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Article ; Online: Effect of K

Thorat, Amey / Chauhan, Rohit / Sartape, Rohan / Singh, Meenesh R / Shah, Jindal K

The journal of physical chemistry. B

2024 Volume 128, Issue 15, Page(s) 3707–3719

Abstract: ... EG). Four different force fields were used to represent the K ...

Abstract	Predicting ionic conductivity is crucial for developing efficient electrolytes for energy storage and conversion and other electrochemical applications. An accurate estimate of ionic conductivity requires understanding complex ion-ion and ion-solvent interactions governing the charge transport at the molecular level. Molecular simulations can provide key insights into the spatial and temporal behavior of electrolyte constituents. However, such insights depend on the ability of force fields to describe the underlying phenomena. In this work, molecular dynamics simulations were leveraged to delineate the impact of force field parameters on ionic conductivity predictions of potassium hydroxide (KOH) in ethylene glycol (EG). Four different force fields were used to represent the K
Language	English
Publishing date	2024-04-04
Publishing country	United States
Document type	Journal Article
ISSN	1520-5207
ISSN (online)	1520-5207
DOI	10.1021/acs.jpcb.3c08480
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Article ; Online: Human endogenous retrovirus K contributes to a stem cell niche in glioblastoma.

Shah, Ashish H / Rivas, Sarah R / Doucet-O'Hare, Tara T / Govindarajan, Vaidya / DeMarino, Catherine / Wang, Tongguang / Ampie, Leonel / Zhang, Yong / Banasavadi-Siddegowda, Yeshavanth Kumar / Walbridge, Stuart / Maric, Dragan / Garcia-Montojo, Marta / Suter, Robert K / Lee, Myoung-Hwa / Zaghloul, Kareem A / Steiner, Joseph / Elkahloun, Abdel G / Chandar, Jay / Seetharam, Deepa /

Desgraves, Jelisah / Li, Wenxue / Johnson, Kory / Ivan, Michael E / Komotar, Ricardo J / Gilbert, Mark R / Heiss, John D / Nath, Avindra

The Journal of clinical investigation

2023 Volume 133, Issue 13

Abstract: ... of the human genome. Although normally silenced, the most recently integrated provirus HERV-K (HML-2) can be ...

Abstract	Human endogenous retroviruses (HERVs) are ancestral viral relics that constitute nearly 8% of the human genome. Although normally silenced, the most recently integrated provirus HERV-K (HML-2) can be reactivated in certain cancers. Here, we report pathological expression of HML-2 in malignant gliomas in both cerebrospinal fluid and tumor tissue that was associated with a cancer stem cell phenotype and poor outcomes. Using single-cell RNA-Seq, we identified glioblastoma cellular populations with elevated HML-2 transcripts in neural progenitor-like cells (NPC-like) that drive cellular plasticity. Using CRISPR interference, we demonstrate that HML-2 critically maintained glioblastoma stemness and tumorigenesis in both glioblastoma neurospheres and intracranial orthotopic murine models. Additionally, we demonstrate that HML-2 critically regulated embryonic stem cell programs in NPC-derived astroglia and altered their 3D cellular morphology by activating the nuclear transcription factor OCT4, which binds to an HML-2-specific long-terminal repeat (LTR5Hs). Moreover, we discovered that some glioblastoma cells formed immature retroviral virions, and inhibiting HML-2 expression with antiretroviral drugs reduced reverse transcriptase activity in the extracellular compartment, tumor viability, and pluripotency. Our results suggest that HML-2 fundamentally contributes to the glioblastoma stem cell niche. Because persistence of glioblastoma stem cells is considered responsible for treatment resistance and recurrence, HML-2 may serve as a unique therapeutic target.
MeSH term(s)	Humans ; Animals ; Mice ; Endogenous Retroviruses/genetics ; Glioblastoma/genetics ; Stem Cell Niche ; Proviruses/genetics
Language	English
Publishing date	2023-07-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI167929
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Article ; Online: Disruption of K

Justice, Jason A / Schulien, Anthony J / He, Kai / Hartnett, Karen A / Aizenman, Elias / Shah, Niyathi H

Neuroscience

2017 Volume 354, Page(s) 158–167

Abstract: As the predominant mediator of the delayed rectifier current, K ...

