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Gantas Perez-Mockus, Khalil Mazouni, Vanessa Roca, Giulia Corradi, Vito Conte, François Schweisguth
Embryo-scale morphogenesis arises from patterned mechanical forces. During Drosophila gastrulation, actomyosin contractility drives apical constriction in ventral cells, leading to furrow formation and mesoderm invagination. It remains unclear whether and how mechanical properties of the ectoderm influence this process. Here, we show that Neuralized (Neur), an E3 ubiquitin ligase active in the mesoderm, regulates collective apical constriction and furrow formation. Conversely, the Bearded (Brd) proteins antagonize maternal Neur and lower medial-apical contractility in the ectoderm: in Brd-mutant embryos, the ventral furrow invaginates properly but rapidly unfolds as medial MyoII levels increase in the ectoderm...
November 17, 2017: Nature Communications
Nicole Berndt, Ekaterina Seib, Soya Kim, Tobias Troost, Marvin Lyga, Jessica Langenbach, Sebastian Haensch, Konstantina Kalodimou, Christos Delidakis, Thomas Klein
Ubiquitylation (ubi) by the E3-ligases Mindbomb1 (Mib1) and Neuralized (Neur) is required for activation of the DSL ligands Delta (Dl) and Serrate (Ser) to activate Notch signalling. These ligases transfer ubiquitin to lysines of the ligands' intracellular domains (ICDs), which sends them into an Epsin-dependent endocytic pathway. Here, we have tested the requirement of ubi of Dl for signalling. We found that Dl requires ubi for its full function, but can also signal in two ubi-independent modes, one dependent and one independent of Neur...
September 29, 2017: ELife
Gantas Perez-Mockus, Francois Schweisguth
Notch is a mechanosensitive receptor that requires direct cell-cell contact for its activation. Both the strength and the range of notch signaling depend on the size and geometry of the contact sites between cells. These properties of cell-cell contacts in turn depend on cell shape and polarity. At the molecular level, the E3 ubiquitin ligase Neuralized (Neur) links receptor activation with epithelial cell remodeling. Neur regulates the endocytosis of the Notch ligand Delta (Dl), hence Notch activation. It also targets the apical polarity protein Stardust (Sdt) to promote the endocytosis of the Crumbs complex, thereby contributing to epithelium remodeling...
September 21, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
Lawrence Blonde, Michel Marre, Maya Vincent, Sandrine Brette, Valerie Pilorget, Nicholas Danchin, Giacomo Vespasiani, Philip Home
AIMS: A number of insulin regimens are used in type 2 diabetes. This analysis aims to better understand the evolution of insulin therapy in different regions of Europe. METHODS: Data from people starting any insulin were collected in eastern Europe (EEur: Croatia, Russia, Ukraine), northern Europe (NEur: Finland, Germany, UK) and southern Europe (SEur: France, Italy, Portugal, Spain). Retrospective data on starting insulin and prospective follow-up data were extracted from clinical records...
November 2017: Diabetes Research and Clinical Practice
Gantas Perez-Mockus, Vanessa Roca, Khalil Mazouni, François Schweisguth
Crumbs (Crb) is a conserved determinant of apical membrane identity that regulates epithelial morphogenesis in many developmental contexts. In this study, we identify the Crb complex protein Stardust (Sdt) as a target of the E3 ubiquitin ligase Neuralized (Neur) in Drosophila melanogaster Neur interacts with and down-regulates specific Sdt isoforms containing a Neur binding motif (NBM). Using a CRISPR (clustered regularly interspaced short palindromic repeats)-induced deletion of the NBM-encoding exon, we found that Sdt is a key Neur target and that Neur acts via Sdt to down-regulate Crb...
May 1, 2017: Journal of Cell Biology
Jan Rusz, Michal Novotny, Jan Hlavnicka, Tereza Tykalova, Evzen Ruzicka
Recently, based on voice cepstral analysis, Benba et al. (IEEE T. Neur. Sys. Reh., vol. 24, pp. 1100-1108, 2016) have reported discrimination between patients with Parkinson's disease and different neurological disorders with high classification accuracy up to 90%. Using the same approach, we were able to experimentally separate two groups of normal healthy speakers with 96% classification accuracy and showed that the method proposed by Benba et al. may not be appropriate for discrimination between different neurological diseases...
