Digital Commons Network^™

Association Of Longitudinal Changes In Cerebrospinal Fluid Total Tau And Phosphorylated Tau 181 And Brain Atrophy With Disease Progression In Patients With Alzheimer Disease, Jorge J. Llibre-Guerra, Yan Li, Suzanne E. Schindler, Brian A. Gordon, Anne M. Fagan, John C. Morris, Tammie L.S. Benzinger, Jason Hassenstab, Sarah B. Berman, David M. Holtzman, Chengjie Xiong, Randall J. Bateman, Eric Mcdade

Open Access Publications

Importance: The amyloid/tau/neurodegeneration (A/T/N) framework uses cerebrospinal fluid (CSF) levels of total tau (tTau) as a marker of neurodegeneration and CSF levels of phosphorylated tau 181 (pTau181) as a marker of tau tangles. However, it is unclear whether CSF levels of tTau and pTau181 have similar or different trajectories over the course of Alzheimer disease.

Objectives: To examine the rates of change in CSF levels of tTau and pTau181 across the Alzheimer disease course and how the rates of change are associated with brain atrophy as measured by magnetic resonance imaging.

Design, Setting, and Participants: This cohort study was set …

A Novel Detrimental Homozygous Mutation In The Wfs1 Gene In Two Sisters From Nonconsanguineous Parents With Untreated Diabetes Insipidus, Dimitrios T Papadimitriou, Kleanthis Kleanthous, Emmanouil Manolakos, Anatoly Tiulpakov, Thomas Nikolopoulos, Alexandros Delides, Gerasimos Voros, Argyrios Dinopoulos, George Zoupanos, Anastasios Papadimitriou, Georgios Mastorakos, Fumihiko Urano

Open Access Publications

Given the limited lifespan and with the recent progress in experimental treatments for WS, timely diagnosis and multidisciplinary treatment for DI/DM, hydronephrosis, and visual/psychiatric status-maintaining quality of life-are of crucial importance.

Tricarboxylic Acid Cycle Enzyme Activities In A Mouse Model Of Methylmalonic Aciduria, Parith Wongkittichote, Gary Cunningham, Marshall L Summar, Elena Pumbo, Patrick Forny, Matthias R Baumgartner, Kimberly A Chapman

Open Access Publications

Methylmalonic acidemia (MMA) is a propionate pathway disorder caused by dysfunction of the mitochondrial enzyme methylmalonyl-CoA mutase (MMUT). MMUT catalyzes the conversion of methylmalonyl-CoA to succinyl-CoA, an anaplerotic reaction which feeds into the tricarboxylic acid (TCA) cycle. As part of the pathological mechanisms of MMA, previous studies have suggested there is decreased TCA activity due to a "toxic inhibition" of TCA cycle enzymes by MMA related metabolites, in addition to reduced anaplerosis. Here, we have utilized mitochondria isolated from livers of a mouse model of MMA (Mut-ko/ki) and their littermate controls (Ki/wt) to examine the amounts and enzyme functions of …

Reports Of Injury Risks And Reasons For Choice Of Sleep Environments For Infants And Toddlers, N J Scheers, Chauncey Dayton, Mary Batcher, Bradley T Thach

Open Access Publications

OBJECTIVE: Compare mothers' reports of injuries for infants and toddlers sleeping with crib-bumpers/mesh-liners/no-barriers and reasons for these sleep environment choices.

METHODS: A cross-sectional survey of mothers subscribing to a parenting magazine and using crib bumpers (n = 224), mesh liners (n = 262), and no barriers (n = 842). Analyses of four possible injuries (face-covered, climb-out/fall, slat-entrapment, hit-head) including multivariate logistic regression adjusted for missing data/demographics and Chi squared analyses of reasons for mothers' choices.

