Search

Your search keyword '"Dean, A J"' showing total 2,011 results
Start Over Author "Dean, A J" Publication Type Academic Journals

Refine your results

more »

more »

more »

more »

more »

more »
2,011 results on '"Dean, A J"'

5. Strong interaction physics at the luminosity frontier with 22 GeV electrons at Jefferson Lab

Author

Accardi, A., Achenbach, P., Adhikari, D., Afanasev, A., Akondi, C. S., Akopov, N., Albaladejo, M., Albataineh, H., Albrecht, M., Almeida-Zamora, B., Amaryan, M., Androić, D., Armstrong, W., Armstrong, D. S., Arratia, M., Arrington, J., Asaturyan, A., Austregesilo, A., Avakian, H., Averett, T., Gayoso, C. Ayerbe, Bacchetta, A., Balantekin, A. B., Baltzell, N., Barion, L., Barry, P. C., Bashir, A., Battaglieri, M., Bellini, V., Belov, I., Benhar, O., Benkel, B., Benmokhtar, F., Bentz, W., Bertone, V., Bhatt, H., Bianconi, A., Bibrzycki, L., Bijker, R., Binosi, D., Biswas, D., Boër, M., Boeglin, W., Bogacz, S. A., Boglione, M., Bondí, M., Boos, E. E., Bosted, P., Bozzi, G., Brash, E. J., Briceño, R. A., Brindza, P. D., Briscoe, W. J., Brodsky, S. J., Brooks, W. K., Burkert, V. D., Camsonne, A., Cao, T., Cardman, L. S., Carman, D. S., Carpinelli, M., Cates, G. D., Caylor, J., Celentano, A., Celiberto, F. G., Cerutti, M., Chang, L., Chatagnon, P., Chen, C., Chen, J.-P., Chetry, T., Christopher, A., Christy, E., Chudakov, E., Cisbani, E., Cloët, I. C., Cobos-Martinez, J. J., Cohen, E. O., Colangelo, P., Cole, P. L., Constantinou, M., Contalbrigo, M., Costantini, G., Cosyn, W., Cotton, C., Courtoy, A., Dusa, S. Covrig, Crede, V., Cui, Z.-F., D’Angelo, A., Döring, M., Dalton, M. M., Danilkin, I., Davydov, M., Day, D., De Fazio, F., De Napoli, M., De Vita, R., Dean, D. J., Defurne, M., de Paula, W., de Téramond, G. F., Deur, A., Devkota, B., Dhital, S., Di Nezza, P., Diefenthaler, M., Diehl, S., Dilks, C., Ding, M., Djalali, C., Dobbs, S., Dupré, R., Dutta, D., Edwards, R. G., Egiyan, H., Ehinger, L., Eichmann, G., Elaasar, M., Elouadrhiri, L., Alaoui, A. El, Fassi, L. El, Emmert, A., Engelhardt, M., Ent, R., Ernst, D. J., Eugenio, P., Evans, G., Fanelli, C., Fegan, S., Fernández-Ramírez, C., Fernandez, L. A., Fernando, I. P., Filippi, A., Fischer, C. S., Fogler, C., Fomin, N., Frankfurt, L., Frederico, T., Freese, A., Fu, Y., Gamberg, L., Gan, L., Gao, F., Garcia-Tecocoatzi, H., Gaskell, D., Gasparian, A., Gates, K., Gavalian, G., Ghoshal, P. K., Giachino, A., Giacosa, F., Giannuzzi, F., Gilfoyle, G.-P., Girod, F.-X., Glazier, D. I., Gleason, C., Godfrey, S., Goity, J. L., Golubenko, A. A., Gonzàlez-Solís, S., Gothe, R. W., Gotra, Y., Griffioen, K., Grocholski, O., Grube, B., Guèye, P., Guo, F.-K., Guo, Y., Guo, L., Hague, T. J., Hammoud, N., Hansen, J.-O., Hattawy, M., Hauenstein, F., Hayward, T., Heddle, D., Heinrich, N., Hen, O., Higinbotham, D. W., Higuera-Angulo, I. M., Hiller Blin, A. N., Hobart, A., Hobbs, T., Holmberg, D. E., Horn, T., Hoyer, P., Huber, G. M., Hurck, P., Hutauruk, P. T. P., Ilieva, Y., Illari, I., Ireland, D. G., Isupov, E. L., Italiano, A., Jaegle, I., Jarvis, N. S., Jenkins, D. J., Jeschonnek, S., Ji, C.-R., Jo, H. S., Jones, M., Jones, R. T., Jones, D. C., Joo, K., Junaid, M., Kageya, T., Kalantarians, N., Karki, A., Karyan, G., Katramatou, A. T., Kay, S. J. D., Kazimi, R., Keith, C. D., Keppel, C., Kerbizi, A., Khachatryan, V., Khanal, A., Khandaker, M., Kim, A., Kinney, E. R., Kohl, M., Kotzinian, A., Kriesten, B. T., Kubarovsky, V., Kubis, B., Kuhn, S. E., Kumar, V., Kutz, T., Leali, M., Lebed, R. F., Lenisa, P., Leskovec, L., Li, S., Li, X., Liao, J., Lin, H.-W., Liu, L., Liuti, S., Liyanage, N., Lu, Y., MacGregor, I. J. D., Mack, D. J., Maiani, L., Mamo, K. A., Mandaglio, G., Mariani, C., Markowitz, P., Marukyan, H., Mascagna, V., Mathieu, V., Maxwell, J., Mazouz, M., McCaughan, M., McKeown, R. D., McKinnon, B., Meekins, D., Melnitchouk, W., Metz, A., Meyer, C. A., Meziani, Z.-E., Mezrag, C., Michaels, R., Miller, G. A., Mineeva, T., Miramontes, A. S., Mirazita, M., Mizutani, K., Mkrtchyan, A., Mkrtchyan, H., Moffit, B., Mohanmurthy, P., Mokeev, V. I., Monaghan, P., Montaña, G., Montgomery, R., Moretti, A., Chàvez, J. M. Morgado, Mosel, U., Movsisyan, A., Musico, P., Nadeeshani, S. A., Nadolsky, P. M., Nakamura, S. X., Nazeer, J., Nefediev, A. V., Neupane, K., Nguyen, D., Niccolai, S., Niculescu, I., Niculescu, G., Nocera, E. R., Nycz, M., Olness, F. I., Ortega, P. G., Osipenko, M., Pace, E., Pandey, B., Pandey, P., Papandreou, Z., Papavassiliou, J., Pappalardo, L. L., Paredes-Torres, G., Paremuzyan, R., Park, S., Parsamyan, B., Paschke, K. D., Pasquini, B., Passemar, E., Pasyuk, E., Patel, T., Paudel, C., Paul, S. J., Peng, J.-C., Pentchev, L., Perrino, R., Perry, R. J., Peters, K., Petratos, G. G., Phelps, W., Piasetzky, E., Pilloni, A., Pire, B., Pitonyak, D., Pitt, M. L., Polosa, A. D., Pospelov, M., Postuma, A. C., Poudel, J., Preet, L., Prelovsek, S., Price, J. W., Prokudin, A., Puckett, A. J. R., Pybus, J. R., Qin, S.-X., Qiu, J.-W., Radici, M., Rashidi, H., Rathnayake, A. D., Raue, B. A., Reed, T., Reimer, P. E., Reinhold, J., Richard, J.-M., Rinaldi, M., Ringer, F., Ripani, M., Ritman, J., West, J. Rittenhouse, Rivero-Acosta, A., Roberts, C. D., Rodas, A., Rodini, S., Rodríguez-Quintero, J., Rogers, T. C., Rojo, J., Rossi, P., Rossi, G. C., Salmè, G., Santiesteban, S. N., Santopinto, E., Sargsian, M., Sato, N., Schadmand, S., Schmidt, A., Schmidt, S. M., Schnell, G., Schumacher, R. A., Schweitzer, P., Scimemi, I., Scott, K. C., Seay, D. A., Segovia, J., Semenov-Tian-Shansky, K., Seryi, A., Sharda, A. S., Shepherd, M. R., Shirokov, E. V., Shrestha, S., Shrestha, U., Shvedunov, V. I., Signori, A., Slifer, K. J., Smith, W. A., Somov, A., Souder, P., Sparveris, N., Spizzo, F., Spreafico, M., Stepanyan, S., Stevens, J. R., Strakovsky, I. I., Strauch, S., Strikman, M., Su, S., Sumner, B. C. L., Sun, E., Suresh, M., Sutera, C., Swanson, E. S., Szczepaniak, A. P., Sznajder, P., Szumila-Vance, H., Szymanowski, L., Tadepalli, A.-S., Tadevosyan, V., Tamang, B., Tarasov, V. V., Thiel, A., Tong, X.-B., Tyson, R., Ungaro, M., Urciuoli, G. M., Usman, A., Valcarce, A., Vallarino, S., Vaquera-Araujo, C. A., Venturelli, L., Vera, F., Vladimirov, A., Vossen, A., Wagner, J., Wei, X., Weinstein, L. B., Weiss, C., Williams, R., Winney, D., Wojtsekhowski, B., Wood, M. H., Xiao, T., Xu, S.-S., Ye, Z., Yero, C., Yuan, C.-P., Yurov, M., Zachariou, N., Zhang, Z., Zhao, Y., Zhao, Z. W., Zheng, X., Zhou, X., Ziegler, V., and Zihlmann, B.

