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https://www.readbyqxmd.com/read/29161594/clathrin-assembly-defines-the-onset-and-geometry-of-cortical-patterning
#1
Yang Yang, Ding Xiong, Anne Pipathsouk, Orion D Weiner, Min Wu
Assembly of the endocytic machinery is a constitutively active process that is important for the organization of the plasma membrane, signal transduction, and membrane trafficking. Existing research has focused on the stochastic nature of endocytosis. Here, we report the emergence of the collective dynamics of endocytic proteins as periodic traveling waves on the cell surface. Coordinated clathrin assembly provides the earliest spatial cue for cortical waves and sets the direction of propagation. Surprisingly, the onset of clathrin waves, but not individual endocytic events, requires feedback from downstream factors, including FBP17, Cdc42, and N-WASP...
November 20, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29161016/selective-voltage-gated-sodium-channel-peptide-toxins-from-animal-venom-pharmacological-probes-and-analgesic-drug-development
#2
Ying Wu, Hui Ma, Fan Zhang, Chun-Lei Zhang, Xiaohan Zou, Zhengyu Cao
Voltage-gated sodium channels (Navs) play critical roles in action potential generation and propagation. Nav channelopathy as well as pathological sensitization contribute to allodynia and hyperalgesia. Recent evidence has demonstrated the significant roles of Nav subtypes (Nav1.3, 1.7, 1.8 and 1.9) in nociceptive transduction and therefore these Navs may represent attractive targets for analgesic drug discovery. Animal toxins are structurally diverse peptides that are highly potent yet selective on ion channel subtypes and therefore representing valuable probes to elucidate the structures, gating properties and cellular functions of ion channels...
November 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29160116/assessment-of-aav-serotype-tropism-in-human-retinal-explants
#3
Luke Aaron Wiley, Erin Burnight, Emily E Kaalberg, Chunhua Jiao, Megan J Riker, Jennifer A Halder, Meagan A Luse, Ian C Han, Stephen R Russell, Elliott H Sohn, Edwin Stone, Budd A Tucker, Robert F Mullins
Advances in the discovery of the causes of monogenic retinal disorders, combined with technologies for the delivery of DNA to the retina, offer enormous opportunities for the treatment of previously untreatable blinding diseases. However, for gene augmentation to be most effective, vectors that have the correct cell-type specificity are needed. While animal models are very useful, they often exhibit differences in retinal cell surface receptors compared to human retina. In this study, we evaluated the use of an ex vivo organotypic explant system to test the transduction efficiency and tropism of 7 different adeno-associated viral type 2 (AAV2) serotypes in human retina and retinal pigment epithelium-choroid: AAV2/1, AAV2/2, AAV2/4, AAV2/5, AAV2/6, AAV2/8, and AAV2/9, all driving expression of GFP under control of the cytomegalovirus promoter...
November 21, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29160106/display-of-the-albumin-binding-domain-in-the-envelope-improves-lentiviral-vector-bioavailability
#4
Antonio Rodriguez, Guillermo Garaulet, Juan José Lazcano, Hernán Alarcón, Sergio de Frutos, Jorge Luis Martínez-Torrecuadrada
Vesicular stomatitis virus G glycoprotein (VSVg) is extensively used for retroviral and lentiviral vector (LV) pseudotyping. However, VSVg pseudotyped vectors are serum inactivated, blocking the in vivo gene delivery. Several strategies have been employed to prevent complement inactivation, including chemical and genetic envelope modifications. Here we have employed the streptococcal Albumin Binding Domain (ABD) to generate a construct to express ABD as a GPI-anchored protein. LV particles bearing ABD are able to bind bovine and human serum albumin in vitro...
November 21, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/29160102/improving-the-infection-of-bone-marrow-derived-cells-with-an-integrase-defective-lentiviral-vector
#5
S Louise Pay, Xiaoping Qi, Jeffrey F Willard, Juliana Godoy, Kavya Sankhavaram, Ranier Horton, Sayak K Mitter, Judith Quigley, Chang Lung-Ji, Maria B Grant, Michael E Boulton
In lentiviral vector (LV) applications where transient transgene expression is sufficient, integrase-defective lentiviral vectors (IDLVs) are beneficial for reducing the potential for off-target effects associated with insertional mutagenesis. We previously demonstrated that human RPE65 mRNA expression from an integrating lentiviral vector (ILV) induces endogenous Rpe65 and Cralbp mRNA expression in murine bone marrow-derived cells (BMDCs), initiating programming of the cells to retinal pigment epithelium (RPE)-like cells...
