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https://www.readbyqxmd.com/read/28213922/expression-of-kv3-1b-potassium-channel-is-widespread-in-macaque-motor-cortex-pyramidal-cells-a-histological-comparison-between-rat-and-macaque
#1
David Soares, Isabelle Goldrick, Roger N Lemon, Alexander Kraskov, Linda Greensmith, Bernadett Kalmar
There are substantial differences across species in the organisation and function of the motor pathways. These differences extend to basic electrophysiological properties. Thus, in rat motor cortex, pyramidal cells have long duration action potentials, while in the macaque, some pyramidal neurons exhibit short duration 'thin' spikes. These differences may be related to the expression of the fast potassium channel Kv3.1b, which in rat interneurons is associated with generation of thin spikes. Rat pyramidal cells typically lack these channels, while there are reports that they are present in macaque pyramids...
February 18, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28194435/foxp3-drives-oxidative-phosphorylation-and-protection-from-lipotoxicity
#2
Duncan Howie, Stephen Paul Cobbold, Elizabeth Adams, Annemieke Ten Bokum, Andra Stefania Necula, Wei Zhang, Honglei Huang, David J Roberts, Benjamin Thomas, Svenja S Hester, David J Vaux, Alexander G Betz, Herman Waldmann
Tregs can adopt a catabolic metabolic program with increased capacity for fatty acid oxidation-fueled oxidative phosphorylation (OXPHOS). It is unclear why this form of metabolism is favored in Tregs and, more specifically, whether this program represents an adaptation to the environment and developmental cues or is "hardwired" by Foxp3. Here we show, using metabolic analysis and an unbiased mass spectroscopy-based proteomics approach, that Foxp3 is both necessary and sufficient to program Treg-increased respiratory capacity and Tregs' increased ability to utilize fatty acids to fuel oxidative phosphorylation...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28165465/apical-dendrite-degeneration-a-novel-cellular-pathology-for-betz-cells-in-als
#3
Barış Genç, Javier H Jara, Amiko K B Lagrimas, Peter Pytel, Raymond P Roos, M Marsel Mesulam, Changiz Geula, Eileen H Bigio, P Hande Özdinler
Apical dendrites of Betz cells are important sites for the integration of cortical input, however their health has not been fully assessed in ALS patients. We investigated the primary motor cortices isolated from post-mortem normal control subjects, patients with familial ALS (fALS), sporadic ALS (sALS), ALS with frontotemporal dementia (FTD-ALS), and Alzheimer's disease (AD), and found profound apical dendrite degeneration of Betz cells in both fALS and sALS, as well as FTD-ALS patients. In contrast, Betz cells of AD patients and normal controls retain cellular integrity in the motor cortex, and CA1 pyramidal neurons show abnormalities predominantly within their soma, rather than the apical dendrite...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28164445/holographic-optical-tweezers-based-in-vivo-manipulations-in-zebrafish-embryos
#4
Florian Hörner, Robert Meissner, Sruthi Polali, Jana Pfeiffer, Timo Betz, Cornelia Denz, Erez Raz
Understanding embryonic development requires the characterization of the forces and the mechanical features that shape cells and tissues within the organism. In addition, experimental application of forces on cells and altering cell and organelle shape allows determining the role such forces play in morphogenesis. Here, we present a holographic optical tweezers-based new microscopic platform for in vivo applications in the context of a developing vertebrate embryo that unlike currently used setups allows simultaneous trapping of multiple objects and rapid comparisons of viscoelastic properties in different locations...
