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Статті в журналах з теми "Panetta"

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Автор: Grafiati

Опубліковано: 10 грудня 2022

Оновлено: 28 січня 2023

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1

Fernández-Bañares, Fernando, Mercé Rosinach, and Maria Esteve. "Reply to Dr. Panetta et al.'s letter." Journal of Crohn's and Colitis 6, no. 7 (August 2012): 806. http://dx.doi.org/10.1016/j.crohns.2012.04.004.

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2

MARGARIT, D. H., and L. ROMANELLI. "A SIMPLE MODEL FOR CONTROL OF TUMOR CELLS." Journal of Biological Systems 23, supp01 (January 2015): S33—S41. http://dx.doi.org/10.1142/s0218339015400033.

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The Kirschner-Panetta model describes the poblational competition between effector cells and tumor cells. We analize external changes in the parameters and mechanisms to obtain the decreasing of tumor cells. These variations were performed by three different ways: Oscillations, spikes with the natural frequency of the system, and spikes with Normal Distribution. It was observed that the amount of tumor cells decreases to zero if we change simultaneously the parameters properly.

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3

Banerjee, Sandip. "Immunotherapy with Interleukin-2: A Study Based on Mathematical Modeling." International Journal of Applied Mathematics and Computer Science 18, no. 3 (September 1, 2008): 389–98. http://dx.doi.org/10.2478/v10006-008-0035-6.

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Immunotherapy with Interleukin-2: A Study Based on Mathematical ModelingThe role of interleukin-2 (IL-2) in tumor dynamics is illustrated through mathematical modeling, using delay differential equations with a discrete time delay (a modified version of the Kirshner-Panetta model). Theoretical analysis gives an expression for the discrete time delay and the length of the time delay to preserve stability. Numerical analysis shows that interleukin-2 alone can cause the tumor cell population to regress.

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4

Edwards, Richard E. "In Defense of Utopia: A Response to Katsulas, Herbeck, and Panetta." Argumentation and Advocacy 24, no. 2 (September 1987): 112–18. http://dx.doi.org/10.1080/00028533.1987.11951362.

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5

Starkov, Konstantin E., and Luis N. Coria. "Global dynamics of the Kirschner–Panetta model for the tumor immunotherapy." Nonlinear Analysis: Real World Applications 14, no. 3 (June 2013): 1425–33. http://dx.doi.org/10.1016/j.nonrwa.2012.10.006.

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6

Banerjee, Sandip, and Alexei Tsygvintsev. "Stability and bifurcations of equilibria in a delayed Kirschner–Panetta model." Applied Mathematics Letters 40 (February 2015): 65–71. http://dx.doi.org/10.1016/j.aml.2014.09.010.

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7

Yafia, Radouane. "Hopf bifurcation in a delayed model for tumor-immune system competition with negative immune response." Discrete Dynamics in Nature and Society 2006 (2006): 1–9. http://dx.doi.org/10.1155/ddns/2006/95296.

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The dynamics of the model for tumor-immune system competition with negative immune response and with one delay investigated. We show that the asymptotic behavior depends crucially on the time delay parameter. We are particularly interested in the study of the Hopf bifurcation problem to predict the occurrence of a limit cycle bifurcating from the nontrivial steady state, by using the delay as a parameter of bifurcation. The obtained results provide the oscillations given by the numerical study in M. Gałach (2003), which are observed in reality by Kirschner and Panetta (1998).

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8

Starkov, Konstantin E., and Alexander P. Krishchenko. "Ultimate dynamics of the Kirschner–Panetta model: Tumor eradication and related problems." Physics Letters A 381, no. 39 (October 2017): 3409–16. http://dx.doi.org/10.1016/j.physleta.2017.08.048.

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9

Cross, Sharyl. "Not Whether But When: The U.S. Decision to Enlarge NATO. By James M. Goldgeier. Washington, D.C.: Brookings Institution Press, 1999. 218p. $42.95 cloth, $18.95 paper." American Political Science Review 96, no. 1 (March 2002): 208–9. http://dx.doi.org/10.1017/s0003055402284324.

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James M. Goldgeier makes a major contribution to the contemporary case study literature concerning American foreign policy formation. Based on extensive interviews with more than 75 key participants (William Perry, Richard Holbrooke, John Shalikashvili, Leon Panetta, Anthony Lake, Strobe Talbott, and so forth), Goldgeier reconstructs a richly detailed account of the policy process that culminated in the decision to expand the NATO alliance eastward. The study illuminates the complex interplay of political considerations, bureaucratic interests, and individual preferences and skills (even chutzpah) that led to the admission of the first tier of new NATO member nations in Eastern/Central Europe.

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10

Bruzzi, Silvia. "Per una storia incrociata tra l’Italia e la Libia: Il percorso dell’etnologa e arabista Ester Panetta (1894-1983)." Studi Magrebini 18, no. 1 (March 25, 2020): 22–47. http://dx.doi.org/10.1163/2590034x-12340017.

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Abstract This paper is a contribution to the entangled history between Italy and Libya through the trajectory life of Ester Panetta (1894-1983), a leading scholar who devoted her life to develop the knowledge of the language, history and cultures of Libya. After her Arabic and colonial studies at the Oriental Institutes in Naples and in Paris, she lived in Libya until the outbreak of the Second World War when she definitively came back to Italy. Her experience as single woman in colonial lands is not isolated at all, as the stories of single women crossing the territory of the Empire as travellers, teachers and missionaries testify.

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11

P. Krishchenko, Alexander, and StarkovKonstantin E. "The four-dimensional Kirschner-Panetta type cancer model: How to obtain tumor eradication?" Mathematical Biosciences & Engineering 15, no. 5 (2018): 1243–54. http://dx.doi.org/10.3934/mbe.2018057.

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12

Tsygvintsev, Alexei, and Sandip Banerjee. "Bounded immune response in immunotherapy described by the deterministic delay Kirschner–Panetta model." Applied Mathematics Letters 35 (September 2014): 90–94. http://dx.doi.org/10.1016/j.aml.2013.11.006.

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13

Burgman, Mark A., Michael A. McCarthy, Andrew Robinson, Susan M. Hester, Marissa F. McBride, Jane Elith, and F. Dane Panetta. "Improving decisions for invasive species management: reformulation and extensions of the Panetta-Lawes eradication graph." Diversity and Distributions 19, no. 5-6 (May 2013): 603–7. http://dx.doi.org/10.1111/ddi.12055.

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14

Biber, Douglas. "CONTRASTIVE RHETORIC REVISITED AND REDEFINED. Clayann Gilliam Panetta (Ed.). Mahwah, NJ: Erlbaum, 2001. Pp. xx + 134. $39.95 cloth, $17.95 paper." Studies in Second Language Acquisition 25, no. 3 (August 4, 2003): 463–64. http://dx.doi.org/10.1017/s0272263103260198.

