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Article ; Online: The effect of light conditions on interpreting oil composition engineering in Arabidopsis seeds.

Karki, Nischal / Bates, Philip D

Plant direct

2018 Volume 2, Issue 6, Page(s) e00067

Abstract: Arabidopsis ... ...

Abstract	Arabidopsis thaliana
Language	English
Publishing date	2018-06-26
Publishing country	England
Document type	Journal Article
ISSN	2475-4455
ISSN (online)	2475-4455
DOI	10.1002/pld3.67
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cryptochromes: Photochemical and structural insight into magnetoreception.

Karki, Nischal / Vergish, Satyam / Zoltowski, Brian D

Protein science : a publication of the Protein Society

2021 Volume 30, Issue 8, Page(s) 1521–1534

Abstract: Cryptochromes (CRYs) function as blue light photoreceptors in diverse physiological processes in nearly all kingdoms of life. Over the past several decades, they have emerged as the most likely candidates for light-dependent magnetoreception in animals, ... ...

Abstract	Cryptochromes (CRYs) function as blue light photoreceptors in diverse physiological processes in nearly all kingdoms of life. Over the past several decades, they have emerged as the most likely candidates for light-dependent magnetoreception in animals, however, a long history of conflicts between in vitro photochemistry and in vivo behavioral data complicate validation of CRYs as a magnetosensor. In this review, we highlight the origins of conflicts regarding CRY photochemistry and signal transduction, and identify recent data that provides clarity on potential mechanisms of signal transduction in magnetoreception. The review primarily focuses on examining differences in photochemistry and signal transduction in plant and animal CRYs, and identifies potential modes of convergent evolution within these independent lineages that may identify conserved signaling pathways.
MeSH term(s)	Animals ; Cryptochromes ; Magnetic Phenomena ; Models, Molecular ; Photobiology ; Photochemistry ; Plants/chemistry ; Plants/metabolism ; Signal Transduction
Chemical Substances	Cryptochromes
Language	English
Publishing date	2021-06-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	1106283-6
ISSN	1469-896X ; 0961-8368
ISSN (online)	1469-896X
ISSN	0961-8368
DOI	10.1002/pro.4124
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Article ; Online: Allosteric regulation in STAT3 interdomains is mediated by a rigid core: SH2 domain regulation by CCD in D170A variant.

Zhao, Tingting / Karki, Nischal / Zoltowski, Brian D / Matthews, Devin A

PLoS computational biology

2022 Volume 18, Issue 12, Page(s) e1010794

Abstract: Signal Transducer and Activator of Transcription 3 (STAT3) plays a crucial role in cancer development and thus is a viable target for cancer treatment. STAT3 functions as a dimer mediated by phosphorylation of the SRC-homology 2 (SH2) domain, a key ... ...

Abstract	Signal Transducer and Activator of Transcription 3 (STAT3) plays a crucial role in cancer development and thus is a viable target for cancer treatment. STAT3 functions as a dimer mediated by phosphorylation of the SRC-homology 2 (SH2) domain, a key target for therapeutic drugs. While great efforts have been employed towards the development of compounds that directly target the SH2 domain, no compound has yet been approved by the FDA due to a lack of specificity and pharmacologic efficacy. Studies have shown that allosteric regulation of SH2 via the coiled-coil domain (CCD) is an alternative drug design strategy. Several CCD effectors have been shown to modulate SH2 binding and affinity, and at the time of writing at least one drug candidate has entered phase I clinical trials. However, the mechanism for SH2 regulation via CCD is poorly understood. Here, we investigate structural and dynamic features of STAT3 and compare the wild type to the reduced function variant D170A in order to delineate mechanistic differences and propose allosteric pathways. Molecular dynamics simulations were employed to explore conformational space of STAT3 and the variant, followed by structural, conformation, and dynamic analysis. The trajectories explored show distinctive conformational changes in the SH2 domain for the D170A variant, indicating long range allosteric effects. Multiple analyses provide evidence for long range communication pathways between the two STAT3 domains, which seem to be mediated by a rigid core which connects the CCD and SH2 domains via the linker domain (LD) and transmits conformational changes through a network of short-range interactions. The proposed allosteric mechanism provides new insight into the understanding of intramolecular signaling in STAT3 and potential pharmaceutical control of STAT3 specificity and activity.
MeSH term(s)	src Homology Domains/genetics ; STAT3 Transcription Factor/genetics ; STAT3 Transcription Factor/metabolism ; Allosteric Regulation ; Molecular Dynamics Simulation ; Phosphorylation
Chemical Substances	STAT3 Transcription Factor
Language	English
Publishing date	2022-12-21
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1010794
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Article ; Online: Allosteric regulation in STAT3 interdomains is mediated by a rigid core

Tingting Zhao / Nischal Karki / Brian D Zoltowski / Devin A Matthews

PLoS Computational Biology, Vol 18, Iss 12, p e

SH2 domain regulation by CCD in D170A variant.

