Heterocellular cadherin connections: coordinating adhesive cues in homeostasis and cancer

This short insight covers some of the recent topics relevant to the field of cadherin-catenin adhesion in mediating connections between different cell types, so-called heterotypic or heterocellular connections, in both homeostasis and cancer. These scientific discoveries are increasing our understanding of how multiple cells residing in complex tissues can be instructed by cadherin adhesion receptors to regulate tissue architecture and function and how these cadherin-mediated heterocellular connections spur tumor growth and the acquisition of malignant characteristics in tumor cells. Overall, the findings that have emerged over the past few years are elucidating the complexity of the functional roles of the cadherin-catenin complexes. Future exciting research lies ahead in order to understand the physical basis of these heterotypic interactions and their influence on the behavior of heterogeneous cellular populations as well as their roles in mediating phenotypic and genetic changes as cells evolve through complex environments during morphogenesis and cancer.The Perez-Moreno lab is supported by grants from the Spanish Ministry of Economy and Competitiveness/European Regional Development Fund (ERDF), European Union (BFU2015-71376-R), and the Worldwide Cancer Research UK Foundation (15-1219 to Mirna Perez-Moreno). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Clasp2 ensures mitotic fidelity and prevents differentiation of epidermal keratinocytes

Epidermal homeostasis is tightly controlled by a balancing act of self-renewal or terminal differentiation of proliferating basal keratinocytes. An increase in DNA content as a consequence of a mitotic block is a recognized mechanism underlying keratinocyte differentiation, but the molecular mechanisms involved in this process are not yet fully understood. Using cultured primary keratinocytes, here we report that the expression of the mammalian microtubule and kinetochore-associated protein Clasp2 is intimately associated with the basal proliferative makeup of keratinocytes, and its deficiency leads to premature differentiation. Clasp2-deficient keratinocytes exhibit increased centrosomal numbers and numerous mitotic alterations, including multipolar spindles and chromosomal misalignments that overall result in mitotic stress and a high DNA content. Such mitotic block prompts premature keratinocyte differentiation in a p53-dependent manner in the absence of cell death. Our findings reveal a new role for Clasp2 in governing keratinocyte undifferentiated features and highlight the presence of surveillance mechanisms that prevent cell cycle entry in cells that have alterations in the DNA content.This work was supported by grants from the Spanish Ministerio de Economia y Competitividad (MINECO) [BFU2012-33910 and BFU2015-71376-R (MINECO/ European Regional Development Fund (ERDF), European Union) to M.P.-M.]. Deposited in PMC for immediate release.S

Análisis empírico de la MDO en el español: tensión armónica entre iconicidad y economía

Differential Object Marking (DOM) is a linguistic phenomenon of many languages like Spanish, in which the preposition ‘a’ appears before direct objects. Current theory states that this phenomenon is ruled by the tension between iconicity (markedness) and economy (omission), In order to test this hypothesis, a 218-million tweets corpora representing all varieties of Spanish was used. 4,967 DOM cases showing marking, omission and optional marking were found in the Colombian Spanish corpus, which were tagged manually with 12 binary features and used to study other varieties. Through statistical analysis, it was discovered that this phenomenon is ruled by two highly correlated (r=0,92) tensions that can be associated with iconicity (13,47%) and economy (86,53%). This finding suggests that these tensions are not independent but rather controlled by a common factor named, in this study, as harmonic tension. This study provides the degree of importance of the features analyzed, which is used to propose a new feature hierarchy that confirms empirically other small ones proposed before. It can be concluded that this harmonic tension is an empirical plausible model to demonstrate the percentage of DOM in Spanish.La marcación diferencial del objeto es un fenómeno gramatical de varias lenguas como el español, en la cual el morfema ‘a’ aparece ante ciertos objetos directos. La teoría actual plantea que este fenómeno está dominado por la tensión entre: la iconicidad (marcación) y la economía (omisión). Para probar esta hipótesis, se utilizó un corpus de 218 millones de tuits de distintas variedades del español. Se encontraron 4.967 casos de marcación, opcionalidad y omisión de la MDO del español de Colombia que se caracterizaron manualmente con 12 rasgos semánticos binarios y que fueron utilizados para estudiar las demás variedades. El análisis estadístico arrojó que el fenómeno está gobernado por dos fuerzas altamente correlacionadas (r=0,92) que se pueden asociar a la iconicidad (13,47%) y la economía (86,53%). Estas fuerzas no son independientes; están controladas por un factor común, el cual se nombra en este estudio como tensión armónica. Se reporta el grado de importancia de los 12 rasgos para proponer una nueva jerarquía que confirma empíricamente otras antes propuestas. Se concluye que la tensión armónica es un modelo plausible con soporte empírico para modelar el porcentaje de la MDO del español