October 26, 2016: IEEE Transactions on Neural Systems and Rehabilitation Engineering
Jan Rusz, Michal Novotny, Jan Hlavnicka, Tereza Tykalova, Evzen Ruzicka
Recently, based on voice cepstral analysis, Benba et al. (IEEE T. Neur. Sys. Reh., vol. 24, pp. 1100-1108, 2016) have reported discrimination between patients with Parkinson's disease and different neurological disorders with high classification accuracy up to 90%. Using the same approach, we were able to experimentally separate two groups of normal healthy speakers with 96% classification accuracy and showed that the method proposed by Benba et al. may not be appropriate for discrimination between different neurological diseases...
October 26, 2016: IEEE Transactions on Neural Systems and Rehabilitation Engineering
Kristina Endres, Sven Reinhardt, Anastasia Geladaris, Julia Knies, Marcus Grimm, Tobias Hartmann, Ulrich Schmitt
BACKGROUND: Murine models of Alzheimer's disease (AD) are mainly based on overexpression of pathologic amyloid precursor protein and/or presenilins. Those genes resemble underlying cause of early onset type of AD while about 99 % of all human cases are to be characterized as sporadic, late onset. Appropriate animal models for this type of AD are still missing. We here investigated, if transnasal delivery of A-beta 42 peptides might serve to mimic pathological effects in mice. RESULTS: A-beta 42 peptides, used for the behavioral study, showed the expected dose-dependent toxicity in neur oblastoma cell line SH-SY5Y and were able to form higher molecular weight species in vitro...
July 4, 2016: BMC Neuroscience
X He, S Zhou, G E St Armour, T F C Mackay, R R H Anholt
The extent to which epistasis affects the genetic architecture of complex traits is difficult to quantify, and identifying variants in natural populations with epistatic interactions is challenging. Previous studies in Drosophila implicated extensive epistasis between variants in genes that affect neural connectivity and contribute to natural variation in olfactory response to benzaldehyde. In this study, we implemented a powerful screen to quantify the extent of epistasis as well as identify candidate interacting variants using 203 inbred wild-derived lines with sequenced genomes of the Drosophila melanogaster Genetic Reference Panel (DGRP)...
February 2016: Genes, Brain, and Behavior
Paul Gozzard, Caroline Chapman, Angela Vincent, Bethan Lang, Paul Maddison
PURPOSE: Favourable small cell lung carcinoma (SCLC) survival outcomes have been reported in patients with paraneoplastic neurological disorders (PNDs) associated with neuronal antibodies (Neur-Abs), but the presence of a PND might have expedited diagnosis. Our aim was to establish whether neuronal antibodies, independent of clinical neurological features, correlate with SCLC survival. EXPERIMENTAL DESIGN: 262 consecutive SCLC patients were examined: of these, 24 with neurological disease were excluded from this study...
2015: PloS One
Jingwen Zhou, Jiahui Wu, Jintao Zhang, Tan Xu, Huan Zhang, Yonghong Zhang, Shaoyan Zhang
BACKGROUND: To investigate the association of short-term clinical outcomes with coexistence of hyperglycemia and elevated biomarkers of inflammation among acute ischemic stroke (AIS) patients. METHODS: We performed a retrospective study of 2675 patients diagnosed with AIS from January 2006 to December 2008. The study outcomes were defined as neurologic deficiency (National Institutes of Health Stroke Scale score ≥5) at discharge or death during hospitalization...
June 2015: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Toru Sasaki, Masafumi Yamanaka, Nobuyuki Kagami
The Publisher regrets that this article is an accidental duplication of an article that has already been published, The duplicate article has therefore been withdrawn.
December 12, 2012: Neuroscience Research
Marianne Udd, Outi Lindström, Harri Mustonen, Leif Bäck, Jorma Halttunen, Leena Kylänpää
OBJECTIVE: Percutaneous endoscopic gastrostomy (PEG) is used for long-term enteral nutrition in neurological patients with dysphagia (NEUR), in head and neck cancer patients prior to chemoradiation therapy (head and neck malignancy group [HNM]), or in cases of oropharyngeal or esophageal tumor obstruction or stricture (OBSTR). Considerable morbidity and overall mortality is reported. Aim was to analyze the complication rates and mortality with PEG and to identify subgroups with poor outcomes...
February 2015: Scandinavian Journal of Gastroenterology
Steven W Miller, Mark Rebeiz, Jenny E Atanasov, James W Posakony
Transcriptional cis-regulatory modules (CRMs), or enhancers, are responsible for directing gene expression in specific territories and cell types during development. In some instances, the same gene may be served by two or more enhancers with similar specificities. Here we show that the utilization of dual, or "shadow", enhancers is a common feature of genes that are active specifically in neural precursor (NP) cells in Drosophila. By genome-wide computational discovery of statistically significant clusters of binding motifs for both proneural activator (P) proteins and basic helix-loop-helix (bHLH) repressor (R) factors (a "P+R" regulatory code), we have identified NP-specific enhancer modules associated with multiple genes expressed in this cell type...