February 6, 2017: Journal of Biophotonics
https://www.readbyqxmd.com/read/28106950/confocal-laser-endomicroscopy-in-head-and-neck-malignancies-using-fitc-labelled-epcam-and-egf-r-antibodies-in-cell-lines-and-tumor-biopsies
#5
Anna S Englhard, Alexander Palaras, Veronika Volgger, Herbert Stepp, Brigitte Mack, Darko Libl, Olivier Gires, Christian S Betz
Intraoperative detection of residual malignant cells at tumor margins following excision of primary tumors could help improving surgery and thus patients' outcome. The feasibility of the tumor antigens epidermal growth factor receptor (EGF-R) and epithelial cell adhesion molecule (EpCAM) for antibody-dependent confocal laser scanning endomicroscopy (CLE)-mediated visualization of malignant cells was addressed. Both tumor antigens are highly and frequently expressed in the majority of carcinomas, including head and neck squamous cell carcinomas (HNSCC), and represent prognostic and therapeutic tumor target molecules...
January 20, 2017: Journal of Biophotonics
https://www.readbyqxmd.com/read/28054585/osseous-differentiation-of-human-fat-tissue-grafts-from-tissue-engineering-to-tissue-differentiation
#6
Maryna Bondarava, Chiara Cattaneo, Bin Ren, Wolfgang E Thasler, Volkmar Jansson, Peter E Müller, Oliver B Betz
Conventional bone tissue engineering approaches require isolation and in vitro propagation of autologous cells, followed by seeding on a variety of scaffolds. Those protracted procedures impede the clinical applications. Here we report the transdifferentiation of human fat tissue fragments retrieved from subcutaneous fat into tissue with bone characteristics in vitro without prior cell isolation and propagation. 3D collagen-I cultures of human fat tissue were cultivated either in growth medium or in osteogenic medium (OM) with or without addition of Bone Morphogenetic Proteins (BMPs) BMP-2, BMP-7 or BMP-9...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28028542/syrosingopine-sensitizes-cancer-cells-to-killing-by-metformin
#7
Don Benjamin, Marco Colombi, Sravanth K Hindupur, Charles Betz, Heidi A Lane, Mahmoud Y M El-Shemerly, Min Lu, Luca Quagliata, Luigi Terracciano, Suzette Moes, Timothy Sharpe, Aleksandra Wodnar-Filipowicz, Christoph Moroni, Michael N Hall
We report that the anticancer activity of the widely used diabetic drug metformin is strongly potentiated by syrosingopine. Synthetic lethality elicited by combining the two drugs is synergistic and specific to transformed cells. This effect is unrelated to syrosingopine's known role as an inhibitor of the vesicular monoamine transporters. Syrosingopine binds to the glycolytic enzyme α-enolase in vitro, and the expression of the γ-enolase isoform correlates with nonresponsiveness to the drug combination. Syrosingopine sensitized cancer cells to metformin and its more potent derivative phenformin far below the individual toxic threshold of each compound...
December 2016: Science Advances
https://www.readbyqxmd.com/read/27982100/spontaneous-isopeptide-bond-formation-as-a-powerful-tool-for-engineering-site-specific-antibody-drug-conjugates
#8
Vanessa Siegmund, Birgit Piater, Bijan Zakeri, Thomas Eichhorn, Frank Fischer, Carl Deutsch, Stefan Becker, Lars Toleikis, Björn Hock, Ulrich A K Betz, Harald Kolmar
Spontaneous isopeptide bond formation, a stabilizing posttranslational modification that can be found in gram-positive bacterial cell surface proteins, has previously been used to develop a peptide-peptide ligation technology that enables the polymerization of tagged-proteins catalyzed by SpyLigase. Here we adapted this technology to establish a novel modular antibody labeling approach which is based on isopeptide bond formation between two recognition peptides, SpyTag and KTag. Our labeling strategy allows the attachment of a reporting cargo of interest to an antibody scaffold by fusing it chemically to KTag, available via semi-automated solid-phase peptide synthesis (SPPS), while equipping the antibody with SpyTag...