Photo-z optimization for measurements of the BAO radial direction

Baryon Acoustic Oscillations (BAO) in the radial direction offer a method to directly measure the Universe expansion history, and to set limits to space curvature when combined to the angular BAO signal. In addition to spectroscopic surveys, radial BAO might be measured from accurate enough photometric redshifts obtained with narrow-band filters. We explore the requirements for a photometric survey using Luminous Red Galaxies (LRG) to competitively measure the radial BAO signal and discuss the possible systematic errors of this approach. If LRG were a highly homogeneous population, we show that the photo-z accuracy would not substantially improve by increasing the number of filters beyond $\sim 10$, except for a small fraction of the sources detected at high signal-to-noise, and broad-band filters would suffice to achieve the target $\sigma_z = 0.003 (1+z)$ for measuring radial BAO. Using the LRG spectra obtained from SDSS, we find that the spectral variability of LRG substantially worsens the achievable photometric redshift errors, and that the optimal system consists of $\sim$ 30 filters of width $\Delta \lambda / \lambda \sim 0.02$. A $S/N > 20$ is generally necessary at the filters on the red side of the $H\alpha$ break to reach the target photometric accuracy. We estimate that a 5-year survey in a dedicated telescope with etendue in excess of 60 ${\rm m}^2 {\rm deg}^2$ would be necessary to obtain a high enough density of galaxies to measure radial BAO with sufficiently low shot noise up to $z= 0.85$. We conclude that spectroscopic surveys have a superior performance than photometric ones for measuring BAO in the radial direction.Comment: Replaced with minor editorial comments and one extra figure. Results unchange

Shoc2/Sur8 protein regulates neurite outgrowth

This is an openaccess article distributed under the terms of the Creative Commons Attribution License.-- et al.The Shoc2 protein has been implicated in the positive regulation of the Ras-ERK pathway by increasing the functional binding interaction between Ras and Raf, leading to increased ERK activity. Here we found that Shoc2 overexpression induced sustained ERK phosphorylation, notably in the case of EGF stimulation, and Shoc2 knockdown inhibited ERK activation. We demonstrate that ectopic overexpression of human Shoc2 in PC12 cells significantly promotes neurite extension in the presence of EGF, a stimulus that induces proliferation rather than differentiation in these cells. Finally, Shoc2 depletion reduces both NGF-induced neurite outgrowth and ERK activation in PC12 cells. Our data indicate that Shoc2 is essential to modulate the Ras-ERK signaling outcome in cell differentiation processes involved in neurite outgrowth.GL, TG and LMD were recipients of fellowships from the Ministerio de Educación y Ciencia (MEC) (to GL, TG), and Fondo de Investigaciones Sanitarias (FIS) (to LMD). LSR held a postdoctoral research contract from CIBERNED. This work was supported by FIS grant (PI10/00815) to JLO; CIBERNED to MC; SAF2008-01951, Comunidad Autónoma de Madrid (CAM) SSAL-0202-2006-01 and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) to TI; FIS grant PI12/00775 and ISCIII-RETIC (Red Temática de Investigación Cooperativa en Cáncer) RD12/0036/0027 from the Instituto de Salud Carlos III to PSG; and FIS grants (PI09/0562 and PI13/00703), ISCIIIRETIC (RD06/0020/0003 and RD12/0036/0021), and the Spanish Association Against Cancer (AECC) to JMR.Peer Reviewe

Shoc2/Sur8 Protein Regulates Neurite Outgrowth

The Shoc2 protein has been implicated in the positive regulation of the Ras-ERK pathway by increasing the functional binding interaction between Ras and Raf, leading to increased ERK activity. Here we found that Shoc2 overexpression induced sustained ERK phosphorylation, notably in the case of EGF stimulation, and Shoc2 knockdown inhibited ERK activation. We demonstrate that ectopic overexpression of human Shoc2 in PC12 cells significantly promotes neurite extension in the presence of EGF, a stimulus that induces proliferation rather than differentiation in these cells. Finally, Shoc2 depletion reduces both NGF-induced neurite outgrowth and ERK activation in PC12 cells. Our data indicate that Shoc2 is essential to modulate the Ras-ERK signaling outcome in cell differentiation processes involved in neurite outgrowth.This work was supported by FIS grant (PI10/00815) to JLO; CIBERNED to MC; SAF2008-01951, Comunidad Autónoma de Madrid (CAM) S-SAL-0202-2006-01 and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) to TI; FIS grant PI12/00775 and ISCIII-RETIC (Red Temática de Investigación Cooperativa en Cáncer) RD12/0036/0027 from the Instituto de Salud Carlos III to PSG; and FIS grants (PI09/0562 and PI13/00703), ISCIII-RETIC (RD06/0020/0003 and RD12/0036/0021), and the Spanish Association Against Cancer (AECC) to JMR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Increased Circulating Endothelial Microparticles and Carotid Atherosclerosis in Obstructive Sleep Apnea

