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Active release

Skyler L Jackman, Christopher H Chen, Selmaan N Chettih, Shay Q Neufeld, Iain R Drew, Chimuanya K Agba, Isabella Flaquer, Alexis N Stefano, Thomas J Kennedy, Justine E Belinsky, Keiramarie Roberston, Celia C Beron, Bernardo L Sabatini, Christopher D Harvey, Wade G Regehr
Optical methods of interrogating neural circuits have emerged as powerful tools for understanding how the brain drives behaviors. Optogenetic proteins are widely used to control neuronal activity, while genetically encoded fluorescent reporters are used to monitor activity. These proteins are often expressed by injecting viruses, which frequently leads to inconsistent experiments due to misalignment of expression and optical components. Here, we describe how silk fibroin films simplify optogenetic experiments by providing targeted delivery of viruses...
March 20, 2018: Cell Reports
Daehun Park, Unghwi Lee, Eunji Cho, Haiyan Zhao, Jung Ah Kim, Byoung Ju Lee, Philip Regan, Won-Kyung Ho, Kwangwook Cho, Sunghoe Chang
Despite being a highly enriched synaptic vesicle (SV) protein and a candidate gene for autism, the physiological function of SCAMP5 remains mostly enigmatic. Here, using optical imaging and electrophysiological experiments, we demonstrate that SCAMP5 plays a critical role in release site clearance at the active zone. Truncation analysis revealed that the 2/3 loop domain of SCAMP5 directly interacts with adaptor protein 2, and this interaction is critical for its role in release site clearance. Knockdown (KD) of SCAMP5 exhibited pronounced synaptic depression accompanied by a slower recovery of the SV pool...
March 20, 2018: Cell Reports
Manami Yamashita, Shin-Ya Kawaguchi, Tetsuya Hori, Tomoyuki Takahashi
Synaptic efficacy plays crucial roles in neuronal circuit operation and synaptic plasticity. Presynaptic determinants of synaptic efficacy are neurotransmitter content in synaptic vesicles and the number of vesicles undergoing exocytosis at a time. Bursts of presynaptic firings depress synaptic efficacy, mainly due to depletion of releasable vesicles, whereas recovery from strong depression is initiated by endocytic vesicle retrieval followed by refilling of vesicles with neurotransmitter. We washed out presynaptic cytosolic GABA to induce a rundown of IPSCs at cerebellar inhibitory cell pairs in slices from rats and then allowed fast recovery by elevating GABA concentration using photo-uncaging...
March 20, 2018: Cell Reports
Jie Gao, Jun Li, Wen-Chao Geng, Fang-Yuan Chen, Xingchen Duan, Zhe Zheng, Dan Ding, Dong-Sheng Guo
Activatable phototheranostics is highly appealing to meet the demand of precision medicine. However, although displaying the efficacy in construction of activatable photosensitizers (PSs), direct covalent decoration still shows some inevitable issues, such as complex molecular design, tedious synthesis, possible photoactivity changes and potential toxicity. Herein, we propose a novel concept of biomarker displacement activation (BDA) using host-guest strategy. To exemplify BDA, we engineered a PS-loaded nanocarrier by utilizing a macrocyclic amphiphile, where the fluorescence and photoactivity of PS were completely annihilated by the complexation of macrocyclic receptor (OFF state)...
March 21, 2018: Journal of the American Chemical Society
Aurelia Vasile, Maria Ignat, Mirela Fernanda Zaltariov, Liviu Sacarescu, Iulian Stoleriu, Dan Draganescu, Mihai Dumitras, Lacramioara Ochiuz
The present study reports the first time use of MCM-41 mesoporous silica as highly efficient carrier for bexarotene - an antineoplastic agent specific for cutaneous T-cell lymphoma treatment. Bexarotene is highly toxic and poor-water soluble, having low bioavailability in the conventional pharmaceutical forms. Comparative uptake of bexarotene on amino-functionalized silica host at various functionalization degrees is discussed in details taking into account all structural features, of matrix as well as properties of the drug molecules...
March 2018: Acta Chimica Slovenica
J L de Deus, A L A Dagostin, W A Varanda
Testosterone synthesis within Leydig cells is a calcium-dependent process. Intracellular calcium levels are regulated by different processes including ATP-activated P2X purinergic receptors, T-type Ca2+ channels modulated by the luteinizing hormone, and intracellular calcium storages recruited by a calcium-induced calcium release mechanism. On the other hand, nitric oxide (NO) is reported to have an inhibitory role in testosterone production. Based on these observations, we investigated the interaction between the purinergic and nitrergic systems in Leydig cells of adult mice...
March 15, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Germano Guerra, Angela Lucariello, Angelica Perna, Laura Botta, Antonio De Luca, Francesco Moccia
BACKGROUND: Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity (NA) leads to local elevation in cerebral blood flow (CBF) to match the metabolic requirements of firing neurons. Following synaptic activity, an increase in neuronal and/or astrocyte Ca2+ concentration leads to the synthesis of multiple vasoactive messengers. Curiously, the role of endothelial Ca2+ signaling in NVC has been rather neglected, although endothelial cells are known to control the vascular tone in a Ca2+ -dependent manner throughout peripheral vasculature...
