Ex uniuerso disciplinarum theologicarum systemate secundum angelici doctoris doctrinam constituto illustriores propositiones ... [Texto impreso]

Hay un ejemplar encuadernado con: Philosophiae theses : (XVIII/262).Tesis-Colegio S. Joaquin, Padres Escolapios (Valencia)Esc. mariano en portSign.: [calderón]4, A-I

Specific Roles of XRCC4 Paralogs PAXX and XLF during V(D)J Recombination.

Paralog of XRCC4 and XLF (PAXX) is a member of the XRCC4 superfamily and plays a role in nonhomologous end-joining (NHEJ), a DNA repair pathway critical for lymphocyte antigen receptor gene assembly. Here, we find that the functions of PAXX and XLF in V(D)J recombination are masked by redundant joining activities. Thus, combined PAXX and XLF deficiency leads to an inability to join RAG-cleaved DNA ends. Additionally, we demonstrate that PAXX function in V(D)J recombination depends on its interaction with Ku. Importantly, we show that, unlike XLF, the role of PAXX during the repair of DNA breaks does not overlap with ATM and the RAG complex. Our findings illuminate the role of PAXX in V(D)J recombination and support a model in which PAXX and XLF function during NHEJ repair of DNA breaks, whereas XLF, the RAG complex, and the ATM-dependent DNA damage response promote end joining by stabilizing DNA ends.Cancer Research UK (Grant IDs: C6/A18796, C6946/A14492, C6/A18796), European Research Council (Grant ID: 310917), Wellcome Trust (Grant ID: WT092096), University of Cambridge, Institut PasteurThis is the final version of the article. It first appeared from Elsevier (Cell Press) via http://dx.doi.org/10.1016/j.celrep.2016.08.06

CartoCell, a high-content pipeline for 3D image analysis, unveils cell morphology patterns in epithelia

Decades of research have not yet fully explained the mechanisms of epithelial self-organization and 3D packing. Single-cell analysis of large 3D epithelial libraries is crucial for understanding the assembly and function of whole tissues. Combining 3D epithelial imaging with advanced deep-learning segmentation methods is essential for enabling this high-content analysis. We introduce CartoCell, a deep-learning-based pipeline that uses small datasets to generate accurate labels for hundreds of whole 3D epithelial cysts. Our method detects the realistic morphology of epithelial cells and their contacts in the 3D structure of the tissue. CartoCell enables the quantification of geometric and packing features at the cellular level. Our single-cell cartography approach then maps the distribution of these features on 2D plots and 3D surface maps, revealing cell morphology patterns in epithelial cysts. Additionally, we show that CartoCell can be adapted to other types of epithelial tissues.This work is supported by the project PID2019-103900GB-I00 funded by MCIN/AEI /10.13039/501100011033 and Programa Operativo FEDER Andalucía 2014–2020 (US-1380953) to L.M.E. Work by L.M.E. and J.A.A.-S.R. has been funded by the Junta de Andalucía (Consejerı´a de economı´a, conocimiento, empresas y Universidad) grant PY18-631 co-funded by FEDER funds. A.T. has been funded by a ‘‘Contrato predoctoral PIF’’ from Universidad de Sevilla. C.G.-V. has been funded by a ‘‘Contrato predoctoral para la formacio´ n de doctores’’ BES-2017-082306. G.B. was supported by a Comunidad de Madrid contract (CAM) and by an FPI grant from MINECO (BES-2022-077789). F.M.-B. was supported by MICINN (PID2020-120367GB-I00) and Fundacio´ n Ramo´ n Areces (CIVP18A3904). P.G.-G. has been funded by Margarita Salas Fellowship – NextGenerationEU. C.H.F.-E. has been funded by Marı´a Zambrano Fellowship – NextGenerationEU. I.A.-C. would like to acknowledge that his work has been partially supported by the University of the Basque Country UPV/EHU grant GIU19/027 and by grant PID2021-126701OB-I00, funded by MCIN/AEI/10.13039/501100011033 and by ‘‘ERDF A way of making Europe." L.M.E. also wants to thank PIE-202120E047 – Conexiones-Life network for networking and input

CartoCell, a high-content pipeline for 3D image analysis, unveils cell morphology patterns in epithelia

Decades of research have not yet fully explained the mechanisms of epithelial self-organization and 3D packing. Single-cell analysis of large 3D epithelial libraries is crucial for understanding the assembly and function of whole tissues. Combining 3D epithelial imaging with advanced deep-learning segmentation methods is essential for enabling this high-content analysis. We introduce CartoCell, a deep-learning-based pipeline that uses small datasets to generate accurate labels for hundreds of whole 3D epithelial cysts. Our method detects the realistic morphology of epithelial cells and their contacts in the 3D structure of the tissue. CartoCell enables the quantification of geometric and packing features at the cellular level. Our single-cell cartography approach then maps the distribution of these features on 2D plots and 3D surface maps, revealing cell morphology patterns in epithelial cysts. Additionally, we show that CartoCell can be adapted to other types of epithelial tissues

Genetic and Molecular Basis of Individual Differences in Human Umami Taste Perception

