Medicine and Health Sciences Commons^™

The Serotonin Receptor 3e Variant Is A Risk Factor For Female Ibs-D, Nikola Fritz, Gregory Sayuk, Et Al.

2020-Current year OA Pubs

Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT

Dose-Dependent Seizure Control With Mek Inhibitor Therapy For Progressive Glioma In A Child With Neurofibromatosis Type 1, Evan Cantor, Ashley Meyer, Stephanie M Morris, Judith L Z Weisenberg, Nicole M Brossier

2020-Current year OA Pubs

BACKGROUND: Low-grade gliomas (LGGs) occurring in children can result in many different neurologic complications, including seizures. MEK inhibitors are increasingly being used to treat LGG, but their effect on associated neurologic symptoms has not been established.

RESULTS: Here, we report a patient with neurofibromatosis type 1 (NF1), medically refractory epilepsy (MRE), and an extensive optic pathway glioma (OPG) who developed dose-dependent seizure control while being treated with selumetinib. Seizure frequency rebounded after dose reduction for cardiac toxicity, then improved, and finally ceased after restarting full dosing, allowing confidence in the cause of improvement.

CONCLUSION: Selumetinib may have promise in epilepsy …

Loneliness, Social Isolation, And Social Support In Older Adults With Active Cancer During The Covid-19 Pandemic, Katherine Clifton, Feng Gao, Joann Jabbari, Mary Van Aman, Patricia Dulle, Janice Hanson, Tanya M Wildes

2020-Current year OA Pubs

INTRODUCTION: The COVID-19 pandemic has had a considerable impact on mental health. The social distancing and stay-at-home orders have likely also impacted loneliness, social isolation, and social support. Older adults, particularly those with comorbidities such as cancer, have a greater potential to be impacted. Here we assessed loneliness, social isolation, and social support in older adults undergoing active cancer treatment during the pandemic.

MATERIALS AND METHODS: A mixed methods study in which quantitative data and qualitative response items were collected in parallel was conducted in 100 older adults with cancer. Participants completed a survey by telephone with a series of …

Genome-Wide Meta-Analysis For Alzheimer's Disease Cerebrospinal Fluid Biomarkers, Iris E Jansen, Muhammad Ali, Yun Ju Sung, Carlos Cruchaga, Duber Gomez-Fonseca, Et Al.

2020-Current year OA Pubs

Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for …

Implementation Of An Electronic, Secure, Web-Based Application To Support Routine Hand Hygiene Observation With Immediate Direct Feedback And Anonymized Benchmarking, Simon Simonet, Jonas Marschall, Rolf Kuhn, Matthias Schlegel, Christian R Kahlert

2020-Current year OA Pubs

A secure web-based electronic tool was developed and implemented to record adherence to hand hygiene during routine care and to provide direct feedback including anonymized benchmarking. It was found suitable for documenting hand hygiene improvements in a local campaign and following rollout to other institutions in 2013, the tool is currently used in >100 hospitals in Switzerland and will play a major part in upcoming national hand hygiene campaigns.

Covariance-Based Vs. Correlation-Based Functional Connectivity Dissociates Healthy Aging From Alzheimer Disease, Jeremy F. Strain, Matthew R. Brier, Aaron Tanenbaum, Brian A. Gordon, John E. Mccarthy, Aylin Dincer, Daniel S. Marcus, Richard J. Perrin, John C. Morris, Tammie L. S. Benzinger, Randall J. Bateman, Beau M. Ances, Abraham Z. Snyder, Et Al.

2020-Current year OA Pubs

Prior studies of aging and Alzheimer disease have evaluated resting state functional connectivity (FC) using either seed-based correlation (SBC) or independent component analysis (ICA), with a focus on particular functional systems. SBC and ICA both are insensitive to differences in signal amplitude. At the same time, accumulating evidence indicates that the amplitude of spontaneous BOLD signal fluctuations is physiologically meaningful. We systematically compared covariance-based FC, which is sensitive to amplitude, vs. correlation-based FC, which is not, in affected individuals and controls drawn from two cohorts of participants including autosomal dominant Alzheimer disease (ADAD), late onset Alzheimer disease (LOAD), and age-matched …

A Comparison Of Methods To Harmonize Cortical Thickness Measurements Across Scanners And Sites, Delin Sun, Evan Gordon, Et Al.