Published
2024
Full Text
View/download PDF

16. Transcriptome-wide changes in gene expression, splicing, and lncRNAs in response to a live attenuated dengue virus vaccine

Author

Kim, Eun-Young, Che, Yan, Dean, Hansi J, Lorenzo-Redondo, Ramon, Stewart, Michael, Keller, Caroline K, Whorf, Daniel, Mills, Dawson, Dulin, Nikita N, Kim, Tiffany, Votoupal, Megan, Walter, Miriam, Fernandez-Sesma, Ana, Kim, Heejin, and Wolinsky, Steven M

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biodefense, Immunization, Biotechnology, Infectious Diseases, Genetics, Rare Diseases, Prevention, Vaccine Related, Vector-Borne Diseases, Emerging Infectious Diseases, Infection, Good Health and Well Being, Antibodies, Neutralizing, Antibodies, Viral, Dengue, Dengue Vaccines, Dengue Virus, Humans, Immunogenicity, Vaccine, RNA, Long Noncoding, Transcriptome, Vaccines, Attenuated, Viral Vaccines, gene correlation networks, live attenuated dengue virus vaccine, long noncoding RNA, modular transcriptional repertoire, splicing, transcriptome, Biochemistry and Cell Biology, Medical Physiology, Biological sciences
Abstract

The tetravalent dengue vaccine candidate, TAK-003, induces a functional antibody response, but the titers of antibodies against the four serotypes of the dengue virus (DENV) can vary. Here, through a transcriptomic analysis on whole blood collected from recipients of a two-dose schedule of TAK-003, we examine gene expression, splicing, and transcript isoform-level changes for both protein-coding and noncoding genes to broaden our understanding of the immune response. Our analysis reveals a dynamic pattern of vaccine-associated regulation of long noncoding RNAs (lncRNAs), differential splicing of interferon-stimulated gene exons, and gene expression changes related to multiple signaling pathways that detect viral infection. Co-expression networks isolate immune cell-type-related and interferon-response modules that represent specific biological processes that correlate with more robust antibody responses. These data provide insights into the early determinants of the variable immune response to the vaccine, highlighting the significance of splicing and isoform-level gene regulatory mechanisms in defining vaccine immunogenicity.

Published
2022

21. Psychosocial drivers of land management behaviour: How threats, norms, and context influence deforestation intentions

Author

Simmons, B Alexander, Wilson, Kerrie A, and Dean, Angela J

Subjects
Climate Change Impacts and Adaptation, Economics, Environmental Sciences, 1.2 Psychological and socioeconomic processes, Life on Land, Attitude, Australia, Conservation of Natural Resources, Intention, Queensland, Behaviour change, Environmental behaviour, Land clearing, Natural resource management, Protection Motivation Theory, Theory of Planned Behaviour, Ecology
Abstract

Understanding how private landholders make deforestation decisions is of paramount importance for conservation. Behavioural frameworks from the social sciences have a lot to offer researchers and practitioners, yet these insights remain underutilised in describing what drives landholders' deforestation intentions under important political, social, and management contexts. Using survey data of private landholders in Queensland, Australia, we compare the ability of two popular behavioural models to predict future deforestation intentions, and propose a more integrated behavioural model of deforestation intentions. We found that the integrated model outperformed other models, revealing the importance of threat perceptions, attitudes, and social norms for predicting landholders' deforestation intentions. Social capital, policy uncertainty, and years of experience are important contextual moderators of these psychological factors. We conclude with recommendations for promoting behaviour change in this deforestation hotspot and highlight how others can adopt similar approaches to illuminate more proximate drivers of environmental behaviours in other contexts.