Umami taste (corresponds to savory in English) is elicited by L-glutamate, typically as its Na salt (monosodium glutamate: MSG), and is one of five basic taste qualities that plays a key role in intake of amino acids. A particular property of umami is the synergistic potentiation of glutamate by purine nucleotide monophosphates (IMP, GMP). A heterodimer of a G protein coupled receptor, TAS1R1 and TAS1R3, is proposed to function as its receptor. However, little is known about genetic variation of TAS1R1 and TAS1R3 and its potential links with individual differences in umami sensitivity. Here we investigated the association between recognition thresholds for umami substances and genetic variations in human TAS1R1 and TAS1R3, and the functions of TAS1R1/TAS1R3 variants using a heterologous expression system. Our study demonstrated that the TAS1R1-372T creates a more sensitive umami receptor than -372A, while TAS1R3-757C creates a less sensitive one than -757R for MSG and MSG plus IMP, and showed a strong correlation between the recognition thresholds and in vitro dose - response relationships. These results in human studies support the propositions that a TAS1R1/TAS1R3 heterodimer acts as an umami receptor, and that genetic variation in this heterodimer directly affects umami taste sensitivity

T1R3: A human calcium taste receptor

Many animals can detect the taste of calcium but it is unclear how or whether humans have this ability. We show here that calcium activates hTAS1R3-transfected HEK293 cells and that this response is attenuated by lactisole, an inhibitor of hT1R3. Moreover, trained volunteers report that lactisole reduces the calcium intensity of calcium lactate. Thus, humans can detect calcium by taste, T1R3 is a receptor responsible for this, and lactisole can reduce the taste perception of calcium by acting on T1R3

Effects of intragastric infusion of inosine monophosphate and l-glutamate on vagal gastric afferent activity and subsequent autonomic reflexes

In this study we investigated the effects of intragastric infusion of palatable basic taste substances (umami, sweet, and salty) on the activity of the vagal gastric afferent nerve (VGA), the vagal celiac efferent nerve (VCE), and the splanchnic adrenal efferent nerve (SAE) in anesthetized rats. To test the three selected taste groups, rats were infused with inosine monophosphate (IMP) and l-glutamate (GLU) for umami, with glucose and sucrose for sweet, and with sodium chloride (NaCl) for salty. Infusions of IMP and GLU solutions significantly increased VGA activity and induced the autonomic reflex, which activated VCE and SAE; these reflexes were abolished after sectioning of the VGA. Infusions of glucose, sucrose and NaCl solutions, conversely, had no significant effects on VGA activity. These results suggest that umami substances in the stomach send information through the VGA to the brain and play a role in the reflex regulation of visceral functions

Physics and Applications of Laser Diode Chaos

An overview of chaos in laser diodes is provided which surveys experimental achievements in the area and explains the theory behind the phenomenon. The fundamental physics underpinning this behaviour and also the opportunities for harnessing laser diode chaos for potential applications are discussed. The availability and ease of operation of laser diodes, in a wide range of configurations, make them a convenient test-bed for exploring basic aspects of nonlinear and chaotic dynamics. It also makes them attractive for practical tasks, such as chaos-based secure communications and random number generation. Avenues for future research and development of chaotic laser diodes are also identified.Comment: Published in Nature Photonic

Status of Muon Collider Research and Development and Future Plans

The status of the research on muon colliders is discussed and plans are outlined for future theoretical and experimental studies. Besides continued work on the parameters of a 3-4 and 0.5 TeV center-of-mass (CoM) energy collider, many studies are now concentrating on a machine near 0.1 TeV (CoM) that could be a factory for the s-channel production of Higgs particles. We discuss the research on the various components in such muon colliders, starting from the proton accelerator needed to generate pions from a heavy-Z target and proceeding through the phase rotation and decay ($\pi \to \mu \nu_{\mu}$) channel, muon cooling, acceleration, storage in a collider ring and the collider detector. We also present theoretical and experimental R & D plans for the next several years that should lead to a better understanding of the design and feasibility issues for all of the components. This report is an update of the progress on the R & D since the Feasibility Study of Muon Colliders presented at the Snowmass'96 Workshop [R. B. Palmer, A. Sessler and A. Tollestrup, Proceedings of the 1996 DPF/DPB Summer Study on High-Energy Physics (Stanford Linear Accelerator Center, Menlo Park, CA, 1997)].Comment: 95 pages, 75 figures. Submitted to Physical Review Special Topics, Accelerators and Beam

Supplemental information CartoCell, a high-content pipeline for 3D image analysis, unveils cell morphology patterns in epithelia

Document S1. Figures S1–S6 Table S1. Extracted features from 353 curated cysts (104 cysts at 4 days, 103 cysts at 7 days, 116 cysts at 10 days), related to Figure 2 Table S2. Hyperparameter search space for our proposed 3D ResU-Net, related to Figure 1 Table S3. Performance evaluation of our pipeline (CartoCell) on images of different epithelial tissues and comparison with other state-of-the-art segmentation methods, using the evaluation metrics described in STAR Methods, related to Figure 1 Table S4. Relative error between features extracted using automatically segmented cysts and manually curated cysts (STAR Methods), related to Figure 1 Table S5. Cyst morphology and scutoid location statistics, related to Figure 2 Table S6. Comparison of morphology and packing features of normoxic and hypoxic MDCK cysts, related to Figure 2 Table S7. Classification of the developmental stages of Drosophila egg chambers employed, related to Figure 3 Document S2. Article plus supplemental informationPeer reviewe