Article
Chemistry, Medicinal
Melanie Rodriguez, Ashari Kannangara, Julita Chlebowicz, Radha Akella, Haixia He, Uttam K. Tambar, Elizabeth J. Goldsmith
Summary: A new class of trihalo-sulfone compounds was identified as effective inhibitors of WNK1, and the necessary chemical features for inhibition of WNK1 were determined through chemical synthesis and X-ray crystallography.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Cell Biology
Zhenan Liu, Joonho Yoon, Chonlarat Wichaidit, Ankita B. Jaykumar, Hashem A. Dbouk, Addie E. Embry, Liping Liu, Joel M. Henderson, Audrey N. Chang, Melanie H. Cobb, Richard Tyler Miller
Summary: Calcineurin inhibitors can protect podocytes and glomerular capillaries by preserving podocyte cytoskeletal structure, preventing injury in many glomerular diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Inorganic & Nuclear
Rishav Chatterjee, Indira Bhattacharya, Souryadip Roy, Kallol Purkait, Tuhin Subhra Koley, Arnab Gupta, Arindam Mukherjee
Summary: The study investigated N,O-donor ligands with and without pendant morpholine units in metal complexes, finding that these complexes showed excellent in vitro antiproliferative activity under specific conditions, but the presence of pendant morpholine did not enhance the efficacy of the dose. Furthermore, cells treated with the complexes exhibited antiproliferative activity, but favored a necrotic pathway of cell killing.
INORGANIC CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Lindsey Mayes-Hopfinger, Aura Enache, Jian Xie, Chou-Long Huang, Robert Kochl, Victor L. J. Tybulewicz, Teresa Fernandes-Alnemri, Emad S. Alnemri
Summary: WNK1 is identified as a negative regulator of the NLRP3 inflammasome, balancing intracellular Cl- and K+ concentrations to suppress NLRP3 activation and reduce inflammatory responses.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Ankita B. Jaykumar, Ji-Ung Jung, Pravat Kumar Parida, Tuyen T. Dang, Chonlarat Wichaidit, Ashari Rashmi Kannangara, Svetlana Earnest, Elizabeth J. Goldsmith, Gray W. Pearson, Srinivas Malladi, Melanie H. Cobb
Summary: The protein kinase WNK1 has been identified as a key player in promoting migration and invasion of breast cancer cells, with its inhibition showing promising results in reducing metastasis. Depletion or inhibition of WNK1 was found to suppress AXL expression, a tyrosine kinase involved in metastasis. These findings suggest that targeting WNK1 may provide a new therapeutic avenue for invasive breast cancers.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Chemistry, Organic
Sarah K. I. Watt, Janique G. Charlebois, Christopher N. Rowley, Jeffrey W. Keillor
Summary: Irreversible enzyme inhibitors permanently limit their target's function by covalently binding to it. The nucleophilic group targeted for reaction with the electrophilic warhead of these inhibitors is often the thiol group on cysteine residues. In this study, the mechanism of thiol addition to N-phenylchloroacetamide was investigated, revealing an early transition state for the attack by the thiolate. The reactivity of chloroacetamide was compared to acrylamides commonly used in irreversible inhibitor drugs.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Energy & Fuels
Caifeng Yang, Mucong Zi, Guozhong Wu, Xue Zou, Kai Liu, Daoyi Chen
Summary: This study evaluated the influence of kinetic hydrate inhibitor (KHI) on methane - propane hydrate formation kinetics under different subcooling and concentration conditions. It proposed a "concentration effect" concept that highlighted the nonmonotonic relationship between KHI performance and concentration. Two hypotheses were proposed to explain this phenomenon, and the results showed that the concentration effect became less obvious under certain experimental conditions.
Article
Multidisciplinary Sciences
Ru-pin Alicia Chi, Xiaojiang Xu, Jian-Liang Li, Xin Xu, Guang Hu, Paula Brown, Cynthia Willson, Oleksandr Kirsanov, Christopher Geyer, Chou-Long Huang, Marcos Morgan, Francesco Demayo
Summary: WNK1 is an important regulator in many physiological functions, and our study uncovered an MTOR-regulating factor in the male germline with potential implications in translation.
