Kevin P. Larsen

ORCID: 0000-0002-3464-2023
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About
Contact & Profiles
Research Areas
  • HIV Research and Treatment
  • HIV/AIDS drug development and treatment
  • RNA and protein synthesis mechanisms
  • Cellular transport and secretion
  • RNA Research and Splicing
  • DNA and Nucleic Acid Chemistry
  • RNA modifications and cancer
  • Chemical Synthesis and Analysis
  • Antimicrobial Peptides and Activities
  • Protein Structure and Dynamics
  • Calcium signaling and nucleotide metabolism
  • Lipid Membrane Structure and Behavior
  • Receptor Mechanisms and Signaling
  • Complement system in diseases
  • Lysosomal Storage Disorders Research
  • Pharmacological Receptor Mechanisms and Effects
  • COVID-19 Clinical Research Studies
  • Mosquito-borne diseases and control
  • Tryptophan and brain disorders
  • Enzyme Structure and Function
  • Academic Publishing and Open Access
  • Biochemical and Molecular Research
  • Travel-related health issues
  • Molecular spectroscopy and chirality
  • Advanced X-ray Imaging Techniques

University of California, Berkeley
2022-2024

QB3
2022-2024

Stanford University
2015-2023

Casma Therapeutics (United States)
2022

Clinica de Pneumologie Iaşi
2021

Centre Hospitalier Universitaire de La Réunion
2020-2021

Weatherford College
2021

University of Wisconsin–La Crosse
2012-2014

The endosomal sorting complex required for transport (ESCRT) machinery is centrally involved in the repair of damage to both plasma and lysosome membranes. ESCRT recruitment sites occurs on a fast time scale, Ca2+ has been proposed play key signaling role process. Here, we show that Ca2+-binding regulatory protein ALG-2 binds directly negatively charged membranes Ca2+-dependent manner. Next, by monitoring colocalization ALIX with membranes, recruits membrane. Furthermore, membrane...

10.1073/pnas.2205590119 article EN cc-by Proceedings of the National Academy of Sciences 2022-08-22

Apoptosis linked Gene-2 (ALG-2) is a multifunctional intracellular Ca 2+ sensor and the archetypal member of penta-EF hand protein family. ALG-2 functions in repair damage to both plasma lysosome membranes COPII-dependent budding at e ndoplasmic r eticulum xit s ites (ERES). In presence , binds ESCRT-I ALIX membrane SEC31A ERES. also directly acidic by combination electrostatic hydrophobic interactions. By combining giant unilamellar vesicle-based experiments molecular dynamics simulations,...

10.1073/pnas.2318046121 article EN cc-by Proceedings of the National Academy of Sciences 2024-02-22

The endosomal sorting complexes required for transport (ESCRT) system is an ancient and ubiquitous membrane scission machinery that catalyzes the budding of membranes. ESCRT-mediated events, exemplified by those involved in HIV-1, are usually directed away from cytosol ("reverse topology"), but they can also be toward ("normal topology"). ESCRT-III subunits CHMP1B IST1 coat constrict positively curved tubes, suggesting these could catalyze normal topology severing. bind recruit...

10.1073/pnas.2204536119 article EN cc-by Proceedings of the National Academy of Sciences 2022-07-11

Rough endoplasmic reticulum (ER) sheets are a fundamental domain of the ER and gateway into secretory pathway. Although reticulon proteins stabilize high-curvature tubules, it is unclear whether other scaffold flat membranes rough sheets. Through proteomics screen using sheet-localized RNA-binding as bait, we identify sigma-1 receptor (SigmaR1) an sheet-shaping factor. High-resolution live cell imaging electron tomography assign SigmaR1 factor whose levels determine amount in cells....

10.1016/j.devcel.2024.06.005 article EN cc-by Developmental Cell 2024-07-05

Reverse transcription of the HIV-1 viral RNA genome (vRNA) is an integral step in virus replication. Upon entry, reverse transcriptase (RT) initiates from a host tRNALys3 primer bound to vRNA and target key antivirals, such as non-nucleoside inhibitors (NNRTIs). Initiation proceeds slowly with discrete pausing events along template. Despite prior medium-resolution structural characterization initiation complexes (RTICs), higher-resolution structures RTIC are needed understand molecular...

10.1038/s41467-021-22628-9 article EN cc-by Nature Communications 2021-05-04

Reverse transcription is a key process in the early steps of HIV infection. This initiates within specific complex formed by 5′ UTR genomic RNA (vRNA) and host primer tRNA Lys 3 . Using nuclear magnetic resonance (NMR) spectroscopy single-molecule fluorescence spectroscopy, we detect two distinct conformers adopted tRNA/vRNA initiation complex. We directly show that an interaction between conserved 8-nucleotide viral activation signal (PAS) occurs one these conformers. intermolecular PAS...

10.1261/rna.056804.116 article EN RNA 2016-09-09

Abstract This study aimed to evaluate the incidence of co-infection with different types pathogens in patients hypoxemic pneumonia due coronavirus disease 2019 (COVID-19) Reunion Island. observational using a prospectively collected database COVID-19 cases was conducted at Félix Guyon University Hospital Island, France. Between 18 March 2020 and 15 April 2020, 156 were admitted our hospital for COVID-19. A total 36 had (23.1%) Thirty these (83.3%) imported by travelers returning mainly from...