2020-Current year OA Pubs

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants' demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LME

Quantification Of Sulcal Emergence Timing And Its Variability In Early Fetal Life: Hemispheric Asymmetry And Sex Difference, Hyuk Jin Yun, Hyun Ju Lee, Joo Young Lee, Tomo Tarui, Caitlin K. Rollins, Cynthia M. Ortinau, Henry A. Feldman, P. Ellen Grant, Kiho Im

2020-Current year OA Pubs

Human fetal brains show regionally different temporal patterns of sulcal emergence following a regular timeline, which may be associated with spatiotemporal patterns of gene expression among cortical regions. This study aims to quantify the timing of sulcal emergence and its temporal variability across typically developing fetuses by fitting a logistic curve to presence or absence of sulcus. We found that the sulcal emergence started from the central to the temporo-parieto-occipital lobes and frontal lobe, and the temporal variability of emergence in most of the sulci was similar between 1 and 2 weeks. Small variability (< 1 week) was found in the left central and postcentral sulci and larger variability (>2 weeks) was shown in …

Trim-Nhl Protein, Nhl-2, Modulates Cell Fate Choices In The C. Elegans Germ Line, John L. Brenner, Erin M. Jyo, Ariz Mohammad, Paul Fox, Vovanti Jones, Elaine Mardis, Tim Schedl, Eleanor M. Maine

2020-Current year OA Pubs

Many tissues contain multipotent stem cells that are critical for maintaining tissue function. In Caenorhabditis elegans, germline stem cells allow gamete production to continue in adulthood. In the gonad, GLP-1/Notch signaling from the distal tip cell niche to neighboring germ cells activates a complex regulatory network to maintain a stem cell population. GLP-1/Notch signaling positively regulates production of LST-1 and SYGL-1 proteins that, in turn, interact with a set of PUF/FBF proteins to positively regulate the stem cell fate. We previously described sog (suppressor of glp-1 loss of function) and teg (tumorous enhancer of glp-1 gain of function) genes that …

Facial Paresis As The First Sign In Atypical Facioscapulohumeral Muscular Dystrophy, Nneoma S. Wamkpah, John J. Chi

2020-Current year OA Pubs

No abstract provided.

Comparison Of Plasma And Csf Biomarkers In Predicting Cognitive Decline, Andrew J Aschenbrenner, Yan Li, Rachel L Henson, Katherine Volluz, Jason Hassenstab, Philip Verghese, Tim West, Matthew R Meyer, Kristopher M Kirmess, Anne M Fagan, Chengjie Xiong, David Holtzman, John C Morris, Randall J Bateman, Suzanne E Schindler

2020-Current year OA Pubs

OBJECTIVES: Concentrations of amyloid-β peptides (Aβ42/Aβ40) and neurofilament light (NfL) can be measured in plasma or cerebrospinal fluid (CSF) and are associated with Alzheimer's disease brain pathology and cognitive impairment. This study directly compared plasma and CSF measures of Aβ42/Aβ40 and NfL as predictors of cognitive decline.

METHODS: Participants were 65 years or older and cognitively normal at baseline with at least one follow-up cognitive assessment. Analytes were measured with the following types of assays: plasma Aβ42/Aβ40, immunoprecipitation-mass spectrometry; plasma NfL, Simoa; CSF Aβ42/Aβ40, automated immunoassay; CSF NfL plate-based immunoassay. Mixed effects models evaluated the global cognitive composite score over …

Herpes Simplex Virus And Rates Of Cognitive Decline Or Whole Brain Atrophy In The Dominantly Inherited Alzheimer Network, Charlotte Warren-Gash, Brian A Gordon, Eric Mcdade, Randall J Bateman, John C Morris, Et Al.

2020-Current year OA Pubs

OBJECTIVE: To investigate whether herpes simplex virus type 1 (HSV-1) infection was associated with rates of cognitive decline or whole brain atrophy among individuals from the Dominantly Inherited Alzheimer Network (DIAN).