RESULTS: Maternal reports of finding infants/toddlers with face covered had 3.5 times higher adjusted odds (aOR) for crib bumper versus mesh liner use. Breathing difficulties …

Linking The Effects Of Helminth Infection, Diet And The Gut Microbiota With Human Whole-Blood Signatures, Soo Ching Lee, Mei San Tang, Alice V. Easton, Joseph Cooper Devlin, Ling Ling Chua, Ilseung Cho, Foong Ming Moy, Tsung Fei Khang, Yvonne A. L. Lim, P'Ng Loke

Open Access Publications

Helminth infection and dietary intake can affect the intestinal microbiota, as well as the immune system. Here we analyzed the relationship between fecal microbiota and blood profiles of indigenous Malaysians, referred to locally as Orang Asli, in comparison to urban participants from the capital city of Malaysia, Kuala Lumpur. We found that helminth infections had a larger effect on gut microbial composition than did dietary intake or blood profiles. Trichuris trichiura infection intensity also had the strongest association with blood transcriptional profiles. By characterizing paired longitudinal samples collected before and after deworming treatment, we determined that changes in serum zinc …

The Shift Of Obesity Burden By Socioeconomic Status Between 1998 And 2017 In Latin America And The Caribbean: A Cross-Sectional Series Study, Safia S Jiwani, Rodrigo M Carrillo-Larco, Akram Hernández-Vásquez, Tonatiuh Barrientos-Gutiérrez, Ana Basto-Abreu, Laura Gutierrez, Vilma Irazola, Ramfis Nieto-Martínez, Bruno P Nunes, Diana C Parra, J Jaime Miranda

Open Access Publications

BACKGROUND: The burden of obesity differs by socioeconomic status. We aimed to characterise the prevalence of obesity among adult men and women in Latin America and the Caribbean by socioeconomic measures and the shifting obesity burden over time.

METHODS: We did a cross-sectional series analysis of obesity prevalence by socioeconomic status by use of national health surveys done between 1998 and 2017 in 13 countries in Latin America and the Caribbean. We generated equiplots to display inequalities in, the primary outcome, obesity by wealth, education, and residence area. We measured obesity gaps as the difference in percentage points between the …

Early Surgical Intervention Among Patients With Acute Central Cord Syndrome Is Not Associated With Higher Mortality And Morbidity, Jakub Godzik, Jonathan Dalton, Courtney Hemphill, Corey Walker, Kristina Chapple, Alan Cook, Juan S. Uribe, Jay D. Turner

Open Access Publications

Background: Conflicting reports exist regarding mortality and morbidity of early surgical decompression in the setting of acute central cord syndrome (ACS) in multisystem trauma despite evidence of improved neurological outcomes. Consequently, optimal decompression timing in ACS in multisystem trauma patients remains controversial. This study aims to determine the association between early surgery for acute traumatic central cord and all-cause mortality among multisystem trauma patients in the National Trauma Data Bank (NTDB) using propensity score matching.

Methods: We used the NTDB (years 2011-2014) to perform a retrospective cohort study, which included patients >18 years, with ACS (identified using ICD-9 coding). Collected …

Successful Left Gonadal Vein To Inferior Vena Cava Bypass For Symptomatic May-Thurner Syndrome, Martha M O Mcgilvray, Joshua Balderman, Senthil N Jayarajan

Open Access Publications

We report the management of symptomatic May-Thurner syndrome refractory to endovascular techniques with left gonadal vein to inferior vena cava bypass. The patient's presentation was exceptional-a young individual with end-stage renal disease status post four failed kidney transplants, dwindling options for dialysis access, and an unusable left thigh arteriovenous graft owing to severe lower extremity edema secondary to common iliac vein compression. Postoperatively, swelling was markedly alleviated and the thigh graft was functional. Discussed are endovascular and venous bypass techniques for management of May-Thurner-associated lesions, as well as approaches to end-stage hemodialysis access salvage.