Published
2021

22. Immunocompromised-Associated Pediatric Acute Respiratory Distress Syndrome: Experience From the 2016/2017 Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Prospective Cohort Study*

Author

Gertz, Shira J., Bhalla, Anoopindar, Chima, Ranjit S., Emeriaud, Guillaume, Fitzgerald, Julie C., Hsing, Deyin D., Jeyapalan, Asumthia S., Pike, Francis, Sallee, Colin J., Thomas, Neal J., Yehya, Nadir, Rowan, Courtney M., Sforza, Jesica, Poterala, Rossana, Fernandez, Analia, Avila Vera, Antonio, Orqueda, Daniel, Agueda Vidal, Nilda, Rosemary, Deheza, Turon, Gonzalo, Monjes, Cecilia, Fernando Espanol, Segundo, Siaba Serrate, Alejandro, Iolster, Thomas, Torres, Silvio, Cinquegrani, Karina, Jose Montes, Maria, Capocasa, Patricia, Ferreyra, Marcela, Castellani, Pablo, Giampieri, Martin, Pedraza, Claudia, Martin Landry, Luis, Althabe, Maria, Vanesa Fortini, Yanina, Botta, Priscila, Paziencia, Fernando, Erickson, Simon, Barr, Samantha, Shea, Sara, Butt, Warwick, Delzoppo, Carmel, Pintimalla, Alyssa, Martinez Leon, Alejandro Fabio, Guzman Rivera, Gustavo Alfredo, Jouvet, Philippe, Emeriaud, Guillaume, Dumitrascu, Mariana, Ellen French, Mary, Caro, Daniel, Castillo, I, Andres, E., Cruces Romero, Pablo, Medina, Tania, Pavez Madrid, Paula, Cortez, Ambar, Alvear, Jimena, Acuna, Carlos, Diaz, Franco, Jose Nunez, Maria, Wegner Araya, Adriana, Godoy Mundaca, Loreto, Chen, Yang, Perez Lozano, German, Pardo Carrero, Rosalba, Lopez Alarcon, Yurika Paola, Mazzillo Vega, Liliana, Maria Izquierdo, Ledys, Piñeres Olave, Byron Enrique, Zuluaga Orrego, Cesar, Quinonez Lopez, Deyanira, Vasquez Hoyos, Pablo, Vavrina, Martin, Zurek, Jiri, Campos-Miño, Santiago, Yerovi, Rocio, Bridier, Armelle, Payen, Valerie, Milesi, Christophe, Bourgoin, Pierre, Travert, Brendan, Genuini, Mathieu, Starck, Julie, Maria, Matthieu, Guichoux, Julie, Baudin, Florent, Briassoulis, George, Ilia, Stavroula, Di Nardo, Matteo, Camporesi, Anna, Chiusolo, Fabrizio, Shime, Nobuaki, Ohshimo, Shinichiro, Kida, Yoshiko, Kyo, Michihito, Tabata, Yuichi, Fong Tang, Swee, Wern Tai, Chian, See Lum, Lucy Chai, Elghuwael, Ismail, Jimenez Rivera, Nestor Javier, Jarillo Quijada, Alberto E, Kneyber, Martin, Dijkstra, Sandra, Beca, John, Sherring, Claire, Miriam, Rea, Vargas G, Sonia I, Vasquez Miranda, Daniel, Ramirez Cortez, Grimaldo, Tantalean, Jose, Pagowska-Klimek, Izabela, Gil Escobar, Carlos, Sousa Moniz, Marta, Camilo, Cristina, Hazwani, Tarek, Aldairi, Nedaa, Al Amoudi, Ahmed, Alahmadti, Ahmad, Taylor, Ryan, Mendizabal, Mikel, Goni Orayen, Concepcion, Lopez Fernandez, Yolanda, Ramon Valle, Juan, Martinez, Lidia, Pilar Orive, Javier, Brezmes, Marta, Lopez-Herce, Jesus, Parrilla, Julio, Gaboli, Mirella, Gonzalez Gomez, Jose Manuel, Morales Martinez, Antonio, Alapont, Vicent Modesto I, Sanchez Diaz, Juan Ignacio, Llorente de la Fuente, Ana M., Palanca Arias, Daniel, Madurga Revilla, Paula, Martinez de Azagra, Amelia, Garcia Gonzalez, Maria, Arjona Villanueva, David, Garcia Casas, Paula, Brio Sanagustin, Sonia, Pons Odena, Marti, Medina, Alberto, Onate Vergara, Eider, Rodriguez Campoy, Patricia, Reyes Dominguez, Susana, Dursun, Oguz, Atike Ongun, Ebru, Kamit Can, Fulya, Berna Anil, Ayse, Baines, Paul, Walsh, Laura, Jones, Dawn, Sadasivam, Kalaimaran, Mildner, Reinout, Plunkett, Adrian, Lillie, Jon, Tibby, Shane, Wellman, Paul, Belfield, Holly, Brierley, Joe, Dominguez, Troy E., Abaleke, Eugenia, Feinstein, Yael, Deep, Akash, Sundararajan, Santosh, Oruganti, Siva, Silvestre, Catarina, Weitz, James, Sheward, Victoria, Macrae, Duncan, Aramburo, Angela, Fortune, Peter-Marc, Subramanian, Gayathri, Jennings, Claire, Dwarakanathan, Buvana, Inwald, David, Feather, Calandra, Agbeko, Rachel, Lawton-Woodhall, Angela, McIntyre, Karen, Sykes, Kim, Pappachan, Jon, Gale, Helen, Mellish, Christie, McCorkell, Jenni, Torero, Luis, Nofziger, Ryan, Latifi, Samir, Anthony, Heather, Sanders, Ron, Hefley, Glenda, Virk, Manpreet, Jaimon, Nancy, Maddux, Aline B., Mourani, Peter M., Ralston, Kimberly, Sierra, Yamila, Khemani, Robinder, Newth, Christopher, Bhalla, Anoopindar, Kwok, Jeni, Morzov, Rica, Mahapatra, Sidharth, Truemper, Edward, Kustka, Lucinda, Nett, Sholeen T., Singleton, Marcy, Dean Jarvis, J., Yehya, Nadir, Napolitano, Natalie, Murphy, Marie, Ronan, Laurie, Morgan, Ryan, Kubis, Sherri, Broden, Elizabeth, Willson, Douglas, Henderson, Grace, Gedeit, Rainer, Murkowski, Kathy, Woods, Katherine, Kasch, Mary, Han, Yong Y, Affolter, Jeremy T, Tieves, Kelly S, Hughes-Schalk, Amber, Chima, Ranjit S., Krallman, Kelli, Stoneman, Erin, Benken, Laura, Yunger, Toni, Schneider, James, Sweberg, Todd, Kessel, Aaron, Carroll, Christopher L., Santanelli, James, Ackerman, Kate G, Cullimore, Melissa, Rowan, Courtney, Bales, Melissa, Keith Dockery, W., Jafari-Namin, Shirin, Barry, Dana, Jane’t, Keary, Alibrahim, Omar, Patankar, Nikhil, Qiao, Haiping, Gertz, Shira, Su, Felice, Haileselassie, Bereketeab, Song, Hanqiu, Bysani, Kris, Monjure, Tracey, Beltramo, Fernando, Totapally, Balagangadhar, Govantes, Beatriz, Coates, Bria, Wellisch, Lawren, Allen, Kiona, Shukla, Avani, Thomas, Neal J., Spear, Debbie, Shein, Steven L., Gertz, Shira, Parker, Margaret M., Sloniewsky, Daniel, Allen, Christine, Harrell, Amy, Pinto, Neethi, Kniola, Allison, Rodgers, Chiara, Cvijanovich, Natalie, Typpo, Katri, Kelley, Connor, King, Caroline, Sapru, Anil, Ratiu, Anna, Ashtari, Neda, Sikora, Lindsay, Jeyapalan, Asumthia S., Coronado-Munoz, Alvaro, Flori, Heidi, Dahmer, Mary K., Jayachandran, Chaandini, Hume, Janet, Nerheim, Dan, Smith, Rebecca, Spaeder, Michael, Adu-Darko, Michelle, Smith, Lincoln, Hartmann, Silvia, Sullivan, Erin, Merritt, Courtney, Al-Subu, Awni, Blom, Andrea, Lin, John C., Spinella, Philip, Hsing, Deyin D., Pon, Steve, Brian Estil, Jim, Gautam, Richa, Giuliano, John S., Jr, and Tala, Joana

