Pratap Karki
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View article: A bacteriophytochrome Pr/Pfr heterodimer as obtained by single-ms TR cryo-EM
A bacteriophytochrome Pr/Pfr heterodimer as obtained by single-ms TR cryo-EM Open
Phytochromes are red/far-red light photoreceptors found across many kingdoms of life1. Upon light absorption, they reversibly interconvert between a red-absorbing Pr state and a far-red–absorbing Pfr state. Bacterial phytochromes (BphPs) r…
View article: Novel small molecule inhibitor of GPR68 attenuates endothelial dysfunction and lung injury caused by bacterial lipopolysaccharide
Novel small molecule inhibitor of GPR68 attenuates endothelial dysfunction and lung injury caused by bacterial lipopolysaccharide Open
The treatment of acute respiratory distress syndrome (ARDS) associated with high mortality remains a major global clinical challenge. Role of pulmonary endothelial dysfunction in uncontrolled lung inflammation and alveolar flooding is incr…
View article: Adrenomedullin-RAMP2 enhances endothelial cell homeostasis synergically with shear stress
Adrenomedullin-RAMP2 enhances endothelial cell homeostasis synergically with shear stress Open
Analysis of pulmonary vascular dysfunction in various lung pathologies remains challenging due to the lack of functional ex vivo models. Paracrine signaling in the lung plays a critical role in regulating endothelial maturation and vascula…
View article: Structures of myxobacterial phytochrome revealed by cryo-EM using the Spotiton technique and with x-ray crystallography
Structures of myxobacterial phytochrome revealed by cryo-EM using the Spotiton technique and with x-ray crystallography Open
Phytochromes are red-light photoreceptors first identified in plants, with homologs found in bacteria and fungi, that regulate a variety of critical physiological processes. They undergo a reversible photocycle between two distinct states:…
View article: Inhibition of proton sensor <scp>GPR68</scp> suppresses endothelial dysfunction and acute lung injury caused by <i>Staphylococcus aureus</i> bacterial particles
Inhibition of proton sensor <span>GPR68</span> suppresses endothelial dysfunction and acute lung injury caused by <i>Staphylococcus aureus</i> bacterial particles Open
Lung bacterial infections, including hospital‐acquired pneumonia, remain a serious problem for public health. Endothelial cell (EC) exposure to heat‐killed Staphylococcus aureus (HKSA) represents a clinical scenario of high titers of kille…
View article: GPR68 Mediates Lung Endothelial Dysfunction Caused by Bacterial Inflammation and Tissue Acidification
GPR68 Mediates Lung Endothelial Dysfunction Caused by Bacterial Inflammation and Tissue Acidification Open
Tissue acidification resulting from dysregulated cellular bioenergetics accompanies various inflammatory states. GPR68, along with other members of proton-sensing G protein-coupled receptors, responds to extracellular acidification and has…
View article: Exploiting fourth-generation synchrotron radiation for enzyme and photoreceptor characterization
Exploiting fourth-generation synchrotron radiation for enzyme and photoreceptor characterization Open
The upgrade of the European Synchrotron Radiation Facility (ESRF) in Grenoble, France to an Extremely Brilliant Source (EBS) is expected to enable time-resolved synchrotron serial crystallography (SSX) experiments with sub-millisecond time…
View article: Aberrant GPA expression and regulatory function of red blood cells in sickle cell disease
Aberrant GPA expression and regulatory function of red blood cells in sickle cell disease Open
Glycophorin A (GPA), a red blood cell (RBC) surface glycoprotein, can maintain peripheral blood leukocyte quiescence through interaction with a sialic acid–binding Ig-like lectin (Siglec-9). Under inflammatory conditions such as sickle cel…
View article: Steady-state modelling of PEM fuel cell for evaluation of performance.