November 21, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/29159601/activating-fgfr1-mutations-in-sporadic-pheochromocytomas
#6
Jenny Welander, Małgorzata Łysiak, Michael Brauckhoff, Laurent Brunaud, Peter Söderkvist, Oliver Gimm
INTRODUCTION: Pheochromocytomas are neuroendocrine tumors of the adrenal glands. Up to 40% of the cases are caused by germline mutations in one of at least 15 susceptibility genes, making them the human neoplasms with the highest degree of heritability. Recurrent somatic alterations are found in about 50% of the more common sporadic tumors with NF1 being the most common mutated gene (20-25%). In many sporadic tumors, however, a genetic explanation is still lacking. MATERIALS AND METHODS: We investigated the genomic landscape of sporadic pheochromocytomas with whole-exome sequencing of 16 paired tumor and normal DNA samples and extended confirmation analysis in 2 additional cohorts comprising a total of 80 sporadic pheochromocytomas...
November 20, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/29159326/overexpression-of-id1-reverses-the-repression-of-human-dental-pulp-stem-cells-differentiation-induced-by-twist1-silencing
#7
Izabela Maciejewska, Monika Sakowicz-Burkiewicz, Marta Krzeminska, Tadeusz Pawelczyk
Multiple studies showed that the cessation of TWIST1 expression is the prerequisite for osteoblasts' maturation. However, recent reports revealed that the function of TWIST1 is different in the dental pulp stem cells (DPSCs), where a high level of TWIST1 expression promoted DPSCs' differentiation. The aim of the study was to investigate the impact of TWIST1 and ID1 on the differentiation process in the human DPSCs. METHODS: TWIST1 and ID1 expression in the DSPCs was modulated by lentivirus transduction...
November 20, 2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/29159146/lactobacillus-plantarum-induces-apoptosis-in-oral-cancer-kb-cells-through-upregulation-of-pten-and-downregulation-of-mapk-signalling-pathways
#8
Abbas Asoudeh-Fard, Abolfazl Barzegari, Alireza Dehnad, Sepideh Bastani, Asal Golchin, Yadollah Omidi
Introduction: The oral tumor is the sixth most prevalent type of cancer worldwide and the second leading cause of cancer-related mortality. Although chemotherapy and immunotherapy are the main strategies for the treatment of oral cancer, an emergence of inevitable resistance to these treatment modalities is the major drawback that causes recurrence of the disease. Nowadays, probiotics have been suggested as adjunctive and complementary treatment modalities for improving the impacts of chemotherapy and immunotherapy agents...
2017: BioImpacts: BI
https://www.readbyqxmd.com/read/29158815/tethering-interleukin-22-to-apolipoprotein-a-i-ameliorates-mice-from-acetaminophen-induced-liver-injury
#9
Wei Chen, Xuyao Zhang, Jiajun Fan, Wenjing Zai, Jingyun Luan, Yubin Li, Shaofei Wang, Qicheng Chen, Yichen Wang, Yanxu Liang, Dianwen Ju
Increasing evidence indicates that interleukin-22 (IL-22) holds tremendous potential as a protective agent in preventing liver injury, but its pleiotropic effects and pathogenic role in carcinogenesis, rheumatoid arthritis and psoriasis restrict its systemic application. Here, we first developed a nanoparticle (liposIA) as a liver-targeted agent through IL-22 tethered to apolipoprotein A-I (ApoA-I) in a gene therapy vector. LiposIA was prepared using thin film dispersion method and the complexes exhibited desirable nanoparticle size, fine polydisperse index, highly efficient transfection, and excellent serum and storage stability...
2017: Theranostics
https://www.readbyqxmd.com/read/29158608/a-fully-coupled-space-time-multiscale-modeling-framework-for-predicting-tumor-growth
#10
Mohammad Mamunur Rahman, Yusheng Feng, Thomas E Yankeelov, J Tinsley Oden
Most biological systems encountered in living organisms involve highly complex heterogeneous multi-component structures that exhibit different physical, chemical, and biological behavior at different spatial and temporal scales. The development of predictive mathematical and computational models of multiscale events in such systems is a major challenge in contemporary computational biomechanics, particularly the development of models of growing tumors in humans. The aim of this study is to develop a general framework for tumor growth prediction by considering major biological events at tissue, cellular, and subcellular scales...