Published
2024
Full Text
View/download PDF

23. Monitoring coronary blood flow by laser speckle contrast imaging after myocardial ischaemia reperfusion injury in adult and aged mice

Author

Juma El-Awaisi, Dean P. J. Kavanagh, and Neena Kalia

Subjects
laser speckle contrast imaging LSCI, myocardial infarction, coronary microcirculation, ageing, ischaemia-reperfusion injury, interleukin-36, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

IntroductionInvestigating coronary microvascular perfusion responses after myocardial infarction (MI) would aid in the development of flow preserving therapies. Laser speckle contrast imaging (LSCI) is a powerful tool used for real-time, non-contact, full-field imaging of blood flow in various tissues/organs. However, its use in the beating heart has been limited due to motion artifacts.MethodsIn this paper, we report the novel use of LSCI, combined with custom speckle analysis software (SpAn), to visualise and quantitate changes in ventricular perfusion in adult and aged mice undergoing ischaemia-reperfusion (IR) injury. The therapeutic benefit of inhibiting the actions of the pro-inflammatory cytokine interleukin-36 (IL-36) was also investigated using an IL-36 receptor antagonist (IL-36Ra).ResultsImaging from uncovered and covered regions of the left ventricle demonstrated that whilst part of the LSCI flux signal was derived from beating motion, a significant contributor to the flux signal came from ventricular microcirculatory blood flow. We show that a biphasic flux profile corresponding to diastolic and systolic phases of the cardiac cycle can be detected without mathematically processing the total flux data to denoise motion artifacts. Furthermore, perfusion responses to ischaemia and postischaemia were strong, reproducible and could easily be detected without the need to subtract motion-related flux signals. LSCI also identified significantly poorer ventricular perfusion in injured aged mice following IR injury which markedly improved with IL-36Ra.DiscussionWe therefore propose that LSCI of the heart is possible despite motion artifacts and may facilitate future investigations into the role of the coronary microcirculation in cardiovascular diseases and development of novel therapies.

Published
2024
Full Text
View/download PDF

26. Lost in translation: understanding divergent perspectives on a depleted fish stock

Author

Dean, Micah J., Hoffman, William S., Buchan, Nicholas C., Scyphers, Steven B., and Grabowski, Jonathan H.

Subjects
Fish stocking -- Environmental aspects, Stock assessment (Wildlife management) -- Environmental aspects, Company distribution practices, Earth sciences
Abstract

Fishers commonly disagree with stock assessment results, particularly when a stock declines and strict harvest controls become necessary. Such regulations alter fisher perceptions of stock dynamics, contributing to a divergence in perspectives. Some assessments have inconsistent terminal year values (retrospective patterns) which fuel distrust in scientific advice. When assessment and fishery perspectives disagree, independent surveys can help identify biases and interpret discrepancies. We examine fishery trends and assessment results for Atlantic cod in the Gulf of Maine, a stock which has declined for decades. Trends were compared to a scientific industry cooperative trawl survey and a telephone survey of fisher perceptions. Trawl survey results generally corroborate the assessment perspective on population scale and decline, yet suggest a different view of the age structure. Fisher perceptions were at odds with the assessment and trawl survey and likely resulted from regulations that altered fisher behavior, causing catch rates to increase while the stock declined. Divergent perspectives may be an unavoidable consequence of fishery management, yet acknowledging the underlying mechanisms might help avoid future conflict. Key words: Gulf of Maine, Atlantic cod, targeting, fishing regulations, trip limits, social capital, Introduction Wild fish populations are constantly subject to change, whether it is environmentally driven, arising from endogenous factors, or caused by variation in human harvest (Hjort 1914; Sissenwine 1984). While [...]

Published
2023
Full Text
View/download PDF

27. Longitudinal Assessment and Functional Neuroimaging of Movement Variability Reveal Novel Insights Into Motor Dysfunction in Clinical High Risk for Psychosis.