Abstract	As the predominant mediator of the delayed rectifier current, K
MeSH term(s)	Animals ; Apoptosis/genetics ; Apoptosis/physiology ; Cells, Cultured ; Cerebral Cortex/cytology ; Cholinesterase Inhibitors/pharmacology ; Cricetulus ; Dendrites/genetics ; Dendrites/metabolism ; Embryo, Mammalian ; Enzyme Inhibitors/pharmacology ; Ethylenediamines/pharmacology ; Female ; Immunosuppressive Agents/pharmacology ; Membrane Potentials/drug effects ; Membrane Potentials/genetics ; Microglia/metabolism ; Neurons/cytology ; Neurons/physiology ; Pregnancy ; Pyridines/toxicity ; Rats ; Shab Potassium Channels/genetics ; Shab Potassium Channels/metabolism ; Tacrolimus/analogs & derivatives ; Tacrolimus/pharmacology
Chemical Substances	Cholinesterase Inhibitors ; Enzyme Inhibitors ; Ethylenediamines ; Immunosuppressive Agents ; Pyridines ; Shab Potassium Channels ; 2,2'-dithiobis(5-nitropyridine) (2127-10-8) ; immunomycin (AUF4U5NSJK) ; N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (R9PTU1U29I) ; Tacrolimus (WM0HAQ4WNM)
Language	English
Publishing date	2017-04-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	196739-3
ISSN	1873-7544 ; 0306-4522
ISSN (online)	1873-7544
ISSN	0306-4522
DOI	10.1016/j.neuroscience.2017.04.034
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Article ; Online: The subthreshold-active K

Martinello, Katiuscia / Giacalone, Elisabetta / Migliore, Michele / Brown, David A / Shah, Mala M

Communications biology

2019 Volume 2, Page(s) 145

Abstract: ... that the K ...

Abstract	Little is known about the properties and function of ion channels that affect synaptic terminal-resting properties. One particular subthreshold-active ion channel, the Kv7 potassium channel, is highly localized to axons, but its role in regulating synaptic terminal intrinsic excitability and release is largely unexplored. Using electrophysiological recordings together with computational modeling, we found that the K
MeSH term(s)	Action Potentials/physiology ; Animals ; CA3 Region, Hippocampal/metabolism ; Calcium/metabolism ; Computational Biology/methods ; Excitatory Postsynaptic Potentials/physiology ; KCNQ Potassium Channels/metabolism ; Male ; Mossy Fibers, Hippocampal/metabolism ; Neuronal Plasticity/physiology ; Presynaptic Terminals/metabolism ; Pyramidal Cells/metabolism ; Rats ; Rats, Sprague-Dawley ; Synapses/metabolism ; Synaptic Transmission/physiology
Chemical Substances	KCNQ Potassium Channels ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2019-04-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-019-0408-4
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Article ; Online: Revealing the Structural, Elastic, Electronic, and Optical Properties of K

Shah, Saima Ahmad / Husain, Mudasser / Rahman, Nasir / Sfina, Nourreddine / Elhadi, Muawya / Tirth, Vineet / Alotaibi, Afraa / Khan, Aurangzeb

ACS omega

2024 Volume 9, Issue 14, Page(s) 16860–16867

Abstract: The optoelectronic, structural, and elastic properties of K ...

Abstract	The optoelectronic, structural, and elastic properties of K
Language	English
Publishing date	2024-03-29
Publishing country	United States
Document type	Journal Article
ISSN	2470-1343
ISSN (online)	2470-1343
DOI	10.1021/acsomega.4c01923
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Article ; Online: The Role of HERV-K in Cancer Stemness.

Rivas, Sarah R / Valdez, Mynor J Mendez / Govindarajan, Vaidya / Seetharam, Deepa / Doucet-O'Hare, Tara T / Heiss, John D / Shah, Ashish H

Viruses

2022 Volume 14, Issue 9

Abstract: Human endogenous retrovirus-K (HERV-K) is the most recently integrated retrovirus ... silenced in normal adult cells, dysregulation of HERV-K (HML-2) elements has been observed in cancer ... of carcinogenesis have been proposed, here we discuss the role of HERV-K (HML-2) in the promotion and maintenance ...

Abstract	Human endogenous retrovirus-K (HERV-K) is the most recently integrated retrovirus in the human genome, with implications for multiple disorders, including cancer. Although typically transcriptionally silenced in normal adult cells, dysregulation of HERV-K (HML-2) elements has been observed in cancer, including breast, germ cell tumors, pancreatic, melanoma, and brain cancer. While multiple methods of carcinogenesis have been proposed, here we discuss the role of HERV-K (HML-2) in the promotion and maintenance of the stem-cell in cancer. Aberrant expression of HERV-K has been shown to promote expression of stem cell markers and promote dedifferentiation. In this review, we discuss HERV-K (HML-2) as a potential therapeutic target based on evidence that some tumors depend on the expression of its proteins for survival.
MeSH term(s)	Adult ; Endogenous Retroviruses/genetics ; Genome, Human ; Humans ; Melanoma/genetics
Language	English
Publishing date	2022-09-12
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, N.I.H., Intramural
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14092019
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Article ; Online: Interfacial behavior of Proteinase K enzyme at air-saline subphase.