March 21, 2018: International Journal of Molecular Sciences
Lucas C Klemm, Evan Czerwonka, Mary L Hall, Philip G Williams, Alejandro M S Mayer
Cosmopolitan Gram-negative cyanobacteria may affect human and animal health by contaminating terrestrial, marine and freshwater environments with toxins, such as lipopolysaccharide (LPS). The cyanobacterial genus Scytonema ( S ) produces several toxins, but to our knowledge the bioactivity of genus Scytonema LPS has not been investigated. We recently reported that cyanobacterium Oscillatoria sp. LPS elicited classical and alternative activation of rat microglia in vitro. Thus, we hypothesized that treatment of brain microglia in vitro with either cyanobacteria S...
March 21, 2018: Toxins
Wuxing Dong, Alison C Todd, Angelika Bröer, Sarah R Hulme, Stefan Bröer, Brian Billups
Astrocytes are glial cells that have an intimate physical and functional association with synapses in the brain. One of their main roles is to recycle the neurotransmitters glutamate and gamma-aminobutyric acid (GABA), as a component of the glutamate/GABA-glutamine cycle. They perform this function by sequestering neurotransmitters and releasing glutamine via the neutral amino acid transporter SNAT3. In this way, astrocytes regulate the availability of neurotransmitters and subsequently influence synaptic function...
March 21, 2018: International Journal of Molecular Sciences
Lei Lei, Kesava Phaneendra Cherukuri, Uria Alcolombri, Diana Meltzer, Dan S Tawfik
Marine organisms release dimethylsulfide (DMS) via cleavage of dimethylsulfoniopropionate (DMSP). Different genes encoding proteins with DMSP lyase activity are known, yet these exhibit highly variable levels of activity. Most assigned bacterial DMSP lyases, including DddK, DddL, DddQ, DddW and DddY, appear to belong to one, cupin-like superfamily. Here, we attempted to define and map this superfamily dubbed Cupin-DLL: DMSP lyases and lyase-like. To this end, we have pursued the characterization of various recombinant DMSP lyases belonging to this superfamily of metallo-enzymes, and especially of DddY and DddL that seem to be the most active DMSP lyases in this superfamily...
March 21, 2018: Biochemistry
Zhuoyue Chen, Zhen Zhang, Juantao Feng, Yayuan Guo, Yuan Yu, Jihong Cui, Hongmin Li, Lijun Shang
One of the key challenges in bone healing and regeneration is the implant with osteoinductive activity. Therapeutic application of recombinant human bone morphogenetic protein-2 (rhBMP-2) is a promising approach to enhance osteogenesis. However, high dose and uncontrolled burst in the release kinetics of BMP-2 may introduce oedema, bone overgrowth, cyst-like bone formation and significant inflammation. In this study, low dose BMP-2 of 1µg was used to design PLA-PD-BMP for functionalization of polylactic acid (PLA) implants via mussel-inspired polydopamine (PD) assist...
March 21, 2018: ACS Applied Materials & Interfaces
Dong-Min Kim, Dong Ho Kim, Woong Jung, Kye Young Lee, Dong-Eun Kim
Mutations in epidermal growth factor receptor (EGFR) are known as biomarkers that cause non-small cell lung cancer. Particularly, approximately 45% of non-small cell lung cancer patients possess a deletion in exon 19 of the EGFR gene. A less invasive method for detecting the EGFR mutation is required; thus, we developed a simple polymerase chain reaction (PCR)-based method for detecting EGFR exon 19 deletion by using a quencher-free fluorescent probe DNA and graphene oxide (GO). In the presence of the exon 19 deletion mutation, the fluorophore-labeled DNA probe was designed to be fully complementary to the mutant sequences...
March 21, 2018: Analyst
Ji-Young Song, Seong-Gon Kim, Na-Rae Park, Je-Yong Choi
OBJECTIVE: The objectives of this study were to evaluate the suppression of the nuclear factor kappa B (NF-kB) pathway by 4-hexylresorcinol (4HR), which was activated by tumor necrosis factor-α (TNF-α) in osteoblasts, and new bone formation by 4HR-incorporated porcine bone in an animal model. STUDY DESIGN: For the confirmation of successful incorporation of 4HR into porcine bone, scanning electron microscopy (SEM) and Fourier transform-infrared (FT-IR) analysis were performed...
March 20, 2018: Journal of Craniofacial Surgery
S Prakash, K Rajeswari, P Divya, M Ferlin, C T Rajeshwari, B Vanavil
Curdlan gum is a neutral water-insoluble bacterial exopolysaccharide composed primarily of linear β-(1,3) glycosidic linkages. Recently, there has been increasing interest in the applications of curdlan and its derivatives. Curdlan is found to inhibit tumors and its sulfated derivative possess anti- HIV activity. Curdlan is biodegradable, non-toxic towards human, environment and edible which makes it suitable as drug-delivery vehicles for sustained drug release. The increasing demand for the growing applications of curdlan requires an efficient high yield fermentation production process so as to satisfy the industrial needs...