Reproducibility Of Cognitive Endpoints In Clinical Trials: Lessons From Neurofibromatosis Type 1, Jonathan M Payne, David H Gutmann, Et Al

Open Access Publications

OBJECTIVE: Rapid developments in understanding the molecular mechanisms underlying cognitive deficits in neurodevelopmental disorders have increased expectations for targeted, mechanism-based treatments. However, translation from preclinical models to human clinical trials has proven challenging. Poor reproducibility of cognitive endpoints may provide one explanation for this finding. We examined the suitability of cognitive outcomes for clinical trials in children with neurofibromatosis type 1 (NF1) by examining test-retest reliability of the measures and the application of data reduction techniques to improve reproducibility.

METHODS: Data were analyzed from the STARS clinical trial (n = 146), a multi-center double-blind placebo-controlled phase II trial of lovastatin, …

Evaluation Of Oxacillin And Cefoxitin Disk Diffusion And Microbroth Dilution Methods For Detecting Meca-Mediated Β-Lactam Resistance In Contemporary Staphylococcus Epidermidis Isolates, Samia N Naccache, Katrina Callan, Carey-Ann D. Burnham, Meghan A Wallace, Lars F Westblade, Jennifer Dien Bard, Staphylococcus Ad Hoc Working Group Of The Clsi Antimicrobial Susceptibility Testing Subcommittee

Open Access Publications

Methicillin (β-lactam) resistance in

Validity And Reliability Of Telephone Administration Of The Patient-Specific Functional Scale For The Assessment Of Recovery From Snakebite Envenomation, Rebecca G. Theophanous, Michael E. Mullins, Et Al.

Open Access Publications

OBJECTIVES: Although more than 1.8 million people survive snakebite envenomation each year, their recovery is understudied. Obtaining long-term follow-up is challenging in both high- and low-resource settings. The Patient-Specific Functional Scale (PSFS) is an easily administered, well-accepted patient-reported outcome that is validated for assessing limb recovery from snakebite envenomation. We studied whether the PSFS is valid and reliable when administered by telephone.

METHODS: This is a secondary analysis of data from a randomized clinical trial. We analyzed the results of PSFS collected in-person on days 3, 7, 14, 21, and 28 and by telephone on days 10, 17, and 24. …

Telemedicine Infectious Diseases Consultations And Clinical Outcomes: A Systematic Review, Jason P. Burnham, Stephanie A. Fritz, Lauren H. Yaeger, Graham A. Colditz

Open Access Publications

Background: Telemedicine use is increasing in many specialties, but its impact on clinical outcomes in infectious diseases has not been systematically reviewed. We reviewed the current evidence for clinical effectiveness of telemedicine infectious diseases consultations, including outcomes of mortality, hospital readmission, antimicrobial use, cost, length of stay, adherence, and patient satisfaction.

Methods: We queried Ovid MEDLINE 1946-, Embase.com 1947-, Scopus 1823-, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov 1997- through August 5, 2019, for studies looking at clinical outcomes of infectious diseases in the setting of telemedicine use. We did not restrict …

Volvulus Of The Ileal Pouch-Anal Anastomosis: A Meta-Narrative Systematic Review Of Frequency, Diagnosis, And Treatment Outcomes, Muhammad Jawoosh, Samir Haffar, Parakkal Deepak, Alyssa Meyers, Amy L. Lightner, David W. Larson, Laura H. Raffals, M Hassan Murad, Navtej Buttar, Fateh Bazerbachi

Open Access Publications

Background: Proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical procedure of choice for medically refractory ulcerative colitis and familial adenomatous polyposis. While rare, a pouch volvulus can occur. We aimed to determine the frequency, presentation, and management approach of pouch volvulus in patients with IPAA.