Background and Purpose Endothelial impairment is a linking mechanism between obstructive sleep apnea (USA) and cardiovascular diseases Profiles of endothelial micropanicles (EMPs) and endothelial progenitor cells (EPCs) reflect the degree of endothelial impairment The aims of this study were to measure the levels of EMI`s and progenitor cells in USA, determine the correlations between these factors and USA severity and the deuce of atherosclerosis, and document any changes in these factors after therapy Methods Subjects with (n=82) and without (n=22) OSA were recruited prospectively We measured the number of colony-forming units (CM) in cell cultuie as the endothelial progenitor cell index, and the number of EMPs using flow cytometry with CD31 [platelet endothelial cell adhesion molecule (PECAM)], CD42 (platelet glycoprotem), annexm V, and CD62E (E-selectin) antibodies at baseline and Act 4-6 weeks of continuous positive airway pressure (CPA P) therapy Carotid int ima-media thickness (IMT) was regarded as a marker of atherosclerosis Results The levels of PECAM(+)CD42(-) (p<0 001). PECAM(+)annexin V(+) (p<0 001), and E-selectin(+) micropamcles (p=0 001) were higher in USA subjects than in non-USA subjects The number of CRJ did not differ between the two groups OSA severity independently predicted the levels of PECAM(+)CD42(-) (p=0 02) and PECA(+)annexin V(+) (p=0 004) Carotid IMT was correlated with USA severity (p<0 001), PECAM(+)CD42: (p=0 03), and PECAM(+)annexin (p=0 01) Neither USA severity nor carotid IMT was correlated with either the number of CFI) or E-selectin(+) CPAP therapy decreased the occurrence of E-selecte (p<0 001) in 21 of the USA subjects, but had no effect on the other micioparticles of the number CFU Conclusions USA led to the overproduction of EMI`s, which moderately correlated with USA seventy and the degree of atherosclerosis, and partly responded to therapy The endothelial impairment might contribute to future cardiovascular events J Clin Neurol 2010;6`89-98This research was supported by the Stem Cell Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea (#SC4120).de Lima AMJ, 2010, RESPIRATION, V79, P370, DOI 10.1159/000227800Jung KH, 2009, ANN NEUROL, V66, P191, DOI 10.1002/ana.21681Ayers L, 2009, EUR RESPIR J, V33, P574, DOI 10.1183/09031936.00107408Akinnusi ME, 2009, AM J RESP CRIT CARE, V179, P328Christou K, 2009, SLEEP MED, V10, P87, DOI 10.1016/j.sleep.2007.10.011Barcelo A, 2008, THORAX, V63, P946, DOI 10.1136/thx.2007.093740Dorkova Z, 2008, CHEST, V134, P686, DOI 10.1378/chest.08-0556Robinson GV, 2008, THORAX, V63, P855, DOI 10.1136/thx.2007.088096Somers VK, 2008, CIRCULATION, V118, P1080, DOI 10.1161/CIRCULATIONAHA.107.189375Hirschi KK, 2008, ARTERIOSCL THROM VAS, V28, P1584, DOI 10.1161/ATVBAHA.107.155960Daniel L, 2008, NEPHROL DIAL TRANSPL, V23, P2129, DOI 10.1093/ndt/gfn029Martin K, 2008, LUNG, V186, P145, DOI 10.1007/s00408-008-9073-yAmabile N, 2008, AM J RESP CRIT CARE, V177, P1268, DOI 10.1164/rccm.200710-1458OCHeiss C, 2008, J AM COLL CARDIOL, V51, P1760, DOI 10.1016/j.jacc.2008.01.040Chu K, 2008, STROKE, V39, P1441, DOI 10.1161/STROKEAHA.107.499236Jelic S, 2008, CIRCULATION, V117, P2270, DOI 10.1161/CIRCULATIONAHA.107.741512Lee ST, 2008, NEUROLOGY, V70, P1510Bakouboula B, 2008, AM J RESP CRIT CARE, V177, P536, DOI 10.1164/rccm.200706-840OCLopez-Jimenez F, 2008, CHEST, V133, P793, DOI 