,000 emergency department (ED) visits for non-fatal bullet-related injuries (BRI) per year in the United States. Approximately half of these patients are discharged home from the ED. Our objective in this study was to characterize the discharge instructions, prescriptions, and follow-up plans provided to patients discharged from the ED after BRI.

METHODS: This was a single-center, cross-sectional study of the first 100 consecutive patients who presented to an urban, academic, Level I trauma center ED with an acute BRI beginning on January 1, 2020. We queried the electronic health record for patient demographics, insurance status, …


Trpv1-Mediated Sonogenetic Neuromodulation Of Motor Cortex In Freely Moving Mice, Kevin Xu, Yaoheng Yang, Zhongtao Hu, Yimei Yue, Yan Gong, Jianmin Cui, Joseph P Culver, Michael R Bruchas, Hong Chen Feb 2023

Trpv1-Mediated Sonogenetic Neuromodulation Of Motor Cortex In Freely Moving Mice, Kevin Xu, Yaoheng Yang, Zhongtao Hu, Yimei Yue, Yan Gong, Jianmin Cui, Joseph P Culver, Michael R Bruchas, Hong Chen

2020-Current year OA Pubs

No abstract provided.


Membrane Phospholipids Control Gating Of The Mechanosensitive Potassium Leak Channel Trek1, Philipp A M Schmidpeter, John T Petroff 2nd, Leila Khajoueinejad, Aboubacar Wague, Cheryl Frankfater, Wayland W L Cheng, Crina M Nimigean, Paul M Riegelhaupt Feb 2023

Membrane Phospholipids Control Gating Of The Mechanosensitive Potassium Leak Channel Trek1, Philipp A M Schmidpeter, John T Petroff 2nd, Leila Khajoueinejad, Aboubacar Wague, Cheryl Frankfater, Wayland W L Cheng, Crina M Nimigean, Paul M Riegelhaupt

2020-Current year OA Pubs

Tandem pore domain (K2P) potassium channels modulate resting membrane potentials and shape cellular excitability. For the mechanosensitive subfamily of K2Ps, the composition of phospholipids within the bilayer strongly influences channel activity. To examine the molecular details of K2P lipid modulation, we solved cryo-EM structures of the TREK1 K2P channel bound to either the anionic lipid phosphatidic acid (PA) or the zwitterionic lipid phosphatidylethanolamine (PE). At the extracellular face of TREK1, a PA lipid inserts its hydrocarbon tail into a pocket behind the selectivity filter, causing a structural rearrangement that recapitulates mutations and pharmacology known to activate TREK1. At the cytoplasmic …


Mitochondrial Phosphatidylethanolamine Modulates Ucp1 To Promote Brown Adipose Thermogenesis, Jordan M Johnson, Irfan J Lodhi, Et Al. Feb 2023

Mitochondrial Phosphatidylethanolamine Modulates Ucp1 To Promote Brown Adipose Thermogenesis, Jordan M Johnson, Irfan J Lodhi, Et Al.

2020-Current year OA Pubs

Thermogenesis by uncoupling protein 1 (UCP1) is one of the primary mechanisms by which brown adipose tissue (BAT) increases energy expenditure. UCP1 resides in the inner mitochondrial membrane (IMM), where it dissipates membrane potential independent of adenosine triphosphate (ATP) synthase. Here, we provide evidence that phosphatidylethanolamine (PE) modulates UCP1-dependent proton conductance across the IMM to modulate thermogenesis. Mitochondrial lipidomic analyses revealed PE as a signature molecule whose abundance bidirectionally responds to changes in thermogenic burden. Reduction in mitochondrial PE by deletion of phosphatidylserine decarboxylase (PSD) made mice cold intolerant and insensitive to β3 adrenergic receptor agonist-induced increase in whole-body oxygen …


[18f]Tosyl Fluoride As A Versatile [18f]Fluoride Source For The Preparation Of 18f-Labeled Radiopharmaceuticals, Dong Zhou, Wenhua Chu, Jinbin Xu, Sally Schwarz, John A Katzenellenbogen Feb 2023

[18f]Tosyl Fluoride As A Versatile [18f]Fluoride Source For The Preparation Of 18f-Labeled Radiopharmaceuticals, Dong Zhou, Wenhua Chu, Jinbin Xu, Sally Schwarz, John A Katzenellenbogen

2020-Current year OA Pubs

Positron emission tomography (PET) is an in vivo imaging technology that utilizes positron-emitting radioisotope-labeled compounds as PET radiotracers that are commonly used in clinic and in various research areas, including oncology, cardiology, and neurology. Fluorine-18 is the most widely used PET-radionuclide and commonly produced by proton bombardment of


Genetic Subgroups Inform On Pathobiology In Adult And Pediatric Burkitt Lymphoma, Nicole Thomas, Nancy L. Bartlett, Lee Ratner, Et Al. Feb 2023

Genetic Subgroups Inform On Pathobiology In Adult And Pediatric Burkitt Lymphoma, Nicole Thomas, Nancy L. Bartlett, Lee Ratner, Et Al.