Steady-state modelling of PEM fuel cell for evaluation of performance. Open
The influence of operating variables like temperature, pressure, humidity etc. needs to be reduced to optimize the performance of proton exchange membrane fuel cells (PEMFCs). A model that can accurately simulate the real operating conditi…
View article: Amphipathic Helical Peptide L37pA Protects against Lung Vascular Endothelial Dysfunction Caused by Truncated Oxidized Phospholipids via Antagonism with CD36 Receptor
Amphipathic Helical Peptide L37pA Protects against Lung Vascular Endothelial Dysfunction Caused by Truncated Oxidized Phospholipids via Antagonism with CD36 Receptor Open
The generation of bioactive truncated oxidized phospholipids (Tr-OxPLs) from oxidation of cell-membrane or circulating lipoproteins is a common feature of various pathological states. Scavenger receptor CD36 is involved in lipid transport …
View article: Aging-Related Accumulation of Truncated Oxidized Phospholipids Augments Infectious Lung Injury and Endothelial Dysfunction via Cluster of Differentiation 36-Dependent Mechanism
Aging-Related Accumulation of Truncated Oxidized Phospholipids Augments Infectious Lung Injury and Endothelial Dysfunction via Cluster of Differentiation 36-Dependent Mechanism Open
Truncated phospholipid oxidation products (Tr-OxPL) increase in blood circulation with aging; however, their role in the severity of vascular dysfunction and bacterial lung injury in aging groups remains poorly understood. We investigated …
View article: Truncated oxidized phospholipids exacerbate endothelial dysfunction and lung injury caused by bacterial pathogens
Truncated oxidized phospholipids exacerbate endothelial dysfunction and lung injury caused by bacterial pathogens Open
View article: Oxidized phospholipids on alkyl-amide scaffold demonstrate anti-endotoxin and endothelial barrier-protective properties
Oxidized phospholipids on alkyl-amide scaffold demonstrate anti-endotoxin and endothelial barrier-protective properties Open
View article: Circulating extracellular histones exacerbate acute lung injury by augmenting pulmonary endothelial dysfunction via TLR4-dependent mechanism
Circulating extracellular histones exacerbate acute lung injury by augmenting pulmonary endothelial dysfunction via TLR4-dependent mechanism Open
Extracellular histones released into the circulation following trauma, sepsis, and ARDS may act as potent damage-associated molecular pattern signals leading to multiple organ failure. Endothelial cell (EC) dysfunction caused by extracellu…
View article: Extracellular Proton Sensing GPR68 Mediates Acid Signaling in Development and Cancer
Extracellular Proton Sensing GPR68 Mediates Acid Signaling in Development and Cancer Open
View article: Oxidized Phospholipids in Control of Endothelial Barrier Function: Mechanisms and Implication in Lung Injury
Oxidized Phospholipids in Control of Endothelial Barrier Function: Mechanisms and Implication in Lung Injury Open
Earlier studies investigating the pathogenesis of chronic vascular inflammation associated with atherosclerosis described pro-inflammatory and vascular barrier disruptive effects of lipid oxidation products accumulated in the sites of vasc…
View article: Microtubules as Major Regulators of Endothelial Function: Implication for Lung Injury
Microtubules as Major Regulators of Endothelial Function: Implication for Lung Injury Open
Endothelial dysfunction has been attributed as one of the major complications in COVID-19 patients, a global pandemic that has already caused over 4 million deaths worldwide. The dysfunction of endothelial barrier is characterized by an in…
View article: Oxidized phospholipids on alkyl-amide scaffold demonstrate anti-endotoxin and endothelial barrier-protective properties
Oxidized phospholipids on alkyl-amide scaffold demonstrate anti-endotoxin and endothelial barrier-protective properties Open
View article: Microtubule‐dependent mechanism of anti‐inflammatory effect of SOCS1 in endothelial dysfunction and lung injury
Microtubule‐dependent mechanism of anti‐inflammatory effect of SOCS1 in endothelial dysfunction and lung injury Open
Suppressors of cytokine signaling (SOCS) provide negative regulation of inflammatory reaction. The role and precise cellular mechanisms of SOCS1 in control of endothelial dysfunction and barrier compromise associated with acute lung injury…
View article: SOCS3–microtubule interaction via CLIP-170 and CLASP2 is critical for modulation of endothelial inflammation and lung injury
SOCS3–microtubule interaction via CLIP-170 and CLASP2 is critical for modulation of endothelial inflammation and lung injury Open
Proinflammatory cytokines such as IL-6 induce endothelial cell (EC) barrier disruption and trigger an inflammatory response in part by activating the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. The pro…
View article: Extracellular histones in lung dysfunction: a new biomarker and therapeutic target?