2022 Volume 1010794

Abstract	Signal Transducer and Activator of Transcription 3 (STAT3) plays a crucial role in cancer development and thus is a viable target for cancer treatment. STAT3 functions as a dimer mediated by phosphorylation of the SRC-homology 2 (SH2) domain, a key target for therapeutic drugs. While great efforts have been employed towards the development of compounds that directly target the SH2 domain, no compound has yet been approved by the FDA due to a lack of specificity and pharmacologic efficacy. Studies have shown that allosteric regulation of SH2 via the coiled-coil domain (CCD) is an alternative drug design strategy. Several CCD effectors have been shown to modulate SH2 binding and affinity, and at the time of writing at least one drug candidate has entered phase I clinical trials. However, the mechanism for SH2 regulation via CCD is poorly understood. Here, we investigate structural and dynamic features of STAT3 and compare the wild type to the reduced function variant D170A in order to delineate mechanistic differences and propose allosteric pathways. Molecular dynamics simulations were employed to explore conformational space of STAT3 and the variant, followed by structural, conformation, and dynamic analysis. The trajectories explored show distinctive conformational changes in the SH2 domain for the D170A variant, indicating long range allosteric effects. Multiple analyses provide evidence for long range communication pathways between the two STAT3 domains, which seem to be mediated by a rigid core which connects the CCD and SH2 domains via the linker domain (LD) and transmits conformational changes through a network of short-range interactions. The proposed allosteric mechanism provides new insight into the understanding of intramolecular signaling in STAT3 and potential pharmaceutical control of STAT3 specificity and activity.
Keywords	Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparative performance of regionalization methods for model parameterization in ungauged Himalayan watersheds

Karki, Nischal / Shakya, Narendra Man / Pandey, Vishnu Prasad / Devkota, Laxmi Prasad / Pradhan, Ananta Man Singh / Lamichhane, Suraj

Journal of Hydrology: Regional Studies. 2023 June, v. 47 p.101359-

2023

Abstract: The study region is 23 different watersheds across Nepal. This study aims at assessing the strengths and weaknesses of widely used regionalization methods for simulating daily hydrograph and flow duration curve in a comparatively large sample of 23 ... ...

Abstract	The study region is 23 different watersheds across Nepal. This study aims at assessing the strengths and weaknesses of widely used regionalization methods for simulating daily hydrograph and flow duration curve in a comparatively large sample of 23 medium to small-sized watersheds across Nepal. We employed a deductive approach based on extractable watershed properties to test the performance of four regionalization methods: principal component regression (PCR), random forests (RF) under regression-based methods, spatial proximity (SP), and physical similarity (PS) under donor-based methods in a leave-one-out cross-validation (LOOCV) setting. The GR4J rainfall-runoff model coupled with Cemaneige snow module (GR4J-CN) could provide good simulation for majority of the watersheds with median NSE of 0.76 and 0.74 for calibration and validation periods respectively. Model simulation using parameter values predicted from different regionalization methods showed satisfactory results in majority of the watersheds for daily hydrograph simulation. While there wasn’t a single method that performed well in all of the watersheds, the physical similarity methods was found to be the most robust. Visual comparison of errors in flow duration curve (FDC) also indicated physical similarity method as a better approach in ungauged watersheds of Nepal. Further experiment using multiple donors using the output averaging option was found to increase the performance of donor-based methods while the parameter averaging option resulted in a drop in performance. The study provides a comprehensive assessment of regionalization methods and advocates the use of hydrological model regionalization as a promising tool for streamflow prediction in ungauged Himalayan watersheds.
Keywords	hydrograph ; hydrologic models ; prediction ; simulation models ; snow ; stream flow ; watersheds ; Nepal ; Cemaneige ; GR4J ; Regionalization ; Ungauged
Language	English
Dates of publication	2023-06
Publishing place	Elsevier B.V.
Document type	Article ; Online
ZDB-ID	2814784-4
ISSN	2214-5818
ISSN	2214-5818
DOI	10.1016/j.ejrh.2023.101359
Database	NAL-Catalogue (AGRICOLA)

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Article: Wellens Syndrome: An Atypical Presentation With Burning Chest and Epigastric Pain.

