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betz cell

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, Cindy Giver, Edmund 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 multi-agent 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 non-human primate model to interrogate the transcriptional signature of T cells during Breakthrough Acute GVHD that occurs in the setting of clinically-relevant immune suppression and compared this to the Hyperacute GVHD, that develops in unprophylaxed or sub-optimally prophylaxed transplant recipients...
October 6, 2016: Blood
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...
October 18, 2016: Acta Neuropathologica
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
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
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 ligation 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 pre-clinical 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...
July 13, 2016: Journal of Clinical Pharmacology
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...
July 7, 2016: Head & Neck
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
V Caorsi, J Lemière, C Campillo, M Bussonnier, J Manzi, T Betz, J Plastino, K Carvalho, C Sykes
Cells modulate their shape to fulfill specific functions, mediated by the cell cortex, a thin actin shell bound to the plasma membrane. Myosin motor activity, together with actin dynamics, contributes to cortical tension. Here, we examine the individual contributions of actin polymerization and myosin activity to tension increase with a non-invasive method. Cell-sized liposome doublets are covered with either a stabilized actin cortex of preformed actin filaments, or a dynamic branched actin network polymerizing at the membrane...
July 20, 2016: Soft Matter
Volker M Betz, Oliver B Betz, Tom Rosin, Alexander Keller, Christian Thirion, Michael Salomon, Suzanne Manthey, Peter Augat, Volkmar Jansson, Peter E Müller, Stefan Rammelt, Hans Zwipp
BACKGROUND: Delivery of bone morphogenetic protein-7 (BMP-7) to bone defects can be improved by applying gene transfer methods. However, traditional ex vivo gene therapy approaches are cumbersome and costly, requiring the extraction and culturing of cells. Therefore, we evaluated a novel, expedited ex vivo BMP-7 gene transfer technology based on the use of fragments of subcutaneous fat tissue. METHODS: We created 5-mm mid-femoral bone defects in the right femora of 23 male, syngeneic Fischer 344 rats...
August 2016: Journal of Gene Medicine
Nyeonju Kang, Evangelos A Christou, Roxana G Burciu, Jae Woo Chung, Jesse C DeSimone, Edward Ofori, Tetsuo Ashizawa, Sankarasubramon H Subramony, David E Vaillancourt
Spinocerebellar ataxia type 6 (SCA6) is a genetic disease that causes degeneration of Purkinje cells, and recent evidence points to degeneration of Betz cells in the motor cortex. The relation between functional activity of motor cortex and symptom severity during a hand-grip motor control in vivo has not yet been investigated. This study explored both functional changes in the sensorimotor cortex and cerebellar regions and structural alterations in the cerebellum for SCA6 patients as compared to age-matched healthy controls using a multimodal imaging approach (task-based fMRI, task-based functional connectivity, and free-water diffusion MRI)...
June 28, 2016: Brain Structure & Function
Katarzyna S Kopanska, Yara Alcheikh, Ralitza Staneva, Danijela Vignjevic, Timo Betz
The mechanical properties of tumors and the tumor environment provide important information for the progression and characterization of cancer. Tumors are surrounded by an extracellular matrix (ECM) dominated by collagen I. The geometrical and mechanical properties of the ECM play an important role for the initial step in the formation of metastasis, presented by the migration of malignant cells towards new settlements as well as the vascular and lymphatic system. The extent of this cell invasion into the ECM is a key medical marker for cancer prognosis...
2016: PloS One
Aaron M Udager, Jonathan B McHugh, Bryan L Betz, Kathleen T Montone, Virginia A Livolsi, Raja R Seethala, Evgeny Yakirevich, O Hans Iwenofu, Bayardo Perez-Ordonez, Kathleen E DuRoss, Helmut C Weigelin, Megan S Lim, Kojo Sj Elenitoba-Johnson, Noah A Brown
Oncocytic sinonasal papillomas (OSPs) are benign tumours of the sinonasal tract, a subset of which are associated with synchronous or metachronous sinonasal squamous cell carcinoma (SNSCC). Activating EGFR mutations were recently identified in nearly 90% of inverted sinonasal papillomas (ISPs) - a related tumour with distinct morphology. EGFR mutations were, however, not found in OSP, suggesting that different molecular alterations drive the oncogenesis of these tumours. In this study, tissue from 51 cases of OSP and five cases of OSP-associated SNSCC was obtained retrospectively from six institutions...
August 2016: Journal of Pathology
Julia Dlugaiczyk, Dietmar Hecker, Christian Neubert, Stefanie Buerbank, Dario Campanelli, Cord-Michael Becker, Heinrich Betz, Marlies Knipper, Lukas Rüttiger, Bernhard Schick
Inhibitory glycine receptors containing the α3 subunit (GlyRα3) regulate sensory information processing in the CNS and retina. In previous work, we demonstrated the presence of postsynaptic GlyRα3 immunoreactivity at efferent synapses of the medial and lateral olivocochlear bundle in the organ of Corti; however, the role of these α3-GlyRs in auditory signalling has remained elusive. The present study analyzes distortion-product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs) of knockout mice with a targeted inactivation of the Glra3 gene (Glra3(-/-)) and their wildtype littermates (Glra3(+/+)) before and seven days after acoustic trauma (AT; 4-16 kHz, 120 dB SPL, 1 h)...