December 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27974362/sharpin-regulates-collagen-architecture-and-ductal-outgrowth-in-the-developing-mouse-mammary-gland
#9
Emilia Peuhu, Riina Kaukonen, Martina Lerche, Markku Saari, Camilo Guzmán, Pia Rantakari, Nicola De Franceschi, Anni Wärri, Maria Georgiadou, Guillaume Jacquemet, Elina Mattila, Reetta Virtakoivu, Yuming Liu, Youmna Attieh, Kathleen A Silva, Timo Betz, John P Sundberg, Marko Salmi, Marie-Ange Deugnier, Kevin W Eliceiri, Johanna Ivaska
SHARPIN is a widely expressed multifunctional protein implicated in cancer, inflammation, linear ubiquitination and integrin activity inhibition; however, its contribution to epithelial homeostasis remains poorly understood. Here, we examined the role of SHARPIN in mammary gland development, a process strongly regulated by epithelial-stromal interactions. Mice lacking SHARPIN expression in all cells (Sharpin(cpdm)), and mice with a stromal (S100a4-Cre) deletion of Sharpin, have reduced mammary ductal outgrowth during puberty...
January 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/27941024/endosomal-phosphatidylinositol-3-phosphate-promotes-gephyrin-clustering-and-gabaergic-neurotransmission-at-inhibitory-postsynapses
#10
Theofilos Papadopoulos, Hong Jun Rhee, Devaraj Subramanian, Foteini Paraskevopoulou, Rainer Mueller, Carsten Schultz, Nils Brose, Jeong-Seop Rhee, Heinrich Betz
The formation of neuronal synapses and the dynamic regulation of their efficacy depend on the proper assembly of the postsynaptic neurotransmitter receptor apparatus. Receptor recruitment to inhibitory GABAergic postsynapses requires the scaffold protein gephyrin and the guanine nucleotide exchange factor collybistin (Cb). In vitro, the pleckstrin homology domain of Cb binds phosphoinositides, specifically phosphatidylinositol 3-phosphate (PI3P). However, whether PI3P is required for inhibitory postsynapse formation is currently unknown...
January 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27866708/mutations-in-three-genes-encoding-proteins-involved-in-hair-shaft-formation-cause-uncombable-hair-syndrome
#11
F Buket Ü Basmanav, Laura Cau, Aylar Tafazzoli, Marie-Claire Méchin, Sabrina Wolf, Maria Teresa Romano, Frederic Valentin, Henning Wiegmann, Anne Huchenq, Rima Kandil, Natalie Garcia Bartels, Arzu Kilic, Susannah George, Damian J Ralser, Stefan Bergner, David J P Ferguson, Ana-Maria Oprisoreanu, Maria Wehner, Holger Thiele, Janine Altmüller, Peter Nürnberg, Daniel Swan, Darren Houniet, Aline Büchner, Lisa Weibel, Nicola Wagner, Ramon Grimalt, Anette Bygum, Guy Serre, Ulrike Blume-Peytavi, Eli Sprecher, Susanne Schoch, Vinzenz Oji, Henning Hamm, Paul Farrant, Michel Simon, Regina C Betz
Uncombable hair syndrome (UHS), also known as "spun glass hair syndrome," "pili trianguli et canaliculi," or "cheveux incoiffables" is a rare anomaly of the hair shaft that occurs in children and improves with age. UHS is characterized by dry, frizzy, spangly, and often fair hair that is resistant to being combed flat. Until now, both simplex and familial UHS-affected case subjects with autosomal-dominant as well as -recessive inheritance have been reported. However, none of these case subjects were linked to a molecular genetic cause...
December 1, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27830219/fluctuations-of-a-membrane-nanotube-revealed-by-high-resolution-force-measurements
#12
F Valentino, P Sens, J Lemière, A Allard, T Betz, C Campillo, C Sykes
Pulling membrane nanotubes from liposomes presents a powerful method to gain access to membrane mechanics. Here we extend classical optical tweezers studies to infer membrane nanotube dynamics with high spatial and temporal resolution. We first validate our force measurement setup by accurately measuring the bending modulus of EPC membrane in tube pulling experiments. Then we record the position signal of a trapped bead when it is connected, or not, to a tube. We derive the fluctuation spectrum of these signals and find that the presence of a membrane nanotube induces higher fluctuations, especially at low frequencies (10-1000 Hz)...