METHODS: Among two subsets of the DIAN cohort (age range 19.6-66.6 years; median follow-up 3.0 years) we examined (i) rate of cognitive decline (N = 164) using change in mini-mental state examination (MMSE) score, (ii) rate of whole brain atrophy (N = 149), derived from serial MR imaging, calculated using the boundary shift integral (BSI) method. HSV-1 antibodies were assayed in baseline sera collected from 2009-2015. Linear mixed-effects models …

Accounting For The Growth Of Observation Stays In The Assessment Of Medicare's Hospital Readmissions Reduction Program, Amber K Sabbatini, Karen E Joynt-Maddox, Joshua M Liao, Anirban Basu, Canada Parrish, William Kreuter, Brad Wright

2020-Current year OA Pubs

IMPORTANCE: Decreases in 30-day readmissions following the implementation of the Medicare Hospital Readmissions Reduction Program (HRRP) have occurred against the backdrop of increasing hospital observation stay use, yet observation stays are not captured in readmission measures.

OBJECTIVE: To examine whether the HRRP was associated with decreases in 30-day readmissions after accounting for observation stays.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included a 20% sample of inpatient admissions and observation stays among Medicare fee-for-service beneficiaries from January 1, 2009, to December 31, 2015. Data analysis was performed from November 2021 to June 2022. A differences-in-differences analysis assessed changes in …

Association Of Noncontrast Computed Tomography And Perfusion Modalities With Outcomes In Patients Undergoing Late-Window Stroke Thrombectomy, Guilherme B F Porto, Joshua Osbun, Et Al.

2020-Current year OA Pubs

IMPORTANCE: There is substantial controversy with regards to the adequacy and use of noncontrast head computed tomography (NCCT) for late-window acute ischemic stroke in selecting candidates for mechanical thrombectomy.

OBJECTIVE: To assess clinical outcomes of patients with acute ischemic stroke presenting in the late window who underwent mechanical thrombectomy stratified by NCCT admission in comparison with selection by CT perfusion (CTP) and diffusion-weighted imaging (DWI).

DESIGN, SETTING, AND PARTICIPANTS: In this multicenter retrospective cohort study, prospectively maintained Stroke Thrombectomy and Aneurysm (STAR) database was used by selecting patients within the late window of acute ischemic stroke and emergent large vessel …

Upper Limb Nerve Transfer Surgery In Patients With Tetraplegia, Saad Javeed, Christopher F Dibble, Jacob K Greenberg, Justin K Zhang, Jawad M Khalifeh, Yikyung Park, Thomas J Wilson, Eric L Zager, Amir H Faraji, Mark A Mahan, Lynda J Yang, Rajiv Midha, Neringa Juknis, Wilson Z Ray

2020-Current year OA Pubs

IMPORTANCE: Cervical spinal cord injury (SCI) causes devastating loss of upper extremity function and independence. Nerve transfers are a promising approach to reanimate upper limbs; however, there remains a paucity of high-quality evidence supporting a clinical benefit for patients with tetraplegia.

OBJECTIVE: To evaluate the clinical utility of nerve transfers for reanimation of upper limb function in tetraplegia.

DESIGN, SETTING, AND PARTICIPANTS: In this prospective case series, adults with cervical SCI and upper extremity paralysis whose recovery plateaued were enrolled between September 1, 2015, and January 31, 2019. Data analysis was performed from August 2021 to February 2022.

INTERVENTIONS: Nerve …

Quantitative Tumor Depth Determination Using Dual Wavelength Excitation Fluorescence, Christine M. O'Brien, Kevin W. Bishop, Haini Zhang, Xiao Xu, Leo Shmuylovich, Elizabeth Conley, Karen Nwosu, Kathleen Duncan, Suman B. Mondal, Gail Sudlow

2020-Current year OA Pubs

No abstract provided.

Self-Care Management Of Bothersome Symptoms As Recommended By Clinicians For Patients With A Chronic Condition: A Delphi Study, Heleen Westland, Shayleigh Dickson Page, Michelle Van Rijn, Subhash Aryal, Kenneth E Freedland, Christopher Lee, Anna Strömberg, Ercole Vellone, Douglas J Wiebe, Tiny Jaarsma, Barbara Riegel

2020-Current year OA Pubs

BACKGROUND: Chronically medically ill patients often need clinical assistance with symptom management, as well as self-care interventions that can help to reduce the impact of bothersome symptoms. Experienced clinicians can help to guide the development of more effective self-care interventions.

