707 results on '"Kanneganti A"'
Search Results
2. Optimizing intrauterine insemination and spontaneous conception in women with unilateral hydrosalpinx or tubal pathology: A systematic review and narrative synthesis
- Author
-
Jia Yun Yip, Abhiram Kanneganti, Nurulhuda binte Ahmad, Mei Xian Karen Lim, Siong Lin Stephen Chew, and Zhongwei Huang
- Subjects
Reproductive Medicine ,Obstetrics and Gynecology - Published
- 2023
3. ADAR1 and ZBP1 in innate immunity, cell death, and disease
- Author
-
Rajendra Karki and Thirumala-Devi Kanneganti
- Subjects
Immunology ,Immunology and Allergy - Published
- 2023
4. House Prices Advanced Regression Techniques
- Author
-
Gadde Vinay Venkata Abhinav Kumar, Kanneganti Subba Rayudu, Gutta Ajay Kumar, and Dr. Thatavarti Satish
- Subjects
General Medicine - Abstract
The real estate industry is seeing an increase in the use of data mining. The capacity of data mining to extricate helpful data from crude information makes it especially helpful for anticipating home estimations, essential housing characteristics, and a great many different elements. Homeowners and the real estate industry frequently feel anxious about price swings, according to research. The most useful models and important criteria for predicting home values are examined in a literature review. The adoption of Random Forest and XGBoost as the most effective models in comparison to others was confirmed by this study's findings. Additionally, our data suggest that locational and structural characteristics are significant forecasting variables for housing values. In order to identify the most effective machine learning model for conducting a study in this field and the most significant factors that influence home prices, this study will be very helpful, particularly to housing developers and academics.
- Published
- 2023
5. An Unusual Manifestation of Cardiac Tamponade in Autoimmune Thyroiditis
- Author
-
Vikas Suri, Ashish Bhalla, Vineetha Kanneganti, and Harpreet Singh
- Subjects
Pharmacology ,Ecology ,Physics and Astronomy (miscellaneous) ,Physiology ,General Chemical Engineering ,Organic Chemistry ,Biomedical Engineering ,Pharmaceutical Science ,General Physics and Astronomy ,Plant Science ,General Chemistry ,Condensed Matter Physics ,Biochemistry ,Analytical Chemistry ,Surfaces, Coatings and Films ,Complementary and alternative medicine ,Nuclear Energy and Engineering ,Drug Discovery ,Molecular Medicine ,Agronomy and Crop Science ,Ecology, Evolution, Behavior and Systematics - Published
- 2023
6. Estimating sewage flow rate in Jefferson County, Kentucky, using machine learning for wastewater-based epidemiology applications
- Author
-
Dhiraj Kanneganti, Lauren E. Reinersman, Rochelle H. Holm, and Ted Smith
- Subjects
Water Science and Technology - Abstract
Direct measurement of the flow rate in sanitary sewer lines is not always feasible and is an important parameter for the normalization of data used in wastewater-based epidemiology applications. Machine learning to estimate past wastewater influent flow rates supporting public health applications has not been studied. The aim of this study was to assess wastewater treatment plant influent flow rates when compared with weather data and to retrospectively estimate flow rates in Louisville, Kentucky (USA), based on other data-types using machine learning. A random forest model was trained using a range of variables, such as feces-related indicators, weather data that could be associated with dilution in sewage systems, and area demographics. The developed algorithm successfully estimated the flow rate with an accuracy of 91.7%, although it did not perform as well with short-term (one-day) high flow rates. This study suggests that using variables such as precipitation (mm/day) and population size are more important for wastewater flow estimation. The fecal indicator concentration (cross-assembly phage and pepper mild mottle virus) was less important. Our study challenges currently accepted opinions by showing the important public health potential application of artificial intelligence in wastewater treatment plant flow rate estimation for wastewater-based epidemiological applications.
- Published
- 2022
7. Clinical outcomes of patients with Liver Imaging Reporting and Data System 3 or Liver Imaging Reporting and Data System 4 observations in patients with cirrhosis: A systematic review
- Author
-
Mounika Kanneganti, Jorge A. Marrero, Neehar D. Parikh, Fasiha Kanwal, Takeshi Yokoo, Mishal Mendiratta‐Lala, Nicole E. Rich, Purva Gopal, and Amit G. Singal
- Subjects
Male ,Liver Cirrhosis ,Transplantation ,Carcinoma, Hepatocellular ,Hepatology ,Liver Neoplasms ,Humans ,Contrast Media ,Surgery ,Magnetic Resonance Imaging ,Sensitivity and Specificity ,Retrospective Studies ,Liver Transplantation - Abstract
Patients with indeterminate liver nodules, classified as LR-3 and LR-4 observations per the Liver Imaging Reporting and Data System, are at risk of developing hepatocellular carcinoma (HCC), but risk estimates remain imprecise. We conducted a systematic review of Ovid MEDLINE, EMBASE, and Cochrane databases from inception to December 2021 to identify cohort studies examining HCC incidence among patients with LR-3 or LR-4 observations on computed tomography (CT) or magnetic resonance imaging (MRI). Predictors of HCC were abstracted from each study, when available. Of 13 total studies, nine conducted LR-3 observation-level analyses, with the proportions of incident HCC ranging from 1.2% to 12.5% at 12 months and 4.2% to 44.4% during longer study follow-up. Among three studies with patient-level analyses, 8%-22.2% of patients with LR-3 lesions developed LR-4 observations and 11.1%-24.5% developed HCC. Among nine studies conducting LR-4 observation-level analyses, incident HCC ranged from 30.8% to 44.0% at 12 months and 30.9% to 71.0% during study follow-up; conversely, 6%-42% of observations were downgraded to LR-3 or lower. Patient-level factors associated with HCC included older age, male sex, higher alpha-fetoprotein levels, viral etiology, and prior history of HCC; observation-level factors included maximum diameter, threshold growth, T2 hyperintensity, and visibility on ultrasound. Studies were limited by small sample sizes, inclusion of patients with prior HCC, short follow-up duration, and failure to account for clustering of observations in patients or competing risks of transplantation and death. LR-3 and LR-4 observations have elevated but variable risks of HCC. Higher quality studies are necessary to identify high-risk patients who warrant close CT or MRI-based follow-up.
- Published
- 2022
8. Management of positional axillary artery compression in a baseball pitcher with embolic ischemia of the upper extremity
- Author
-
Manasa Kanneganti, Baris Yildirim, Samuel R. Montgomery, A. Bobby Chhabra, and Margaret C. Tracci
- Subjects
Orthopedics and Sports Medicine ,Surgery ,General Medicine - Published
- 2022
9. Minimally-invasive approach to emergent colorectal surgery in aging adults: A report from the Surgical Care Outcomes Assessment Program
- Author
-
Alex Charboneau, Timothy Feldmann, Shalini Kanneganti, Jennifer A. Kaplan, Ravi Moonka, Arthur Sillah, Richard C. Thirlby, and Vlad V. Simianu
- Subjects
Aging ,Outcome Assessment, Health Care ,Humans ,Minimally Invasive Surgical Procedures ,Surgery ,General Medicine ,Length of Stay ,Colorectal Surgery ,Aged ,Retrospective Studies - Abstract
Despite known benefits of minimally invasive surgery(MIS) in elective settings, MIS use in emergency colorectal surgery(CRS) is limited. Older adults are more likely to require emergent CRS, and MIS is used less frequently with increasing age.A retrospective cohort was constructed of emergent CRS cases performed between 2011 and 2019. Discharge(DC) disposition, adverse events, and length of stay(LOS) between MIS and open surgery were compared and stratified by age. Adjustment was made for selected confounders using inverse probability weighting.Of 6913 emergent CRS cases across 50 hospitals, 1616(23%) were approached MIS. MIS cases were more likely [OR(95%CI)] to DC home [65yo:1.7(1.3,2.2); 65-74:1.5(1.1,1.9); 75+:1.2(0.9,1.5)] and have fewer adverse events [65yo:0.6(0.5,0.8); 65-74:0.7(0.5,0.9); 75+:0.7(0.5,0.9)]. LOS was shorter [Mean difference in days(95%CI)] [65yo: 2.2(-2.9,-1.4); 65-74: 0.9(-2.7,1.0); 75+: 0.7(-1.7,0.2)].MIS in emergent CRS is associated with increased DC to home, fewer adverse events, and shorter LOS. Benefits persisted with age after adjustment, suggesting an opportunity for improved MIS delivery in older adults.
- Published
- 2022
10. Towards Temporal Scaling Laws for the Risk Analysis of Rare Flood Events
- Author
-
Kanneganti Bhargav Kumar and Pradeep P Mujumdar
- Abstract
Extreme flood events are rare but catastrophic and have tremendous adverse impacts on human lives and the economy. The frequency and magnitude of such events have increased globally and are likely to worsen in the future. Traditional flood risk methods estimate the extreme quantiles based on the assumption that historical data recorded at gauge stations contain a spectrum of extreme flood magnitudes. However, the available gauge station record lengths are small for several gauge stations, and these records are less likely to capture the full range of likely flood magnitudes. Hence, it is necessary to develop methods to extrapolate better the dynamics of large and rare events from historical data containing only small but frequent fluctuations. This study aims to use the scaling relation of return intervals, which is invariant for various thresholds in long-term correlated historical records and accurately estimate the risk associated with rare events. The analysis is carried out on 212 daily streamflow series across the major river basins in peninsular India. Persistence in the streamflow series is examined by estimating the Hurst coefficient with a Detrended Fluctuation Analysis. Return level distribution parameters are then estimated using the analytic equations between parameters and the Hurst coefficient. The threshold-invariant scaling of the probability of return intervals and the ratio of return levels to mean return levels allows the formulation of hazard functions, which are, in turn, used to estimate the risk of rare events. This work provides an approach for obtaining flood event sets that may contain a wider range of magnitudes than present in the historical data. The present study contributes towards improving the at-site frequency analysis of floods using the temporal scaling law of return levels. Simultaneous occurrence of different extremes may alter the return levels of rare events such as, for example, flooding in coastal areas caused by the compound effect of storm surge and streamflow. This work can be extended to understand the effect of long-term memory and the cross-correlation of causal factors on risk estimation of compound extremes.