Extracellular histones in lung dysfunction: a new biomarker and therapeutic target? Open
Extracellular histones released from injured or dying cells following trauma and other severe insults can act as potent damage‐associated molecular patterns. In fact, elevated levels of histones are present in human circulation in hyperinf…
View article: SIRT7 deficiency suppresses inflammation, induces EndoMT, and increases vascular permeability in primary pulmonary endothelial cells
SIRT7 deficiency suppresses inflammation, induces EndoMT, and increases vascular permeability in primary pulmonary endothelial cells Open
Acute lung injury (ALI), a common condition in critically ill patients, has limited treatments and high mortality. Aging is a risk factor for ALI. Sirtuins (SIRTs), central regulators of the aging process, decrease during normal aging and …
View article: Induction of Lung Endothelial Barrier Dysfunction by Serum Factors of Traumatic Brain Injury in Rat
Induction of Lung Endothelial Barrier Dysfunction by Serum Factors of Traumatic Brain Injury in Rat Open
View article: Role of Cingulin in Magnitude-Dependent Regulation of Pulmonary Endothelial Barrier Under Cyclic Stretch
Role of Cingulin in Magnitude-Dependent Regulation of Pulmonary Endothelial Barrier Under Cyclic Stretch Open
View article: Oxidized Phospholipids in Healthy and Diseased Lung Endothelium
Oxidized Phospholipids in Healthy and Diseased Lung Endothelium Open
Circulating and cell membrane phospholipids undergo oxidation caused by enzymatic and non-enzymatic mechanisms. As a result, a diverse group of bioactive oxidized phospholipids generated in these conditions have both beneficial and harmful…
View article: Rho and Reactive Oxygen Species at Crossroads of Endothelial Permeability and Inflammation
Rho and Reactive Oxygen Species at Crossroads of Endothelial Permeability and Inflammation Open
Significance: Increased endothelial permeability and inflammation are two major hallmarks of the life-threatening conditions such as acute respiratory distress syndrome and sepsis. There is a growing consensus in the field th…
View article: Coupling Metastasis to pH-Sensing GPR68 Using a Novel Small Molecule Inhibitor
Coupling Metastasis to pH-Sensing GPR68 Using a Novel Small Molecule Inhibitor Open
An acidic milieu is a hallmark of the glycolytic metabolism that occurs in cancerous cells. The acidic environment is known to promote cancer progression, but the underlying signaling and cell biological underpinnings of these phenomena ar…
View article: Mechanosensitive Rap1 activation promotes barrier function of lung vascular endothelium under cyclic stretch
Mechanosensitive Rap1 activation promotes barrier function of lung vascular endothelium under cyclic stretch Open
Mechanical ventilation remains an imperative treatment for the patients with acute respiratory distress syndrome, but can also exacerbate lung injury. We have previously described a key role of RhoA GTPase in high cyclic stretch (CS)–induc…
View article: Staphylococcus aureus–induced endothelial permeability and inflammation are mediated by microtubule destabilization
Staphylococcus aureus–induced endothelial permeability and inflammation are mediated by microtubule destabilization Open
Staphylococcus aureus is a major etiological agent of sepsis and induces endothelial cell (EC) barrier dysfunction and inflammation, two major hallmarks of acute lung injury. However, the molecular mechanisms of bacterial pathogen-i…
View article: Role of truncated oxidized phospholipids in acute endothelial barrier dysfunction caused by particulate matter
Role of truncated oxidized phospholipids in acute endothelial barrier dysfunction caused by particulate matter Open
Particulate matter (PM) air pollution is a global environmental health problem contributing to more severe lung inflammation and injury. However, the molecular and cellular mechanisms of PM-induced exacerbation of lung barrier dysfunction …