March 21, 2018: Preparative Biochemistry & Biotechnology
Janicy Arantes Carvalho, Alexandro Silva Abreu, Vitória Tonini Porto Ferreira, Erika Peterson Gonçalves, Antonio Claudio Tedesco, Juliana Guerra Pinto, Juliana Ferreira-Strixino, Milton Beltrame Junior, Andreza Ribeiro Simioni
Gelatin nanoparticles have recently been receiving considerable attention because they offer a good option as release systems due to their low cost, biocompatibility, biodegradability and its application in several types of formulations. This study aim was to evaluate the potential application of gelatin nanoparticles entrapping a photosensitizer in Photodynamic Therapy. Gelatin nanoparticles were studied by steady-state techniques and the biological activity evaluated by in vitro MTT assay. The particles were spherical in shape exhibiting a 273 nm diameter with a low tendency to aggregate...
March 21, 2018: Journal of Biomaterials Science. Polymer Edition
Nicolás De Silva, Mirian Samblas, J Alfredo Martínez, Fermín I Milagro
Obesity is usually associated with low-grade inflammation, which determines the appearance of comorbidities like atherosclerosis and insulin resistance. Infiltrated macrophages in adipose tissue are partly responsible of this inflammatory condition. Numerous studies point to the existence of close intercommunication between macrophages and adipocytes and pay particular attention to the proinflammatory cytokines released by both cell types. However, it has been recently described that in both, circulation and tissue level, there are extracellular vesicles (including microvesicles and exosomes) containing miRNAs, mRNAs, and proteins that can influence the inflammatory response...
March 20, 2018: Journal of Physiology and Biochemistry
Giuseppe Cardellini, Tatiana Valada, Claire Cornillier, Estelle Vial, Marian Dragoi, Venceslas Goudiaby, Volker Mues, Bruno Lasserre, Arkadiusz Gruchala, Per Kristian Rørstad, Mathias Neumann, Miroslav Svoboda, Risto Sirgmets, Olli-Pekka Näsärö, Frits Mohren, Wouter M J Achten, Liesbet Vranken, Bart Muys
Life cycle assessment (LCA) has become a common methodology to analyze environmental impacts of forestry systems. Although LCA has been widely applied to forestry since the 90s, the LCAs are still often based on generic Life Cycle Inventory (LCI). With the purpose of improving LCA practices in the forestry sector, we developed a European Life Cycle Inventory of Forestry Operations (EFO-LCI) and analyzed the available information to check if within the European forestry sector national differences really exist...
March 20, 2018: Environmental Management
Han Wu, Xin Rui, Wei Li, Yu Xiao, Jianzhong Zhou, Mingsheng Dong
This study explored a novel strategy to develop solid-state whole-grain oats as a novel carrier of lactic acid bacteria and a nutraceutical supplement rich in ACE inhibitory peptides. Oats were fermented by Lactobacillus plantarum B1-6, Rhizopus oryzae, or a combination of L. plantarum B1-6 and R. oryzae. L. plantarum showed a much better growth performance in oats when it was combined with R. oryzae than when it was cultured alone, as evidenced by an increase in viable cell count to 9.70 log cfu g-1 after 72 h of fermentation...
March 21, 2018: Food & Function
Tenpei Akita, Kazushi Aoto, Mitsuhiro Kato, Masaaki Shiina, Hiroki Mutoh, Mitsuko Nakashima, Ichiro Kuki, Shin Okazaki, Shinichi Magara, Takashi Shiihara, Kenji Yokochi, Kaori Aiba, Jun Tohyama, Chihiro Ohba, Satoko Miyatake, Noriko Miyake, Kazuhiro Ogata, Atsuo Fukuda, Naomichi Matsumoto, Hirotomo Saitsu
Objective: α ( CAMK2A ) and β ( CAMK2B ) isoforms of Calcium/calmodulin-dependent protein kinase II (CaMKII) play a pivotal role in neuronal plasticity and in learning and memory processes in the brain. Here, we explore the possible involvement of α - and β -CaMKII variants in neurodevelopmental disorders. Methods: Whole-exome sequencing was performed for 976 individuals with intellectual disability, developmental delay, and epilepsy. The effect of CAMK2A and CAMK2B variants on CaMKII structure and firing of neurons was evaluated by computational structural analysis, immunoblotting, and electrophysiological analysis...
March 2018: Annals of Clinical and Translational Neurology
Anish Sharda, Robert Flaumenhaft
Platelet granules are unique among secretory vesicles in both their content and their life cycle. Platelets contain three major granule types-dense granules, α-granules, and lysosomes-although other granule types have been reported. Dense granules and α-granules are the most well-studied and the most physiologically important. Platelet granules are formed in large, multilobulated cells, termed megakaryocytes, prior to transport into platelets. The biogenesis of dense granules and α-granules involves common but also distinct pathways...
2018: F1000Research
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