10.1097/md.0000000000024524 article EN cc-by-nc Medicine 2021-01-29

Abstract RNA-protein assemblies carry out many critical biological functions including translation, RNA splicing, and telomere extension. Increasingly, cryo-electron microscopy (cryoEM) is used to determine the structures of these complexes, but nearly all maps determined with this method have regions in which local resolution does not permit manual coordinate tracing. Because coordinates typically cannot be by docking crystal separate components existing structure prediction algorithms yet...

10.1101/332791 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2018-05-30

The aim of this study was to evaluate the occurrence pulmonary embolism in returning travelers with hypoxemic pneumonia due COVID-19. All Reunion Island COVID-19 underwent computed tomography angiography (CTPA) and were included cohort. Thirty-five patients had recently returned from one countries most affected by outbreak (mainly France Comoros archipelago). Five (14.3%) found have two (5.9%) incidentally deep vein thrombosis on CTPA. Patients or higher D-dimer levels than those without (P...

10.4269/ajtmh.20-0597 article EN other-oa American Journal of Tropical Medicine and Hygiene 2020-07-02

This study aimed to evaluate the prognosis of COVID-19 patients in Reunion Island, with a particular focus on management hypoxemic pneumonia. retrospective observational was conducted from 11 March 17 April 2020 at only hospital authorized manage Island. Over period, 164 out 398 (41.2%) infected were admitted Félix Guyon University Hospital. Of these, 36 (22%) developed Patients pneumonia aged 66 [56–77] years, 69% male and 33% had hypertension. Ten (27.8%) hospitalized intensive care unit...

10.1016/j.jgar.2020.08.001 article EN cc-by-nc-nd Journal of Global Antimicrobial Resistance 2020-08-20

Abstract The endosomal sorting complexes required for transport (ESCRT) system is an ancient and ubiquitous membrane scission machinery that catalyzes the budding of membranes. ESCRT-mediated events, exemplified by those involved in HIV-1, are usually directed away from cytosol (‘reverse-topology’), but they can also be towards (‘normal-topology’). Of ESCRT 0-III, ESCRT-III most directly implicated severing. Various subunits recruit AAA + ATPase VPS4, which essential disassembly reverse...

10.1101/2022.02.03.479062 preprint EN cc-by-nc bioRxiv (Cold Spring Harbor Laboratory) 2022-02-04

Since 2018, a dengue epidemic has been ongoing in the French overseas department of Reunion Island, Indian Ocean, with more than 25,000 serologically confirmed cases. Currently, three serotypes have identified Réunion Island (DENV-1, DENV-2, and DENV-3) progressing form outbreaks. This arbovirus is mainly transmitted by mosquitoes genus Aedes may be responsible for serious clinical forms. To date, very few cases kidney transplant-related virus infection described. Here we report first case...

10.4269/ajtmh.21-0137 article EN American Journal of Tropical Medicine and Hygiene 2021-05-03

Conformational dynamics play essential roles in RNA function. However, detailed structural characterization of excited states remains challenging. Here, we apply high hydrostatic pressure (HP) to populate conformational tRNA Lys3 , and structurally characterize them using a combination HP 2D-NMR, HP-SAXS (HP-small-angle X-ray scattering), computational modeling. HP-NMR revealed that disrupts the interactions imino protons uridine guanosine U–A G–C base pairs . profiles showed change shape,...

10.1073/pnas.2215556120 article EN cc-by-nc-nd Proceedings of the National Academy of Sciences 2023-06-20

SUMMARY Rough ER sheets are a fundamental domain of the and gateway into secretory pathway. While reticulon proteins stabilize high-curvature tubules, it is unclear if other scaffold flat membranes rough sheets. Through proteomics screen using sheet localized RNA-binding as bait, we identify Sigma-1 receptor (SigmaR1) an shaping factor. High-resolution live cell imaging electron tomography assign SigmaR1 sheet-localized factor whose levels determine amount in cells. Structure-guided...

10.1101/2023.10.06.559866 preprint EN cc-by bioRxiv (Cold Spring Harbor Laboratory) 2023-10-06

In this work, we collected radiation-damage-free data from a set of cryo-cooled crystals for novel 30S ribosomal subunit mutant using goniometer-based femtosecond crystallography. Crystal quality assessment these samples was conducted at the X-ray Pump Probe end-station Linac Coherent Light Source (LCLS) recently introduced instrumentation. These were genetically engineered to omit 26-residue protein, Thx, which is present in wild-type Thermus thermophilus subunit. We are primarily...

10.1063/1.4919407 article EN cc-by Structural Dynamics 2015-04-30

Abstract The endosomal sorting complex required for transport (ESCRT) machinery has been shown to be centrally involved in repair of damage both the plasma and lysosome membranes. ESCRT recruitment sites occurs on a fast time scale, Ca 2+ proposed play key signaling role process. Here, we show that -binding regulatory protein ALG-2 binds directly negatively charged membranes -dependent manner. Next, by monitoring colocalization ALIX with membranes, recruits membrane. Furthermore, membrane...

10.1101/2022.03.30.486420 preprint EN cc-by-nc bioRxiv (Cold Spring Harbor Laboratory) 2022-03-30

One of Baltasar Gracián's strengths as a critic and theorist is the breadth his literary background.Not content merely to appreciate from distance traditions other than own, he has mastered their respective classics, citing in Agudeza y arte de ingenio variety passages them -in original languages-in order illustrate support own theories.In true spirit European Baroque, crosses cultural linguistic barriers, rather erecting them, thus demonstrates that poetic agudeza are by no means exclusive...

10.5070/m3101013646 article EN Mester 1981-01-01
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