Article
Biochemistry & Molecular Biology
Marko Novinec, Primoz Bembic, Milica Jankovic, Marija Kisilak, Jakob Kljun, Iztok Turel
Summary: Heavy metal ions, such as gallium and cerium, can inhibit the activity of human papain-like cysteine endopeptidases, while zinc and lead ions are known inhibitors of thiol enzymes. The inhibition constants of Ga3+, Ce3+, and Ce4+ ions are comparable to Zn2+ ions, indicating their potential as cysteine cathepsin inhibitors. These ions also inhibit the degradation of elastin, suggesting their possible application in treating inflammatory diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Physiology
Mauricio Ostrosky-Frid, Maria Chavez-Canales, Jinwei Zhang, Olena Andrukhova, Eduardo R. Argaiz, Fernando Lerdo-de-Tejada, Adrian Murillo-de-Ozores, Andrea Sanchez-Navarro, Lorena Rojas-Vega, Norma A. Bobadilla, Norma Vazquez, Maria Castaneda-Bueno, Dario R. Alessi, Gerardo Gamba
Summary: The kidney-specific isoform of WNK1, KS-WNK1, is capable of stimulating the NaCl cotransporter by activating WNK4. Research shows that the activity of KS-WNK1 is influenced by specific amino acid residues.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Tino Pleiner, Masami Hazu, Giovani Pinton Tomaleri, Kurt Januszyk, Robert S. Oania, Michael J. Sweredoski, Annie Moradian, Alina Guna, Rebecca M. Voorhees
Summary: The assembly of nascent proteins into multi-subunit complexes is regulated by WNK1, which stabilizes EMC2 and promotes assembly of EMC, playing a key role in cellular homeostasis. Depletion of WNK1 destabilizes both EMC and its membrane protein clients.
Article
Biochemistry & Molecular Biology
Bader Huwaimel, Sravan Jonnalagadda, Shirisha Jonnalagadda, Fatema T. Zahra, Alessio Nocentini, Claudiu T. Supuran, Constantinos M. Mikelis, Paul C. Trippier
Summary: Angiogenesis inhibitors, such as chlorinated benzothiadiazines, have been found to suppress VEGF-induced endothelial cell proliferation by inhibiting VEGFR2 phosphorylation. These inhibitors show selectivity and lack cytotoxicity against various cell lines. Compound 17b, in particular, demonstrates high selectivity and potential as a novel angiogenesis inhibitor for further development.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Analytical
Yassine Rahib, Valerie Leroy-Cancellieri, Dominique Cancellieri, Yann Quilichini
Summary: This research aims to analyze the solid-state thermal degradation behavior and pyrolysis kinetics of Mediterranean Genista Salzmannii Needles (GSN) and provide information for wildland fire research. Proximate, ultimate, and microstructural analyses were conducted to characterize GSN. A thermogravimetric system coupled with Fourier Transform Infrared spectrometry (TG-FTIR) was used to analyze the pyrolytic behavior and gaseous products. The results showed that GSN has a high content of volatile and carbon. The cut GSN exhibited a higher mass loss rate than the grinded GSN during pyrolysis. CO2, C=O bond, C=C bond, C-H and/or C-O bond, aliphatic C-H (CH4), and H2O were the dominant gases released during pyrolysis. The kinetic analysis revealed that the cut GSN had slightly higher average apparent activation energy (E-alpha) than the grinded GSN. The thermal decomposition of hemicellulose and cellulose was best described by random nucleation and nucleation growth mechanisms, while char formation was consistent with the high-order reaction model. The simulated data showed good agreement with the experimental data.