OBJECTIVE: To create a consensus-based list of common bothersome symptoms of chronic conditions and of self-care management behaviors recommended to patients by clinicians to reduce the impact of these symptoms.

METHODS: A two-round Delphi study was performed among an international panel of 47 clinicians using online surveys to identify common and bothersome symptoms and related self-care management behaviors recommended to …

Guidance For The Diagnosis And Treatment Of Hypolipidemia Disorders, Cindy Bredefeld, Nicholas O Davidson, Et Al.

2020-Current year OA Pubs

The Abetalipoproteinemia and Related Disorders Foundation was established in 2019 to provide guidance and support for the life-long management of inherited hypocholesterolemia disorders. Our mission is "to improve the lives of individuals and families affected by abetalipoproteinemia and related disorders". This review explains the molecular mechanisms behind the monogenic hypobetalipoproteinemia disorders and details their specific pathophysiology, clinical presentation and management throughout the lifespan. In this review, we focus on abetalipoproteinemia, homozygous hypobetalipoproteinemia and chylomicron retention disease; rare genetic conditions that manifest early in life and cause severe complications without appropriate treatment. Absent to low plasma lipid levels, in particular cholesterol …

Engineering Diverse Fatty Acid Compositions Of Phospholipids In Escherichia Coli, Wenqin Bai, Winston E Anthony, Christopher J Hartline, Shaojie Wang, Bin Wang, Jie Ning, Fong-Fu Hsu, Gautam Dantas, Fuzhong Zhang

2020-Current year OA Pubs

Bacterial fatty acids (FAs) are an essential component of the cellular membrane and are an important source of renewable chemicals as they can be converted to fatty alcohols, esters, ketones, and alkanes, and used as biofuels, detergents, lubricants, and commodity chemicals. Most prior FA bioconversions have been performed on the carboxylic acid group. Modification of the FA hydrocarbon chain could substantially expand the structural and functional diversity of FA-derived products. Additionally, the effects of such modified FAs on the growth and metabolic state of their producing cells are not well understood. Here we engineer novel Escherichia coli phospholipid biosynthetic pathways, …

International Consensus Guidelines For Adjuvant Radiation Therapy For Bladder Cancer After Radical Cystectomy: Update From An Ibis Workgroup, Flor Verghote, Paul Sargos, John P Christodouleas, Vedang Murthy, Brian C Baumann, Piet Dirix, Charlien Berghen, Leen Paelinck, Tom Vercauteren, Valérie Fonteyne

2020-Current year OA Pubs

PURPOSE: In 2016, international consensus clinical target volume (CTV) guidelines for adjuvant radiation treatment after radical cystectomy in patients with muscle-invasive bladder cancer with high risk for locoregional failure (LRF) were published. A subsequent external validation study recommended several CTV optimizations (CTV-OPT). This study aimed to update international consensus guidelines based on new clinical experiences.

METHODS AND MATERIALS: Phase 1 (delineation interobserver variability): Four observers delineated the CTV of 9 patients post radical cystectomy, as in clinical practice. Interobserver agreement in contouring was evaluated using volume- and κ-statistics. Phase 2 (pattern of failure analysis): Among a prospective cohort of 72 …

Inositol Phosphorylceramide Synthase Null Leishmania Are Viable And Virulent In Animal Infections Where Salvage Of Host Sphingomyelin Predominates, F Matthew Kuhlmann, Phillip N Key, Suzanne M Hickerson, John Turk, Fong-Fu Hsu, Stephen M Beverley

2020-Current year OA Pubs

Many pathogens synthesize inositol phosphorylceramide (IPC) as the major sphingolipid (SL), differing from the mammalian host where sphingomyelin (SM) or more complex SLs predominate. The divergence between IPC synthase and mammalian SL synthases has prompted interest as a potential drug target. However, in the trypanosomatid protozoan Leishmania, cultured insect stage promastigotes lack de novo SL synthesis (Δspt2

The Programmed Death-1 Signaling Axis Modulates Inflammation And Lv Structure/Function In A Stress-Induced Cardiomyopathy Model, Tomohiro Hayashi, Sajal K Tiwary, Kory J Lavine, Sandeep Acharya, Michael Brent, Luigi Adamo, Attila Kovacs, Douglas L Mann