November 10, 2016: Soft Matter
https://www.readbyqxmd.com/read/27790742/the-utility-of-etv1-etv4-and-etv5-rna-in-situ-hybridization-in-the-diagnosis-of-cic-dux-sarcomas
#13
Steven C Smith, Nallasivam Palanisamy, Elizabeth Martin, Jorge Almenara, Jonathan B McHugh, Eun-Young K Choi, David R Lucas, Bryan L Betz, Dafydd Thomas, Rajiv M Patel
AIMS: A recently characterized group of undifferentiated small round cell sarcomas harbours fusions of the genes CIC and DUX4. Studies report a distinctive gene expression profile for these sarcomas, including expression of E26 transformation-specific (ETS) family proto-oncogenic transcription factors ETV1, ETV4 and ETV5. To test the utility of an ancillary diagnostic technique for these tumours, we evaluated chromogenic RNA in-situ hybridization assays for ETV1, ETV4 and ETV5 as diagnostic adjuncts for this emerging group of highly malignant sarcomas...
March 2017: Histopathology
https://www.readbyqxmd.com/read/27758873/systems-analysis-uncovers-inflammatory-th-tc17-driven-modules-during-acute-gvhd-in-monkey-and-human-t-cells
#14
Scott N Furlan, Benjamin Watkins, Victor Tkachev, Sarah Cooley, Angela Panoskaltsis-Mortari, Kayla Betz, Melanie Brown, Daniel J Hunt, John B Schell, Katie Zeleski, Alison Yu, Cynthia R Giver, Edmund K Waller, Jeffrey S Miller, Bruce R Blazar, Leslie S Kean
One of the central challenges of transplantation is the development of alloreactivity despite the use of multiagent immunoprophylaxis. Effective control of this immune suppression-resistant T-cell activation represents one of the key unmet needs in the fields of both solid-organ and hematopoietic stem cell transplant (HCT). To address this unmet need, we have used a highly translational nonhuman primate (NHP) model to interrogate the transcriptional signature of T cells during breakthrough acute graft-versus-host disease (GVHD) that occurs in the setting of clinically relevant immune suppression and compared this to the hyperacute GVHD, which develops in unprophylaxed or suboptimally prophylaxed transplant recipients...
November 24, 2016: Blood
https://www.readbyqxmd.com/read/27757524/pathological-tdp-43-changes-in-betz-cells-differ-from-those-in-bulbar-and-spinal-%C3%AE-motoneurons-in-sporadic-amyotrophic-lateral-sclerosis
#15
Heiko Braak, Albert C Ludolph, Manuela Neumann, John Ravits, Kelly Del Tredici
Two nerve cells types, Betz cells in layer Vb of the primary motor neocortex and α-motoneurons of the lower brainstem and spinal cord, become involved at the beginning of the pathological cascade underlying sporadic amyotrophic lateral sclerosis (sALS). In both neuronal types, the cell nuclei forfeit their normal (non-phosphorylated) expression of the 43-kDa transactive response DNA-binding protein (TDP-43). Here, we present initial evidence that in α-motoneurons the loss of normal nuclear TDP-43 expression is followed by the formation of phosphorylated TDP-43 aggregates (pTDP-43) within the cytoplasm, whereas in Betz cells, by contrast, the loss of normal nuclear TDP-43 expression remains mostly unaccompanied by the development of cytoplasmic aggregations...
January 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/27503823/-an-autopsy-case-of-globular-glial-tauopathy-presenting-with-amyotrophic-lateral-sclerosis-with-dementia
#16
Ryogen Sasaki, Maya Mimuro, Yasumasa Kokubo, Hiroshi Imai, Mari Yoshida, Hidekazu Tomimoto
We report an autopsy case of globular glial tauopathy (GGT) presenting clinically with amyotrophic lateral sclerosis (ALS) with dementia. A 79-year-old female developed weakness in the right upper limb, which progressed gradually. She developed apathy and speech disorder at 80 years of age. On neurological examination, she showed signs of upper and lower motor neuron disorder and dementia, but no extrapyramidal signs. The clinical diagnosis was ALS with dementia. The autopsy revealed left predominant marked atrophy of the frontal lobe due to severe neuronal loss and Gliosis...