June 15, 2017: Computer Methods in Applied Mechanics and Engineering
https://www.readbyqxmd.com/read/29158110/diabetes-mellitus-and-alzheimer-s-disease-gsk-3%C3%AE-as-a-potential-link
#11
REVIEW
Ying Zhang, Nan-Qu Huang, Fei Yan, Hai Jin, Shao-Yu Zhou, Jing-Shan Shi, Feng Jin
It is well known that Alzheimer's disease (AD) is closely related to diabetes mellitus (DM), and AD is also regarded as Type 3 diabetes (T3D). However, the exact link between AD and DM is still unclear. Recently, more and more evidence has shown that glycogen synthase kinase-3β (GSK-3β) may be the potential link between DM and AD. In DM, GSK-3β is the crucial enzyme of glycogen synthesis, which plays a key role in regulating blood glucose. More importantly, GSK-3β is one of the key factors leading to insulin deficiency and insulin resistance, and insulin resistance is an important hallmark of the occurrence and development of DM...
November 17, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29157948/neurturin-is-a-pgc-1%C3%AE-1-controlled-myokine-that-promotes-motor-neuron-recruitment-and-neuromuscular-junction-formation
#12
Richard Mills, Hermes Taylor-Weiner, Jorge C Correia, Leandro Z Agudelo, Ilary Allodi, Christina Kolonelou, Vicente Martinez-Redondo, Duarte M S Ferreira, Susanne Nichterwitz, Laura H Comley, Vanessa Lundin, Eva Hedlund, Jorge L Ruas, Ana I Teixeira
OBJECTIVE: We examined whether skeletal muscle overexpression of PGC-1α1 or PGC-1α4 affected myokine secretion and neuromuscular junction (NMJ) formation. METHODS: A microfluidic device was used to model endocrine signaling and NMJ formation between primary mouse myoblast-derived myotubes and embryonic stem cell-derived motor neurons. Differences in hydrostatic pressure allowed for fluidic isolation of either cell type or unidirectional signaling in the fluid phase...
November 7, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29157829/sulfated-galactans-from-the-red-seaweed-gracilaria-fisheri-exerts-anti-migration-effect-on-cholangiocarcinoma-cells
#13
Thannicha Sae-Lao, Natthanej Luplertlop, Tavan Janvilisri, Rutaiwan Tohtong, David O Bates, Kanokpan Wongprasert
BACKGROUND: Seaweeds have a long history of use in Asian countries as functional foods, medicinal herbs, and the treatment of cancer. Polysaccharides from various seaweeds have shown anti-tumor activity. Cholangiocarcinoma (CCA), often with metastatic disease, is highly prevalent in Thailand as a consequence of liver fluke infection. Recently, we extracted sulfated galactans (SG) from Gracilaria fisheri (G. fisheri), a south east Asian seaweed, and found it exhibited anti-proliferation effect on CCA cells...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29157825/1-6-di-o-caffeoyl-%C3%AE-d-glucopyranoside-a-natural-compound-from-callicarpa-nudiflora-hook-impairs-p2y12-and-thromboxane-a2-receptor-mediated-amplification-of-platelet-activation-and-aggregation
#14
Jianjiang Fu, Xiaocui Zhu, Wei Wang, Hong Lu, Zhoumiao Zhang, Ting Liu, Huanjun Xu, Huizheng Fu, Shuangcheng Ma, Yuehua Luo
BACKGROUND: Platelet activation and subsequent accumulation at sites of vascular injury perform a central role in thrombus formation, which is believed to be the trigger of several cardiovascular diseases, such as atherosclerosis, myocardial infarction and strokes. In this sense, the search for agents that are capable of blocking platelets aggregation has important implications for these diseases. Callicarpa nudiflora (C. nudiflora) Hook is a traditional Chinese medicine herb for eliminating stasis to subdue swelling and hemostasis...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29157665/lipopolysaccharide-induced-increase-in-intestinal-epithelial-tight-permeability-is-mediated-by-toll-like-receptor-4-myeloid-differentiation-primary-response-88-myd88-activation-of-myosin-light-chain-kinase-expression
#15
Meghali Nighot, Rana Al-Sadi, Shuhong Guo, Manmeet Rawat, Prashant Nighot, Martin D Watterson, Thomas Y Ma
Lipopolysaccharides (LPSs) are a major component of the Gram-negative bacterial cell wall and play an important role in mediating intestinal inflammatory responses in inflammatory bowel disease. Although recent studies suggested that physiologically relevant concentrations of LPS (0 to 1 ng/mL) cause an increase in intestinal epithelial tight junction (TJ) permeability, the mechanisms that mediate an LPS-induced increase in intestinal TJ permeability remain unclear. Herein, we show that myosin light chain kinase (MLCK) plays a central role in the LPS-induced increase in TJ permeability...