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Contrastive rhetoric—an analytical framework for the study of second language writing—has had incredible staying power. Since Kaplan's (1966) original paper, this framework has been used in dozens of studies that compare the rhetorical organizations of written texts produced by writers from different cultures and native languages (L1s). Additionally, the framework has been elaborated and refined considerably to account for the extensive range of linguistic variability found among written texts from different text types; more recent treatments include Grabe and Kaplan (1996, chap. 7) and Connor (1996).

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15

Saptaningtyas, Fitriyana Yuli, Lina Aryati, Fajar Adikusumo, and Wim T. Van Horssen. "Using perturbation theory to explain the existence of infected equilibrium point of immune-cervical cancer model." Bulletin of Applied Mathematics and Mathematics Education 2, no. 2 (December 15, 2022): 65–78. http://dx.doi.org/10.12928/bamme.v2i2.3955.

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Immunotherapy give a new hope for cervical cancer treatment. The Kirschner-Panetta model describe the interaction between effector cells, cancer cells, and interleukin-2(IL-2) with two immunotherapy, i.e.Â Adoptive Cellular Immunotherapy(ACI) and Cytokine therapy. The infected equilibrium point can give an idea of the cure level, but no one has discussed analytically. The function of cancer in steady state is a quintic polynomial that cannot be solved analytically. This study discusses the existence and bifurcation of the infected equilibrium point. Both, can explain the level of cure through analysis of the amount of cancer cells. We use the Singular Perturbation Method because the presents of the small parameter in the leading coefficient. The combination of Naive expansion and dominant balance technique are used. A consistent polynomial rescale is used to find the lost root due to Naive expansion solutions. The four infected equilibrium points get from the Naive and one from the dominant balance technique. ACI and cytokine therapy alone can reduce the cancer cells but with an imbalance of effector cells and IL-2. With both therapies, the cancer cells are close to zero which indicates a good level of cure. It is necessary to study further regarding the bifurcation causes other important parameters besides antigenicity.

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16

CRUZ, MAYO de COM HENRY. "LA VISIÓN POR COMPUTADORA Y LAS FUTURAS APLICACIONES TECNOLÓGICAS EN DIVERSOS ESCENARIOS." Revista de la Academia del Guerra del Ejército Ecuatoriano 12, no. 1 (July 14, 2021): 5. http://dx.doi.org/10.24133/age.n12.2019.13.

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La supervivencia de la humanidad está ligada al desarrollo de la tecnología, la misma que le ha permitido solventar necesidades fisiológicas, de seguridad, sociales, entre otras. Según el Hiperciclo de Gartner1, las principales tecnologías que se encuentran en el pico de la innovación y la expectación, están asociadas a la inteligencia artificial2, el aprendizaje automático3 y las plataformas del internet de las cosas (IoT) 4 (Panetta, 2018). Justamente, a partir de estas tecnologías se espera que para los próximos años se desarrollen un sin número de aplicaciones relacionadas a la toma de decisiones en; el transporte (vehículos autónomos), asistentes personales y gru- pales (robots autónomos inteligentes, asistentes vir- tuales), hogares digitales conectados, interfaces cere- bro - computadora, biochips, etc. Aunque pareciera que estas tecnologías proceden de la ciencia ficción, no es así, pues en este momento grupos y redes de investigación alrededor del mundo están trabajando en perfeccionar las mismas, de tal forma de disponer de insumos tecnológicos innova- dores. Muchas de las aplicaciones en desarrollo, de- penden de sensores que proporcionen información del entorno y que permiten al organismo artificial5 entrenar una serie de datos, para la posterior toma de decisiones. Precisamente la visión por computadora o también llamada visión artificial es una rama de la inteligencia artificial, que facilita a este organismo interpretar el entorno que le rodea a través del procesa- miento digital de las imágenes y/o señales.

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17

Voitkāne, Vita. "INCLUSIVE EDUCATION IN ITALY." SOCIETY. INTEGRATION. EDUCATION. Proceedings of the International Scientific Conference 3 (May 26, 2017): 136. http://dx.doi.org/10.17770/sie2017vol3.2281.

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European member States implement Inclusive Education policies thus contributing to a sustainable, inclusive society, although each country is at a different stage in this process. Italy, one of the first countries to launch integrative learning, has set an example since the 1970s, although the quality of inclusive education is unpredictable due to many issues. Authors Cantoni and Panetta (2006) emphasize that, although the culture of integration in Italy exists, much needs to be done to improve the quality of inclusive education and at present new, innovative projects are exploring strategies to this effect, the results of which will lead to a national reform on Special Needs Education. The aim of this study is to learn about Italian solutions to inclusive education, the obstacles presented, results achieved and people's attitudes to inclusivity, by carrying out theoretical and empirical research using Action as Research method. A survey was carried out on pupils’ parents and educational staff, the results of which reveal a variety of existing issues around quality assurance in inclusive education. Consequently people's thoughts and attitudes towards inclusive education are divided, however the majority of people are in agreement that Inclusive education is the best solution for everyone concerned, pupils, parents and teachers. This research is in agreement with the the Salamanca Declaration (1994, IX) which states that inclusive education is an evolving process - not the end result.

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18

Jougla, Thibault, and David G. Dritschel. "On the energetics of a two-layer baroclinic flow." Journal of Fluid Mechanics 816 (March 8, 2017): 586–618. http://dx.doi.org/10.1017/jfm.2017.79.

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The formation, evolution and co-existence of jets and vortices in turbulent planetary atmospheres is examined using a two-layer quasi-geostrophic $\unicode[STIX]{x1D6FD}$-channel shallow-water model. The study in particular focuses on the vertical structure of jets. Following Panetta & Held (J. Atmos. Sci., vol. 45 (22), 1988, pp. 3354–3365), a vertical shear arising from latitudinal heating variations is imposed on the flow and maintained by thermal damping. Idealised convection between the upper and lower layers is implemented by adding cyclonic/anti-cyclonic pairs, called hetons, to the flow, though the qualitative flow evolution is evidently not sensitive to this or other small-scale stochastic forcing. A very wide range of simulations have been conducted. A characteristic simulation which exhibits alternation between two different phases, quiescent and turbulent, is examined in detail. We study the energy transfers between different components and modes, and find the classical picture of barotropic/baroclinic energy transfers to be too simplistic. We also discuss the dependence on thermal damping and on the imposed vertical shear. Both have a strong influence on the flow evolution. Thermal damping is a major factor affecting the stability of the flow while vertical shear controls the number of jets in the domain, qualitatively through the Rhines scale $L_{Rh}=\sqrt{U/\unicode[STIX]{x1D6FD}}$.

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19

Witts, Emily C., Filipe Nascimento, and Gareth B. Miles. "Adenosine-mediated modulation of ventral horn interneurons and spinal motoneurons in neonatal mice." Journal of Neurophysiology 114, no. 4 (October 2015): 2305–15. http://dx.doi.org/10.1152/jn.00574.2014.