Methods: A systematic search of published literature was performed by a medical reference librarian on 10 August 2018 and two independent reviewers identified relevant publications, extracted data, and assessed the methodological quality based on a validated tool. A retrospective review of the Mayo Clinic electronic medical records identified one case of pouch volvulus between …

Executive Task-Based Brain Function In Children With Type 1 Diabetes: An Observational Study, Lara C. Foland-Ross, Bruce Buckingam, Nelly Mauras, Ana Maria Arbelaez, William V. Tamborlane, Eva Tsalikian, Allison Cato, Gabby Tong, Kimberly Englert, Paul K. Mazaika, Allan L. Reiss, Diabetes Research In Children Network (Direcnet)

Open Access Publications

BACKGROUND: Optimal glycemic control is particularly difficult to achieve in children and adolescents with type 1 diabetes (T1D), yet the influence of dysglycemia on the developing brain remains poorly understood.

METHODS AND FINDINGS: Using a large multi-site study framework, we investigated activation patterns using functional magnetic resonance imaging (fMRI) in 93 children with T1D (mean age 11.5 ± 1.8 years; 45.2% female) and 57 non-diabetic (control) children (mean age 11.8 ± 1.5 years; 50.9% female) as they performed an executive function paradigm, the go/no-go task. Children underwent scanning and cognitive and clinical assessment at 1 of 5 different sites. Group …

Online And Clicker Quizzing On Jargon Terms Enhances Definition-Focused But Not Conceptually Focused Biology Exam Performance, Steven C. Pan, James Cooke, Jeri L. Little, Mark A. Mcdaniel, Erin R. Foster, Lisa Tabor Connor, Timothy C. Rickard

Open Access Publications

Mastery of jargon terms is an important part of student learning in biology and other science, technology, engineering, and mathematics domains. In two experiments, we investigated whether prelecture quizzes enhance memory for jargon terms, and whether that enhanced familiarity can facilitate learning of related concepts that are encountered during subsequent lectures and readings. Undergraduate students enrolled in neuroanatomy and physiology courses completed 10-minute low-stakes quizzes with feedback on jargon terms either online (experiment 1) or using in-class clickers (experiment 2). Quizzes occurred before conventional course instruction in which the terms were used. On exams occurring up to 12 weeks later, …

Clonal Hematopoiesis And Risk Of Acute Myeloid Leukemia, Andrew L. Young, R Spencer Tong, Brenda M. Birmann, Todd E. Druley

Open Access Publications

Nearly all adults harbor acute myeloid leukemia (AML)-related clonal hematopoietic mutations at a variant allele fraction (VAF) of ≥0.0001, yet relatively few develop hematologic malignancies. We conducted a nested analysis in the Nurses' Health Study and Health Professionals Follow-Up Study blood subcohorts, with up to 22 years of follow up to investigate associations of clonal mutations of ≥0.0001 allele frequency with future risk of AML. We identified 35 cases with AML that had pre-diagnosis peripheral blood samples and matched two controls without history of cancer per case by sex, age, and ethnicity. We conducted blinded error-corrected sequencing on all study …

Signal Regulatory Protein Alpha Initiates Cachexia Through Muscle To Adipose Tissue Crosstalk, Jiao Wu, Jiangling Dong, Daniela Verzola, Keith Hruska, Giacomo Garibotto, Zhaoyong Hu, William E Mitch, Sandhya S Thomas

Open Access Publications

BACKGROUND: Muscle wasting from chronic kidney disease (CKD) or from defective insulin signalling results in morbidity and, ultimately, mortality. We have identified an endogenous mediator of insulin resistance, signal regulatory protein alpha (SIRPα), which leads to cachexia in mice and is associated with cachexia in patients with CKD.