- Published
- 2023
11. Apoptotic cell death in disease-Current understanding of the NCCD 2023
- Author
-
Vitale, Ilio, Pietrocola, Federico, Guilbaud, Emma, Aaronson, Stuart A, Abrams, John M, Adam, Dieter, Agostini, Massimiliano, Agostinis, Patrizia, Alnemri, Emad S, Altucci, Lucia, Amelio, Ivano, Andrews, David W, Aqeilan, Rami I, Arama, Eli, Baehrecke, Eric H, Balachandran, Siddharth, Bano, Daniele, Barlev, Nickolai A, Bartek, Jiri, Bazan, Nicolas G, Becker, Christoph, Bernassola, Francesca, Bertrand, Mathieu JM, Bianchi, Marco E, Blagosklonny, Mikhail V, Blander, J Magarian, Blandino, Giovanni, Blomgren, Klas, Borner, Christoph, Bortner, Carl D, Bove, Pierluigi, Boya, Patricia, Brenner, Catherine, Broz, Petr, Brunner, Thomas, Damgaard, Rune Busk, Calin, George A, Campanella, Michelangelo, Candi, Eleonora, Carbone, Michele, Carmona-Gutierrez, Didac, Cecconi, Francesco, Chan, Francis K-M, Chen, Guo-Qiang, Chen, Quan, Chen, Youhai H, Cheng, Emily H, Chipuk, Jerry E, Cidlowski, John A, Ciechanover, Aaron, Ciliberto, Gennaro, Conrad, Marcus, Cubillos-Ruiz, Juan R, Czabotar, Peter E, D'Angiolella, Vincenzo, Daugaard, Mads, Dawson, Ted M, Dawson, Valina L, De Maria, Ruggero, De Strooper, Bart, Debatin, Klaus-Michael, Deberardinis, Ralph J, Degterev, Alexei, Del Sal, Giannino, Deshmukh, Mohanish, Di Virgilio, Francesco, Diederich, Marc, Dixon, Scott J, Dynlacht, Brian D, El-Deiry, Wafik S, Elrod, John W, Engeland, Kurt, Fimia, Gian Maria, Galassi, Claudia, Ganini, Carlo, Garcia-Saez, Ana J, Garg, Abhishek D, Garrido, Carmen, Gavathiotis, Evripidis, Gerlic, Motti, Ghosh, Sourav, Green, Douglas R, Greene, Lloyd A, Gronemeyer, Hinrich, Häcker, Georg, Hajnóczky, György, Hardwick, J Marie, Haupt, Ygal, He, Sudan, Heery, David M, Hengartner, Michael O, Hetz, Claudio, Hildeman, David A, Ichijo, Hidenori, Inoue, Satoshi, Jäättelä, Marja, Janic, Ana, Joseph, Bertrand, Jost, Philipp J, and Kanneganti, Thirumala-Devi
- Subjects
Mammals ,Biochemistry & Molecular Biology ,Cell Death ,Carcinogenesis ,Liver Disease ,1.1 Normal biological development and functioning ,Apoptosis ,Biological Sciences ,Medical and Health Sciences ,Good Health and Well Being ,Underpinning research ,Caspases ,Animals ,Humans ,Generic health relevance ,Digestive Diseases - Abstract
Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. Here, the Nomenclature Committee on Cell Death (NCCD) gathered to critically summarize anabundant pre-clinical literature mechanistically linking the core apoptotic apparatus to organismal homeostasis in the context of disease.
- Published
- 2023
12. Epithelial aryl hydrocarbon receptor regulates IL-22 producing colonic group 3 innate lymphoid cells to augment microbial metabolite mediated protection in colitis
- Author
-
Sweta Ghosh, Zachary M. Vanwinkle, Gerald W Dryden, Thirumala-Devi Kanneganti, Bodduluri Haribabu, and Venkatakrishna R JALA
- Subjects
Physiology - Abstract
The intestinal barrier dysfunction is intimately associated with inflammatory bowel diseases (IBD) as the gut barrier provides the first line of protection to host from external factors. The pathogenesis of IBD is multifactorial resulting from combinations of genetic polymorphism, environmental factors, diet, altered microbiota and the immune system. Aryl hydrocarbon receptor (AhR) is a ligand-activated basic-helix-loop-helix transcription factor which upon activation can regulate many pathophysiological functions like inflammation and gut barrier homeostasis. Recently, we identified that microbial metabolite Urolithin A (UroA) mitigated colitis in pre-clinical models through activation of AhR-dependent pathways at two distinct levels by preserving the gut barrier function and reducing systemic and acute inflammation. However, the interplay between the enhanced barrier function and reduction in inflammation and the requirement of specific cell types to mediate the UroA activities remains to be established. In the current study, we evaluated the UroA mediated cell specific requirement of AhR by using transgenic mice AhRfx-VillinCre (AhR is deleted in intestinal epithelial cells) and AhRfx-LysMCre (AhR is deleted in myeloid cells) mice. Our studies showed that UroA mediated activation of gut AhR is critical for regulation of intestinal homeostasis in dextran sodium sulphate (DSS) induced colitis. UroA also activated intestinal AhR dependent signaling to induce IL-22 production from type 3 innate lymphoid cells (ILC3). Further, our data from intestinal organoids revealed that AhR dependent-induction of IL-18 from intestinal epithelial cells is responsible for IL-22 production from immune cells. These studies revealed the novel findings that microbial metabolite mediated selective activation of AhR regulates the IL-18/IL-22-axis to maintain gut homeostasis and enhance gut barrier function to attenuate IBD pathogenesis. Current studies are supported by NIH/NIGMS COBRE project P20-GM125504-01 and JHFEREG from University of Louisville. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
- Published
- 2023
13. Apoptotic cell death in disease—Current understanding of the NCCD 2023
- Author
-
Vitale, Ilio, Pietrocola, Federico, Guilbaud, Emma, Aaronson, Stuart A, Abrams, John M, Adam, Dieter, Agostini, Massimiliano, Agostinis, Patrizia, Alnemri, Emad S, Altucci, Lucia, Amelio, Ivano, Andrews, David W, Aqeilan, Rami I, Arama, Eli, Baehrecke, Eric H, Balachandran, Siddharth, Bano, Daniele, Barlev, Nickolai A, Bartek, Jiri, Bazan, Nicolas G, Becker, Christoph, Bernassola, Francesca, Bertrand, Mathieu J M, Bianchi, Marco E, Blagosklonny, Mikhail V, Blander, J Magarian, Blandino, Giovanni, Blomgren, Klas, Borner, Christoph, Bortner, Carl D, Bove, Pierluigi, Boya, Patricia, Brenner, Catherine, Broz, Petr, Brunner, Thomas, Damgaard, Rune Busk, Calin, George A, Campanella, Michelangelo, Candi, Eleonora, Carbone, Michele, Carmona-Gutierrez, Didac, Cecconi, Francesco, Chan, Francis K-M, Chen, Guo-Qiang, Chen, Quan, Chen, Youhai H, Cheng, Emily H, Chipuk, Jerry E, Cidlowski, John A, Ciechanover, Aaron, Ciliberto, Gennaro, Conrad, Marcus, Cubillos-Ruiz, Juan R, Czabotar, Peter E, D'Angiolella, Vincenzo, Daugaard, Mads, Dawson, Ted M, Dawson, Valina L, De Maria, Ruggero, De Strooper, Bart, Debatin, Klaus-Michael, Deberardinis, Ralph J, Degterev, Alexei, Del Sal, Giannino, Deshmukh, Mohanish, Di Virgilio, Francesco, Diederich, Marc, Dixon, Scott J, Dynlacht, Brian D, El-Deiry, Wafik S, Elrod, John W, Engeland, Kurt, Fimia, Gian Maria, Galassi, Claudia, Ganini, Carlo, Garcia-Saez, Ana J, Garg, Abhishek D, Garrido, Carmen, Gavathiotis, Evripidis, Gerlic, Motti, Ghosh, Sourav, Green, Douglas R, Greene, Lloyd A, Gronemeyer, Hinrich, Häcker, Georg, Hajnóczky, György, Hardwick, J Marie, Haupt, Ygal, He, Sudan, Heery, David M, Hengartner, Michael O, Hetz, Claudio, Hildeman, David A, Ichijo, Hidenori, Inoue, Satoshi, Jäättelä, Marja, Janic, Ana, Joseph, Bertrand, Jost, Philipp J, Kanneganti, Thirumala-Devi, Karin, Michael, Kashkar, Hamid, Kaufmann, Thomas, Kelly, Gemma L, Kepp, Oliver, Kimchi, Adi, Kitsis, Richard N, Klionsky, Daniel J, Kluck, Ruth, Krysko, Dmitri V, Kulms, Dagmar, Kumar, Sharad, Lavandero, Sergio, Lavrik, Inna N, Lemasters, John J, Liccardi, Gianmaria, Linkermann, Andreas, Lipton, Stuart A, Lockshin, Richard A, López-Otín, Carlos, Luedde, Tom, MacFarlane, Marion, Madeo, Frank, Malorni, Walter, Manic, Gwenola, Mantovani, Roberto, Marchi, Saverio, Marine, Jean-Christophe, Martin, Seamus J, Martinou, Jean-Claude, Mastroberardino, Pier G, Medema, Jan Paul, Mehlen, Patrick, Meier, Pascal, Melino, Gerry, Melino, Sonia, Miao, Edward A, Moll, Ute M, Muñoz-Pinedo, Cristina, Murphy, Daniel J, Niklison-Chirou, Maria Victoria, Novelli, Flavia, Núñez, Gabriel, Oberst, Andrew, Ofengeim, Dimitry, Opferman, Joseph T, Oren, Moshe, Pagano, Michele, Panaretakis, Theocharis, Pasparakis, Manolis, Penninger, Josef M, Pentimalli, Francesca, Pereira, David M, Pervaiz, Shazib, Peter, Marcus E, Pinton, Paolo, Porta, Giovanni, Prehn, Jochen H M, Puthalakath, Hamsa, Rabinovich, Gabriel A, Rajalingam, Krishnaraj, Ravichandran, Kodi S, Rehm, Markus, Ricci, Jean-Ehrland, Rizzuto, Rosario, Robinson, Nirmal, Rodrigues, Cecilia