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Neuromodulation allows neural networks to adapt to varying environmental and biomechanical demands. Purinergic signaling is known to be an important modulatory system in many parts of the CNS, including motor control circuitry. We have recently shown that adenosine modulates the output of mammalian spinal locomotor control circuitry (Witts EC, Panetta KM, Miles GB. J Neurophysiol 107: 1925–1934, 2012). Here we investigated the cellular mechanisms underlying this adenosine-mediated modulation. Whole cell patch-clamp recordings were performed on ventral horn interneurons and motoneurons within in vitro mouse spinal cord slice preparations. We found that adenosine hyperpolarized interneurons and reduced the frequency and amplitude of synaptic inputs to interneurons. Both effects were blocked by the A1-type adenosine receptor antagonist DPCPX. Analysis of miniature postsynaptic currents recorded from interneurons revealed that adenosine reduced their frequency but not amplitude, suggesting that adenosine acts on presynaptic receptors to modulate synaptic transmission. In contrast to interneurons, recordings from motoneurons revealed an adenosine-mediated depolarization. The frequency and amplitude of synaptic inputs to motoneurons were again reduced by adenosine, but we saw no effect on miniature postsynaptic currents. Again these effects on motoneurons were blocked by DPCPX. Taken together, these results demonstrate differential effects of adenosine, acting via A1 receptors, in the mouse spinal cord. Adenosine has a general inhibitory action on ventral horn interneurons while potentially maintaining motoneuron excitability. This may allow for adaptation of the locomotor pattern generated by interneuronal networks while helping to ensure the maintenance of overall motor output.

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20

Panetti, Tracee, S. "Tyrosine phosphorylation of paxillin, FAK, AND p130CAS: effects on cell spreading and migration." Frontiers in Bioscience 7, no. 1-3 (2002): d143. http://dx.doi.org/10.2741/panetti.

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21

Benbow, Susan M. "Psychiatric Illness in Women: Emerging Treatment and Research. Edited by F. Lewis-Hall, T. S. Williams, J. A. Panetta and J. M. Herrera. American Psychiatric Publishing Inc., Washington, 2002. Pages: 658." International Journal of Geriatric Psychiatry 18, no. 11 (2003): 1065. http://dx.doi.org/10.1002/gps.1008.

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22

Kohen, Dora. "Psychiatric Illness in Women. Emerging Treatment and Research. Edited By Freda Lewis-Hall, Teresa S. Williams, Jill A. Panetta & John M. Herrera Washington, DC: American Psychiatric Publishing. 2002. 680 pp. US$65.00 (pb). ISBN 1 58562 003 3." British Journal of Psychiatry 182, no. 5 (May 2003): 460–61. http://dx.doi.org/10.1192/bjp.182.5.460-a.

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23

Kermanchi, Jasmin. "Open Documentary Platforms Enabling Forms of Democratization and Community Experience." Interactive Film & Media Journal 2, no. 4 (December 30, 2022): 86–94. http://dx.doi.org/10.32920/ifmj.v2i4.1666.

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In recent years, there has been an increase in open documentary projects on the web providing platforms for those affected by social problems to tell their stories. During the COVID-19 lockdowns, they gained significance as collaborative projects responding to pressing questions. They offered virtual spaces for community interaction and the interactive negotiation of meanings and perceptions of reality as face-to-face interactions on the ground became unfeasible. As networks of mutual support in times of uncertainty, they responded to the various needs of many people worldwide and avoided a hierarchical approach in favor of participatory, partly dialogical practices and a polyphonic form of presentation. This makes them compelling examples for discussing the democratic potentials and social-communicative functions of interactivity on such documentary platforms. This contribution analyzes two documentary projects: Corona Haikus (initiated by Sandra Gaudenzi and Sandra Tabares-Duque, 2020), launched as a Facebook group for visual poetry referring to the reality of the lockdowns and documenting the experiences during isolation, and Corona Diaries (initiated by Francesca Panetta et al., 2020), a database for voice recordings. The paper argues that interactivity in the two examples, first of all, fosters democratic processes on the level of production and decision-making processes as well as on the level of meaning construction; further – as an adjacent claim – the contribution suggests that the projects as complex assemblages allowed for the experience of virtual communities. By combining material and praxeological analyses and drawing on approaches from political theory, philosophy, and social sciences in addition to the media studies-oriented analyses, the paper identifies the transformative dimension of collaborative interactive documentaries, especially in times of crisis. Despite different medial approaches with additional advantages – visual poetry that encourages reflection and intimate voice recordings that enable effectively attentive listening –both platforms function as a medial in-between that enables collective identification and solidarity forms. The difference between Corona Haikus and Corona Diaries is: that Corona Haikus uses the democratic potentials of the interactive communication network for collective negotiations of meanings, dialogue, and co-creation, while Corona Diaries focuses more on low participation thresholds for a – in terms of content – highly open space, which in turn does not allow for interactions among the participants. What the projects have in common is that the active participation in the open space without the classical hierarchies between professional media makers and subjects, the collective narrative processes, and the sharing of emotions can lead to the feeling of being part of a developing community, which in turn can help individual participants to cope with their experiences. Additionally, the nonlinear, polyphonic platforms open up new perspectives and relations not seen before. Another result of the paper is that future research should differentiate more nuancedly between forms of participation rather than arguing based on an artificial distinction between interactivity and participation.

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24

Haubrich, William S. "Paneth of Paneth Cells." Gastroenterology 134, no. 3 (March 2008): 661. http://dx.doi.org/10.1053/j.gastro.2008.01.046.

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25

Stahl, Martin, Sarah Tremblay, Marinieve Montero, Wayne Vogl, Lijun Xia, Kevan Jacobson, Alfredo Menendez, and Bruce A. Vallance. "The Muc2 mucin coats murine Paneth cell granules and facilitates their content release and dispersion." American Journal of Physiology-Gastrointestinal and Liver Physiology 315, no. 2 (August 1, 2018): G195—G205. http://dx.doi.org/10.1152/ajpgi.00264.2017.

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Paneth cells are a key subset of secretory epithelial cells found at the base of small intestinal crypts. Unlike intestinal goblet cells, which secrete the mucin Muc2, Paneth cells are best known for producing an array of antimicrobial factors. We unexpectedly identified Muc2 staining localized around Paneth cell granules. Electron microscopy (EM) confirmed an electron lucent halo around these granules, which was lost in Paneth cells from Muc2-deficient (−/−) mice. EM and immunostaining for lysozyme revealed that Muc2−/− Paneth cells contained larger, more densely packed granules within their cytoplasm, and we detected defects in the transcription of key antimicrobial genes in the ileal tissues of Muc2−/− mice. Enteroids derived from the small intestine of wild-type and Muc2−/− mice revealed phenotypic differences in Paneth cells similar to those seen in vivo. Moreover, lysozyme-containing granule release from Muc2−/− enteroid Paneth cells was shown to be impaired. Surprisingly, Paneth cells within human ileal and duodenal tissues were found to be Muc2 negative. Thus Muc2 plays an important role in murine Paneth cells, suggesting links in function with goblet cells; however human Paneth cells lack Muc2, highlighting that caution should be applied when linking murine to human Paneth cell functions. NEW & NOTEWORTHY We demonstrate for the first time that murine Paneth cell granules possess a halo comprised of the mucin Muc2. The presence of Muc2 exerts an impact on Paneth cell granule size and number and facilitates the release and dispersal of antimicrobials into the mucus layer. Interestingly, despite the importance of Muc2 in murine Paneth cell function, our analysis of Muc2 in human intestinal tissues revealed no trace of Muc2 expression by human Paneth cells.