METHODS: We assessed insulin signalling and mechanisms causing muscle atrophy plus white adipose tissue (WAT) metabolism in mouse models of CKD or acute diabetes (streptozotocin treatment). We then examined these factors in mice with global knockout (KO) of SIRPα and sought mediators of metabolic responses in muscle and adipose tissues of mice …

Sengstaken-Blakemore Tube As A Rescue Treatment For Hemorrhagic Shock Secondary To Laparoscopic Adjustable Gastric Banding Erosion, Gretchen Evans, J Christopher Eagon, Vladimir Kushnir

Open Access Publications

Gastrointestinal bleeding is an uncommon but potentially life-threatening complication of laparoscopic adjustable gastric banding (LAGB) erosion. We present the use of a Sengstaken-Blakemore tube as a treatment device for severe gastrointestinal bleeding secondary to persistent LAGB erosion. A 72-year-old woman post-LAGB placement presented with hemorrhagic shock from gastric band erosion that was not responsive to endoscopic and angiographic interventions. A salvage attempt to tamponade with a Sengstaken-Blakemore tube resulted in successful resuscitation of the patient. When used judiciously, balloon tamponade serves as a replicable technique to control severe gastric band erosion refractory to standard management.

Nonlinear Z-Score Modeling For Improved Detection Of Cognitive Abnormality, John Kornak, Nupur Ghoshal, Lynne Jones, Et Al

Open Access Publications

Introduction: Conventional Z-scores are generated by subtracting the mean and dividing by the standard deviation. More recent methods linearly correct for age, sex, and education, so that these "adjusted" Z-scores better represent whether an individual's cognitive performance is abnormal. Extreme negative Z-scores for individuals relative to this normative distribution are considered indicative of cognitive deficiency.

Methods: In this article, we consider nonlinear shape constrained additive models accounting for age, sex, and education (correcting for nonlinearity). Additional shape constrained additive models account for varying standard deviation of the cognitive scores with age (correcting for heterogeneity of variance).

Results: Corrected Z-scores based …

Standard Operating Procedure For Curation And Clinical Interpretation Of Variants In Cancer, Arpad M Danos, Kilannin Krysiak, Erica K Barnell, Adam C Coffman, Joshua F Mcmichael, Susanna Kiwala, Nicholas C Spies, Lana M Sheta, Shahil P Pema, Lynzey Kujan, Kaitlin A Clark, Amber Z Wollam, Alex H Wagner, Malachi Griffith, Obi L Griffith, Et Al

Open Access Publications

Manually curated variant knowledgebases and their associated knowledge models are serving an increasingly important role in distributing and interpreting variants in cancer. These knowledgebases vary in their level of public accessibility, and the complexity of the models used to capture clinical knowledge. CIViC (Clinical Interpretation of Variants in Cancer - www.civicdb.org) is a fully open, free-to-use cancer variant interpretation knowledgebase that incorporates highly detailed curation of evidence obtained from peer-reviewed publications and meeting abstracts, and currently holds over 6300 Evidence Items for over 2300 variants derived from over 400 genes. CIViC has seen increased adoption by, and also undertaken collaboration …

Pd-1 Signaling Promotes Control Of Chronic Viral Infection By Restricting Type-I-Interferon-Mediated Tissue Damage, Saravanan Raju, Daniel J Verbaro, Takeshi Egawa

Open Access Publications

Immune responses are essential for pathogen elimination but also cause tissue damage, leading to disease or death. However, it is unclear how the host immune system balances control of infection and protection from the collateral tissue damage. Here, we show that PD-1-mediated restriction of immune responses is essential for durable control of chronic LCMV infection in mice. In contrast to responses in the chronic phase, PD-1 blockade in the subacute phase of infection paradoxically results in viral persistence. This effect is associated with damage to lymphoid architecture and subsequently decreases adaptive immune responses. Moreover, this tissue damage is type I …

Mutations In Lamb2 Are Associated With Albuminuria And Optic Nerve Hypoplasia With Hypopituitarism, Mona Tahoun, Jennifer C Chandler, Emma Ashton, Scott Haston, Athia Hannan, Ji Soo Kim, Felipe D'Arco, D Bockenhauer, G Anderson, Meei-Hua Lin, Salah Marzouk, Marwa H Saied, Jeffrey H Miner, Mehul T Dattani, Aoife M Waters

Open Access Publications

CONTEXT: Mutations in LAMB2, encoding the basement membrane protein, laminin β2, are associated with an autosomal recessive disorder characterized by congenital nephrotic syndrome, ocular abnormalities, and neurodevelopmental delay (Pierson syndrome).