M P, Rotblat, Barak, Rothlin, Carla V, Rubinsztein, David C, Rudel, Thomas, Rufini, Alessandro, Ryan, Kevin M, Sarosiek, Kristopher A, Sawa, Akira, Sayan, Emre, Schroder, Kate, Scorrano, Luca, Sesti, Federico, Shao, Feng, Shi, Yufang, Sica, Giuseppe S, Silke, John, Simon, Hans-Uwe, Sistigu, Antonella, Stephanou, Anastasis, Stockwell, Brent R, Strapazzon, Flavie, Strasser, Andreas, Sun, Liming, Sun, Erwei, Sun, Qiang, Szabadkai, Gyorgy, Tait, Stephen W G, Tang, Daolin, Tavernarakis, Nektarios, Troy, Carol M, Turk, Boris, Urbano, Nicoletta, Vandenabeele, Peter, Vanden Berghe, Tom, Vander Heiden, Matthew G, Vanderluit, Jacqueline L, Verkhratsky, Alexei, Villunger, Andreas, von Karstedt, Silvia, Voss, Anne K, Vousden, Karen H, Vucic, Domagoj, Vuri, Daniela, Wagner, Erwin F, Walczak, Henning, Wallach, David, Wang, Ruoning, Wang, Ying, Weber, Achim, Wood, Will, Yamazaki, Takahiro, Yang, Huang-Tian, Zakeri, Zahra, Zawacka-Pankau, Joanna E, Zhang, Lin, Zhang, Haibing, Zhivotovsky, Boris, Zhou, Wenzhao, Piacentini, Mauro, Kroemer, Guido, Galluzzi, Lorenzo, Vitale, Ilio, Pietrocola, Federico, Guilbaud, Emma, Aaronson, Stuart A, Kumar, Sharad, Galluzzi, Lorenzo, Associazione Italiana per la Ricerca sul Cancro, Italian Institute for Genomic Medicine, Compagnia di San Paolo, Aaronson, Stuart A., Dieter, Adam, Agostini, Massimiliano, Agostinis, Patrizia, Alnemri, Emad S., Altucci, Lucia, Amelio, Ivano, Andrews, David W., Aqeilan, Rami I., Arama, Eli, Balachandran, Siddharth, Bano, Daniele, Bartek, Jiri, Bazan, Nicolas G., Bernassola, Francesca, Bertrand, Mathieu J. M., Bianchi, Marco Emilio, Blander, J. Magarian, Blandino, Giovanni, Blomgren, Klas, Bortner, Carl D., Bove, Pierluigi, Boya, Patricia, Broz, Petr, Damgaard, Rune Busk, Calin, George A., Campanella, Michelangelo, Candi, Eleonora, Carbone, Michele, Carmona-Gutierrez, Didac, Cecconi, Francesco, Chen, Guo‑Qiang, Cheng, Emily H., Chipuk, Jerry E., Cidlowski, John A., Ciechanover, Aaron, Ciliberto, Gennaro, Conrad, Marcus, Czabotar, Peter E., D’Angiolella, Vincenzo, Daugaard, Mads, Dawson, Valina L., De Maria, Ruggero, Debatin, Klaus-Michael, Deberardinis, Ralph J., Degterev, Alexei, Del Sal, Giannino, Deshmukh, Mohanish, Di Virgilio, Francesco, Diederich, Marc, Dixon, Scott J., El-Deiry, Wafik S., Elrod, John W., Engeland, Kurt, Fimia, Gian María, Ganini, Carlo, García-Sáez, Ana J., Garg, Abhishek D., Garrido, Carmen, Gavathiotis, Evripidis, Ghosh, Sourav, Green, Douglas R., Gronemeyer, Hinrich, Häcker, Georg, Hajnóczky, György, Hardwick, J. Marie, Haupt, Ygal, He, Sudan, Heery, David M., Hengartner, Michael O., Hetz, Claudio, Hildeman, David A., Ichijo, Hidenori, Jäättelä, Marja, Janic, Ana, Joseph, Bertrand, Jost, Philipp J., Kanneganti, Thirumala-Devi, Karin, Michael, Kashkar, Hamid, Kaufmann, Thomas, Kelly, Gemma L., Kepp, Oliver, Kimchi, Adi, Klionsky, Daniel J., Kluck, Ruth, Krysko, Dmitri V., Kulms, Dagmar, Lavandero, Sergio, Lavrik, Inna N., Liccardi, Gianmaria, Linkermann, Andreas, Lipton, Stuart A., Lockshin, Richard A., López-Otín, Carlos, Luedde, Tom, MacFarlane, Marion, Madeo, Frank, Malorni, Walter, Manic, Gwenola, Marchi, Saverio, Marine, Jean-Christophe, Martin, Seamus J., Martinou, Jean-Claude, Mastroberardino, Pier G., Medema, Jan Paul, Mehlen, Patrick, Meier, Pascal, Melino, Gerry, Melino, Sonia, Miao, Edward A., Moll, Ute M., Muñoz-Pinedo, Cristina, Murphy, Daniel J., Niklison-Chirou, Maria Victoria, Novelli, Flavia, Oberst, Andrew, Ofengeim, Dimitry, Opferman, Joseph T., Oren, Moshe, Pagano, Michele, Panaretakis, Theocharis, Pasparakis, Manolis, Penninger, Josef M., Pentimalli, Francesca, Pereira, David M., Pervaiz, Shazib, Peter, Marcus E., Pinton, Paolo, Porta, Giovanni, Puthalakath, Hamsa, Rabinovich, Gabriel A., Rajalingam, Krishnaraj, Ravinchandran, Kodi S., Rehm, Markus, Ricci, Jean-Ehrland, Rizzuto, Rosario, Robinson, Nirmal, Rotblat, Barak, Rothlin, Carla V., Rubinsztein, David C., Rufini, Alessandro, Ryan, Kevin M., Sarosiek, Kristopher A., Sawa, Akira, Sayan, Emre, Schroder, Kate, Scorrano, Luca, Sesti, Federico, Shi, Yufang, Sica, Giuseppe, Silke, John, Simon, Hans-Uwe, Sistigu, Antonella, Stockwell, Brent R., Strappazzon, Flavie, Sun, Liming, Sun, Erwei, Szabadkai, G, Tait, Stephen W. G., Tang, Daolin, Tavernarakis, Nektarios, Turk, Boris, Urbano, Nicoletta, Vandenabeele, Peter, Vanden Berghe, Tom, Vander Heiden, Matthew G., Vanderluit, Jacqueline L., Verkhratsky, A., Villunger, Andreas, Von Karstedt, Silvia, Voss, Anne K., Vucic, Domagoj, Vuri, Daniela, Wagner, Erwin F., Walczak, Henning, Wallach, David, Wang, Ruoning, Weber, Achim, Yamazaki, Takahiro, Zakeri, Zahra, Zawacka-Pankau, Joanna E., Zhivotovsky, Boris, Piacentini, Mauro, Kroemer, Guido, Vitale, Ilio [0000-0002-5918-1841], Piacentini, Mauro [0000-0003-2919-1296], Kroemer, Guido [0000-0002-9334-4405], Galluzzi, Lorenzo [0000-0003-2257-8500], Apollo - University of Cambridge Repository, Abrams, John M, Adam, Dieter, Alnemri, Emad S, Andrews, David W, Aqeilan, Rami I, Baehrecke, Eric H, Barlev, Nickolai A, Bazan, Nicolas G, Becker, Christoph, Bertrand, Mathieu J M, Bianchi, Marco E, Blagosklonny, Mikhail V, Blander, J Magarian, Blomgren, Kla, Borner, Christoph, Bortner, Carl D, Brenner, Catherine, Brunner, Thoma, Calin, George A, Chan, Francis K-M, Chen, Guo-Qiang, Chen, Quan, Chen, Youhai H, Cheng, Emily H, Chipuk, Jerry E, Cidlowski, John A, Conrad, Marcu, Cubillos-Ruiz, Juan R, Czabotar, Peter E, D'Angiolella, Vincenzo, Daugaard, Mad, Dawson, Ted M, Dawson, Valina L, De Strooper, Bart, Deberardinis, Ralph J, Dixon, Scott J, Dynlacht, Brian D, El-Deiry, Wafik S, Elrod, John W, Fimia, Gian Maria, Galassi, Claudia, Garcia-Saez, Ana J, Garg, Abhishek D, Gavathiotis, Evripidi, Gerlic, Motti, Green, Douglas R, Greene, Lloyd A, Hardwick, J Marie, Heery, David M, Hengartner, Michael O, Hildeman, David A, Inoue, Satoshi, Jost, Philipp J, Kaufmann, Thoma, Kelly, Gemma L, Kitsis, Richard N, Klionsky, Daniel J, Krysko, Dmitri V, Lavrik, Inna N, Lemasters, John J, Linkermann, Andrea, Lipton, Stuart A, Lockshin, Richard A, López-Otín, Carlo, Macfarlane, Marion, Mantovani, Roberto, Martin, Seamus J, Mastroberardino, Pier G, Miao, Edward A, Moll, Ute M, Murphy, Daniel J, Núñez, Gabriel, Opferman, Joseph T, Panaretakis, Theochari, Pasparakis, Manoli, Penninger, Josef M, Pereira, David M, Peter, Marcus E, Prehn, Jochen H M, Rabinovich, Gabriel A, Ravichandran, Kodi S, Rehm, Marku, Rodrigues, Cecilia M P, Rothlin, Carla V, Rubinsztein, David C, Rudel, Thoma, Ryan, Kevin M, Sarosiek, Kristopher A, Shao, Feng, Sica, Giuseppe S, Stephanou, Anastasi, Stockwell, Brent R, Strapazzon, Flavie, Strasser, Andrea, Sun, Qiang, Szabadkai, Gyorgy, Tait, Stephen W G, Tavernarakis, Nektario, Troy, Carol M, Turk, Bori, Vander Heiden, Matthew G, Vanderluit, Jacqueline L, Verkhratsky, Alexei, Villunger, Andrea, von Karstedt, Silvia, Voss, Anne K, Vousden, Karen H, Wagner, Erwin F, Wang, Ying, Wood, Will, Yang, Huang-Tian, Zawacka-Pankau, Joanna E, Zhang, Lin, Zhang, Haibing, Zhivotovsky, Bori, and Zhou, Wenzhao
- Subjects
Mammals ,genetics [Caspases] ,Cell Death ,Settore BIO/11 ,Carcinogenesis ,Cell death, diseases ,Settore BIO/12 ,metabolism [Mammals] ,Apoptosis ,Cell Biology ,genetic strategies ,regulated cell death (RCD) ,SDG 3 - Good Health and Well-being ,cell loss and tissue damage ,Settore BIO/10 - Biochimica ,Caspases ,Animals ,Humans ,metabolism [Caspases] ,ddc:610 ,Settore BIO/10 ,610 Medizin und Gesundheit ,Molecular Biology ,genetics [Apoptosis] - Abstract