2020-Current year OA Pubs

Burkitt lymphoma (BL) accounts for most pediatric non-Hodgkin lymphomas, being less common but significantly more lethal when diagnosed in adults. Much of the knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult BL (aBL) and other adult lymphomas not fully explored. We sought to more thoroughly identify the somatic changes that underlie lymphomagenesis in aBL and any molecular features that associate with clinical disparities within and between pBL and aBL. Through comprehensive whole-genome sequencing of 230 BL and 295 diffuse large B-cell lymphoma (DLBCL) tumors, we identified …


Child Adult Relationship Enhancement In Primary Care (Pricare): Study Design/Protocol For A Randomized Trial Of A Primary Care-Based Group Parenting Intervention To Prevent Child Maltreatment, Samantha Schilling, Byron J Powell, Paul W Stewart, Joanne N Wood Feb 2023

Child Adult Relationship Enhancement In Primary Care (Pricare): Study Design/Protocol For A Randomized Trial Of A Primary Care-Based Group Parenting Intervention To Prevent Child Maltreatment, Samantha Schilling, Byron J Powell, Paul W Stewart, Joanne N Wood

2020-Current year OA Pubs

BACKGROUND: Child maltreatment (CM) is a pervasive public health problem and there is a critical need for brief, effective, scalable prevention programs. Problematic parent-child relationships lie at the heart of CM. Parents who maltreat their children are more likely to have punitive parenting styles characterized by high rates of negative interaction and ineffective discipline strategies with over-reliance on punishment. Thus, parenting interventions that strengthen parent-child relationships, teach positive discipline techniques, decrease harsh parenting, and decrease child behavioral problems hold promise as CM prevention strategies. Challenges in engaging parents, particularly low-income and minority parents, and a lack of knowledge regarding effective …


Allogeneic Natural Killer Cell Therapy, Melissa M Berrien-Elliott, Miriam T Jacobs, Todd A Fehniger Feb 2023

Allogeneic Natural Killer Cell Therapy, Melissa M Berrien-Elliott, Miriam T Jacobs, Todd A Fehniger

2020-Current year OA Pubs

Interest in adoptive cell therapy for treating cancer is exploding owing to early clinical successes of autologous chimeric antigen receptor (CAR) T lymphocyte therapy. However, limitations using T cells and autologous cell products are apparent as they (1) take weeks to generate, (2) utilize a 1:1 donor-to-patient model, (3) are expensive, and (4) are prone to heterogeneity and manufacturing failures. CAR T cells are also associated with significant toxicities, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and prolonged cytopenias. To overcome these issues, natural killer (NK) cells are being explored as an alternative cell source for allogeneic cell …


Using Wearable Sensors To Assess Freezing Of Gait In The Real World, David S May, Lauren E Tueth, Gammon M Earhart, Pietro Mazzoni Feb 2023

Using Wearable Sensors To Assess Freezing Of Gait In The Real World, David S May, Lauren E Tueth, Gammon M Earhart, Pietro Mazzoni

2020-Current year OA Pubs

Freezing of gait (FOG) is a debilitating symptom of Parkinson's disease (PD) that remains difficult to assess. Wearable movement sensors and associated algorithms can be used to quantify FOG in laboratory settings, but the utility of such methods for real world use is unclear. We aimed to determine the suitability of our wearable sensor-based FOG assessment method for real world use by assessing its performance during in-clinic simulated real world activities. Accuracy of the sensor-based method during simulated real-world tasks was calculated using expert rated video as the gold standard. To determine feasibility for unsupervised home use, we also determined …


The Toxoplasma Micropore Mediates Endocytosis For Selective Nutrient Salvage From Host Cell Compartments, Wenyan Wan, Hui Dong, De-Hua Lai, Jiong Yang, Kai He, Xiaoyan Tang, Qun Liu, Geoff Hide, Xing-Quan Zhu, L David Sibley, Zhao-Rong Lun, Shaojun Long Feb 2023

The Toxoplasma Micropore Mediates Endocytosis For Selective Nutrient Salvage From Host Cell Compartments, Wenyan Wan, Hui Dong, De-Hua Lai, Jiong Yang, Kai He, Xiaoyan Tang, Qun Liu, Geoff Hide, Xing-Quan Zhu, L David Sibley, Zhao-Rong Lun, Shaojun Long