JOURNAL OF ANALYTICAL AND APPLIED PYROLYSIS
(2022)
Article
Microbiology
Xiaomeng An, Long Yu, Sen Wang, Yangsiqi Ao, Xueyan Zhan, Qin Liu, Yangnan Zhao, Muxiao Li, Xiang Shu, Fangjie Li, Lan He, Junlong Zhao
Summary: The study cloned, expressed, and purified B. microti PYK I, demonstrating its specificity through Western blotting. Enzymatic activity testing showed maximum catalytic activity at pH 7.0, with K-m values for PEP and ADP determined. The effects of 13 compounds on BmPYKI and the growth of B. microti were investigated, revealing potential new anti-Babesia drug targets.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Environmental Sciences
Natarajan Rajamohan, Subrajit Bosu, Manivasagan Rajasimman, Sunita Varjani
Summary: In this research, a novel nano sorbent IL-MCNT was used to remove Selenium from aqueous media. The optimal operating conditions were determined as pH 2.0, 100 mg/L of IL-MCNT dosage, 308 K temperature, 45 min of contact time, and 110 g of IL-MCNT dosage. The Langmuir isotherm and pseudo-second-order model were found to fit the experimental data well.
ENVIRONMENTAL RESEARCH
(2023)
Article
Biotechnology & Applied Microbiology
Shunichi Kobayashi, Shota Atsumi, Kazunori Ikebukuro, Koji Sode, Ryutaro Asano
Summary: In this study, a green light-inducible alcohol production system was successfully integrated into cyanobacteria to produce value-added chemicals without using expensive chemical inducers. This eco-friendly and cost-effective approach increases the feasibility of cyanobacterial bioprocesses.
MICROBIAL CELL FACTORIES
(2022)
Article
Chemistry, Analytical
Mika Hatada, Ellie Wilson, Mukund Khanwalker, David Probst, Junko Okuda-Shimazaki, Koji Sode
Summary: Diabetes is a rapidly growing global health emergency, and comprehensive management is necessary for patients. Therefore, the development of diabetes POCT sensors for real-time testing is important for the management of diabetic patients.
SENSORS AND ACTUATORS B-CHEMICAL
(2022)
Article
Endocrinology & Metabolism
Yutaro Inoue, Yasuhide Kusaka, Kotaro Shinozaki, Inyoung Lee, Koji Sode
Summary: In this study, a miniaturized integrated electrode combined with DET-type FADGDH enzyme was successfully developed for continuous glucose monitoring. The sensor showed a linear response to glucose concentration up to 500 mg/dL over an 11-day continuous measurement, and its performance was not significantly affected by acetaminophen and oxygen partial pressure.
JOURNAL OF DIABETES SCIENCE AND TECHNOLOGY
(2022)
Article
Endocrinology & Metabolism
Takeyuki Moriuchi, Yuto Otaki, Hiroya Satou, Fumihiko Chai, Yuma Hayashida, Ryokei Aikawa, Takayuki Sugiyama, Koji Sode
Summary: A new, highly accurate BGM system based on the latest optical measurement system and introducing a rare metal-free green-strip was developed. This system achieved the highest reported accuracy in clinical research, using venous blood from patients with diabetes. The sensor strip also exhibited high heat resistance.
JOURNAL OF DIABETES SCIENCE AND TECHNOLOGY
(2022)
Article
Biophysics
Shouhei Takamatsu, Inyoung Lee, Jinhee Lee, Ryutaro Asano, Wakako Tsugawa, Kazunori Ikebukuro, Jeffrey E. Dick, Koji Sode
Summary: This study reports a novel sensing principle for o-serine using transient potentiometry based o-serine sensor with engineered DAAOx. The sensor showed rapid and sensitive signals, suitable for monitoring with different time resolution and concentration ranges.
BIOSENSORS & BIOELECTRONICS
(2022)
Article
Biophysics
Mukund Khanwalker, Rinko Fujita, Jinhee Lee, Ellie Wilson, Kohei Ito, Ryutaro Asano, Kazunori Ikebukuro, Jeffrey LaBelle, Koji Sode
Summary: This study focuses on utilizing anti-insulin single chain variable fragment as a biosensing molecule combined with single frequency faradaic electrochemical impedance spectroscopy to develop a sensor for efficient insulin detection. By comparing two immobilization methods, the study demonstrates the sensor's effectiveness and determines the optimal measurement frequency.