August 2016: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/27488962/normal-stroma-suppresses-cancer-cell-proliferation-via-mechanosensitive-regulation-of-jmjd1a-mediated-transcription
#17
Riina Kaukonen, Anja Mai, Maria Georgiadou, Markku Saari, Nicola De Franceschi, Timo Betz, Harri Sihto, Sami Ventelä, Laura Elo, Eija Jokitalo, Jukka Westermarck, Pirkko-Liisa Kellokumpu-Lehtinen, Heikki Joensuu, Reidar Grenman, Johanna Ivaska
Tissue homeostasis is dependent on the controlled localization of specific cell types and the correct composition of the extracellular stroma. While the role of the cancer stroma in tumour progression has been well characterized, the specific contribution of the matrix itself is unknown. Furthermore, the mechanisms enabling normal-not cancer-stroma to provide tumour-suppressive signals and act as an antitumorigenic barrier are poorly understood. Here we show that extracellular matrix (ECM) generated by normal fibroblasts (NFs) is softer than the CAF matrix, and its physical and structural features regulate cancer cell proliferation...
2016: Nature Communications
https://www.readbyqxmd.com/read/27406873/prt062607-achieves-complete-inhibition-of-the-spleen-tyrosine-kinase-at-tolerated-exposures-following-oral-dosing-in-healthy-volunteers
#18
Greg Coffey, Aradhana Rani, Andreas Betz, Yvonne Pak, Helena Haberstock-Debic, Anjali Pandey, Stanley Hollenbach, Daniel D Gretler, Tim Mant, Stipo Jurcevic, Uma Sinha
The spleen tyrosine kinase (SYK) regulates immune cell activation in response to engagement of a variety of receptors, making it an intriguing target for the treatment of inflammatory and autoimmune disorders as well as certain B-cell malignancies. We have previously reported on the discovery and preclinical characterization of PRT062607, a potent and highly selective inhibitor of SYK that exhibits robust anti-inflammatory activity in a variety of animal models. Here we present data from our first human studies aimed at characterizing the pharmacokinetics (PK), pharmacodynamics (PD), and safety of PRT062607 in healthy volunteers following single and multiple oral administrations...
February 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27385398/impact-of-comorbidity-and-anemia-in-patients-with-oropharyngeal-cancer-primarily-treated-with-surgery-in-the-human-papillomavirus-era
#19
Philipp Baumeister, Josepha Rauch, Christian Jacobi, Ulrich Kisser, Christian Betz, Sven Becker, Maximilian Reiter
BACKGROUND: Comorbidity and anemia strongly influence treatment and outcome of oropharyngeal squamous cell carcinomas (SCCs), but respective data are frequently lacking in clinical studies. We evaluated 149 cases of oropharyngeal SCC primarily treated with surgery regarding the impact of these factors on disease-free survival (DFS) and overall survival (OS). METHODS: Data were recorded during treatment and follow-up visits. Human papillomavirus (HPV) association of oropharyngeal SCC was detected by p16 immunohistochemistry...
January 2017: Head & Neck
https://www.readbyqxmd.com/read/27381223/cell-behaviors-and-dynamics-during-angiogenesis
#20
REVIEW
Charles Betz, Anna Lenard, Heinz-Georg Belting, Markus Affolter
Vascular networks are formed and maintained through a multitude of angiogenic processes, such as sprouting, anastomosis and pruning. Only recently has it become possible to study the behavior of the endothelial cells that contribute to these networks at a single-cell level in vivo This Review summarizes what is known about endothelial cell behavior during developmental angiogenesis, focusing on the morphogenetic changes that these cells undergo.
July 1, 2016: Development
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