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26

Stevens, KyleeAnn. "Expert Opinion in a Post-Panetti Era." Psychiatric Annals 45, no. 12 (December 1, 2015): 610–14. http://dx.doi.org/10.3928/00485713-20151102-01.

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27

Panetti, Grace B., Jerome R. Robinson, Patrick J. Carroll, Michael R. Gau, Brian C. Manor, Patrick J. Walsh, and Eric J. Schelter. "Correction: Synthesis of novel copper-rare earth BINOLate frameworks from a hydrogen bonding DBU-H rare earth BINOLate complex." Dalton Transactions 48, no. 43 (2019): 16460. http://dx.doi.org/10.1039/c9dt90225b.

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28

Takakuwa, Akiko, Kiminori Nakamura, Mani Kikuchi, Rina Sugimoto, Shuya Ohira, Yuki Yokoi та Tokiyoshi Ayabe. "Butyric Acid and Leucine Induce α-Defensin Secretion from Small Intestinal Paneth Cells". Nutrients 11, № 11 (18 листопада 2019): 2817. http://dx.doi.org/10.3390/nu11112817.

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The intestine not only plays a role in fundamental processes in digestion and nutrient absorption, but it also has a role in eliminating ingested pathogenic bacteria and viruses. Paneth cells, which reside at the base of small intestinal crypts, secrete α-defensins and contribute to enteric innate immunity through potent microbicidal activities. However, the relationship between food factors and the innate immune functions of Paneth cells remains unknown. Here, we examined whether short-chain fatty acids and amino acids induce α-defensin secretion from Paneth cells in the isolated crypts of small intestine. Butyric acid and leucine elicit α-defensin secretion by Paneth cells, which kills Salmonella typhimurium. We further measured Paneth cell secretion in response to butyric acid and leucine using enteroids, a three-dimensional ex vivo culture system of small intestinal epithelial cells. Paneth cells expressed short-chain fatty acid receptors, Gpr41, Gpr43, and Gpr109a mRNAs for butyric acid, and amino acid transporter Slc7a8 mRNA for leucine. Antagonists of Gpr41 and Slc7a8 inhibited granule secretion by Paneth cells, indicating that these receptor and transporter on Paneth cells induce granule secretion. Our findings suggest that Paneth cells may contribute to intestinal homeostasis by secreting α-defensins in response to certain nutrients or metabolites.

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29

Adolph, Timon E., Lisa Mayr, Felix Grabherr, and Herbert Tilg. "Paneth Cells and their Antimicrobials in Intestinal Immunity." Current Pharmaceutical Design 24, no. 10 (May 28, 2018): 1121–29. http://dx.doi.org/10.2174/1381612824666180327161947.

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Since the initial description of granular-rich small-intestinal crypt-based epithelial cells in 1872, today referred to as Paneth cells, a plethora of recent studies underlined their function in intestinal homeostasis. Paneth cells are evolutionary conserved highly secretory cells that produce antimicrobials to control gut microbial communities. Moreover, Paneth cells emerged as stem cell regulators that translate environmental cues into intestinal epithelial responses. Paneth cell disturbances may instigate intestinal inflammation and provide susceptibility to infection. Altered Paneth cell functions have been associated with a variety of inflammatory disease models and were linked to human intestinal disease processes including inflammatory bowel diseases such as Crohn´s disease and ulcerative colitis. This review summarizes our current understanding of Paneth cells and their antimicrobials in health and disease.

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30

Bolaños-Cardona, Lina Constanza, Ingrid Alejandra Briñez-Javela, and Juan Sebastian Ramírez-Navas. "Evaluación termodinámica de variables críticas en la Estabilidad de la panela de caña de azúcar." Revista Facultad de Ciencias Básicas 14, no. 2 (December 3, 2019): 100–110. http://dx.doi.org/10.18359/rfcb.3167.

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El objetivo de este trabajo fue determinar la vida útil de la panela evaluando variables críticas de estabilidad. Para tal fin, se almacenaron tres presentaciones comerciales de panela (granulada, cuadrada y redonda), durante 129 días en cámaras bioclimáticas de dos ambientes de almacenamiento (ambiente: 30±2°C/75±5%HR y acelerado: 40±2°C/75±5%HR). Se evaluaron los parámetros de humedad, azúcares totales y actividad acuosa en las muestras previamente homogenizadas a los tiempos 0, 27, 35, 55, 76 y 129 días. Debido al incremento de la actividad acuosa y ganancia de humedad se evidenció cambio en la calidad del producto, variación del color y la textura, con señales de reblandecimiento (panela cuadrada y redonda) y aglutinación (panela granulada). Con los resultados obtenidos se predice que almacenando a 25oC los tiempos de vida útil para las muestras son: 398 días para panela redonda 164 días para panela cuadrada y 206 días para panela granulada.

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Hurt, R. "Matthias Paneth." BMJ 345, sep05 1 (September 5, 2012): e5671-e5671. http://dx.doi.org/10.1136/bmj.e5671.

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van Es, Johan H., and Hans Clevers. "Paneth cells." Current Biology 24, no. 12 (June 2014): R547—R548. http://dx.doi.org/10.1016/j.cub.2014.04.049.

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Chung, Hee K., Lan Xiao, Krishna C. Jaladanki, and Jian-Ying Wang. "Regulation of Paneth Cell Function by RNA-Binding Proteins and Noncoding RNAs." Cells 10, no. 8 (August 17, 2021): 2107. http://dx.doi.org/10.3390/cells10082107.

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Paneth cells are specialized intestinal epithelial cells that are located at the base of small intestinal crypts and play a vital role in preserving the gut epithelium homeostasis. Paneth cells act as a safeguard from bacterial translocation across the epithelium and constitute the niche for intestinal stem cells in the small intestine by providing multiple niche signals. Recently, Paneth cells have become the focal point of investigations defining the mechanisms underlying the epithelium-microbiome interactions and pathogenesis of chronic gut mucosal inflammation and bacterial infection. Function of Paneth cells is tightly regulated by numerous factors at different levels, while Paneth cell defects have been widely documented in various gut mucosal diseases in humans. The post-transcription events, specific change in mRNA stability and translation by RNA-binding proteins (RBPs) and noncoding RNAs (ncRNAs) are implicated in many aspects of gut mucosal physiology by modulating Paneth cell function. Deregulation of RBPs and ncRNAs and subsequent Paneth cell defects are identified as crucial elements of gut mucosal pathologies. Here, we overview the posttranscriptional regulation of Paneth cells by RBPs and ncRNAs, with a particular focus on the increasing evidence of RBP HuR and long ncRNA H19 in this process. We also discuss the involvement of Paneth cell dysfunction in altered susceptibility of the intestinal epithelium to chronic inflammation and bacterial infection following disrupted expression of HuR and H19.