December 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29156097/4-aminopyridine-a-pan-kv-channel-inhibitor-that-enhances-kv7-4-currents-and-inhibits-noradrenaline-mediated-contraction-of-rat-mesenteric-small-arteries
#16
Makhala M Khammy, Sukhan Kim, Bo H Bentzen, Soojung Lee, Inyeoung Choi, Christian Aalkjaer, Thomas A Jepps
BACKGROUND AND PURPOSE: Kv7.4 and Kv7.5 channels are regulators of vascular tone. 4-aminopyridine (4-AP) is considered a broad inhibitor of voltage-gated potassium (KV ) channels, with little inhibitory effect on Kv7 family members at millimolar concentrations. However, the effect of 4-AP on Kv7 channels has not been systematically studied. The aim of this study was to investigate the pharmacological activity of 4-AP on Kv7.4 and Kv7.5 channels and characterise the effect of 4-AP on rat resistance arteries...
November 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29155979/epigenetic-editing-of-the-dlg4-psd95-gene-improves-cognition-in-aged-and-alzheimer-s-disease-mice
#17
Fernando J Bustos, Estibaliz Ampuero, Nur Jury, Rodrigo Aguilar, Fahimeh Falahi, Jorge Toledo, Juan Ahumada, Jaclyn Lata, Paula Cubillos, Berta Henríquez, Miguel V Guerra, Jimmy Stehberg, Rachael L Neve, Nibaldo C Inestrosa, Ursula Wyneken, Marco Fuenzalida, Steffen Härtel, Miguel Sena-Esteves, Lorena Varela-Nallar, Marianne G Rots, Martin Montecino, Brigitte van Zundert
The Dlg4 gene encodes for post-synaptic density protein 95 (PSD95), a major synaptic protein that clusters glutamate receptors and is critical for plasticity. PSD95 levels are diminished in ageing and neurodegenerative disorders, including Alzheimer's disease and Huntington's disease. The epigenetic mechanisms that (dys)regulate transcription of Dlg4/PSD95, or other plasticity genes, are largely unknown, limiting the development of targeted epigenome therapy. We analysed the Dlg4/PSD95 epigenetic landscape in hippocampal tissue and designed a Dlg4/PSD95 gene-targeting strategy: a Dlg4/PSD95 zinc finger DNA-binding domain was engineered and fused to effector domains to either repress (G9a, Suvdel76, SKD) or activate (VP64) transcription, generating artificial transcription factors or epigenetic editors (methylating H3K9)...
November 16, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29155792/assessment-of-dictyostelium-discoideum-response-to-acute-mechanical-stimulation
#18
Yulia Artemenko, Peter N Devreotes
Chemotaxis, or migration up a gradient of a chemoattractant, is the best understood mode of directed migration. Studies using social amoeba Dictyostelium discoideum revealed that a complex signal transduction network of parallel pathways amplifies the response to chemoattractants, and leads to biased actin polymerization and protrusion of a pseudopod in the direction of a gradient. In contrast, molecular mechanisms driving other types of directed migration, for example, due to exposure to shear flow or electric fields, are not known...
November 9, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155785/modeling-neuronal-death-and-degeneration-in-mouse-primary-cerebellar-granule-neurons
#19
Matthew Laaper, Takrima Haque, Ruth S Slack, Arezu Jahani-Asl
Cerebellar granule neurons (CGNs) are a commonly used neuronal model, forming an abundant homogeneous population in the cerebellum. In light of their post-natal development, abundance, and accessibility, CGNs are an ideal model to study neuronal processes, including neuronal development, neuronal migration, and physiological neuronal activity stimulation. In addition, CGN cultures provide an excellent model for studying different modes of cell death including excitotoxicity and apoptosis. Within a week in culture, CGNs express N-methyl-D-aspartate (NMDA) receptors, a specific ionotropic glutamate receptor with many critical functions in neuronal health and disease...
November 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155755/in-vivo-detection-and-analysis-of-rb-protein-sumoylation-in-human-cells
#20
Fengxi Meng, Xiaofeng Li, Hui Ren, Jiang Qian
The post-translational modifications of proteins are critical for the proper regulation of intracellular signal transduction. Among these modifications, small ubiquitin-related modifier (SUMO) is a ubiquitin-like protein that is covalently attached to the lysine residues of a variety of target proteins to regulate cellular processes, such as gene transcription, DNA repair, protein interaction and degradation, subcellular transport, and signal transduction. The most common approach to detecting protein SUMOylation is based on the expression and purification of recombinant tagged proteins in bacteria, allowing for an in vitro biochemical reaction which is simple and suitable for addressing mechanistic questions...
November 2, 2017: Journal of Visualized Experiments: JoVE
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