2020-Current year OA Pubs

Apicomplexan parasite growth and replication relies on nutrient acquisition from host cells, in which intracellular multiplication occurs, yet the mechanisms that underlie the nutrient salvage remain elusive. Numerous ultrastructural studies have documented a plasma membrane invagination with a dense neck, termed the micropore, on the surface of intracellular parasites. However, the function of this structure remains unknown. Here we validate the micropore as an essential organelle for endocytosis of nutrients from the host cell cytosol and Golgi in the model apicomplexan Toxoplasma gondii. Detailed analyses demonstrated that Kelch13 is localized at the dense neck of the organelle and functions as …


Uncovering The Complex Genetic Architecture Of Human Plasma Lipidome Using Machine Learning Methods, Miikael Lehtimäki, Binisha H Mishra, Coral Del-Val, Leo-Pekka Lyytikäinen, Mika Kähönen, C Robert Cloninger, Olli T Raitakari, Reijo Laaksonen, Igor Zwir, Terho Lehtimäki, Pashupati P Mishra Feb 2023

Uncovering The Complex Genetic Architecture Of Human Plasma Lipidome Using Machine Learning Methods, Miikael Lehtimäki, Binisha H Mishra, Coral Del-Val, Leo-Pekka Lyytikäinen, Mika Kähönen, C Robert Cloninger, Olli T Raitakari, Reijo Laaksonen, Igor Zwir, Terho Lehtimäki, Pashupati P Mishra

2020-Current year OA Pubs

Genetic architecture of plasma lipidome provides insights into regulation of lipid metabolism and related diseases. We applied an unsupervised machine learning method, PGMRA, to discover phenotype-genotype many-to-many relations between genotype and plasma lipidome (phenotype) in order to identify the genetic architecture of plasma lipidome profiled from 1,426 Finnish individuals aged 30-45 years. PGMRA involves biclustering genotype and lipidome data independently followed by their inter-domain integration based on hypergeometric tests of the number of shared individuals. Pathway enrichment analysis was performed on the SNP sets to identify their associated biological processes. We identified 93 statistically significant (hypergeometric p-value < 0.01) lipidome-genotype relations. Genotype biclusters in these 93 relations contained 5977 SNPs across 3164 genes. Twenty nine of the 93 relations contained genotype biclusters with more than 50% unique SNPs and participants, thus representing most distinct subgroups. We identified 30 significantly enriched biological processes among the SNPs involved in 21 of these 29 most distinct genotype-lipidome subgroups through which the identified genetic variants can influence and regulate plasma lipid related metabolism and profiles. This study identified 29 distinct genotype-lipidome subgroups in the studied Finnish population that may have distinct disease trajectories and therefore could be useful in precision medicine research.


Identifying Factors Which Influence Eating Disorder Risk During Behavioral Weight Management: A Consensus Study, Hiba Jebeile, Caitlin M Mcmaster, Brittany J Johnson, Sarah P Garnett, Susan J Paxton, Anna L Seidler, Rebecca A Jones, Andrew J Hill, Sarah Maguire, Caroline Braet, Genevieve Dammery, Denise E Wilfley, Louise A Baur, Natalie B Lister, On Behalf Of The Eating Disorders In Weight-Related Therapy (Edit) Collaboration Feb 2023

Identifying Factors Which Influence Eating Disorder Risk During Behavioral Weight Management: A Consensus Study, Hiba Jebeile, Caitlin M Mcmaster, Brittany J Johnson, Sarah P Garnett, Susan J Paxton, Anna L Seidler, Rebecca A Jones, Andrew J Hill, Sarah Maguire, Caroline Braet, Genevieve Dammery, Denise E Wilfley, Louise A Baur, Natalie B Lister, On Behalf Of The Eating Disorders In Weight-Related Therapy (Edit) Collaboration

2020-Current year OA Pubs

This study aimed to understand clinician, researcher and consumer views regarding factors which influence eating disorder (ED) risk during behavioral weight management, including individual risk factors, intervention strategies and delivery features. Eighty-seven participants were recruited internationally through professional and consumer organizations and social media and completed an online survey. Individual characteristics, intervention strategies (5-point scale) and delivery features (important/unimportant/unsure) were rated. Participants were mostly women (n = 81), aged 35-49 y, from Australia or United States, were clinicians and/or reported lived experience of overweight/obesity and/or ED. There was agreement (64% to 99%) that individual characteristics were relevant to ED risk, …