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París Marqués, Amparo. "Seis ápocas de los maestros que intervinieron en la construcción de la iglesia de San Juan de los Panetes de Zaragoza (1722)." Studium, no. 23 (August 12, 2018): 113–31. http://dx.doi.org/10.26754/ojs_studium/stud.2017232607.

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Cuentas y materiales utilizados en la construcción de la iglesia de San Juan de los Panetes de Zaragoza, según seis albaranes de pago a los maestros que intervinieron en las obras. Palabras clave. Orden de San Juan de Jerusalén. Iglesia de San Juan de los Panetes (Zaragoza). Blas Ximénez. Pedro Izaguirre. Francisco de Urbieta. Domingo Sastre. Tomás de Mesa. Lorenzo Arbex. Abstract. Accountancy and materials used in the construction of the church of Saint John de los Panetes, in Zaragoza, according to six slips with the payment to the master builders who took part in the works. Key Words Order of Knights of the Hospital of Saint John of Jerusalem. Church of Saint John de los Panetes (Zaragoza). Blas Ximénez. Pedro Izaguirre. Francisco de Urbieta. Domingo Sastre. Tomás de Mesa. Lorenzo Arbex

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Gaudino, Stephen, Michael Beaupre, Xun Lin, Sonika Rathi, Patrick McLaughlin, Neil Mehta, Onur Eskiocak, et al. "Interleukin-22 receptor signaling in Paneth cells is critical for their maturation and antimicrobial function." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 60.9. http://dx.doi.org/10.4049/jimmunol.204.supp.60.9.

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Abstract Interleukin-22 (IL-22) acts in the intestine to promote critical tissue protective functions. However, since a diverse array of intestinal cell types (absorptive, secretory, and stem cells) express IL-22Ra1, a receptor for IL-22, it has been difficult to determine what cell type(s) specifically respond to IL-22 to mediate mucosal host defense. To address this question, we used entire gut epithelium, intestinal stem cell (ISC)-specific, and Paneth cell-specific IL-22Ra1 knockout mice. Entire epithelium-specific IL-22Ra1 knockout (Il22Ra1fl/fl;Villin-cre) mice displayed defects in Paneth cell function. Using ISC-specific IL-22Ra1 knockout mice (Il22Ra1fl/fl;Lgr5-EGFP-creERT2) and lineage tracing mice, we ruled out the involvement of Lgr5+ ISC-dependent IL-22Ra1 signaling in regulating the lineage commitment of epithelial cells, including Paneth cells. Using novel Paneth cell-specific IL-22Ra1 knockout mice (Il22Ra1fl/fl;Defa6-cre), we show that IL-22Ra1 signaling in Paneth cells is required for small intestinal host defense. We show that Paneth cell maturation, antimicrobial effector functions, gene expression of specific WNTs (Wnt6 and Wnt9b), and enteroid morphogenesis are dependent on cell-intrinsic IL-22Ra1 signaling. Furthermore, IL-22 signaling in Paneth cells regulates the intestinal commensal bacteria and microbiota-dependent IL-17A immune responses. Finally, we show Paneth cell-specific IL-22Ra1 signaling helps provide immunity against Salmonella typhimurium. Collectively, our findings provide a unique and novel role of IL-22 in Paneth cell-mediated small intestinal host defense.

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Liu, Ruixue, Richard Moriggl, Dongsheng Zhang, Haifeng Li, Rebekah Karns, Hai-Bin Ruan, Haitao Niu, et al. "Constitutive STAT5 activation regulates Paneth and Paneth-like cells to control Clostridium difficile colitis." Life Science Alliance 2, no. 2 (April 2019): e201900296. http://dx.doi.org/10.26508/lsa.201900296.

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Clostridium difficile impairs Paneth cells, driving intestinal inflammation that exaggerates colitis. Besides secreting bactericidal products to restrain C. difficile, Paneth cells act as guardians that constitute a niche for intestinal epithelial stem cell (IESC) regeneration. However, how IESCs are sustained to specify Paneth-like cells as their niche remains unclear. Cytokine-JAK-STATs are required for IESC regeneration. We investigated how constitutive STAT5 activation (Ca-pYSTAT5) restricts IESC differentiation towards niche cells to restrain C. difficile infection. We generated inducible transgenic mice and organoids to determine the effects of Ca-pYSTAT5-induced IESC lineages on C. difficile colitis. We found that STAT5 absence reduced Paneth cells and predisposed mice to C. difficile ileocolitis. In contrast, Ca-pYSTAT5 enhanced Paneth cell lineage tracing and restricted Lgr5 IESC differentiation towards pYSTAT5+Lgr5−CD24+Lyso+ or cKit+ niche cells, which imprinted Lgr5hiKi67+ IESCs. Mechanistically, pYSTAT5 activated Wnt/β-catenin signaling to determine Paneth cell fate. In conclusion, Ca-pYSTAT5 gradients control niche differentiation. Lack of pYSTAT5 reduces the niche cells to sustain IESC regeneration and induces C. difficile ileocolitis. STAT5 may be a transcription factor that regulates Paneth cells to maintain niche regeneration.

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Kessler, André. "Detecting and Responding to Alien Plant Incursions. Ecology, Biodiversity, and Conservation. By John R. Wilson, F. Dane Panetta, and Cory Lindgren. Cambridge and New York: Cambridge University Press. $104.00 (hardcover); $54.99 (paper). xviii + 265 p.; ill.; index. ISBN: 978-1-107-09560-1 (hc); 978-1-107-47948-7 (pb). 2017." Quarterly Review of Biology 94, no. 1 (March 2019): 93. http://dx.doi.org/10.1086/702367.

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Alula, Kibrom M., Dakota N. Jackson, Andrew D. Smith, Daniel S. Kim, Kevin Turner, Elizabeth Odstrcil, Benny A. Kaipparettu, et al. "Targeting Mitochondrial Damage as a Therapeutic for Ileal Crohn’s Disease." Cells 10, no. 6 (May 29, 2021): 1349. http://dx.doi.org/10.3390/cells10061349.