2020-Current year OA Pubs

The role of immune checkpoints in the setting of tissue injury remains unknown. Using an experimental model of isoproterenol (ISO)-induced stress cardiomyopathy, we show that ISO-induced myocardial injury provokes tissue-autonomous up-regulation of the programmed death-1 (PD-1):programmed death ligand (PD-L) axis in cardiac resident innate immune cells and T cells. PD-1 signaling was responsible for modulating the acute inflammatory response, as well as normalization of impaired left ventricular structure and function after ISO injection. Necrotic cardiac extracts were sufficient to increase the expression of PD-1 in macrophages and T cells in vitro. Viewed together these studies suggest that the PD-1:PD-L signaling …

Peroxisomal Regulation Of Energy Homeostasis: Effect On Obesity And Related Metabolic Disorders, Brian Kleiboeker, Irfan J Lodhi

2020-Current year OA Pubs

BACKGROUND: Peroxisomes are single membrane-bound organelles named for their role in hydrogen peroxide production and catabolism. However, their cellular functions extend well beyond reactive oxygen species (ROS) metabolism and include fatty acid oxidation of unique substrates that cannot be catabolized in mitochondria, and synthesis of ether lipids and bile acids. Metabolic functions of peroxisomes involve crosstalk with other organelles, including mitochondria, endoplasmic reticulum, lipid droplets and lysosomes. Emerging studies suggest that peroxisomes are important regulators of energy homeostasis and that disruption of peroxisomal functions influences the risk for obesity and the associated metabolic disorders, including type 2 diabetes and hepatic …

A Phase I First-In-Human Study Of Abbv-383, A B-Cell Maturation Antigen × Cd3 Bispecific T-Cell Redirecting Antibody, In Patients With Relapsed/Refractory Multiple Myeloma, Anita D'Souza, Ravi Vij, Et Al.

2020-Current year OA Pubs

PURPOSE: ABBV-383, a B-cell maturation antigen × CD3 T-cell engaging bispecific antibody, has demonstrated promising results in an ongoing first-in-human phase I study (ClinicalTrials.gov identifier: NCT03933735) in patients with relapsed/refractory multiple myeloma (RRMM). Herein, we report safety and efficacy outcomes of this phase I dose escalation/expansion study.

METHODS: Patients with RRMM (≥ three prior lines including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody) were eligible. ABBV-383 was administered intravenously over 1-2 hours once every 3 weeks, without any step dosing. A 3 + 3 design with backfilling for dose escalation was used (intrapatient escalation to highest …

American Cochlear Implant Alliance Task Force Guidelines For Clinical Assessment And Management Of Adult Cochlear Implantation For Single-Sided Deafness, Margaret T. Dillon, Armine Kocharyan, Ghazal S. Daher, Matthew L. Carlson, William H. Shapiro, Hillary A. Snapp, Jill B. Firszt

2020-Current year OA Pubs

The indications for cochlear implantation have expanded to include individuals with profound sensorineural hearing loss in the impaired ear and normal hearing (NH) in the contralateral ear, known as single-sided deafness (SSD). There are additional considerations for the clinical assessment and management of adult cochlear implant candidates and recipients with SSD as compared to conventional cochlear implant candidates with bilateral moderate to profound sensorineural hearing loss. The present report reviews the current evidence relevant to the assessment and management of adults with SSD. A systematic review was also conducted on published studies that investigated outcomes of cochlear implant use on …

A Randomized Phase Ii Study Of Sm-88 Plus Methoxsalen, Phenytoin, And Sirolimus In Patients With Metastatic Pancreatic Cancer Treated In The Second Line And Beyond, Marcus S Noel, Semmie Kim, Marion L Hartley, Steve Wong, Vincent J Picozzi, Harry Staszewski, Dae Won Kim, Jan M Van Tornout, Philip Agop Philip, Vincent Chung, Allyson J Ocean, Andrea Wang-Gillam

2020-Current year OA Pubs

BACKGROUND: This trial explores SM-88 used with methoxsalen, phenytoin, and sirolimus (MPS) in pretreated metastatic pancreatic ductal adenocarcinoma (mPDAC) METHODS: Forty-nine patients were randomized to daily 460 or 920 mg oral SM-88 with MPS (SM-88 Regimen). The primary endpoint was objective response rate (RECIST 1.1).