CASE DESCRIPTION: This report describes a 12-year-old boy with short stature, visual impairment, and developmental delay who presented with macroscopic hematuria and albuminuria. He had isolated growth hormone deficiency, optic nerve hypoplasia, and a small anterior pituitary with corpus callosum dysgenesis on his cranial magnetic resonance imaging, thereby supporting a diagnosis of optic nerve hypoplasia syndrome. Renal histopathology revealed focal segmental glomerulosclerosis. Using next-generation sequencing on a targeted gene panel …

Entry By Multiple Picornaviruses Is Dependent On A Pathway That Includes Tnk2, Wasl, And Nck1, Hongbing Jiang, Christian Leung, Stephen Tahan, David Wang

Open Access Publications

Comprehensive knowledge of the host factors required for picornavirus infection would facilitate antiviral development. Here we demonstrate roles for three human genes,

Three Genetic-Environmental Networks For Human Personality, Igor Zwir, Coral Del-Val, Dragan M Svrakic, Nigel Lester, Sandor Rozsa, Maribel Martinez, Daniel Mamah, C Charles Gu, C Robert Cloninger, Et Al

Open Access Publications

Phylogenetic, developmental, and brain-imaging studies suggest that human personality is the integrated expression of three major systems of learning and memory that regulate (1) associative conditioning, (2) intentionality, and (3) self-awareness. We have uncovered largely disjoint sets of genes regulating these dissociable learning processes in different clusters of people with (1) unregulated temperament profiles (i.e., associatively conditioned habits and emotional reactivity), (2) organized character profiles (i.e., intentional self-control of emotional conflicts and goals), and (3) creative character profiles (i.e., self-aware appraisal of values and theories), respectively. However, little is known about how these temperament and character components of personality are …

Metabolism Of Non-Enzymatically Derived Oxysterols: Clues From Sterol Metabolic Disorders, William J Griffiths, Eylan Yutuc, Jonas Abdel-Khalik, Peter J Crick, Thomas Hearn, Alison Dickson, Brian W Bigger, Teresa Hoi-Yee Wu, Anu Goenka, Arunabha Ghosh, Simon A. Jones, Douglas F Covey, Daniel S Ory, Yuqin Wang

Open Access Publications

Cholestane-3β,5α,6β-triol (3β,5α,6β-triol) is formed from cholestan-5,6-epoxide (5,6-EC) in a reaction catalysed by cholesterol epoxide hydrolase, following formation of 5,6-EC through free radical oxidation of cholesterol. 7-Oxocholesterol (7-OC) and 7β-hydroxycholesterol (7β-HC) can also be formed by free radical oxidation of cholesterol. Here we investigate how 3β,5α,6β-triol, 7-OC and 7β-HC are metabolised to bile acids. We show, by monitoring oxysterol metabolites in plasma samples rich in 3β,5α,6β-triol, 7-OC and 7β-HC, that these three oxysterols fall into novel branches of the acidic pathway of bile acid biosynthesis becoming (25R)26-hydroxylated then carboxylated, 24-hydroxylated and side-chain shortened to give the final products 3β,5α,6β-trihydroxycholanoic, 3β-hydroxy-7-oxochol-5-enoic and …

The Impact Of Systemic Precision Medicine And Immunotherapy Treatments On Brain Metastases, Rowland H. Han, Gavin P. Dunn, Milan G. Chheda, Albert H. Kim