July 2016: Hearing Research
Gordon C Hard, John Curtis Seely, Laura J Betz
In order to harmonize diagnostic terminology, confirm diagnostic criteria, and describe aspects of tumor biology characteristic of different tumor types, a total of 165 cases of mesenchyme-related tumors and nephroblastomas of the rat kidney were reexamined from the National Toxicology Program (NTP) Archives. This survey demonstrated that renal mesenchymal tumor (RMT) was the most common spontaneous nonepithelial tumor in the rat kidney, also occurring more frequently in the NTP studies than nephroblastoma...
August 2016: Toxicologic Pathology
F S Salah, M Ebbinghaus, V Y Muley, Z Zhou, K R D Al-Saadi, M Pacyna-Gengelbach, G A O'Sullivan, H Betz, R König, Z-Q Wang, R Bräuer, I Petersen
GABARAP belongs to an evolutionary highly conserved gene family that has a fundamental role in autophagy. There is ample evidence for a crosstalk between autophagy and apoptosis as well as the immune response. However, the molecular details for these interactions are not fully characterized. Here, we report that the ablation of murine GABARAP, a member of the Atg8/LC3 family that is central to autophagosome formation, suppresses the incidence of tumor formation mediated by the carcinogen DMBA and results in an enhancement of the immune response through increased secretion of IL-1β, IL-6, IL-2 and IFN-γ from stimulated macrophages and lymphocytes...
2016: Cell Death & Disease
Guillaume N Fiches, Nicholas S Eyre, Amanda L Aloia, Kylie Van Der Hoek, Brigit Betz-Stablein, Fabio Luciani, Abha Chopra, Michael R Beard
The spatiotemporal dynamics of Hepatitis C Virus (HCV) RNA localisation are poorly understood. To address this we engineered HCV genomes harbouring MS2 bacteriophage RNA stem-loops within the 3'-untranslated region to allow tracking of HCV RNA via specific interaction with a MS2-Coat-mCherry fusion protein. Despite the impact of these insertions on viral fitness, live imaging revealed that replication of tagged-HCV genomes induced specific redistribution of the mCherry-tagged-MS2-Coat protein to motile and static foci...
June 2016: Virology
Josefine Betz, Isabel Dorn, Ivan U Kouzel, Andreas Bauwens, Iris Meisen, Björn Kemper, Martina Bielaszewska, Michael Mormann, Lena Weymann, Walter Sibrowski, Helge Karch, Peter Schlenke, Johannes Müthing
Haemolytic anaemia is one of the characteristics of life-threatening extraintestinal complications in humans during infection with enterohaemorrhagic Escherichia coli (EHEC). Shiga toxins (Stxs) of EHEC preferentially damage microvascular endothelial cells of the kidney and the brain, whereby occluded small blood vessels may elicit anaemia through mechanical erythrocyte disruption. Here we show for the first time that Stx2a, the major virulence factor of EHEC, is also capable of direct targeting developing human erythrocytes...
October 2016: Cellular Microbiology
Katarina Klepac, Ana Kilić, Thorsten Gnad, Loren M Brown, Beate Herrmann, Andrea Wilderman, Aileen Balkow, Anja Glöde, Katharina Simon, Martin E Lidell, Matthias J Betz, Sven Enerbäck, Jürgen Wess, Marc Freichel, Matthias Blüher, Gabi König, Evi Kostenis, Paul A Insel, Alexander Pfeifer
Brown adipose tissue (BAT) dissipates nutritional energy as heat via the uncoupling protein-1 (UCP1) and BAT activity correlates with leanness in human adults. Here we profile G protein-coupled receptors (GPCRs) in brown adipocytes to identify druggable regulators of BAT. Twenty-one per cent of the GPCRs link to the Gq family, and inhibition of Gq signalling enhances differentiation of human and murine brown adipocytes. In contrast, activation of Gq signalling abrogates brown adipogenesis. We further identify the endothelin/Ednra pathway as an autocrine activator of Gq signalling in brown adipocytes...
2016: Nature Communications
Rose Bosire, Bourke Betz, Adam Aluisio, James P Hughes, Ruth Nduati, James Kiarie, Bhavna H Chohan, Michele Merkel, Barbara Lohman-Payne, Grace John-Stewart, Carey Farquhar
BACKGROUND: Exclusive breastfeeding (EBF) is recommended for 6 months after delivery as the optimal infant feeding method and is especially important for prevention of mother-to-child HIV transmission (PMTCT). However, EBF promotion efforts among HIV-infected mothers in sub-Saharan Africa have achieved mixed success and require context-specific interventions. METHODS: HIV-positive, pregnant women from six clinics in Nairobi were enrolled into a clinic-level, before-after counseling intervention study...
March 2016: Breastfeeding Medicine: the Official Journal of the Academy of Breastfeeding Medicine
Auda A Eltahla, Simone Rizzetto, Mehdi R Pirozyan, Brigid D Betz-Stablein, Vanessa Venturi, Katherine Kedzierska, Andrew R Lloyd, Rowena A Bull, Fabio Luciani
Heterogeneity of T cells is a hallmark of a successful adaptive immune response, harnessing the vast diversity of antigen-specific T cells into a coordinated evolution of effector and memory outcomes. The T cell receptor (TCR) repertoire is highly diverse to account for the highly heterogeneous antigenic world. During the response to a virus multiple individual clones of antigen specific CD8+ (Ag-specific) T cells can be identified against a single epitope and multiple epitopes are recognised. Advances in single-cell technologies have provided the potential to study Ag-specific T cell heterogeneity at both surface phenotype and transcriptome levels, thereby allowing investigation of the diversity within the same apparent sub-population...
July 2016: Immunology and Cell Biology
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