BIOSENSORS & BIOELECTRONICS
(2022)
Article
Chemistry, Analytical
Madoka Nagata, Jinhee Lee, Stephen Henley, Kazunori Ikebukuro, Koji Sode
Summary: The study introduces the use of amine-reactive phenazine ethosulfate (arPES) in electrochemical aptamer-based biosensors (E-ABs) for thrombin detection, showing stable signal at physiological pH and potential application in a simultaneous multianalyte detection system.
Article
Endocrinology & Metabolism
Inyoung Lee, Tsugawa Wakako, Kazunori Ikebukuro, Koji Sode
Summary: This study demonstrates a DET-type OCP glucose sensor with long-term operational stability, making it suitable for next generation CGM technology.
JOURNAL OF DIABETES SCIENCE AND TECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Takumi Yanase, Junko Okuda-Shimazaki, Ryutaro Asano, Kazunori Ikebukuro, Koji Sode, Wakako Tsugawa
Summary: The aim of this research is to develop a versatile method for creating a DET-type oxidoreductase complex based on the SpyCatcher/SpyTag technique. By combining SpyCatcher-fused heme c and SpyTag-fused non-DET-type oxidoreductases, DET-type oxidoreductase complexes with retained enzymatic activity and electron transfer ability to the electrode were successfully formed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pathology
Tomoaki Murakami, Toshisuke Kaku, Kaori Tsukakoshi, Susumu Iwaide, Yoshiyuki Itoh, Miki Hisada, Kohji Nomura, Rikako Kubo, Kazunori Ikebukuro, Yukiko Sassa-O'Brien, Fuyuki Kametani
Summary: This study identified a novel amyloid precursor protein, alpha-S1-casein (CASA1), in canine mammary tumor-associated amyloidosis (MTAA) and elucidated its etiology. The truncation of CASA1's N-terminal region and its excessive synthesis were found to be responsible for the amyloid formation in MTAA. These findings provide valuable insights into the understanding of related proteopathies.
VETERINARY PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Madoka Nagata, Jinhee Lee, Taro Saito, Kazunori Ikebukuro, Koji Sode
Summary: This study presents an anti-idiotype aptamer-based electrochemical sensor for measuring the therapeutic antibody bevacizumab. The sensor was able to detect the target antibody within 30 minutes using a modified anti-idiotype bivalent aptamer. The sensor achieved detection of bevacizumab in the range of 1-100 nM without the need for free redox probes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Inyoung Lee, Sheng Tong, Mika Hatada, Adrianna Masterson, Kentaro Hiraka, Junko Okuda-Shimazaki, Wakako Tsugawa, Gary Hughes, Koji Sode
Summary: In this study, researchers constructed a TG sensor using engineered glycerol 3-phosphate oxidase (GlpO) and electrochemical detection. By using disposable interdigitated electrode (IDE), a highly sensitive electrochemical sensor for TG was achieved, with a sensitivity of 0.4 μA/mM, 2.4 times higher than that of the conventional screen-printed carbon electrode (SPCE).
SENSORS AND ACTUATORS REPORTS
(2023)
Article
Biotechnology & Applied Microbiology
David Probst, Inyoung Lee, Jeffrey E. Dick, Koji Sode
Summary: In this study, we presented the application of a closed bipolar electrode for measuring the change in open circuit potential (OCP) of Prussian blue/white as a function of chloride ion concentration. The bipolar scheme consisted of two separate cells connected by a shared electrode, with one end sensitive to chloride ions and the other electrodeposited with Prussian blue. By monitoring the changes in the ratio of Prussian blue/Prussian white over the Prussian blue electrode, we demonstrated the capability of quantifying chloride ions independently of electrode surface area.
SENSORS AND ACTUATORS REPORTS
(2023)