RESULTS: Thirty-seven patients completed ≥ one cycle of SM-88 Regimen (response evaluable population). Disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) did not differ significantly between dose levels. Stable disease was achieved in 9/37 patients (DCR, 24.3%); there were no complete or partial responses. Quality-of-life (QOL) was maintained and trended in favor …

A New Mouse Model Of Charcot-Marie-Tooth 2j Neuropathy Replicates Human Axonopathy And Suggest Alteration In Axo-Glia Communication, Ghjuvan'ghjacumu Shackleford, Yo Sasaki, Et Al.

2020-Current year OA Pubs

Myelin is essential for rapid nerve impulse propagation and axon protection. Accordingly, defects in myelination or myelin maintenance lead to secondary axonal damage and subsequent degeneration. Studies utilizing genetic (CNPase-, MAG-, and PLP-null mice) and naturally occurring neuropathy models suggest that myelinating glia also support axons independently from myelin. Myelin protein zero (MPZ or P0), which is expressed only by Schwann cells, is critical for myelin formation and maintenance in the peripheral nervous system. Many mutations in MPZ are associated with demyelinating neuropathies (Charcot-Marie-Tooth disease type 1B [CMT1B]). Surprisingly, the substitution of threonine by methionine at position 124 of P0 …

Assessment Of Infectious Diseases Risks From Dental Aerosols In Real-World Settings, Shruti Choudhary, Tracey Bach, Meghan A Wallace, Daniel C Stoeckel, Martin H Thornhill, Peter B Lockhart, Jennie H Kwon, Stephen Y Liang, Carey-Ann D Burnham, Pratim Biswas, Heidi M Steinkamp, Michael J Durkin

2020-Current year OA Pubs

BACKGROUND: Infectious diseases physicians are leaders in assessing the health risks in a variety of community settings. An understudied area with substantial controversy is the safety of dental aerosols. Previous studies have used in vitro experimental designs and/or indirect measures to evaluate bacteria and viruses from dental surfaces. However, these findings may overestimate the occupational risks of dental aerosols. The purpose of this study was to directly measure dental aerosol composition to assess the health risks for dental healthcare personnel and patients.

METHODS: We used a variety of aerosol instruments to capture and measure the bacterial, viral, and inorganic composition …

Comparison Of Indirect Fungal Diagnostic Tests In Patients With Proven Histoplasmosis, Gayathri Krishnan, Margaret Power, J Ryan Bariola, Ryan Dare

2020-Current year OA Pubs

BACKGROUND: Histoplasmosis is a common cause of invasive fungal infection in endemic regions and accurate diagnosis is difficult without direct tissue culture or pathology. Indirect fungal antigen testing for various fungal pathogens are typically performed to assist with diagnostic workup, though cross-reaction can lead to difficulty in interpreting results. We aimed to compare indirect fungal diagnostic tests and evaluate prevalence of positive antigen testing for non-

METHODS: We performed a single-center retrospective review of adult patients with proven histoplasmosis diagnosed by fungal culture and/or cytology from January 2010 to March 2018. Patient demographics, clinical characteristics, and results of fungal antigen …

Profilin-1 Regulates Dna Replication Forks In A Context-Dependent Fashion By Interacting With Snf2h And Bod1l, Cuige Zhu, Mari Iwase, Ziqian Li, Faliang Wang, Annabel Quinet, Alessandro Vindigni, Jieya Shao

2020-Current year OA Pubs

DNA replication forks are tightly controlled by a large protein network consisting of well-known core regulators and many accessory factors which remain functionally undefined. In this study, we report previously unknown nuclear functions of the actin-binding factor profilin-1 (PFN1) in DNA replication, which occur in a context-dependent fashion and require its binding to poly-L-proline (PLP)-containing proteins instead of actin. In unperturbed cells, PFN1 increases DNA replication initiation and accelerates fork progression by binding and stimulating the PLP-containing nucleosome remodeler SNF2H. Under replication stress, PFN1/SNF2H increases fork stalling and functionally collaborates with fork reversal enzymes to enable the over-resection of unprotected …