Author

Dean, Derek J, Bernard, Jessica A, Damme, Katherine SF, O’Reilly, Randall, Orr, Joseph M, and Mittal, Vijay A

Subjects
Clinical Research, Neurosciences, Behavioral and Social Science, Mental Health, Brain Disorders, Pediatric, Serious Mental Illness, Aetiology, 2.1 Biological and endogenous factors, Neurological, Mental health, Adolescent, Adult, Cerebral Cortex, Child, Corpus Striatum, Disease Progression, Disease Susceptibility, Female, Functional Neuroimaging, Hand Strength, Handwriting, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Motor Activity, Motor Skills, Nerve Net, Psychotic Disorders, Risk, Young Adult, clinical high risk, motor control, variability, handwriting, power grip, longitudinal, functional magnetic resonance imaging, clinical high risk, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Motor dysfunction in youth at clinical high risk (CHR) for psychosis is thought to reflect abnormal neurodevelopment within cortical-subcortical motor circuits and may be important for understanding clinical trajectories of CHR individuals. However, to date, our perspective of brain-behavior relationships has been informed solely by cross-sectional correlational studies linking behavior in the lab to brain structure or respective resting-state network connectivity. Here, we assess movement dysfunction from 2 perspectives: study 1 investigates the longitudinal progression of handwriting variability and positive symptoms in a sample of 91 CHR and healthy controls during a 12-month follow-up and study 2 involves a multiband functional magnetic resonance imaging task exploring the relationship between power grip force stability and motor network brain activation in a subset of participants. In study 1, we found that greater handwriting variability was a stable feature of CHR participants who experienced worse symptom progression. Study 2 results showed that CHR individuals had greater variability in their grip force and greater variability was related to decreased activation in the associative cortico-striatal network compared to controls. Motor variability may be a stable marker of vulnerability for psychosis risk and possible indicator of a vulnerable cortico-striatal brain network functioning in CHR participants, although the effects of antipsychotic medication should be considered.

Published
2020

32. Improving vasculoprotective effects of MSCs in coronary microvessels – benefits of 3D culture, sub-populations and heparin

Author

Kobkaew Bumroongthai, Dean P. J. Kavanagh, Paul Genever, and Neena Kalia

Subjects
myocardial infarction, myocardial ischaemia-reperfusion injury, coronary microcirculation, mesenchymal stem/stromal cells, intravital microscopy, neutrophils, Immunologic diseases. Allergy, RC581-607
Abstract

IntroductionOpening occluded coronary arteries in patients with myocardial infarction (MI) damages the delicate coronary microvessels through a process called myocardial ischaemia-reperfusion injury. Although mesenchymal stromal cells (MSCs) have the potential to limit this injury, clinical success remains limited. This may be due to (i) poor MSC homing to the heart (ii) infused MSCs, even if derived from the same site, being a heterogeneous population with varying therapeutic efficacy and (iii) conventional 2D culture of MSCs decreasing their homing and beneficial properties. This study investigated whether 3D culture of two distinctly different bone marrow (BM)-derived MSC sub-populations could improve their homing and coronary vasculoprotective efficacy.MethodsIntravital imaging of the anaesthetised mouse beating heart was used to investigate the trafficking and microvascular protective effects of two clonally-derived BM-derived MSC lines, namely CD317neg MSCs-Y201 and CD317pos MSCs-Y202, cultured using conventional monolayer and 3D hanging drop methods.Results3D culture consistently improved the adhesive behaviour of MSCs-Y201 to various substrates in vitro. However, it was their differential ability to reduce neutrophil events within the coronary capillaries and improve ventricular perfusion in vivo that was most remarkable. Moreover, dual therapy combined with heparin further improved the vasculoprotection afforded by 3D cultured MSCs-Y201 by also modifying platelet as well as neutrophil recruitment, which subsequently led to the greatest salvage of viable myocardium. Therapeutic benefit could mechanistically be explained by reductions in coronary endothelial oxidative stress and intercellular adhesion molecule-1 (ICAM-1)/vascular cell adhesion molecule-1 (VCAM-1) expression. However, since this was noted by both 2D and 3D cultured MSCs-Y201, therapeutic benefit is likely explained by the fact that 3D cultured MSCs-Y201 were the most potent sub-population at reducing serum levels of several pro-inflammatory cytokines.ConclusionThis novel study highlights the importance of not only 3D culture, but also of a specific CD317neg MSC sub-population, as being critical to realising their full coronary vasculoprotective potential in the injured heart. Since the smallest coronary blood vessels are increasingly recognised as a primary target of reperfusion injury, therapeutic interventions must be able to protect these delicate structures from inflammatory cells and maintain perfusion in the heart. We propose that relatively feasible technical modifications in a specific BM-derived MSC sub-population could achieve this.

Published
2023
Full Text
View/download PDF

36. Seed size selection in Black-capped Chickadees (Poecile atricapillus)/Selection de tamano de semillas del carbonero cabecinegro (Poecile atricapillus)

Author

Wysinger, Justice A., Dean, Ejun J., and Briggs, Christopher W.

Subjects
Animal behavior, Seeds, Biological sciences
Abstract

Foraging behaviors of animals that promote efficiency can be explained by optimal foraging theory. Previous research suggests that factors associated with nutrition (e.g., oil content) or size (e.g., seed weight and depth) influence the foraging behaviors of Black-capped Chickadees (Poecile atricapillus). In February and March 2020 we examined seed selection in Black-capped Chickadees. Specifically, we collected black oil sunflower seeds discarded from a tube bird feeder by Black-capped Chickadees and compared them with seeds selected at random from the feeder. We measured the depth, length. width, and weight of 180 sunflower seeds. We found that the size and weight of the seeds were both important factors for chickadees in seed selection. In addition, chickadees preferred seeds that were significantly heavier when adjusted for seed size. These findings suggest that Blackcapped Chickadees select seeds based on their size and weight to maximize the nutritional content they intake. Chickadees therefore must also be able to distinguish small differences in seed weight, which may maximize their acquired energy while decreasing the risks of predation when individuals arc exposed during foraging. Received 29 October 2020. Accepted 24 May 2022. Key words: bird feeder, black oil. optimal foraging. sunflower seed. Los comportamientos de forrajeo dc animates que promueven la efkiencia pueden scr explicados por la teoria del forrajeo optimo. Invcstigaeioncs previas sugieren que faetores asociados a la nutricion (ej., contenido de aceites) o tamano (ej.. espesor y peso de las semillas) infiuyen en los comportamientos de forrajeo del carbonero cabecinegro (Poecile atricapillus). En febrero y marzo del 2020 examinamos la seleccion de semillas del carbonero cabecinegro. Especificamentc. colectamos semillas de girasol de aceite negro descartadas de un eomedero de tubo para aves por el carbonero cabecinegro y las comparamos con semillas selcccionadas al azar del eomedero. Medimos el espesor, largo, ancho y peso dc 180 semillas de girasol. Encontramos que el tamano y el peso de las semillas eran faetores importantes para los carboneros al seleceionar las semillas. Adcmas. los carboneros prefirieron semillas que eran significativamente mas pesadas al ajustar las medidas por tamano de semilla. Estos hallazgos sugieren que los carboneros cabecinegros seleecionan las semillas con base en el tamano y el peso para maximizar el contenido nutrieional que ingieren. Los earboneros deben entonees podcr distinguir pequenas difereneias de peso de las semillas, lo que podria maximizar su energia adquirida y a la vez disminuiria los riesgos de depredation a los que se sometcn los individuos durante el forrajeo. Palabras clave: aeeite negro, eomedero de aves. forrajeo Optimo, semilla de girasol., Optimal foraging theory aims to understand the foraging behavior of animals by measuring proxies of foraging efficiency, which can be used to estimate the fitness of the animal (MacArthur and [...]