58 p.-5 fig.-7 box., Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. Here, the Nomenclature Committee on Cell Death (NCCD) gathered to critically summarize an abundant pre-clinical literature mechanistically linking the core apoptotic apparatus to organismal homeostasis in the context of disease., I. Vitale is and has been supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC, IG 2017 #20417 and IG 2022 #27685) and by a startup grant from the Italian Institute for Genomic Medicine (Candiolo, Turin, Italy) and Compagnia di San Paolo (Torino, Italy). M. Piacentini, G. Melino, S. Melino, G. Ciliberto are supported by the Ministro dell’Università (Italy) progetto Heal Italia PE6. L. Galluzzi is/has been supported (as a PI unless otherwise indicated) by two Breakthrough Level 2 grants from the US DoD BCRP (#BC180476P1; #BC210945), by a Transformative Breast Cancer Consortium Grant from the US DoD BCRP (#W81XWH2120034, PI: Formenti), by a U54 grant from NIH/NCI (#CA274291, PI: Deasy, Formenti, Weichselbaum), by the 2019 Laura Ziskin Prize in Translational Research (#ZP-6177, PI: Formenti) from the Stand Up to Cancer (SU2C), by a Mantle Cell Lymphoma Research Initiative (MCL-RI, PI: Chen-Kiang) grant from the Leukemia and Lymphoma Society (LLS), by a Rapid Response Grant from the Functional Genomics Initiative (New York, US), by startup funds from the Dept. of Radiation Oncology at Weill Cornell Medicine (New York, US), by industrial collaborations with Lytix Biopharma (Oslo, Norway), Promontory (New York, US) and Onxeo (Paris, France), as well as by donations from Promontory (New York, US), the Luke Heller TECPR2 Foundation (Boston, US), Sotio a.s. (Prague, Czech Republic), Lytix Biopharma (Oslo, Norway), Onxeo (Paris, France), Ricerchiamo (Brescia, Italy), and Noxopharm (Chatswood, Australia). G. Kroemer is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR) – Projets blancs; AMMICa US23/CNRS UMS3655; Association pour la recherche sur le cancer (ARC); Cancéropôle Ile-de-France; European Research Council Advanced Investigator Grand “ICD-Cancer”, Fondation pour la Recherche Médicale (FRM); a donation by Elior; Equipex Onco-Pheno-Screen; European Joint Programme on Rare Diseases (EJPRD); European Research Council (ICD-Cancer), European Union Horizon 2020 Projects Oncobiome and Crimson; Fondation Carrefour; Institut National du Cancer (INCa); Institut Universitaire de France; LabEx Immuno-Oncology (ANR-18-IDEX-0001); a Cancer Research ASPIRE Award from the Mark Foundation; the RHU Immunolife; Seerave Foundation; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and SIRIC Cancer Research and Personalized Medicine (CARPEM)
- Published
- 2023
14. Flexural performance of sustainable concrete beams containing supplementary cementitious materials and glass fiber
- Author
-
Jyothishya Brahma Chari Kanneganti, Ranga Rao Vummaneni, and Kameswara Rao Burugapalli
- Subjects
Modeling and Simulation ,Industrial and Manufacturing Engineering - Published
- 2023
15. Supplementary Data from A MyD88/IL1R Axis Regulates PD-1 Expression on Tumor-Associated Macrophages and Sustains Their Immunosuppressive Function in Melanoma
- Author
-
Thirumala-Devi Kanneganti, R.K. Subbarao Malireddi, Peter Vogel, Geoffrey Neale, and Sarang Tartey
- Abstract
Supplementary Figures and Tables
- Published
- 2023
16. Data from A MyD88/IL1R Axis Regulates PD-1 Expression on Tumor-Associated Macrophages and Sustains Their Immunosuppressive Function in Melanoma
- Author
-
Thirumala-Devi Kanneganti, R.K. Subbarao Malireddi, Peter Vogel, Geoffrey Neale, and Sarang Tartey
- Abstract
Macrophages are critical mediators of tissue homeostasis, cell proliferation, and tumor metastasis. Tumor-associated macrophages (TAM) are generally associated with tumor-promoting immunosuppressive functions in solid tumors. Here, we examined the transcriptional landscape of adaptor molecules downstream of Toll-like receptors in human cancers and found that higher expression of MYD88 correlated with tumor progression. In murine melanoma, MyD88, but not Trif, was essential for tumor progression, angiogenesis, and maintaining the immunosuppressive phenotype of TAMs. In addition, MyD88 expression in myeloid cells drove melanoma progression. The MyD88/IL1 receptor (IL1R) axis regulated programmed cell death (PD)-1 expression on TAMs by promoting recruitment of NF-κBp65 to the Pdcd1 promoter. Furthermore, a combinatorial immunotherapy approach combining the MyD88 inhibitor with anti–PD-1 blockade elicited strong antitumor effects. Thus, the MyD88/IL1R axis maintains the immunosuppressive function of TAMs and promotes tumor growth by regulating PD-1 expression.Significance:These findings indicate that MyD88 regulates TAM-immunosuppressive activity, suggesting that macrophage-mediated immunotherapy combining MYD88 inhibitors with PD-1 blockade could result in better treatment outcomes in a wide variety of cancers.
- Published
- 2023
17. Supplementary Tables 1-5 from The Development of a Selective Cyclin-Dependent Kinase Inhibitor That Shows Antitumor Activity
- Author
-
R. Charles Coombes, Anthony G.M. Barrett, Eric O. Aboagye, Dennis C. Liotta, James P. Snyder, Seshu K. Kanneganti, Robert S. Tolhurst, Manikandan Periyasamy, Matthew J. Fuchter, Alekasandra Siwicka, Jan Brackow, Hetal Patel, Bodo Scheiper, Ashutosh S. Jogalekar, Sebastian H.B. Kroll, Dean A. Heathcote, and Simak Ali
- Abstract
Supplementary Tables 1-5 from The Development of a Selective Cyclin-Dependent Kinase Inhibitor That Shows Antitumor Activity
- Published
- 2023
18. Supplementary Figures 1-6 from The Development of a Selective Cyclin-Dependent Kinase Inhibitor That Shows Antitumor Activity
- Author
-
R. Charles Coombes, Anthony G.M. Barrett, Eric O. Aboagye, Dennis C. Liotta, James P. Snyder, Seshu K. Kanneganti, Robert S. Tolhurst, Manikandan Periyasamy, Matthew J. Fuchter, Alekasandra Siwicka, Jan Brackow, Hetal Patel, Bodo Scheiper, Ashutosh S. Jogalekar, Sebastian H.B. Kroll, Dean A. Heathcote, and Simak Ali
- Abstract
Supplementary Figures 1-6 from The Development of a Selective Cyclin-Dependent Kinase Inhibitor That Shows Antitumor Activity
- Published
- 2023
19. Supplementary Figure Legends 1-6 from The Development of a Selective Cyclin-Dependent Kinase Inhibitor That Shows Antitumor Activity
- Author
-
R. Charles Coombes, Anthony G.M. Barrett, Eric O. Aboagye, Dennis C. Liotta, James P. Snyder, Seshu K. Kanneganti, Robert S. Tolhurst, Manikandan Periyasamy, Matthew J. Fuchter, Alekasandra Siwicka, Jan Brackow, Hetal Patel, Bodo Scheiper, Ashutosh S. Jogalekar, Sebastian H.B. Kroll, Dean A. Heathcote, and Simak Ali
- Abstract
Supplementary Figure Legends 1-6 from The Development of a Selective Cyclin-Dependent Kinase Inhibitor That Shows Antitumor Activity
- Published
- 2023
20. Generative AI as a Tool for Environmental Health Research Translation
- Author
-
Lauren B. Anderson, Dhiraj Kanneganti, Mary Bentley Houk, Rochelle H. Holm, and Ted Smith
- Subjects
Article - Abstract
Generative artificial intelligence, popularized by services like ChatGPT, has been the source of much recent popular attention for publishing health research. Another valuable application is in translating published research studies to readers in non-academic settings. These might include environmental justice communities, mainstream media outlets, and community science groups. Five recently published (2021-2022) open-access, peer-reviewed papers, authored by University of Louisville environmental health investigators and collaborators, were submitted to ChatGPT. The average rating of all summaries of all types across the five different studies ranged between 3 and 5, indicating good overall content quality. ChatGPT’s general summary request was consistently rated lower than all other summary types. Whereas higher ratings of 4 and 5 were assigned to the more synthetic, insight-oriented activities, such as the production of a plain language summaries suitable for an 8thgrade reading level and identifying the most important finding and real-world research applications. This is a case where artificial intelligence might help level the playing field, for example by creating accessible insights and enabling the large-scale production of high-quality plain language summaries which would truly bring open access to this scientific information. This possibility, combined with the increasing public policy trends encouraging and demanding free access for research supported with public funds, may alter the role journal publications play in communicating science in society. For the field of environmental health science, no-cost AI technology such as ChatGPT holds the promise to improve research translation, but it must continue to be improved (or improve itself) from its current capability.