Open Access Publications

Metastases from melanoma, lung and breast cancer are among the most common causes of intracranial malignancy. Standard of care for brain metastases include a combination of surgical resection, stereotactic radiosurgery, and whole-brain radiation. However, evidence continues to accumulate regarding the efficacy of molecularly-targeted systemic treatments and immunotherapy. For non-small cell lung cancer (NSCLC), numerous clinical trials have demonstrated intracranial activity for inhibitors of EGFR and ALK. Patients with melanoma brain metastases may benefit from systemic therapy using BRAF-inhibitors with and without trametinib. Several targeted options are available for breast cancer brain metastases that overexpress HER2, although agents with intracranial activity …

Gut Microbiota: From The Forgotten Organ To A Potential Key Player In The Pathology Of Alzheimer's Disease, Dong-Oh Seo, David M Holtzman

Open Access Publications

More than 300 years ago, Antony van Leewenhoeck first described observing single-celled microorganisms, which he termed "animalcules," examining his saliva under a microscope. Although the idea of the coexistence of microorganisms in our body is not new, we have only recently been able to investigate their ecological relationship to our body, with the development of high-throughput molecular techniques. The diverse microorganism communities residing in our guts are established and maintained by complex interactions among microorganisms and their host. Notably, their alteration has been implicated in influencing various diseases including neurological diseases. Alzheimer's disease (AD) is the most common cause of …

Associations Of Race And Ethnicity With Risk Of Developing Invasive Breast Cancer After Lobular Carcinoma In Situ, Vanessa Dania, Ying Liu, Foluso Ademuyiwa, Jason D Weber, Graham A Colditz

Open Access Publications

BACKGROUND: Lobular carcinoma in situ (LCIS) of the breast is a risk factor of developing invasive breast cancer. We evaluated the racial differences in the risks of subsequent invasive breast cancer following LCIS.

METHODS: We utilized data from the Surveillance, Epidemiology, and End Results registries to identify 18,835 women diagnosed with LCIS from 1990 to 2015. Cox proportional hazards regression was used to estimate race/ethnicity-associated hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of subsequent invasive breast cancer.

RESULTS: During a median follow-up of 90 months, 1567 patients developed invasive breast cancer. The 10-year incidence was 7.9% for Asians, …

Direct Binding Of Phosphatidylglycerol At Specific Sites Modulates Desensitization Of A Ligand-Gated Ion Channel, Ailing Tong, John T. Petroff Ii, Fong-Fu Hsu, Philipp A.M. Schmidpeter, Crina M. Nimigean, Liam Sharp, Grace Brannigan, Wayland W.L. Cheng

Open Access Publications

Pentameric ligand-gated ion channels (pLGICs) are essential determinants of synaptic transmission, and are modulated by specific lipids including anionic phospholipids. The exact modulatory effect of anionic phospholipids in pLGICs and the mechanism of this effect are not well understood. Using native mass spectrometry, coarse-grained molecular dynamics simulations and functional assays, we show that the anionic phospholipid, 1-palmitoyl-2-oleoyl phosphatidylglycerol (POPG), preferentially binds to and stabilizes the pLGIC, Erwinia ligand-gated ion channel (ELIC), and decreases ELIC desensitization. Mutations of five arginines located in the interfacial regions of the transmembrane domain (TMD) reduce POPG binding, and a subset of these mutations increase ELIC …

Long-Term Culture Captures Injury-Repair Cycles Of Colonic Stem Cells, Yi Wang, I-Ling Chiang, Takahiro E Ohara, Satoru Fujii, Jiye Cheng, Brian D Muegge, Aaron Ver Heul, Nathan D Han, Qiuhe Lu, Shanshan Xiong, Feidi Chen, Chin-Wen Lai, Hana Janova, Renee Wu, Charles E Whitehurst, Kelli L Vandussen, Ta-Chiang Liu, Jeffrey I Gordon, L David Sibley, Thaddeus S Stappenbeck

Open Access Publications

The colonic epithelium can undergo multiple rounds of damage and repair, often in response to excessive inflammation. The responsive stem cell that mediates this process is unclear, in part because of a lack of in vitro models that recapitulate key epithelial changes that occur in vivo during damage and repair. Here, we identify a Hopx