December 2, 2014: Proceedings of the National Academy of Sciences of the United States of America
Lei Bi, Jinman Kim, Dagan Feng, Michael Fulham
Positron emission tomography computed tomography (PET-CT) is the preferred imaging modality for the evaluation of the lymphomas. Disease involvement in the lymphomas usually appear as foci of increased Fluorodeoxyglucose (FDG) uptake. Thresholding methods are applied to separate different regions of involvement. However, the main limitation of thresholding is that it also includes regions where there is normal FDG excretion and FDG uptake (NEUR) in structures such as the brain, bladder, heart and kidneys. We refer to these regions as NEURs (the normal excretion and uptake (of FDG) regions)...
2014: Medical Image Computing and Computer-assisted Intervention: MICCAI ..
Chiyedza Small, Johnny Ramroop, Maria Otazo, Lawrence H Huang, Shireen Saleque, Shubha Govind
A fundamental question in hematopoietic development is how multipotent progenitors achieve precise identities, while the progenitors themselves maintain quiescence. In Drosophila melanogaster larvae, multipotent hematopoietic progenitors support the production of three lineages, exhibit quiescence in response to cues from a niche, and from their differentiated progeny. Infection by parasitic wasps alters the course of hematopoiesis. Here we address the role of Notch (N) signaling in lamellocyte differentiation in response to wasp infection...
June 2014: Genetics
Zhouheng Ye, Rongjia Zhang, Xuejun Sun
Argon is a noble gas in group 18 of the periodic table. Certificated to exist in air atmosphere merely one century ago, discovery of argon shows interesting stories of researching and exploring. It was assumed to have no chemical activity. However, argon indeed present its biological effect on mammals. Narcotic effect of argon in diving operation and neur-protective function of argon in cerebral injury demonstrate that argon has crucial effect and be concentrated on is necessary. Furthermore, consider to be harmless to human, argon clinical application in therapy would be another option...
2013: Medical Gas Research
Jia-kai Ye, Jin-tao Zhang, Yan Kong, Tan Xu, Ting-ting Zou, Yong-hong Zhang, Shao-yan Zhang
OBJECTIVE: To investigate the relationship between white blood cell count, neutrophils ratio and erythrocyte sedimentation rate and short outcomes among patients with acute ischemic stroke at admission to the hospital. METHODS: A total of 2675 acute ischemic stroke patients were included in this study. Data on demographic characteristics, life style, history of disease, white blood cell count (WBC), neutrophils ratio (NEUR), erythrocyte sedimentation rate (ESR) and clinical outcomes were collected for all the participants...
September 2012: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
Sili Liu, Julia Maeve Bonner, Soline Chanet, Cosimo Commisso, Lara C Skwarek, François Schweisguth, Gabrielle L Boulianne
The Notch pathway plays an integral role in development by regulating cell fate in a wide variety of multicellular organisms. A critical step in the activation of Notch signaling is the endocytosis of the Notch ligands Delta and Serrate. Ligand endocytosis is regulated by one of two E3 ubiquitin ligases, Neuralized (Neur) or Mind bomb. Neur is comprised of a C-terminal RING domain, which is required for Delta ubiquitination, and two Neur homology repeat (NHR) domains. We have previously shown that the NHR1 domain is required for Delta trafficking...
December 2012: Molecular and Cellular Biology
Mónica S Ventura Ferreira, Willi Jahnen-Dechent, Norina Labude, Manfred Bovi, Thomas Hieronymus, Martin Zenke, Rebekka K Schneider, Sabine Neuss, Sabine Neurs
Expansion of multipotent, undifferentiated and proliferating cord blood (CB)-hematopoietic stem cells (HSC) in vitro is limited and insufficient. Bone marrow (BM) engineering in vitro allows mimicking the main components of the hematopoietic niche compared to conventional expansion strategies. In this study, four different 3D biomaterial scaffolds (PCL, PLGA, fibrin and collagen) were tested for freshly isolated cord blood (CB)-CD34(+) cell expansion in presence of (i) efficient exogenous cytokine supplementation and (ii) umbilical cord (UC)-mesenchymal stem cells (MSC)...
October 2012: Biomaterials
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