- Published
- 2023
21. A New cross-domain strategy based XAI models for fake news detection
- Author
-
Kanneganti, Deepak
- Subjects
FOS: Computer and information sciences ,Artificial Intelligence (cs.AI) ,Computer Science - Computation and Language ,Computer Science - Artificial Intelligence ,Computation and Language (cs.CL) - Abstract
In this study, we presented a four-level cross-domain strategy for fake news detection on pre-trained models. Cross-domain text classification is a task of a model adopting a target domain by using the knowledge of the source domain. Explainability is crucial in understanding the behaviour of these complex models. A fine-tune BERT model is used to. perform cross-domain classification with several experiments using datasets from different domains. Explanatory models like Anchor, ELI5, LIME and SHAP are used to design a novel explainable approach to cross-domain levels. The experimental analysis has given an ideal pair of XAI models on different levels of cross-domain.
- Published
- 2023
22. It's just a phase: NLRP6 phase separations drive signaling
- Author
-
Rebecca E. Tweedell and Thirumala-Devi Kanneganti
- Subjects
Lipopolysaccharides ,Inflammasomes ,Receptors, Cell Surface ,Cell Biology ,Biology ,Research Highlight ,Article ,CARD Signaling Adaptor Proteins ,Intestines ,Intrinsically Disordered Proteins ,Teichoic Acids ,Mice ,Liver ,Chemical physics ,Phase (matter) ,Hepatocytes ,Animals ,RNA Viruses ,Polylysine ,Amino Acid Sequence ,Molecular Biology ,Protein Binding ,RNA, Double-Stranded ,Signal Transduction - Abstract
NLRP6 is important in host defense by inducing functional outcomes including inflammasome activation and interferon production. Here we show that NLRP6 undergoes liquid-liquid phase separation (LLPS) upon interaction with dsRNA in vitro and in cells, and that an intrinsically disordered poly-lysine sequence (K350–354) of NLRP6 is important for multivalent interactions, phase separation and inflammasome activation. Nlrp6-deficient or Nlrp6(K350−354A) mutant mice show reduced inflammasome activation upon mouse hepatitis virus or rotavirus infection, and in steady state stimulated by intestinal microbiota, implicating NLRP6 LLPS in anti-microbial immunity. Recruitment of ASC via helical assembly solidifies NLRP6 condensates, and ASC further recruits and activates caspase-1. Lipoteichoic acid, a known NLRP6 ligand, also promotes NLRP6 LLPS, and DHX15, a helicase in NLRP6-induced interferon signaling, co-forms condensates with NLRP6 and dsRNA. Thus, LLPS of NLRP6 is a common response to ligand stimulation, which serves to direct NLRP6 to distinct functional outcomes depending on the cellular context.
- Published
- 2023
23. EFFECT OF ANHEDRAL AND DIHEDRAL ON THE LATERAL DIRECTIONAL STATIC STABILITY OF THE AIRCRAFT
- Author
-
Girish Kumar Chowdary Kanneganti, Bhaskar Charan, Vesapogu Chandrakala, and V. Varun
- Abstract
Developments and advancements in Aircraft industry have led to an increasing the stability and maneuverability of an aircraft. When the aircraft subjected to unbalanced force it needs the suitable wing to overcome the side slip and maneuverability of an aircraft. This work proposed a Dihedral and Anhedral wing simulation in XFLR5 software to increase the stability and maneuverability of an aircraft. XFLR5 analysis was then carried out for Dihedral and anhedral angles of 5deg, 10deg ,with side slip angles 2deg and 5deg. The aerofoil used in wing is NACA 4412 and in tail is 0009..Lateral-Directional Static Stability of 5,10 deg of both anhedral and dihedral wings are analyzed. The graphs are plotted between co-efficient of rolling moment and side slip angle ; co-efficient of yawing moment and side slip angle. The simulation is done in a free stream velocity of 60 m/s and inviscid flow. Anhedral is a negative dihedral angle .The anhedral reduces the dihedral effect bringing the wing's roll characteristics into a more desirable performance envelope while keeping it stable yet maneuverable.Dihedral is the upward angle of an aircraft's wings, which increases lateral stability in a bank by causing the lower wing to fly at a higher angle of attack than the higher wing.
- Published
- 2022
24. PANoptosome signaling and therapeutic implications in infection: central role for ZBP1 to activate the inflammasome and PANoptosis
- Author
-
Rajendra Karki and Thirumala-Devi Kanneganti
- Subjects
Immunology ,Immunology and Allergy - Published
- 2023
25. Impact of Patient Education on Quality of Life in Gastroesophageal Reflux Disease
- Author
-
Venkateswara Rao Jallepalli, Sreenu Thalla, Siva Bharath Gavini, Jai Divya Tella, Sandeep Kanneganti, Gopi Yemineni, and Rama Rao Nadendla
- Subjects
General Medicine - Published
- 2022
26. Fostering experimental and computational synergy to modulate hyperinflammation
- Author
-
Ilya Potapov, Thirumala-Devi Kanneganti, and Antonio del Sol
- Subjects
Chemokine ,biology ,SARS-CoV-2 ,business.industry ,Immunology ,COVID-19 ,medicine.disease ,Proinflammatory cytokine ,Organ damage ,medicine ,biology.protein ,Cytokines ,Humans ,Immunology and Allergy ,Cytokine Release Syndrome ,Cytokine storm ,business - Abstract
The molecular underpinnings of the uncontrolled release of proinflammatory cytokines and chemokines ('cytokine storm'), which can cause organ damage and even mortality, are not completely understood. Furthermore, targeted therapeutic options to dampen such hyperinflammation are scarce. Here, we highlight the ways in which technological advances have set the stage for a new age of synergy between experimental and computational researchers to guide the discovery of novel therapeutic targets for modulating hyperinflammation.
- Published
- 2022
27. Real time Pothole Detection System – An Application facilitating public safety
- Author
-
Lopamudra Panda, Kanneganti Bhavya Sri, and Reeja S R
- Published
- 2023
28. Evaluation of Caspase Activation to Assess Innate Immune Cell Death
- Author
-
Thirumala-Devi Kanneganti, Rebecca E. Tweedell, and Joo-Hui Han
- Subjects
General Immunology and Microbiology ,General Chemical Engineering ,General Neuroscience ,General Biochemistry, Genetics and Molecular Biology - Published
- 2023
29. CD47 halts Ptpn6 -deficient neutrophils from provoking lethal inflammation
- Author
-
Peter Vogel, Matthew Yorek, Lalita Mazgaeen, David Meyerholz, Thirumala-Devi Kanneganti, Saurabh Saini, and Prajwal Gurung
- Subjects
Multidisciplinary - Abstract
Mice with SHP1 proteins, which have a single amino acid substitution from tyrosine-208 residue to asparagine (hereafter Ptpn6 spin mice), develop an autoinflammatory disease with inflamed footpads. Genetic crosses to study CD47 function in Ptpn6 spin mice bred Ptpn6 spin × Cd47 −/− mice that were not born at the expected Mendelian ratio. Ptpn6 spin bone marrow cells, when transferred into lethally irradiated Cd47 -deficient mice, caused marked weight loss and subsequent death. At a cellular level, Ptpn6 -deficient neutrophils promoted weight loss and death of the lethally irradiated Cd47 −/− recipients. We posited that leakage of gut microbiota promotes morbidity and mortality in Cd47 −/− mice receiving Ptpn6 spin cells. Colonic cell death and gut leakage were substantially increased in the diseased Cd47 −/− mice. Last, IL-1 blockade using anakinra rescued the morbidity and mortality observed in the diseased Cd47 −/− mice. These data together demonstrate a protective role for CD47 in tempering pathogenic neutrophils in the Ptpn6 spin mice.
- Published
- 2023
30. CD47 halts
- Author
-
Lalita, Mazgaeen, Matthew, Yorek, Saurabh, Saini, Peter, Vogel, David K, Meyerholz, Thirumala-Devi, Kanneganti, and Prajwal, Gurung
- Abstract
Mice with SHP1 proteins, which have a single amino acid substitution from tyrosine-208 residue to asparagine (hereafter
- Published
- 2023
31. AIM2 sensors mediate immunity to Plasmodium infection in hepatocytes
- Author
-
Camila Marques-da-Silva, Barun Poudel, Rodrigo P. Baptista, Kristen Peissig, Lisa S. Hancox, Justine C. Shiau, Lecia L. Pewe, Melanie J. Shears, Thirumala-Devi Kanneganti, Photini Sinnis, Dennis E. Kyle, Prajwal Gurung, John T. Harty, and Samarchith P. Kurup
- Subjects
Multidisciplinary - Abstract
Malaria, caused by Plasmodium parasites is a severe disease affecting millions of people around the world. Plasmodium undergoes obligatory development and replication in the hepatocytes, before initiating the life-threatening blood-stage of malaria. Although the natural immune responses impeding Plasmodium infection and development in the liver are key to controlling clinical malaria and transmission, those remain relatively unknown. Here we demonstrate that the DNA of Plasmodium parasites is sensed by cytosolic AIM2 (absent in melanoma 2) receptors in the infected hepatocytes, resulting in Caspase-1 activation. Remarkably, Caspase-1 was observed to undergo unconventional proteolytic processing in hepatocytes, resulting in the activation of the membrane pore-forming protein, Gasdermin D, but not inflammasome-associated proinflammatory cytokines. Nevertheless, this resulted in the elimination of Plasmodium -infected hepatocytes and the control of malaria infection in the liver. Our study uncovers a pathway of natural immunity critical for the control of malaria in the liver.
- Published
- 2023
32. AIM2 sensors mediate immunity to
- Author
-
Camila, Marques-da-Silva, Barun, Poudel, Rodrigo P, Baptista, Kristen, Peissig, Lisa S, Hancox, Justine C, Shiau, Lecia L, Pewe, Melanie J, Shears, Thirumala-Devi, Kanneganti, Photini, Sinnis, Dennis E, Kyle, Prajwal, Gurung, John T, Harty, and Samarchith P, Kurup
- Subjects
DNA-Binding Proteins ,Plasmodium ,Liver ,Caspases ,Hepatocytes ,Animals ,Humans ,Parasites ,Malaria - Abstract
Malaria, caused by
- Published
- 2023
33. State Strategies for Controlling Health Care Costs: Implementation Guides
- Author
-
Hwang, Ann, Bailit, Michael H., Kanneganti, Deepti, and Flaherty, Grace
- Abstract
These implementation guides present a framework to help state policymakers design effective solutions for containing health care costs.