Published
2022
Full Text
View/download PDF

45. Genomic relatedness of colonizing and invasive disease Klebsiella pneumoniae isolates in South African infants.

Author

Olwagen, Courtney P., Izu, Alane, Khan, Shama, Van der Merwe, Lara, Dean, Nicholas J., Mabena, Fikile C., Jones, Stephanie, Kwatra, Gaurav, Andrew, Lubomira, Rajyaguru, Urvi, Donald, Robert G. K., Simon, Raphael, Said, Mohamed, Nakwa, Firdose L., Wadula, Jeannette, Strehlau, Renate, van Niekerk, Anika M., Naidoo, Niree, Ramsamy, Yogandree, and Velaphi, Sithembiso C.

Abstract

Klebsiella pneumoniae (KPn) colonizes multiple anatomical sites and is a leading cause of invasive disease and death in African children; however, there is no comparative genomic analysis between colonizing and invasive strains. This study investigated the genomic relatedness of KPn colonizing and invasive isolates in South African infants; and evaluated the relative invasiveness of KPn isolates based on sequence types (ST), capsular (KL), and lipopolysaccharide (O) loci by calculating case-carrier ratios (CCRs). There was less genomic diversity amongst invasive (22 ST, 17 K-loci) than colonizing isolates (31 ST, 29 K-loci), with invasive isolates being 8.59-fold and 3.49-fold more likely to harbour genes encoding for multi-drug resistance and yersiniabactin production compared with colonizing isolates. The CCRs for KL102 and O1/O2v2 were > 1, and < 1 for KL8, ST1414, and O1O2v1. Identifying high-risk strains, including KL102 and O1O2v2, that may have a higher potential to cause invasive disease, could enhance risk assessment and management strategies in vulnerable populations. [ABSTRACT FROM AUTHOR]

Published
2025
Full Text
View/download PDF

46. Using nature-based citizen science initiatives to enhance nature connection and mental health.

Author

Oh, Rachel R. Y., Suarez-Castro, Andres F., Fuller, Richard A., Tervo, Michael, Rozario, Kevin, Peters, Birte, Chowdhury, Shawan, von Gönner, Julia, Friedrichs-Manthey, Martin, Berger, Ambros, Schultz, Tracy, Dean, Angela J., Tulloch, Ayesha, and Bonn, Aletta

Subjects
MENTAL health, ANXIETY, NATURE conservation, CITIZEN science, MENTAL depression, WELL-being
Abstract

The global rise in mental health issues underscores the critical importance of assessing the mental health benefits of engaging with nature. Beyond their primary aim of involving citizens in scientific data collection, nature-based citizen science initiatives offer significant potential for enhancing outcomes related to conservation (e.g., connection to nature) and human health and wellbeing (e.g., emotions, depression, stress, anxiety). However, the effectiveness of various types of initiatives in achieving specific outcomes remain unclear. This study evaluates changes in eight outcomes related to nature connection and health and wellbeing before and after participation in five initiatives in Australia and Germany. These initiatives varied in ecosystem type (urban parks, terrestrial forests and freshwater streams) and the participation duration (from 15 min to 48 h). We assessed three dimensions of connection to nature (Self, Experience and Perspective) measured by the Nature-Relatedness scale, mental health outcomes (symptoms of depression, stress and anxiety) using the DASS-21 scale, and emotional states (positive and negative emotions) using the Scale of Positive and Negative Experience (SPANE). We found that while participants generally reported improvements across all measured outcomes, only participation in the Queensland Trust for Nature initiative, characterized by its extended duration and social interactions, demonstrated statistically significant enhancements in mental health and emotions after controlling for socio-economic confounders. These findings suggest that while short-term nature-based interventions can effectively alleviate anxiety and stress symptoms and boost emotions, significant changes in nature connection and depression may require more intensive interventions than what is available through typical citizen science experiences. We advocate for reframing nature-based initiatives as integral components of broader health-promoting strategies. By aligning citizen science efforts with health promotion frameworks, these initiatives can achieve greater impact and simultaneously advance scientific understanding, support conservation strategies while improving human health. [ABSTRACT FROM AUTHOR]

Published
2025
Full Text
View/download PDF

47. Identifying Causative Agents of a Paretic Syndrome in Waterbirds in Southern Portugal.

Author

Mena Casero, María V., Turner, Andrew D., Ben-Gigirey, Begoña, Alexander, Ryan P., Dean, Karl J., Hatfield, Robert G., Maskrey, Benjamin H., Mazuet, Christelle, Karamendin, Kobey, and Mateo, Rafael

Subjects
PARALYTIC shellfish toxins, POLLUTANTS, BOTULINUM toxin, AVIAN influenza A virus, NEWCASTLE disease virus
Abstract

Paretic and paralyzing syndromes affecting wild birds are widely described in the literature, with outbreaks showing an increase in frequency and intensity worldwide during recent years. In the Iberian Peninsula, a paretic clinical picture without known etiology affecting mostly gulls has been reported during the last few decades. This paretic syndrome (PS) affects waterbirds and is characterized by a set of signs of ascendent flaccid paralysis, dyspnea, and diarrhea at different levels of severity. This study presents the first macro-analysis of some potential etiological PS agents in wild birds in southern Portugal. Other possible etiologies of PS related to nutritional deficiencies and environmental pollutants were not studied but are also discussed here. A total of 571 samples, belonging to 377 individuals with (n = 336) and without (n = 41) PS signs, have been tested for seven different toxins groups (botulinum neurotoxin (BoNT), paralytic shellfish toxins (PSTs), domoic acid (DA), anatoxin-a (ATX-a), cylindrospermopsin (CYN), tetrodotoxins (TTXs), and microcystins (MCs)) and three viral infections (gull adenovirus (GA), Newcastle disease virus (NVD), and highly pathogenic avian influenza viruses (HPAIV)). Of all the birds tested for botulinum neurotoxin, those with PS signs were positive (100%) and those without PS signs were negative (0%), confirming an association between PS and botulism. Some samples were positive for PSTs and MCs, but the prevalence in birds with PS signs was not significantly higher (2.5% and 5.3%, respectively) than in birds without signs (5.4% and 5.4%, respectively). Two birds without PS signs were positive for highly pathogenic avian influenza virus. The presence of the rest of the toxins and viruses was negative for all the samples tested. Our results support the relevant contribution of botulinum neurotoxin in the PS outbreaks observed in several species of aquatic birds in the last decades in southern Portugal, suggesting it could be one of the main causes of mortality in waterbirds. [ABSTRACT FROM AUTHOR]