Paudyal, Suraj / Sigdel, Ganesh / Shah, Sujit K / Sharma, Shiv K / Grubb, John D / Micic, Miodrag / Caseli, Luciano / Leblanc, Roger M

Journal of colloid and interface science

2022 Volume 616, Page(s) 701–708

Abstract: This study investigates the interfacial behavior of the proteinase K enzyme at air-water interface ... Proteinase K enzyme forms film at air-aqueous interface and demonstrates good stability as shown ...

Abstract	This study investigates the interfacial behavior of the proteinase K enzyme at air-water interface. Adsorption of enzyme on the surface was induced using saline subphase. The surface packing and stability of the enzyme was investigated using of surface pressure-area (π-A) and surface potential-area (ΔV-A) isotherms. Proteinase K enzyme forms film at air-aqueous interface and demonstrates good stability as shown through compression-decompression cycle experiments. To characterize the surface assembly morphology of the interfacial enzymes UV-vis and fluorescence spectroscopic techniques were used. The data revealed that the enzyme Langmuir monolayer has good homogeneity with no evidence of aggregates during compression. The secondary structure of the enzyme at interface was determined to be α-helix using p-polarized infrared-reflection absorption spectroscopy. This was confirmed through Circular dichroism spectra of the enzyme Langmuir-Blodgett (LB) film which showed that the major conformation present were α-helices.
MeSH term(s)	Endopeptidase K ; Protein Structure, Secondary ; Spectrometry, Fluorescence ; Spectrophotometry, Infrared ; Surface Properties ; Water/chemistry
Chemical Substances	Water (059QF0KO0R) ; Endopeptidase K (EC 3.4.21.64)
Language	English
Publishing date	2022-02-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	241597-5
ISSN	1095-7103 ; 0021-9797
ISSN (online)	1095-7103
ISSN	0021-9797
DOI	10.1016/j.jcis.2022.02.084
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Article ; Online: K-29 linked ubiquitination of Arrdc4 regulates its function in extracellular vesicle biogenesis.

Farooq, Ammara Usman / Gembus, Kelly / Sandow, Jarrod J / Webb, Andrew / Mathivanan, Suresh / Manning, Jantina A / Shah, Sonia S / Foot, Natalie J / Kumar, Sharad

Journal of extracellular vesicles

2022 Volume 11, Issue 2, Page(s) e12188

Abstract: Extracellular vesicles (EVs) are important mediators of intercellular communication. However, EV biogenesis remains poorly understood. We previously defined a role for Arrdc4 (Arrestin domain containing protein 4), an adaptor for Nedd4 family ubiquitin ... ...

Abstract	Extracellular vesicles (EVs) are important mediators of intercellular communication. However, EV biogenesis remains poorly understood. We previously defined a role for Arrdc4 (Arrestin domain containing protein 4), an adaptor for Nedd4 family ubiquitin ligases, in the biogenesis of EVs. Here we report that ubiquitination of Arrdc4 is critical for its role in EV secretion. We identified five potential ubiquitinated lysine residues in Arrdc4 using mass spectrometry. By analysing Arrdc4 lysine mutants we discovered that lysine 270 (K270) is critical for Arrdc4 function in EV biogenesis. Arrdc4
MeSH term(s)	Extracellular Vesicles/metabolism ; Nedd4 Ubiquitin Protein Ligases/genetics ; Polyubiquitin/genetics ; Ubiquitin-Protein Ligases/genetics ; Ubiquitination
Chemical Substances	Polyubiquitin (120904-94-1) ; Nedd4 Ubiquitin Protein Ligases (EC 2.3.2.26) ; Ubiquitin-Protein Ligases (EC 2.3.2.27)
Language	English
Publishing date	2022-02-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2683797-3
ISSN	2001-3078 ; 2001-3078
ISSN (online)	2001-3078
ISSN	2001-3078
DOI	10.1002/jev2.12188
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Article ; Online: Inhibition of Na/K-ATPase signaling Attenuates Steatohepatitis and Atherosclerosis in Mice Fed a Western Diet.

Sodhi, Komal / Srikanthan, Krithika / Goguet-Rubio, Perrine / Nichols, Alexandra / Nawab, Athar / Shah, Preeya / Chaudhry, Muhammad / El-Hamdani, Mehiar / Xie, Zijian / Shapiro, Joseph

Cellular and molecular biology (Noisy-le-Grand, France)

2023 Volume 69, Issue 2, Page(s) 162–171

Abstract: We have previously reported that the α1 subunit of sodium-potassium adenosine triphosphatase (Na/K ... pumping function. On this background, we speculated that the blockade of Na/K-ATPase-induced ROS ... this study demonstrates that the Na/K-ATPase/ROS amplification loop contributes significantly ...