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Paneth cell defects in Crohn’s disease (CD) patients (called the Type I phenotype) are associated with worse clinical outcomes. Recent studies have implicated mitochondrial dysfunction in Paneth cells as a mediator of ileitis in mice. We hypothesized that CD Paneth cells exhibit impaired mitochondrial health and that mitochondrial-targeted therapeutics may provide a novel strategy for ileal CD. Terminal ileal mucosal biopsies from adult CD and non-IBD patients were characterized for Paneth cell phenotyping and mitochondrial damage. To demonstrate the response of mitochondrial-targeted therapeutics in CD, biopsies were treated with vehicle or Mito-Tempo, a mitochondrial-targeted antioxidant, and RNA transcriptome was analyzed. During active CD inflammation, the epithelium exhibited mitochondrial damage evident in Paneth cells, goblet cells, and enterocytes. Independent of inflammation, Paneth cells in Type I CD patients exhibited mitochondrial damage. Mito-Tempo normalized the expression of interleukin (IL)-17/IL-23, lipid metabolism, and apoptotic gene signatures in CD patients to non-IBD levels. When stratified by Paneth cell phenotype, the global tissue response to Mito-Tempo in Type I patients was associated with innate immune, lipid metabolism, and G protein-coupled receptor (GPCR) gene signatures. Targeting impaired mitochondria as an underlying contributor to inflammation provides a novel treatment approach for CD.

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López-Arribillaga, Erika, Bing Yan, Teresa Lobo-Jarne, Yolanda Guillén, Silvia Menéndez, Montserrat Andreu, Anna Bigas, Mar Iglesias, and Lluís Espinosa. "Accumulation of Paneth Cells in Early Colorectal Adenomas Is Associated with Beta-Catenin Signaling and Poor Patient Prognosis." Cells 10, no. 11 (October 28, 2021): 2928. http://dx.doi.org/10.3390/cells10112928.

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Background: Previous studies in mice indicated that Paneth cells and c-Kit-positive goblet cells represent the stem cell niche of the small intestine and colon, respectively, partly by supporting Wnt and Notch activation. Whether these cell populations play a similar role in human intestinal cancer remains unexplored. Methods: We performed histopathological evaluation and immunohistochemical analysis of early colorectal adenomas and carcinoma adenoma from patients at the Hospital del Mar in Barcelona. We then determined the possible correlation between the different parameters analyzed and with patient outcomes. Results: Paneth cells accumulate in a subset of human colorectal adenomas directly associated with Notch and Wnt/β-catenin activation. Adenoma areas containing Paneth cells display increased vessel density in the lamina propria and higher levels of the stem cell marker EphB2. In an in-house cohort of 200 colorectal adenoma samples, we also observed a significant correlation between the presence of Paneth cells and Wnt activation. Kaplan–Meier analysis indicated that early adenoma patients carrying Paneth cell-positive tumors display reduced disease-free survival compared with patients with Paneth cell-free lesions. Conclusions: Our results indicate that Paneth cells contribute to the initial steps of cancer progression by providing the stem cell niche to adenoma cells, which could be therapeutically exploited.

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Sherman, Michael P., Stephen H. Bennett, Freda F. Y. Hwang, Jan Sherman, and Charles L. Bevins. "Paneth Cells and Antibacterial Host Defense in Neonatal Small Intestine." Infection and Immunity 73, no. 9 (September 2005): 6143–46. http://dx.doi.org/10.1128/iai.73.9.6143-6146.2005.

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ABSTRACT Paneth cells are specialized epithelia in the small bowel that secrete antimicrobial proteins. Paneth cells are vital to the innate immunity of the small bowel in adult mammals, but their role during neonatal infection of the small bowel is not well established. Dithizone selectively damages Paneth cells, and when dithizone-treated newborn rats are infected enterally with Escherichia coli, the numbers of E. coli cells in their jejunal and ileal lavage fluid are significantly increased compared to controls. The data support that Paneth cells are necessary for neonatal antibacterial defense.

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Martinez Rodriguez, Nadine R., Marjannie D. Eloi, Alexandria Huynh, Teresa Dominguez, Annie H. Cheung Lam, Dayana Carcamo-Molina, Zeina Naser, Robert Desharnais, Nita H. Salzman, and Edith Porter. "Expansion of Paneth Cell Population in Response to Enteric Salmonella enterica Serovar Typhimurium Infection." Infection and Immunity 80, no. 1 (October 17, 2011): 266–75. http://dx.doi.org/10.1128/iai.05638-11.

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ABSTRACTPaneth cells residing at the base of the small intestinal crypts contribute to the mucosal intestinal first line defense by secreting granules filled with antimicrobial polypeptides including lysozyme. These cells derive from the columnar intestinal stem cell located at position 0 and the transit amplifying cell located at position +4 in the crypts. We have previously shown thatSalmonella entericaserovar Typhimurium (ST), a leading cause of gastrointestinal infections in humans, effects an overall reduction of lysozyme in the small intestine. To extend this work, we examined small-intestinal tissue sections at various time points after ST infection to quantify and localize expression of lysozyme and assess Paneth cell abundance, apoptosis, and the expression of Paneth cell differentiation markers. In response to infection with ST, the intestinal Paneth cell-specific lysozyme content, the number of lysozyme-positive Paneth cells, and the number of granules per Paneth cell decreased. However, this was accompanied by increases in the total number of Paneth cells and the frequency of mitotic events in crypts, by increased staining for the proliferation marker PCNA, primarily at the crypt side walls where the transit amplifying cell resides and not at the crypt base, and by apoptotic events in villi. Furthermore, we found a time-dependent upregulation of first β-catenin, followed by EphB3, and lastly Sox9 in response to ST, which was not observed after infection with aSalmonellapathogenicity island 1 mutant deficient in type III secretion. Our data strongly suggest that, in response to ST infection, a Paneth cell differentiation program is initiated that leads to an expansion of the Paneth cell population and that the transit amplifying cell is likely the main progenitor responder. Infection-induced expansion of the Paneth cell population may represent an acute intestinal inflammatory response similar to neutrophilia in systemic infection.

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Budianto, Iskandar Rahardjo, Agus Firmansyah, Yefta Moenadjat, Ahmad Aulia Jusuf, and Vivian Soetikno. "Paneth Cell Hyperplasia and Metaplasia in Hirschsprung-associated Enterocolitis in An Aganglionosis Rat Model." Indonesian Biomedical Journal 14, no. 4 (December 1, 2022): 393–400. http://dx.doi.org/10.18585/inabj.v14i4.2007.