- Published
- 2023
- Full Text
- View/download PDF
34. Complex regulation of alarmins S100A8/A9 and secretion via gasdermin D pores exacerbates autoinflammation in familial Mediterranean fever
- Author
-
Selina K. Jorch, Annika McNally, Philipp Berger, Jonas Wolf, Kim Kaiser, Andrian Chetrusca Covash, Stefanie Robeck, Isabell Pastau, Olesja Fehler, Saskia-L. Jauch-Speer, Sven Hermann, Michael Schäfers, Hanne Van Gorp, Apurva Kanneganti, Joke Dehoorne, Filomeen Haerynck, Federica Penco, Marco Gattorno, Jae Jin Chae, Paul Kubes, Mohamed Lamkanfi, Andy Wullaert, Markus Sperandio, Thomas Vogl, Johannes Roth, and Judith Austermann
- Subjects
Immunology ,Medicine and Health Sciences ,Biology and Life Sciences ,Immunology and Allergy - Published
- 2023
35. Plant Diseases Detection Using Transfer Learning
- Author
-
S. Divya Meena, Katakam Ananth Yasodharan Kumar, Devendra Mandava, Kanneganti Bhavya Sri, Lopamudra Panda, and J. Sheela
- Published
- 2023
36. Regional differences in clinical presentation and prognosis of patients with post-sustained virologic response (SVR) hepatocellular carcinoma
- Author
-
Toyoda, Hidenori, Kanneganti, Mounika, Melendez-Torres, Jonathan, Parikh, Neehar D, Jalal, Prasun K, Piñero, Federico, Mendizabal, Manuel, Ridruejo, Ezequiel, Cheinquer, Hugo, Casadei-Gardini, Andrea, Weinmann, Arndt, Peck-Radosavljevic, Markus, Dufour, Jean-François, Radu, Pompilia, Shiha, Gamal, Soliman, Riham, Sarin, Shiv K, Kumar, Manoj, Wang, Jing-Houng, Tangkijvanich, Pisit, Sukeepaisarnjaroen, Wattana, Atsukawa, Masanori, Uojima, Haruki, Nozaki, Akito, Nakamuta, Makoto, Takaguchi, Koichi, Hiraoka, Atsushi, Abe, Hiroshi, Matsuura, Kentaro, Watanabe, Tsunamasa, Shimada, Noritomo, Tsuji, Kunihiko, Ishikawa, Toru, Mikami, Shigeru, Itobayashi, Ei, Singal, Amit G, and Johnson, Philip J
- Subjects
610 Medicine & health - Abstract
BACKGROUND & Amis: Widespread use of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection has resulted in increased numbers of patients with hepatocellular carcinoma (HCC) after achieving sustained virologic response ('post-SVR HCC') worldwide. Few data compare regional differences in presentation and prognosis of patients with post-SVR HCC. METHODS We identified patients with advanced fibrosis (F3/F4) who developed incident post-SVR HCC between March, 2015 and October, 2021 from 30 sites in Europe, North America, South America, Middle East, South Asia, East Asia, and Southeast Asia. We compared patient demographics, liver dysfunction, and tumor burden by region. We compared overall survival by region using Kaplan-Meier analysis and identified factors associated with survival using multivariable Cox regression analysis. RESULTS Among 8,796 patients with advanced fibrosis or cirrhosis who achieved SVR, 583 (6.6%) developed incident HCC. There was marked regional variation in the proportion of detection by surveillance (range: 59.5-100%), median maximum tumor diameter (range: 1.8-5.0 cm), and proportion with multinodular HCC (range: 15.4-60.8%). Prognosis of patients highly varied by region (HR range: 1.82-9.92), with the highest survival in East Asia, North America, and South America, and lowest in the Middle East and South Asia. After adjusting for geographic region, HCC surveillance was associated with early-stage detection (BCLC stage 0/A: 71.0% vs. 21.3%, p
- Published
- 2023
- Full Text
- View/download PDF
37. Inflammasomes as integral components of PANoptosomes in the regulation of cell death
- Author
-
Rebecca E. Tweedell, Shelbi Christgen, and Thirumala-Devi Kanneganti
- Published
- 2023
38. Contributors
- Author
-
Antonio Abbate, Ivona Aksentijevich, Marcelo Pires Amaral, Magaiver Andrade-Silva, Diego Angosto-Bazarra, Luca Antonioli, Kübra Aral, Juan I. Aróstegui, Jillian Barlow, Laura Benvenuti, Nunzia Bernardini, Massimo Bertinaria, Monika Biasizzo, Karina Ramalho Bortoluci, Dave Boucher, Laura Migliari Branco, David Brough, Petr Broz, Clare E. Bryant, Mark Cahill, Matthew Campbell, Soo Jung Cho, Shelbi Christgen, Rebecca C. Coll, Isabelle Couillin, Brianna Cyr, Sarah Dalmon, Juan Pablo de Rivero Vaccari, Francesco Di Virgilio, Andrea Dorfleutner, Sarah L. Doyle, Vanessa D'Antongiovanni, Ariel E. Feldstein, Matteo Fornai, Carlos García-Palenciano, Simone Gastaldi, Matthias Geyer, François Ghiringhelli, Anna Lisa Giuliani, José Manuel González-Navajas, Iva Hafner-Bratkovič, Shaima'a Hamarsheh, Michael T. Heneka, Thomas Henry, Jun-ichi Hikima, Inga V. Hochheiser, Alexander Hogg, Alexander Hooftman, Christopher Hoyle, Yin Huang, Sarah Huot-Marchand, Laura Hurtado-Navarro, Sushmita Jha, Thirumala-Devi Kanneganti, Benedikt Kaufmann, Andrea D. Kim, Nataša Kopitar-Jerala, Jordana Kron, Silvia Lucena Lage, Beatriz Lozano-Ruiz, Elisabetta Marini, Billie Matchett, Adolfo G. Mauro, Eleonora Mezzaroma, Michael R. Milward, Ingrid Kazue Mizuno Watanabe, Natsuki Morimoto, Sandip Mukherjee, Mar Orzáez, Luke A.J. O'Neill, Pablo Pelegrín, Carolina Pellegrini, Anaïs Perrichet, Joanna Picó, Nicola Potere, Alexander Pronko, Kishore Aravind Ravichandran, Nicolas Riteau, Kim S. Robinson, Cédric Rébé, Fadi N. Salloum, Mónica Sancho, Andrew Sandstrom, Niels Olsen Saraiva Câmara, Florian I. Schmidt, Liang Shan, Eoin Silke, Paula M. Soriano-Teruel, Christian Stehlik, Heather Stout-Delgado, Arianne L. Theiss, Jenny P.-Y. Ting, Stefano Toldo, Elviche L. Tsakem, Rebecca E. Tweedell, Amalia Tzoumpa, K. Venuprasad, Rose Wellens, Robert Zeiser, Franklin L. Zhong, and Alessia Zotta
- Published
- 2023
39. Inflammasome-mediated GSDMD activation facilitates escape of Candida albicans from macrophages
- Author
-
Hongbo Yu, Fei Liu, Hiroto Kambara, Xuemei Xie, Maikel Acosta-Zaldívar, Cunling Zhang, Julia R. Köhler, Jiajia Li, Hongbo R. Luo, Rongxia Guo, Ning-Ning Liu, Ting Bei, Fengxia Ma, Li Zhao, Xionghui Ding, Wenli Han, Xiaoyu Zhang, Wanjun Qi, and Apurva Kanneganti
- Subjects
Programmed cell death ,Inflammasomes ,Science ,Interleukin-1beta ,General Physics and Astronomy ,Kaplan-Meier Estimate ,Kidney ,Article ,General Biochemistry, Genetics and Molecular Biology ,Microbiology ,Sepsis ,Mediator ,Candida albicans ,medicine ,Animals ,Humans ,Cells, Cultured ,Mice, Knockout ,Multidisciplinary ,biology ,Immune cell death ,Macrophages ,Caspase 1 ,Candidiasis ,Intracellular Signaling Peptides and Proteins ,Pyroptosis ,Inflammasome ,General Chemistry ,Phosphate-Binding Proteins ,medicine.disease ,biology.organism_classification ,Corpus albicans ,Mice, Inbred C57BL ,Host-Pathogen Interactions ,Female ,Infection ,Candidalysin ,medicine.drug - Abstract
Candida albicans is the most common cause of fungal sepsis. Inhibition of inflammasome activity confers resistance to polymicrobial and LPS-induced sepsis; however, inflammasome signaling appears to protect against C. albicans infection, so inflammasome inhibitors are not clinically useful for candidiasis. Here we show disruption of GSDMD, a known inflammasome target and key pyroptotic cell death mediator, paradoxically alleviates candidiasis, improving outcomes and survival of Candida-infected mice. Mechanistically, C. albicans hijacked the canonical inflammasome-GSDMD axis-mediated pyroptosis to promote their escape from macrophages, deploying hyphae and candidalysin, a pore-forming toxin expressed by hyphae. GSDMD inhibition alleviated candidiasis by preventing C. albicans escape from macrophages while maintaining inflammasome-dependent but GSDMD-independent IL-1β production for anti-fungal host defenses. This study demonstrates key functions for GSDMD in Candida’s escape from host immunity in vitro and in vivo and suggests that GSDMD may be a potential therapeutic target in C. albicans-induced sepsis., Inflammasome signalling has been shown to protect Candida albicans during infection and as such limits inflammasome inhibitors in this context. Here the authors implicate Gasdermin D in C.ablicans immune evasion and suggests its targeting therapeutically.