Abstract	We have previously reported that the α1 subunit of sodium-potassium adenosine triphosphatase (Na/K-ATPase), acts as a receptor and an amplifier for reactive oxygen species, in addition to its distinct pumping function. On this background, we speculated that the blockade of Na/K-ATPase-induced ROS amplification with a specific peptide, pNaKtide, might attenuate the development of steatohepatitis. To test this hypothesis, pNaKtide was administered to a murine model of NASH: the C57Bl6 mouse fed a "western" diet containing high amounts of fat and fructose. The administration of pNaKtide reduced obesity as well as hepatic steatosis, inflammation and fibrosis. Of interest, we also noted a marked improvement in mitochondrial fatty acid oxidation, insulin sensitivity, dyslipidemia and aortic streaking in this mouse model. To further elucidate the effects of pNaKtide on atherosclerosis, similar studies were performed in ApoE knockout mice also exposed to the western diet. In these mice, pNaKtide not only improved steatohepatitis, dyslipidemia, and insulin sensitivity but also ameliorated significant aortic atherosclerosis. Collectively, this study demonstrates that the Na/K-ATPase/ROS amplification loop contributes significantly to the development and progression of steatohepatitis and atherosclerosis. Furthermore, this study presents a potential treatment, the pNaKtide, for the metabolic syndrome phenotype.
MeSH term(s)	Animals ; Mice ; Diet, Western/adverse effects ; Insulin Resistance ; Reactive Oxygen Species ; Atherosclerosis/drug therapy ; Fatty Liver/drug therapy ; Mice, Inbred C57BL ; Adenosine Triphosphatases
Chemical Substances	Reactive Oxygen Species ; Adenosine Triphosphatases (EC 3.6.1.-)
Language	English
Publishing date	2023-02-28
Publishing country	France
Document type	Journal Article
ZDB-ID	1161779-2
ISSN	1165-158X ; 0145-5680
ISSN (online)	1165-158X
ISSN	0145-5680
DOI	10.14715/cmb/2023.69.2.27
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Article ; Online: Human endogenous retrovirus K contributes to a stem cell niche in glioblastoma

Ashish H. Shah / Sarah R. Rivas / Tara T. Doucet-O’Hare / Vaidya Govindarajan / Catherine DeMarino / Tongguang Wang / Leonel Ampie / Yong Zhang / Yeshavanth Kumar Banasavadi-Siddegowda / Stuart Walbridge / Dragan Maric / Marta Garcia-Montojo / Robert K. Suter / Myoung-Hwa Lee / Kareem A. Zaghloul / Joseph Steiner / Abdel G. Elkahloun / Jay Chandar / Deepa Seetharam /

Jelisah Desgraves / Wenxue Li / Kory Johnson / Michael E. Ivan / Ricardo J. Komotar / Mark R. Gilbert / John D. Heiss / Avindra Nath

The Journal of Clinical Investigation, Vol 133, Iss

2023 Volume 13

Abstract: ... of the human genome. Although normally silenced, the most recently integrated provirus HERV-K (HML-2) can be ...

Abstract	Human endogenous retroviruses (HERVs) are ancestral viral relics that constitute nearly 8% of the human genome. Although normally silenced, the most recently integrated provirus HERV-K (HML-2) can be reactivated in certain cancers. Here, we report pathological expression of HML-2 in malignant gliomas in both cerebrospinal fluid and tumor tissue that was associated with a cancer stem cell phenotype and poor outcomes. Using single-cell RNA-Seq, we identified glioblastoma cellular populations with elevated HML-2 transcripts in neural progenitor–like cells (NPC-like) that drive cellular plasticity. Using CRISPR interference, we demonstrate that HML-2 critically maintained glioblastoma stemness and tumorigenesis in both glioblastoma neurospheres and intracranial orthotopic murine models. Additionally, we demonstrate that HML-2 critically regulated embryonic stem cell programs in NPC-derived astroglia and altered their 3D cellular morphology by activating the nuclear transcription factor OCT4, which binds to an HML-2–specific long-terminal repeat (LTR5Hs). Moreover, we discovered that some glioblastoma cells formed immature retroviral virions, and inhibiting HML-2 expression with antiretroviral drugs reduced reverse transcriptase activity in the extracellular compartment, tumor viability, and pluripotency. Our results suggest that HML-2 fundamentally contributes to the glioblastoma stem cell niche. Because persistence of glioblastoma stem cells is considered responsible for treatment resistance and recurrence, HML-2 may serve as a unique therapeutic target.
Keywords	Stem cells ; Virology ; Medicine ; R
Subject code	571
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	American Society for Clinical Investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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