Shah, Sunil / Jaiswal, Amit K / Neupane, Nischal / Karki, Divya

Cureus

2021 Volume 13, Issue 7, Page(s) e16241

Abstract: Wellens syndrome is a pre-infarction stage due to the critical stenosis of the proximal left anterior descending artery. It is characterized by intermittent chest pain with classical ECG changes. The cardiac biomarker is within the normal limit or only ... ...

Abstract	Wellens syndrome is a pre-infarction stage due to the critical stenosis of the proximal left anterior descending artery. It is characterized by intermittent chest pain with classical ECG changes. The cardiac biomarker is within the normal limit or only slightly elevated in this condition. Early recognition and cardiac intervention are important to prevent adverse cardiac outcomes. We report this rare case of Wellens syndrome in a 70-year-old male with intermittent chest and epigastric pain associated with belching for five days. The patient presented characteristic T-wave changes, symmetric deeply inverted T-waves, in precordial leads (V2-V4). Cardiac biomarkers, including troponin, were negative. He underwent cardiac catheterization and found a clot in the proximal left anterior descending coronary artery, which required a catheter-directed thrombectomy and drug-eluting stent placement. It is important to recognize this condition early and referred on time from primary health centers to higher centers, especially in developing countries like the Maldives, since delays in transfer may lead to a serious outcome.
Language	English
Publishing date	2021-07-07
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.16241
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Kawasaki Disease Shock Syndrome: A Nine-Year-Old Girl With Atypical Presentation of Kawasaki Disease in Emergency Department.

Shah, Sunil / Karki, Divya / Gami, Sumit / Panth, Himal / Neupane, Nischal

Cureus

2021 Volume 13, Issue 6, Page(s) e15471

Abstract: Kawasaki disease (KD) is an acute rheumatological illness usually affecting children between six months and five years of age. It is a vasculitis syndrome of medium-sized vessels that has typical clinical characteristics such as fever, rash, cervical ... ...

Abstract	Kawasaki disease (KD) is an acute rheumatological illness usually affecting children between six months and five years of age. It is a vasculitis syndrome of medium-sized vessels that has typical clinical characteristics such as fever, rash, cervical lymphadenopathy, conjunctivitis, and mucosal changes. However, sometimes, it may present with the features of shock when it is known as Kawasaki disease shock syndrome (KDSS). The actual etiology of this disease is still unknown. The primary treatment of this disease is aspirin and intravenous immunoglobulin (IVIG). The most common and serious complication of KD is cardiac complications which can be avoided by IVIG if given on time. KDSS is the other rare but serious early complication that can be presented to the ED as an initial presenting feature. Early diagnosis of KDSS in the ED and its treatment is very important to prevent early and late complications, including cardiac complications of this disease. Although the usual age group for this disease is under five years, here we have presented a rare case of KDSS in a nine-year-old female child.
Language	English
Publishing date	2021-06-05
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.15471
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Comparative performance of regionalization methods for model parameterization in ungauged Himalayan watersheds

Nischal Karki / Narendra Man Shakya / Vishnu Prasad Pandey / Laxmi Prasad Devkota / Ananta Man Singh Pradhan / Suraj Lamichhane

Journal of Hydrology: Regional Studies, Vol 47, Iss , Pp 101359- (2023)

2023

Abstract: Study region: The study region is 23 different watersheds across Nepal. Study focus: This study aims at assessing the strengths and weaknesses of widely used regionalization methods for simulating daily hydrograph and flow duration curve in a ... ...

Abstract	Study region: The study region is 23 different watersheds across Nepal. Study focus: This study aims at assessing the strengths and weaknesses of widely used regionalization methods for simulating daily hydrograph and flow duration curve in a comparatively large sample of 23 medium to small-sized watersheds across Nepal. We employed a deductive approach based on extractable watershed properties to test the performance of four regionalization methods: principal component regression (PCR), random forests (RF) under regression-based methods, spatial proximity (SP), and physical similarity (PS) under donor-based methods in a leave-one-out cross-validation (LOOCV) setting. New hydrological insights for the region: The GR4J rainfall-runoff model coupled with Cemaneige snow module (GR4J-CN) could provide good simulation for majority of the watersheds with median NSE of 0.76 and 0.74 for calibration and validation periods respectively. Model simulation using parameter values predicted from different regionalization methods showed satisfactory results in majority of the watersheds for daily hydrograph simulation. While there wasn’t a single method that performed well in all of the watersheds, the physical similarity methods was found to be the most robust. Visual comparison of errors in flow duration curve (FDC) also indicated physical similarity method as a better approach in ungauged watersheds of Nepal. Further experiment using multiple donors using the output averaging option was found to increase the performance of donor-based methods while the parameter averaging option resulted in a drop in performance. The study provides a comprehensive assessment of regionalization methods and advocates the use of hydrological model regionalization as a promising tool for streamflow prediction in ungauged Himalayan watersheds.
Keywords	Cemaneige ; GR4J ; Nepal ; Regionalization ; Ungauged ; Physical geography ; GB3-5030 ; Geology ; QE1-996.5
Subject code	310
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Hepatic Encephalopathy among Patients with Chronic Liver Disease Admitted to the Department of Internal Medicine in a Tertiary Care Centre