- Published
- 2021
40. Determining distinct roles of IL-1α through generation of an IL-1α knockout mouse with no defect in IL-1β expression
- Author
-
R.K. Subbarao Malireddi, Ratnakar Bynigeri, Balabhaskararao Kancharana, Bhesh Raj Sharma, Amanda R. Burton, Stephane Pelletier, and Thirumala-Devi Kanneganti
- Subjects
Mice, Knockout ,Mice ,Inflammasomes ,Interleukin-1alpha ,Macrophages ,Interleukin-8 ,Immunology ,Animals ,Immunology and Allergy - Abstract
Interleukin 1α (IL-1α) and IL-1β are the founding members of the IL-1 cytokine family, and these innate immune inflammatory mediators are critically important in health and disease. Early studies on these molecules suggested that their expression was interdependent, with an initial genetic model of IL-1α depletion, the IL-1α KO mouse (Il1a-KOline1), showing reduced IL-1β expression. However, studies using this line in models of infection and inflammation resulted in contrasting observations. To overcome the limitations of this genetic model, we have generated and characterized a new line of IL-1α KO mice (Il1a-KOline2) using CRISPR-Cas9 technology. In contrast to cells from theIl1a-KOline1, where IL-1β expression was drastically reduced, bone marrow-derived macrophages (BMDMs) fromIl1a-KOline2mice showed normal induction and activation of IL-1β. Additionally,Il1a-KOline2BMDMs showed normal inflammasome activation and IL-1β expression in response to multiple innate immune triggers, including both pathogen-associated molecular patterns and pathogens. Moreover, usingIl1a-KOline2cells, we confirmed that IL-1α, independent of IL-1β, is critical for the expression of the neutrophil chemoattractant KC/CXCL1. Overall, we report the generation of a new line of IL-1α KO mice and confirm functions for IL-1α independent of IL-1β. Future studies on the unique functions of IL-1α and IL-1β using these mice will be critical to identify new roles for these molecules in health and disease and develop therapeutic strategies.
- Published
- 2022
- Full Text
- View/download PDF
41. AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host defence
- Author
-
Ravi C. Kalathur, SangJoon Lee, Thirumala-Devi Kanneganti, Lam Nhat Nguyen, Rajendra Karki, and Yaqiu Wang
- Subjects
Male ,Damp ,THP-1 Cells ,Apoptosis ,Herpesvirus 1, Human ,medicine.disease_cause ,Pyrin domain ,Mice ,RIPK1 ,AIM2 ,Pyroptosis ,medicine ,Animals ,Humans ,FADD ,Francisella novicida ,Francisella ,Cells, Cultured ,Multidisciplinary ,Innate immune system ,biology ,Caspase 1 ,RNA-Binding Proteins ,Inflammasome ,Pyrin ,Cell biology ,DNA-Binding Proteins ,Mice, Inbred C57BL ,Necroptosis ,biology.protein ,Cytokines ,Female ,medicine.drug - Abstract
Inflammasomes are important sentinels of innate immune defence, sensing pathogens and inducing cell death in infected cells1. There are several inflammasome sensors that each detect and respond to a specific pathogen- or damage-associated molecular pattern (PAMP or DAMP, respectively)1. During infection, live pathogens can induce the release of multiple PAMPs and DAMPs, which can simultaneously engage multiple inflammasome sensors2–5. Here we found that AIM2 regulates the innate immune sensors pyrin and ZBP1 to drive inflammatory signalling and a form of inflammatory cell death known as PANoptosis, and provide host protection during infections with herpes simplex virus 1 and Francisella novicida. We also observed that AIM2, pyrin and ZBP1 were members of a large multi-protein complex along with ASC, caspase-1, caspase-8, RIPK3, RIPK1 and FADD, that drove inflammatory cell death (PANoptosis). Collectively, our findings define a previously unknown regulatory and molecular interaction between AIM2, pyrin and ZBP1 that drives assembly of an AIM2-mediated multi-protein complex that we term the AIM2 PANoptosome and comprising multiple inflammasome sensors and cell death regulators. These results advance the understanding of the functions of these molecules in innate immunity and inflammatory cell death, suggesting new therapeutic targets for AIM2-, ZBP1- and pyrin-mediated diseases. AIM2 responds to infection with herpes simplex virus 1 or Francisella novicida by driving assembly of a large multi-protein complex containing multiple inflammasome sensors and cell death regulators.
- Published
- 2021
42. Center Variability in Acute Rejection and Biliary Complications After Pediatric Liver Transplantation
- Author
-
Peter L. Abt, Yuan-Shung Huang, Therese Bittermann, Mounika Kanneganti, Elizabeth B. Rand, Douglas E. Schaubel, Brian T. Fisher, Eimear Kitt, and Yuwen Xu
- Subjects
Big Data ,Pediatrics ,medicine.medical_specialty ,Databases, Factual ,medicine.medical_treatment ,Biliary complication ,Liver transplantation ,Article ,Case mix index ,Interquartile range ,Humans ,Medicine ,Center (algebra and category theory) ,Child ,Retrospective Studies ,Transplantation ,Hepatology ,business.industry ,Data Collection ,Graft Survival ,Retrospective cohort study ,Odds ratio ,Tissue Donors ,Transplant Recipients ,United States ,Liver Transplantation ,Surgery ,business - Abstract
Transplant center performance and practice variation for pediatric post-liver transplantation (LT) outcomes other than survival are understudied. This was a retrospective cohort study of pediatric LT recipients who received transplants between January 1, 2006, and May 31, 2017, using United Network for Organ Sharing (UNOS) data that were merged with the Pediatric Health Information System database. Center effects for the acute rejection rate at 1 year after LT (AR1) using UNOS coding and the biliary complication rate at 1 year after LT (BC1) using inpatient billing claims data were estimated by center-specific rescaled odds ratios that accounted for potential differences in recipient and donor characteristics. There were 2216 pediatric LT recipients at 24 freestanding children's hospitals in the United States during the study period. The median unadjusted center rate of AR1 was 36.92% (interquartile range [IQR], 22.36%-44.52%), whereas that of BC1 was 32.29% (IQR, 26.14%-40.44%). Accounting for recipient case mix and donor factors, 5/24 centers performed better than expected with regard to AR1, whereas 3/24 centers performed worse than expected. There was less heterogeneity across the center effects for BC1 than for AR1. There was no relationship observed between the center effects for AR1 or BC1 and center volume. Beyond recipient and allograft factors, differences in transplant center management are an important driver of center AR1 performance, and less so of BC1 performance. Further research is needed to identify the sources of variability so as to implement the most effective solutions to broadly enhance outcomes for pediatric LT recipients.
- Published
- 2021
43. The ‘cytokine storm’: molecular mechanisms and therapeutic prospects
- Author
-
Rajendra Karki and Thirumala-Devi Kanneganti
- Subjects
0301 basic medicine ,Programmed cell death ,medicine.medical_treatment ,Immunology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Tissue damage ,medicine ,Humans ,Immunology and Allergy ,Innate immune system ,business.industry ,Pathogen-Associated Molecular Pattern Molecules ,COVID-19 ,medicine.disease ,Cytokine release syndrome ,030104 developmental biology ,Cytokine ,Immune System ,Cytokines ,Cytokine secretion ,Cytokine Release Syndrome ,business ,Cytokine storm ,030215 immunology - Abstract
Cytokine storm syndrome (CSS) has generally been described as a collection of clinical manifestations resulting from an overactivated immune system. Cytokine storms (CSs) are associated with various pathologies, as observed in infectious diseases, certain acquired or inherited immunodeficiencies and autoinflammatory diseases, or following therapeutic interventions. Despite the role of CS in tissue damage and multiorgan failure, a systematic understanding of its underlying molecular mechanisms is lacking. Recent studies demonstrate a positive feedback loop between cytokine release and cell death pathways; certain cytokines, pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs), can activate inflammatory cell death, leading to further cytokine secretion. Here, we discuss recent progress in innate immunity and inflammatory cell death, providing insights into the cellular and molecular mechanisms of CSs and therapeutics that might quell ensuing life-threatening effects.
- Published
- 2021
44. From pyroptosis, apoptosis and necroptosis to PANoptosis: A mechanistic compendium of programmed cell death pathways
- Author
-
Yaqiu Wang and Thirumala-Devi Kanneganti
- Subjects
Cell death ,Programmed cell death ,Necroptosis ,Biophysics ,Caspase 1 ,Apoptosis ,Review ,Biology ,Caspase 8 ,RIPK3 ,ASC ,Biochemistry ,Caspase 7 ,Inflammasome ,NLRP3 ,Structural Biology ,Genetics ,medicine ,Pyroptosis ,PANoptosis ,ComputingMethodologies_COMPUTERGRAPHICS ,ZBP1 ,PANoptosome ,Gasdermin E ,Computer Science Applications ,Gasdermin D ,Crosstalk (biology) ,Caspase-3 ,Caspase-1 ,Caspase-8 ,Neuroscience ,TP248.13-248.65 ,medicine.drug ,Biotechnology ,Caspase-7 ,MLKL - Abstract
Graphical abstract, Pyroptosis, apoptosis and necroptosis are the most genetically well-defined programmed cell death (PCD) pathways, and they are intricately involved in both homeostasis and disease. Although the identification of key initiators, effectors and executioners in each of these three PCD pathways has historically delineated them as distinct, growing evidence has highlighted extensive crosstalk among them. These observations have led to the establishment of the concept of PANoptosis, defined as an inflammatory PCD pathway regulated by the PANoptosome complex with key features of pyroptosis, apoptosis and/or necroptosis that cannot be accounted for by any of these PCD pathways alone. In this review, we provide a brief overview of the research history of pyroptosis, apoptosis and necroptosis. We then examine the intricate crosstalk among these PCD pathways to discuss the current evidence for PANoptosis. We also detail the molecular evidence for the assembly of the PANoptosome complex, a molecular scaffold for contemporaneous engagement of key molecules from pyroptosis, apoptosis, and/or necroptosis. PANoptosis is now known to be critically involved in many diseases, including infection, sterile inflammation and cancer, and future discovery of novel PANoptotic components will continue to broaden our understanding of the fundamental processes of cell death and inform the development of new therapeutics.