Published
2025
Full Text
View/download PDF

49. Noninvasive Ventilation for Pediatric Acute Respiratory Distress Syndrome: Experience From the 2016/2017 Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Prospective Cohort Study*

Author

Emeriaud, Guillaume, Pons-Òdena, Marti, Bhalla, Anoopindar K., Shein, Steven L., Killien, Elizabeth Y., Modesto i Alapont, Vicent, Rowan, Courtney, Baudin, Florent, Lin, John C., Grégoire, Gabrielle, Napolitano, Natalie, Mayordomo-Colunga, Juan, Diaz, Franco, Cruces, Pablo, Medina, Alberto, Smith, Lincoln, Khemani, Robinder G., Sforza, Jesica, Poterala, Rossana, Fernandez, Analia, Avila Vera, Antonio, Orqueda, Daniel, Agueda Vidal, Nilda, Rosemary, Deheza, Turon, Gonzalo, Monjes, Cecilia, Espanol, Segundo Fernando, Serrate, Alejandro Siaba, Iolster, Thomas, Torres, Silvio, Cinquegrani, Karina, Jose Montes, Maria, Capocasa, Patricia, Ferreyra, Marcela, Castellani, Pablo, Giampieri, Martin, Pedraza, Claudia, Landry, Luis Martin, Althabe, Maria, Fortini, Yanina Vanesa, Botta, Priscila, Paziencia, Fernando, Erickson, Simon, Barr, Samantha, Shea, Sara, Butt, Warwick, Delzoppo, Carmel, Pintimalla, Alyssa, Leon, Alejandro Fabio Martinez, Rivera, Gustavo Alfredo Guzman, Jouvet, Philippe, Emeriaud, Guillaume, Dumitrascu, Mariana, Ellen French, Mary, Caro I, Daniel, Castillo, Andres E., Romero, Pablo Cruces, Medina, Tania, Madrid, Paula Pavez, Cortez, Ambar, Alvear, Jimena, Acuna, Carlos, Diaz, Franco, Nunez, Maria Jose, Araya, Adriana Wegner, Mundaca, Loreto Godoy, Chen, Yang, Lozano, German Perez, Carrero, Rosalba Pardo, Alarcon, Yurika Paola Lopez, Vega, Liliana Mazzillo, Izquierdo, Ledys Maria, Olave, Byron Enrique Piñeres, Orrego, Cesar Zuluaga, Lopez, Deyanira Quinonez, Hoyos, Pablo Vasquez, Vavrina, Martin, Zurek, Jiri, Campos-Miño, Santiago, Yerovi, Rocio, Bridier, Armelle, Payen, Valerie, Milesi, Christophe, Bourgoin, Pierre, Travert, Brendan, Genuini, Mathieu, Starck, Julie, Maria, Matthieu, Guichoux, Julie, Baudin, Florent, Briassoulis, George, Ilia, Stavroula, Di Nardo, Matteo, Camporesi, Anna, Chiusolo, Fabrizio, Shime, Nobuaki, Ohshimo, Shinichiro, Kida, Yoshiko, Kyo, Michihito, Tabata, Yuichi, Tang, Swee Fong, Tai, Chian Wern, Lum, Lucy Chai See, Elghuwael, Ismail, Rivera, Nestor Javier Jimenez, Jarillo Quijada, Alberto E, Kneyber, Martin, Dijkstra, Sandra, Beca, John, Sherring, Claire, Rea, Miriam, Vargas G, Sonia I, Miranda, Daniel Vasquez, Cortez, Grimaldo Ramirez, Tantalean, Jose, Pagowska-Klimek, Izabela, Escobar, Carlos Gil, Moniz, Marta Sousa, Camilo, Cristina, Hazwani, Tarek, Aldairi, Nedaa, Al Amoudi, Ahmed, Alahmadti, Ahmad, Taylor, Ryan, Mendizabal, Mikel, Orayen, Concepcion Goni, Fernandez, Yolanda Lopez, Valle, Juan Ramon, Martinez, Lidia, Orive, Javier Pilar, Brezmes, Marta, Lopez-Herce, Jesus, Parrilla, Julio, Gaboli, Mirella, Gomez, Jose Manuel Gonzalez, Morales Martinez, Antonio, Alapont, Vicent Modesto I, Diaz, Juan Ignacio Sanchez, Llorente de la Fuente, Ana M., Palanca Arias, Daniel, Madurga Revilla, Paula, Martinez de Azagra, Amelia, Garcia Gonzalez, Maria, Arjona Villanueva, David, Garcia Casas, Paula, Brio Sanagustin, Sonia, Pons Odena, Marti, Medina, Alberto, Onate Vergara, Eider, Rodriguez Campoy, Patricia, Reyes Dominguez, Susana, Dursun, Oguz, Atike Ongun, Ebru, Kamit Can, Fulya, Berna Anil, Ayse, Baines, Paul, Walsh, Laura, Jones, Dawn, Sadasivam, Kalaimaran, Mildner, Reinout, Plunkett, Adrian, Lillie, Jon, Tibby, Shane, Wellman, Paul, Belfield, Holly, Brierley, Joe, Dominguez, Troy E., Abaleke, Eugenia, Feinstein, Yael, Deep, Akash, Sundararajan, Santosh, Oruganti, Siva, Silvestre, Catarina, Weitz, James, Sheward, Victoria, Macrae, Duncan, Aramburo, Angela, Fortune, Peter-Marc, Subramanian, Gayathri, Jennings, Claire, Dwarakanathan, Buvana, Inwald, David, Feather, Calandra, Agbeko, Rachel, Lawton-Woodhall, Angela, McIntyre, Karen, Sykes, Kim, Pappachan, Jon, Gale, Helen, Mellish, Christie, McCorkell, Jenni, Torero, Luis, Nofziger, Ryan, Latifi, Samir, Anthony, Heather, Sanders, Ron, Hefley, Glenda, Virk, Manpreet, Jaimon, Nancy, Maddux, Aline B., Mourani, Peter M., Ralston, Kimberly, Sierra, Yamila, Khemani, Robinder, Newth, Christopher, Bhalla, Anoopindar, Kwok, Jeni, Morzov, Rica, Mahapatra, Sidharth, Truemper, Edward, Kustka, Lucinda, Nett, Sholeen T., Singleton, Marcy, Dean Jarvis, J., Yehya, Nadir, Napolitano, Natalie, Murphy, Marie, Ronan, Laurie, Morgan, Ryan, Kubis, Sherri, Broden, Elizabeth, Willson, Douglas, Henderson, Grace, Gedeit, Rainer, Murkowski, Kathy, Woods, Katherine, Kasch, Mary, Han, Yong Y, Affolter, Jeremy T, Tieves, Kelly S, Hughes-Schalk, Amber, Chima, Ranjit S., Krallman, Kelli, Stoneman, Erin, Benken, Laura, Yunger, Toni, Schneider, James, Sweberg, Todd, Kessel, Aaron, Carroll, Christopher L., Santanelli, James, Ackerman, Kate G, Cullimore, Melissa, Rowan, Courtney, Bales, Melissa, Keith Dockery, W., Jafari-Namin, Shirin, Barry, Dana, Jane’t, Keary, Alibrahim, Omar, Patankar, Nikhil, Qiao, Haiping, Gertz, Shira, Su, Felice, Haileselassie, Bereketeab, Song, Hanqiu, Bysani, Kris, Monjure, Tracey, Beltramo, Fernando, Totapally, Balagangadhar, Govantes, Beatriz, Coates, Bria, Wellisch, Lawren, Allen, Kiona, Shukla, Avani, Thomas, Neal J., Spear, Debbie, Shein, Steven L., Gertz, Shira, Parker, Margaret M., Sloniewsky, Daniel, Allen, Christine, Harrell, Amy, Pinto, Neethi, Kniola, Allison, Rodgers, Chiara, Cvijanovich, Natalie, Typpo, Katri, Kelley, Connor, King, Caroline, Sapru, Anil, Ratiu, Anna, Ashtari, Neda, Sikora, Lindsay, Jeyapalan, Asumthia S., Coronado-Munoz, Alvaro, Flori, Heidi, Dahmer, Mary K., Jayachandran, Chaandini, Hume, Janet, Nerheim, Dan, Smith, Rebecca, Spaeder, Michael, Adu-Darko, Michelle, Smith, Lincoln, Hartmann, Silvia, Sullivan, Erin, Merritt, Courtney, Al-Subu, Awni, Blom, Andrea, Lin, John C., Spinella, Philip, Hsing, Deyin D., Pon, Steve, Brian Estil, Jim, Gautam, Richa, Giuliano, John S., Jr, and Tala, Joana