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BACKGROUND: Many hypotheses regarding the pathophysiology of enterocolitis in aganglionic megacolon or Hirschsprung disease (HSCR) has been proposed. Paneth cells are columnar intestinal epithelial cells that have an important role in maintaining of intestinal homeostasis as a bactericide. Since enterocolitis in HSCR may have association with Paneth cells metaplasia and hyperplasia, current study investigated Paneth cells metaplasia and hyperplasia in the sigmoid colon of HSCR rat model and its products, namely a-defensins and IL-1b, in the sigmoid colon tissues.METHODS: Aganglionosis-induced and control Sprague-Dawley rats were euthanized on Day (D)-7, -14, -17, -19, -21, -23, -25, and -28. Sigmoid colon tissue was isolated at each time point, and degree of enterocolitis as well as Paneth cells metaplasia and hyperplasia were analyzed by Hematoxylin-eosin staining, then protein levels of a-defensins and interleukin (IL)-1b were determined by enzyme-linked immunosorbent assay (ELISA).RESULTS: Enterocolitis scores increased with time. The Paneth cells metaplasia and hyperplasia were observed on D14 until D28 (p<0.01 vs. control group) followed by an increased in the levels of IL-1b. The levels of a-defensins protein expression were initially increased (D7-D14; p<0.01 vs. control group) but then undergo reciprocal changes on D19 until D28 (p<0.01 vs. D7 and D14). Positive correlations between the degree of enterocolitis and Paneth cells number were detected in the sigmoid colon (r=0.42).CONCLUSION: Paneth cells underwent metaplasia and hyperplasia in the sigmoid colon of HSCR rats corresponding to an increase in the degree of enterocolitis, but not followed by an increase in the level of a-defensins as well as IL-1b, suggesting that there is an involvement of Paneth cells in the pathophysiology of enterocolitis due to HSCR.KEYWORDS: Hirschsprung, enterocolitis, defensins; metaplasia, Paneth cell, animal model

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van Es, Johan H., Kay Wiebrands, Carmen López-Iglesias, Marc van de Wetering, Laura Zeinstra, Maaike van den Born, Jeroen Korving, et al. "Enteroendocrine and tuft cells support Lgr5 stem cells on Paneth cell depletion." Proceedings of the National Academy of Sciences 116, no. 52 (December 16, 2019): 26599–605. http://dx.doi.org/10.1073/pnas.1801888117.

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Cycling intestinal Lgr5+stem cells are intermingled with their terminally differentiated Paneth cell daughters at crypt bottoms. Paneth cells provide multiple secreted (e.g., Wnt, EGF) as well as surface-bound (Notch ligand) niche signals. Here we show that ablation of Paneth cells in mice, using a diphtheria toxin receptor gene inserted into the P-lysozyme locus, does not affect the maintenance of Lgr5+stem cells. Flow cytometry, single-cell sequencing, and histological analysis showed that the ablated Paneth cells are replaced by enteroendocrine and tuft cells. As these cells physically occupy Paneth cell positions between Lgr5 stem cells, they serve as an alternative source of Notch signals, which are essential for Lgr5+stem cell maintenance. Our combined in vivo results underscore the adaptive flexibility of the intestine in maintaining normal tissue homeostasis.

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Xu, Xingwang, and Paul C. Yang. "Positivity of Paneitz operators." Discrete & Continuous Dynamical Systems - A 7, no. 2 (2001): 329–42. http://dx.doi.org/10.3934/dcds.2001.7.329.

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King, Stephanie L., Jahan J. Mohiuddin, and Christopher M. Dekaney. "Paneth cells expand from newly created and preexisting cells during repair after doxorubicin-induced damage." American Journal of Physiology-Gastrointestinal and Liver Physiology 305, no. 2 (July 15, 2013): G151—G162. http://dx.doi.org/10.1152/ajpgi.00441.2012.

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Paneth cell numbers increase following intestinal damage, but mechanisms driving this process are not understood. We hypothesized that the increase in Paneth cell numbers is due to recruitment of cells from a preexisting pool of secretory progenitors. Mice were given a single injection of doxorubicin (Dox), and intestinal tissue was collected 0–168 h after treatment. Paneth, goblet, and intermediate cells were counted and evaluated for cell morphology. Quantitative RT-PCR was used to measure expression of various genes associated with Paneth cell allocation and maturation. Paneth cells were birth dated using incorporation of thymidine analogs given before or after Dox. Staining revealed “intermediate” cells, which were rarely observed in control crypts but increased significantly in number 96 and 120 h after Dox treatment. Birth dating of intermediate cells 5 days after Dox treatment revealed that 24% of these cells took up thymidine analog given prior to Dox treatment and 36% took up thymidine analog given after Dox treatment. Quantitative RT-PCR demonstrated a significant increase in Spdef, Atoh1, Sox9, EphB3, Mist, Wnt5a, FGF-9, and FGF-18 mRNAs and a significant decrease in Indian hedgehog mRNA. Expansion of the Paneth cell compartment after Dox treatment is due to generation of new cells and recruitment of cells from an existing pool. These cells express Paneth and goblet biomarkers and are found only during repair. Expansion of these cells correlates temporally with reduced Indian hedgehog and increased FGF and Wnt mRNA. These findings are significant, as they provide a first step in understanding mechanisms of Paneth cell expansion during mucosal repair.

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Shimada, Osamu, Harunori Ishikawa, Hisami Tosaka-Shimada, Toshihiro Yasuda, Koichiro Kishi, and Shosuke Suzuki. "Detection of Deoxyribonuclease I Along the Secretory Pathway in Paneth Cells of Human Small Intestine." Journal of Histochemistry & Cytochemistry 46, no. 7 (July 1998): 833–40. http://dx.doi.org/10.1177/002215549804600706.

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The expression and distribution of deoxyribonuclease I (DNase I) in human duodenum, jejunum and ileum were examined by DNase I activity assay and the reverse transcriptase-polymerase chain reaction (RT-PCR), immunofluorescence, in situ hybridization, and immunocytochemical ultrastructural analyses. High levels of DNase I were detected in the cytoplasm of Paneth cells in human small intestine. A tissue homogenate fraction rich in Paneth cells showed strong DNase I-specific enzymatic activity. Immunofluorescence analysis using several specific anti-human DNase I antibodies showed very strong immunoreactivity in the cytoplasm of every Paneth cell. In situ hybridization demonstrated high levels of DNase I mRNA in Paneth cells. Immunogold electron microscopy revealed gold particles localized along the secretory pathway, with the exocrine secretory granules mostly labeled. Our findings strongly suggest that Paneth cells synthesize and secrete DNase I into the intestinal lumen.

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47

Mora, Jorge I., Julieta E. Barroeta, David A. Bernstein, and Juan Lechago. "Paneth Cell Carcinoma of the Ampulla of Vater." Archives of Pathology & Laboratory Medicine 128, no. 8 (August 1, 2004): 908–10. http://dx.doi.org/10.5858/2004-128-908-pccota.

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Abstract We describe a Paneth cell carcinoma arising within the ampulla of Vater in a 64-year-old man. The phenotype of virtually all neoplastic cells was consistent with that of Paneth cells, based on routine morphology and their strong positive immunostaining for lysozyme. Additional widespread positive immunostaining for carcinoembryonic antigen and CA 19.9 supports a totipotential cell as the origin of such neoplastic cells. This case, therefore, represents a true Paneth cell carcinoma, as opposed to inclusion of occasional neoplastic Paneth cells into a poorly differentiated adenocarcinoma. This pattern of differentiation is rare, and predictions regarding its ultimate biological behavior and malignant potential must be guarded.

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Jackson, Dakota N., Marina Panopoulos, William L. Neumann, Kevin Turner, Brandi L. Cantarel, LuAnn Thompson-Snipes, Themistocles Dassopoulos, et al. "Mitochondrial dysfunction during loss of prohibitin 1 triggers Paneth cell defects and ileitis." Gut 69, no. 11 (February 28, 2020): 1928–38. http://dx.doi.org/10.1136/gutjnl-2019-319523.