- Published
- 2021
45. Humans pIKK-up NLRP3 to skip NEK7
- Author
-
R.K. Subbarao Malireddi and Thirumala-Devi Kanneganti
- Subjects
Mice, Inbred C57BL ,Mice ,Inflammasomes ,Immunology ,NLR Family, Pyrin Domain-Containing 3 Protein ,Immunology and Allergy ,Humans ,Animals ,NIMA-Related Kinases ,Protein Serine-Threonine Kinases - Abstract
NLRP3 inflammasome regulation is essential for controlling cell death and inflammation. Mechanistic studies in murine cells suggest a two-step model of priming and activation with an indispensable role for NEK7. However, in a recent article in Immunity, Schmacke et al. report that, in humans, transcription-independent NLRP3 activation occurs by circumventing NEK7 via IKKβ.
- Published
- 2022
46. Filoviruses: Innate Immunity, Inflammatory Cell Death, and Cytokines
- Author
-
Jianlin Lu, Jessica M. Gullett, and Thirumala-Devi Kanneganti
- Subjects
Microbiology (medical) ,Infectious Diseases ,General Immunology and Microbiology ,Immunology and Allergy ,Molecular Biology - Abstract
Filoviruses are a group of single-stranded negative sense RNA viruses. The most well-known filoviruses that affect humans are ebolaviruses and marburgviruses. During infection, they can cause life-threatening symptoms such as inflammation, tissue damage, and hemorrhagic fever, with case fatality rates as high as 90%. The innate immune system is the first line of defense against pathogenic insults such as filoviruses. Pattern recognition receptors (PRRs), including toll-like receptors, retinoic acid-inducible gene-I-like receptors, C-type lectin receptors, AIM2-like receptors, and NOD-like receptors, detect pathogens and activate downstream signaling to induce the production of proinflammatory cytokines and interferons, alert the surrounding cells to the threat, and clear infected and damaged cells through innate immune cell death. However, filoviruses can modulate the host inflammatory response and innate immune cell death, causing an aberrant immune reaction. Here, we discuss how the innate immune system senses invading filoviruses and how these deadly pathogens interfere with the immune response. Furthermore, we highlight the experimental difficulties of studying filoviruses as well as the current state of filovirus-targeting therapeutics.
- Published
- 2022
47. Methotrexate inhibition of muropeptide transporter SLC46A2 controls psoriatic skin inflammation
- Author
-
Ravi Bharadwaj, Christina F. Lusi, Siavash Mashayekh, Abhinit Nagar, Malireddi Subbarao, Griffin I. Kane, Kimberly Wodzanowski, Ashley Brown, Kendi Okuda, Amanda Monahan, Donggi Paik, Anubhab Nandy, Madison Anonick, William E. Goldman, Thirumala-Devi Kanneganti, Megan H. Orzalli, Catherine Leimkuhler Grimes, Prabhani U. Atukorale, and Neal Silverman
- Abstract
SummaryCytosolic innate immune sensing is critical for protecting barrier tissues. NOD1 and NOD2 are cytosolic sensors of small peptidoglycan fragments (muropeptides) derived from the bacterial cell wall. These muropeptides enter cells, especially epithelial cells, through unclear mechanisms. We previously implicated SLC46 transporters in muropeptide transport in Drosophila immunity. Here we focus on Slc46a2, which is highly expressed in mammalian epidermal keratinocytes, and show that it is critical for delivery of DAP-muropeptides and activation of NOD1 in keratinocytes, while the related transporter Slc46a3 is critical for responding to MDP, the NOD2 ligand. In a mouse model, Slc46a2 and Nod1 deficiency strongly suppressed psoriatic inflammation, while methotrexate, a commonly used psoriasis therapeutic, inhibited Slc46a2-dependent transport of DAP-muropeptides. Collectively these studies define SLC46A2 as a transporter of NOD1 activating muropeptides, with critical roles in the skin barrier, and identify this transporter as an important target for anti-inflammatory intervention.
- Published
- 2022
48. Single cell analysis of PANoptosome cell death complexes through an expansion microscopy method
- Author
-
Yaqiu Wang, Nagakannan Pandian, Joo-Hui Han, Balamurugan Sundaram, SangJoon Lee, Rajendra Karki, Clifford S. Guy, and Thirumala-Devi Kanneganti
- Subjects
Pharmacology ,Caspase 8 ,Mice ,Microscopy ,Cellular and Molecular Neuroscience ,Inflammasomes ,Pyroptosis ,Animals ,Molecular Medicine ,Apoptosis ,Cell Biology ,Single-Cell Analysis ,Molecular Biology - Abstract
In response to infection or sterile insults, inflammatory programmed cell death is an essential component of the innate immune response to remove infected or damaged cells. PANoptosis is a unique innate immune inflammatory cell death pathway regulated by multifaceted macromolecular complexes called PANoptosomes, which integrate components from other cell death pathways. Growing evidence shows that PANoptosis can be triggered in many physiological conditions, including viral and bacterial infections, cytokine storms, and cancers. However, PANoptosomes at the single cell level have not yet been fully characterized. Initial investigations have suggested that key pyroptotic, apoptotic, and necroptotic molecules including the inflammasome adaptor protein ASC, apoptotic caspase-8 (CASP8), and necroptotic RIPK3 are conserved components of PANoptosomes. Here, we optimized an immunofluorescence procedure to probe the highly dynamic multiprotein PANoptosome complexes across various innate immune cell death-inducing conditions. We first identified and validated antibodies to stain endogenous mouse ASC, CASP8, and RIPK3, without residual staining in the respective knockout cells. We then assessed the formation of PANoptosomes across innate immune cell death-inducing conditions by monitoring the colocalization of ASC with CASP8 and/or RIPK3. Finally, we established an expansion microscopy procedure using these validated antibodies to image the organization of ASC, CASP8, and RIPK3 within the PANoptosome. This optimized protocol, which can be easily adapted to study other multiprotein complexes and other cell death triggers, provides confirmation of PANoptosome assembly in individual cells and forms the foundation for a deeper molecular understanding of the PANoptosome complex and PANoptosis to facilitate therapeutic targeting.
- Published
- 2022
49. Pancancer transcriptomic profiling identifies key PANoptosis markers as therapeutic targets for oncology
- Author
-
Raghvendra Mall, Ratnakar R Bynigeri, Rajendra Karki, R K Subbarao Malireddi, Bhesh Raj Sharma, and Thirumala-Devi Kanneganti
- Subjects
General Medicine - Abstract
Resistance to programmed cell death (PCD) is a hallmark of cancer. While some PCD components are prognostic in cancer, the roles of many molecules can be masked by redundancies and crosstalks between PCD pathways, impeding the development of targeted therapeutics. Recent studies characterizing these redundancies have identified PANoptosis, a unique innate immune-mediated inflammatory PCD pathway that integrates components from other PCD pathways. Here, we designed a systematic computational framework to determine the pancancer clinical significance of PANoptosis and identify targetable biomarkers. We found that high expression of PANoptosis genes was detrimental in low grade glioma (LGG) and kidney renal cell carcinoma (KIRC). ZBP1, ADAR, CASP2, CASP3, CASP4, CASP8 and GSDMD expression consistently had negative effects on prognosis in LGG across multiple survival models, while AIM2, CASP3, CASP4 and TNFRSF10 expression had negative effects for KIRC. Conversely, high expression of PANoptosis genes was beneficial in skin cutaneous melanoma (SKCM), with ZBP1, NLRP1, CASP8 and GSDMD expression consistently having positive prognostic effects. As a therapeutic proof-of-concept, we treated melanoma cells with combination therapy that activates ZBP1 and showed that this treatment induced PANoptosis. Overall, through our systematic framework, we identified and validated key innate immune biomarkers from PANoptosis which can be targeted to improve patient outcomes in cancers.
- Published
- 2022
50. Occipital Interhemispheric Transtentorial Approach for Tumors of Posterior Third Ventricular Region: Review of Surgical Results
- Author
-
Kanneganti Vidyasagar, NarayanamA Sai Kiran, Rakshith Srinivasa, Laxminadh Sivaraju, Vivek Raj, SunilV Furtado, Sumit Thakar, Saritha Aryan, Dilip Mohan, and AlangarS Hegde
- Subjects
Neurology ,Infarction ,Meningeal Neoplasms ,Humans ,Neurology (clinical) ,Meningioma ,Pineal Gland ,Neurosurgical Procedures ,Third Ventricle - Abstract
Controversies exist regarding the ideal surgical approach for tumors in posterior third ventricular region (PTV).To evaluate the results of occipital interhemispheric transtentorial (OITT) approach for tumors in PTV.Thirty-three patients underwent surgery via OITT approach for PTV tumors at Sri Sathya Sai Institute of Higher Medical Sciences during the study period of 5 years (June 2011-May 2016). Ideal trajectory for OITT approach was determined by neuronavigation. Endoscope was used for removing any residual lesion at the blind spots.Postoperative magnetic resonance imaging (MRI) performed in all the patients revealed gross total or near-total (95%) excision of tumor in 31 patients (93.9%). Preoperative neurological deficits improved either completely or significantly following excision of the tumor in 73.3% (11/15) of the patients. Outcome was good (modified Rankin scale ≤2) at discharge in 93.9% (31/33) and at a final follow-up of 3 months or more in 96.8% (30/31) of the patients. None of the patients died during the postoperative period. Complications included upgaze palsy (transient- 6.1% [2/33], persisting- 3% [1/33]), visual field defects (transient- 3% [1/33], persisting- 3% [1/33]), transient third nerve paresis (1/33-3%), transient hemiparesis (1/33-3%), operative site hematoma (1/33-3%), small posterior cerebral artery (PCA) territory infarct (1/33-3%), and small venous infarct (1/33-3%). At least one follow-up MRI could be performed in 23 patients. Final follow-up MRI revealed no recurrence or increase in the size of the residual lesion compared to postoperative images in 20 patients (20/23-87%) and large recurrence in 3 patients (3/23-13%) with high-grade lesions.Gross total/near-total excision can be performed in majority of the PTV tumors through OITT approach with minimal morbidity and mortality.
- Published
- 2022
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.