Ujjwal Karki / Nischal Upreti / Bindu Gyawali / Sandesh Kumar Shrestha / Chandra Kiran Basnet / Devashish Sharma / Neha Dangol

Journal of Nepal Medical Association, Vol 61, Iss

A Descriptive Cross-sectional Study

2023 Volume 263

Abstract: Introduction: Hepatic encephalopathy is a condition that impairs the neurological and psychiatric function of a patient as a result of advanced liver disease or portosystemic shunt. Early detection and treatment of hepatic encephalopathy can lessen its ... ...

Abstract	Introduction: Hepatic encephalopathy is a condition that impairs the neurological and psychiatric function of a patient as a result of advanced liver disease or portosystemic shunt. Early detection and treatment of hepatic encephalopathy can lessen its severity, length of stay in the hospital and potential fatality. The aim of this study was to find out the prevalence of hepatic encephalopathy among patients with chronic liver disease admitted to the Department of Internal Medicine in a tertiary care centre. Methods: A descriptive cross-sectional study was done among patients with chronic liver disease admitted to the Department of Internal Medicine in a tertiary care centre. Data from 1 October 2021 to 15 May 2023 were collected between 20 May 2023 and 30 May 2023 from the hospital records. Ethical approval was obtained from the Institutional Review Committee (Reference number: 808/2023). The diagnosis was made based on the history, clinical examinations, and gradings were done as per West Haven criteria. Convenience sampling was done. Point estimate and 95% Confidence Interval were calculated. Results: Among 389 patients with chronic liver disease, hepatic encephalopathy was seen in 40 (10.28%) (7.26-13.30, 95% Confidence Interval). The mean age of patients was 55.27±13.52 years. Conclusions: The prevalence of hepatic encephalopathy among patients with chronic liver disease was lower than the studies conducted in similar settings.
Keywords	hepatic encephalopathy ; liver cirrhosis ; liver failure ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	Nepal Medical Association
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The effect of light conditions on interpreting oil composition engineering in Arabidopsis seeds

Karki, Nischal / Bates, Philip D.

Plant direct. 2018 June, v. 2, no. 6

2018

Abstract: Arabidopsis thaliana is the most developed and utilized model plant. In particular, it is an excellent model for proof‐of‐concept seed oil engineering studies because it accumulates approximately 37% seed oil by weight, and it is closely related to ... ...

Abstract	Arabidopsis thaliana is the most developed and utilized model plant. In particular, it is an excellent model for proof‐of‐concept seed oil engineering studies because it accumulates approximately 37% seed oil by weight, and it is closely related to important Brassicaceae oilseed crops. Arabidopsis can be grown under a wide variety of conditions including continuous light; however, the amount of light is strongly correlated with total seed oil accumulation. In addition, many attempts to engineer novel seed oil fatty acid compositions in Arabidopsis have reported significant reductions in oil accumulation; however, the relative reduction from the nontransgenic controls varies greatly within the literature. A set of experiments were conducted to systematically analyze the effect of light conditions (including day/night cycle vs. continuous light, and different light intensities) on the relative accumulation of seed oil between three different transgenic lines producing novel hydroxy fatty acids and their nontransgenic background. Oil content was measured per seed and as a percentage of seed weight. Our results indicate the relative amount of seed oil between transgenic lines and nontransgenic controls is dependent on both the light conditions and the type of oil content measurement utilized. In addition, the light conditions effect the relative accumulation of the novel fatty acids between various transgenic lines. Therefore, the success of novel fatty acid proof‐of‐concept engineering strategies on both oil accumulation and fatty acid composition in Arabidopsis seeds should be considered in light of the select growth and measurement conditions prior to moving engineering strategies into crop plants.
Keywords	Arabidopsis thaliana ; fatty acid composition ; fatty acids ; genetically modified organisms ; lipid content ; models ; oilseeds ; seed oils ; seed weight
Language	English
Dates of publication	2018-06
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ISSN	2475-4455
DOI	10.1002/pld3.67
Database	NAL-Catalogue (AGRICOLA)

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