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ObjectiveAlthough perturbations in mitochondrial function and structure have been described in the intestinal epithelium of Crohn’s disease and ulcerative colitis patients, the role of epithelial mitochondrial stress in the pathophysiology of inflammatory bowel diseases (IBD) is not well elucidated. Prohibitin 1 (PHB1), a major component protein of the inner mitochondrial membrane crucial for optimal respiratory chain assembly and function, is decreased during IBD.DesignMale and female mice with inducible intestinal epithelial cell deletion of Phb1 (Phb1iΔIEC) or Paneth cell-specific deletion of Phb1 (Phb1ΔPC) and Phb1fl/fl control mice were housed up to 20 weeks to characterise the impact of PHB1 deletion on intestinal homeostasis. To suppress mitochondrial reactive oxygen species, a mitochondrial-targeted antioxidant, Mito-Tempo, was administered. To examine epithelial cell-intrinsic responses, intestinal enteroids were generated from crypts of Phb1iΔIEC or Phb1ΔPC mice.ResultsPhb1iΔIEC mice exhibited spontaneous ileal inflammation that was preceded by mitochondrial dysfunction in all IECs and early abnormalities in Paneth cells. Mito-Tempo ameliorated mitochondrial dysfunction, Paneth cell abnormalities and ileitis in Phb1iΔIEC ileum. Deletion of Phb1 specifically in Paneth cells (Phb1ΔPC) was sufficient to cause ileitis. Intestinal enteroids generated from crypts of Phb1iΔIEC or Phb1ΔPC mice exhibited decreased viability and Paneth cell defects that were improved by Mito-Tempo.ConclusionOur results identify Paneth cells as highly susceptible to mitochondrial dysfunction and central to the pathogenesis of ileitis, with translational implications for the subset of Crohn’s disease patients exhibiting Paneth cell defects.

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Burger, Elise, Americo H. Lopez-Yglesias, and Felix Yarovinsky. "Loss of intestinal epithelial autophagy leads to catastrophic susceptibility to acute T. gondii-mediated inflammation." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 208.2. http://dx.doi.org/10.4049/jimmunol.196.supp.208.2.

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Abstract The protozoan parasite Toxoplasma gondii triggers severe small intestinal immunopathology characterized by inflammation, Paneth cell loss and bacterial dysbiosis. Paneth cells are the predominant secretory epithelial cells which reside at the base of the crypt and release antimicrobial peptides that maintain intestinal homeostasis. T. gondii-triggered IFN-γ is a major inducer of Paneth cell death. However, mechanisms of IFN-γ-mediated Paneth cell death are unknown. We recently observed that under steady state conditions Paneth cells undergo active autophagy, which is both microbiota- and IFN-γ-dependent. To study autophagy’s role in T. gondii–induced Paneth cell loss we used mice deficient in the critical autophagy gene Atg5 in the intestinal epithelium (Villin-Cre × ATGfl/fl mice, E-ATG5−/−). Infected E-ATG5−/− mice exhibited catastrophic inflammation, characterized by the complete destruction of the intestinal crypts, establishing ATG5’s protective role during intestinal inflammation. To determine ATG5’s protective mechanism we generated ATG5-deficient intestinal organoids and observed that lack of ATG5 increased sensitivity to the TNF-induced cell death. Organoid death was further exacerbated when TNF stimulation occurred in combination with IFN-γ. Reexamining our in vivo model showed significantly elevated levels of TNF receptor 2 in infected E-ATG5−/− mice, indicating these mice are prone to TNF-triggered small intestinal immunopathology. Our results reveal that ATG5 expression within Paneth cells plays a highly protective role against cytokine-mediated immunopathology in the intestine during acute T. gondii infection.

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Kempen, Cody, Stephen Gaudino, Tej Bahadur, Ankita Singh, and Pawan Kumar. "INTERLEUKIN-17 RECEPTOR SIGNALING TO PANETH CELLS HELPS MAINTAIN INTESTINAL INTEGRITY AFTER GAMMA RADIATION INDUCED INJURY." Inflammatory Bowel Diseases 28, Supplement_1 (January 22, 2022): S18. http://dx.doi.org/10.1093/ibd/izac015.027.

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Abstract BACKGROUND IL-17A/F signaling through the IL-17RA/RC receptor complex plays a vital role in immunity and inflammation. The expression of IL-17RA/RC by diverse intestinal epithelial cell types including Paneth cells and the observation that therapies neutralizing IL-17A or IL-17RA in Crohn’s disease (CD) patients induce adverse events suggest essential homeostatic functions of this cytokine. Paneth cells and their antimicrobial products (a-defensins, lysozyme etc.) play a critical role in mediating small intestinal host defense under homeostatic conditions as well as after injury or infection, and their dysregulation constitutes a pathogenic factor for CD. The specific role of intestinal IL-17A signaling in Paneth cells to regulate host defense at steady state or after intestinal inflammation remains poorly understood. Thus, we hypothesize that intestinal IL-17A signaling, specifically in Paneth cells, plays an important role in regulating microbiota colonization as well as maintaining intestinal integrity after gamma radiation induced injury. METHODS To examine the importance of IL-17RA signaling to Paneth cells, we utilized total, entire gut epithelium (Il17rafl/fl;villin-cre) and Paneth cell-specific IL-17RA knockout mice (Il17rafl/fl;Defa6-cre+). We subjected these mice with gamma irradiation (1200 cGy) to study intestinal injury and regenerative responses. Mice were sacrificed 3/5 days post irradiation. Terminal ilium was collected from naïve or irradiated mice for immunofluorescence imaging, RT-PCR, RNA sequencing, and enteroid cultures. RESULTS Our preliminary data from irradiated Il17ra-/- and Il17rafl/fl;villin-cre mice suggest that IL-17A signaling is important in maintaining intestinal barrier integrity. Specifically, these mice revealed increased microbial dissemination to liver and spleen compared to their respective control mice. Reduced expression of Lyz1 3 days post radiation in the terminal ileum of Il17ra-/- mice suggest impaired Paneth cell function. Cessation of Paneth cell specific IL-17RA signaling, also resulted in systemic bacterial dissemination 5 days post radiation. We also observed increased level of fecal Lcn2 in irradiated Il17rafl/fl;Defa6-cre+ mice. To understand Paneth cell-specific IL-17RA functions, we performed 16S microbial and RNA sequencing from ileum luminal contents and terminal ilea of naïve Il17rafl/fl;Defa6-cre+/- mice, respectively. While microbial 16s sequencing revealed no change to the overall microbial community, specific changes were observed at a select family level. Specifically, the level of Streptococcaceae was increased. RNA sequencing data showed no difference in Paneth cell antimicrobial peptides but did show reduced Caspase 4 expression in Il17rafl/fl;Defa6-cre+ mice. Collectively, our data revealed an important role of IL-17RA signaling in Paneth cell function at steady state and after injury.

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