10.1378/chest.07-0800de la Pena M, 2008, RESPIRATION, V76, P28, DOI 10.1159/000109643WON CHJ, 2008, P AM THORAC SOC, V5, P193Kloner RA, 2007, CIRCULATION, V116, P1306, DOI 10.1161/CIRCULATIONAHA.106.678375El Solh AA, 2007, AM J RESP CRIT CARE, V175, P1186, DOI 10.1164/rccm.200611-1598OCIBER C, 2007, AASM MANUAL SCORINGMONTSERRAT JM, 2007, AM J RESP CRIT CARE, V176, P6Pirro M, 2006, ARTERIOSCL THROM VAS, V26, P2530, DOI 10.1161/01.ATV.0000243941.72375.15Ryan S, 2006, AM J RESP CRIT CARE, V174, P824, DOI 10.1164/rccm.200601-066OCBoulanger CM, 2006, HYPERTENSION, V48, P180, DOI 10.1161/01.HYP.0000231507.00962.b5Arteaga RB, 2006, AM J CARDIOL, V98, P70, DOI 10.1016/j.amjcard.2006.01.054Robinson GV, 2006, EUR RESPIR J, V27, P1229, DOI 10.1183/09031936.06.00062805Werner N, 2005, NEW ENGL J MED, V353, P999Mezentsev A, 2005, AM J PHYSIOL-HEART C, V289, pH1106, DOI 10.1152/ajpheart.00265.2005Minoguchi K, 2005, AM J RESP CRIT CARE, V172, P625, DOI 10.1164/rccm.200412-1652OCMassa M, 2005, BLOOD, V105, P199, DOI 10.1182/blood-2004-05-1831Kim J, 2004, AM J RESP CRIT CARE, V170, P1108, DOI 10.1164/rccm.200404-519OCJy W, 2004, J THROMB HAEMOST, V2, P1842Tramontano AF, 2004, BIOCHEM BIOPH RES CO, V320, P34, DOI 10.1016/j.bbrc.2004.05.127Ip MSM, 2004, AM J RESP CRIT CARE, V169, P348, DOI 10.1164/rccm.200306.767OCBarba C, 2004, LANCET, V363, P157Bernal-Mizrachi L, 2003, AM HEART J, V145, P962, DOI 10.1016/S0002-8703(03)00103-0Jimenez JJ, 2003, THROMB RES, V109, P175, DOI 10.1016/S0049-3848(03)00064-1Hill JM, 2003, NEW ENGL J MED, V348, P593Preston RA, 2003, HYPERTENSION, V41, P211, DOI 10.1161/01.HYP.0000049760.15764.2DSabatier F, 2002, DIABETES, V51, P2840, DOI 10.2337/diabetes.51.9.2840El-Solh AA, 2002, CHEST, V121, P1541Boulanger CM, 2001, CIRCULATION, V104, P2649Barbe F, 2001, ANN INTERN MED, V134, P1015Chin K, 2000, AM J MED, V109, P562Lusis AJ, 2000, NATURE, V407, P233Ohga E, 1999, J APPL PHYSIOL, V87, P10YOUNG T, 1993, NEW ENGL J MED, V328, P1230JOHNS MW, 1991, SLEEP, V14, P540

Kinetics of immune responses elicited after three mRNA COVID-19 vaccine doses in predominantly antibody-deficient individuals

Mass vaccination campaigns reduced COVID-19 incidence and severity. Here, we evaluated the immune responses developed in SARS-CoV-2-uninfected patients with predominantly antibody-deficiencies (PAD) after three mRNA-1273 vaccine doses. PAD patients were classified based on their immunodeficiency: unclassified primary antibody-deficiency (unPAD, n = 9), common variable immunodeficiency (CVID, n = 12), combined immunodeficiency (CID, n = 1), and thymoma with immunodeficiency (TID, n = 1). unPAD patients and healthy controls (HCs, n = 10) developed similar vaccine-induced humoral responses after two doses. However, CVID patients showed reduced binding and neutralizing titers compared to HCs. Of interest, these PAD groups showed lower levels of Spike-specific IFN-γ-producing cells. CVID individuals also presented diminished CD8+T cells. CID and TID patients developed cellular but not humoral responses. Although the third vaccine dose boosted humoral responses in most PAD patients, it had limited effect on expanding cellular immunity. Vaccine-induced immune responses in PAD individuals are heterogeneous, and should be immunomonitored to define a personalized therapeutic strategies.info:eu-repo/semantics/publishedVersio