Published
2023
Full Text
View/download PDF

50. NFIB Haploinsufficiency Is Associated with Intellectual Disability and Macrocephaly

Author

Schanze, Ina, Bunt, Jens, Lim, Jonathan WC, Schanze, Denny, Dean, Ryan J, Alders, Marielle, Blanchet, Patricia, Attié-Bitach, Tania, Berland, Siren, Boogert, Steven, Boppudi, Sangamitra, Bridges, Caitlin J, Cho, Megan T, Dobyns, William B, Donnai, Dian, Douglas, Jessica, Earl, Dawn L, Edwards, Timothy J, Faivre, Laurence, Fregeau, Brieana, Genevieve, David, Gérard, Marion, Gatinois, Vincent, Holder-Espinasse, Muriel, Huth, Samuel F, Izumi, Kosuke, Kerr, Bronwyn, Lacaze, Elodie, Lakeman, Phillis, Mahida, Sonal, Mirzaa, Ghayda M, Morgan, Sian M, Nowak, Catherine, Peeters, Hilde, Petit, Florence, Pilz, Daniela T, Puechberty, Jacques, Reinstein, Eyal, Rivière, Jean-Baptiste, Santani, Avni B, Schneider, Anouck, Sherr, Elliott H, Smith-Hicks, Constance, Wieland, Ilse, Zackai, Elaine, Zhao, Xiaonan, Gronostajski, Richard M, Zenker, Martin, and Richards, Linda J

Subjects
Biomedical and Clinical Sciences, Mental Health, Pediatric, Intellectual and Developmental Disabilities (IDD), Neurosciences, Rare Diseases, Behavioral and Social Science, Genetics, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Mental health, Neurological, Adolescent, Adult, Animals, Cerebral Cortex, Child, Child, Preschool, Codon, Nonsense, Cohort Studies, Corpus Callosum, Female, Haploinsufficiency, Humans, Intellectual Disability, Male, Megalencephaly, Mice, Mice, Knockout, NFI Transcription Factors, Polymorphism, Single Nucleotide, Young Adult, NFIB, agenesis of the corpus callosum, chromosome 9p22.3, chromosome 9p23, developmental delay, haploinsufficiency, intellectual disability, macrocephaly, megalencephaly, nuclear factor I, Biological Sciences, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

The nuclear factor I (NFI) family of transcription factors play an important role in normal development of multiple organs. Three NFI family members are highly expressed in the brain, and deletions or sequence variants in two of these, NFIA and NFIX, have been associated with intellectual disability (ID) and brain malformations. NFIB, however, has not previously been implicated in human disease. Here, we present a cohort of 18 individuals with mild ID and behavioral issues who are haploinsufficient for NFIB. Ten individuals harbored overlapping microdeletions of the chromosomal 9p23-p22.2 region, ranging in size from 225 kb to 4.3 Mb. Five additional subjects had point sequence variations creating a premature termination codon, and three subjects harbored single-nucleotide variations resulting in an inactive protein as determined using an in vitro reporter assay. All individuals presented with additional variable neurodevelopmental phenotypes, including muscular hypotonia, motor and speech delay, attention deficit disorder, autism spectrum disorder, and behavioral abnormalities. While structural brain anomalies, including dysgenesis of corpus callosum, were variable, individuals most frequently presented with macrocephaly. To determine whether macrocephaly could be a functional consequence of NFIB disruption, we analyzed a cortex-specific Nfib conditional knockout mouse model, which is postnatally viable. Utilizing magnetic resonance imaging and histology, we demonstrate that Nfib conditional knockout mice have enlargement of the cerebral cortex but preservation of overall brain structure and interhemispheric connectivity. Based on our findings, we propose that haploinsufficiency of NFIB causes ID with macrocephaly.

Published
2018

Catalog

Books, media, physical & digital resources
See catalog results