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https://www.readbyqxmd.com/read/29039926/zebrafish-a-visual-model-to-evaluate-the-biofate-of-transferrin-receptor-targeted-7peptide-decorated-coumarin-6-micelles
#1
Ye Li, Xiaoning Song, Xiang Yi, Ruibing Wang, Simon Ming-Yuen Lee, Xueqing Wang, Ying Zheng
In the present study, the zebrafish was explored as an in vivo model to assess the biofate of transferrin receptor (TfR)-targeted coumarin 6 (C6) micelles across various biological barriers. Three 7peptide (7pep)-decorated poly-(ethylene glycol)-block-poly (ε-caprolactone) (PEG-b-PCL) micelles loaded with fluorescence coumarin 6 (7pep-M-C6) with different ligand densities were constructed with particle sizes between 30-40 nm. Whole-mount immunostaining revealed that the expression level of TfR in the retina, brain and intestine increased along with development stage...
October 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29034874/pathogenesis-of-plasmodium-berghei-anka-infection-in-the-gerbil-meriones-unguiculatus-as-an-experimental-model-for-severe-malaria
#2
Quazim Olawale Junaid, Loke Tim Khaw, Rohela Mahmud, Kien Chai Ong, Yee Ling Lau, Prajakta Uttam Borade, Jonathan Wee Kent Liew, Sinnadurai Sivanandam, Kum Thong Wong, Indra Vythilingam
BACKGROUND: As the quest to eradicate malaria continues, there remains a need to gain further understanding of the disease, particularly with regard to pathogenesis. This is facilitated, apart from in vitro and clinical studies, mainly via in vivo mouse model studies. However, there are few studies that have used gerbils (Meriones unguiculatus) as animal models. Thus, this study is aimed at characterizing the effects of Plasmodium berghei ANKA (PbA) infection in gerbils, as well as the underlying pathogenesis...
2017: Parasite: Journal de la Société Française de Parasitologie
https://www.readbyqxmd.com/read/29033834/tc299423-a-novel-agonist-for-nicotinic-acetylcholine-receptors
#3
Teagan R Wall, Brandon J Henderson, George Voren, Charles R Wageman, Purnima Deshpande, Bruce N Cohen, Sharon R Grady, Michael J Marks, Daniel Yohannes, Paul J Kenny, Merouane Bencherif, Henry A Lester
(E)-5-(Pyrimidin-5-yl)-1,2,3,4,7,8-hexahydroazocine (TC299423) is a novel agonist for nicotinic acetylcholine receptors (nAChRs). We examined its efficacy, affinity, and potency for α6β2(∗) (α6β2-containing), α4β2(∗), and α3β4(∗) nAChRs, using [(125)I]-epibatidine binding, whole-cell patch-clamp recordings, synaptosomal (86)Rb(+) efflux, [(3)H]-dopamine release, and [(3)H]-acetylcholine release. TC299423 displayed an EC50 of 30-60 nM for α6β2(∗) nAChRs in patch-clamp recordings and [(3)H]-dopamine release assays...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29032304/heterocyclic-homoprostanoid-derivative-attenuates-monoarthritis-in-rats-an-in-vitro-and-in-vivo-preclinical-paradigm
#4
Jayesh Mudgal, S A Manohara Reddy, Geetha Mathew, Anoop Kishore, C Mallikarjuna Rao, Gopalan K Nampurath
From our lab, among the nineteen heterocyclic homoprostanoids (HHPs), three derivatives (compounds 3, 3b and 3c) exerted antioxidant and anti-inflammatory activity. Present study is an extension of the earlier work, and, is designed to establish their therapeutic potential in monoarthritis in rats. In addition, their possible mechanism of action would be investigated. A battery of in vitro tests such as lipopolysaccharide (LPS)-induced nitrite (NO)/reactive oxygen species (ROS) and NO/interleukin (IL)-6 generation in murine macrophages and whole blood (WhB), respectively were conducted...
October 12, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29031852/inhibition-of-cdk5-rejuvenates-inhibitory-circuits-and-restores-experience-dependent-plasticity-in-adult-visual-cortex
#5
Yue Li, Laijian Wang, Xinxin Zhang, Mengyao Huang, Sitong Li, Xinxing Wang, Lin Chen, Bin Jiang, Yupeng Yang
Cyclin-dependent kinase 5 (Cdk5) acts as an essential modulator for neural development and neurological disorders. Here we show that Cdk5 plays a pivotal role in modulating GABAergic signaling and the maturation of visual system. In adult mouse primary visual cortex, Cdk5 formed complex with the GABA synthetic enzyme glutamate decarboxylase GAD67, but not with GAD65. In addition to enhancement in the surface level of NR2B-containing NMDA receptors, inhibition of Cdk5 reduced the protein levels of GADs and Otx2, while leaving intact the expression of vesicular GABA transporter and subunits of GABAA or AMPA receptors...
October 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29030824/distinguishing-states-of-arrest-genome-wide-descriptions-of-cellular-quiescence-using-chip-seq-and-rna-seq-analysis
#6
Surabhi Srivastava, Hardik P Gala, Rakesh K Mishra, Jyotsna Dhawan
Regenerative potential in adult stem cells is closely associated with the establishment of-and exit from-a temporary state of quiescence. Emerging evidence not only provides a rationale for the link between lineage determination programs and cell cycle regulation but also highlights the understanding of quiescence as an actively maintained cellular program, encompassing networks and mechanisms beyond mitotic inactivity or metabolic restriction. Interrogating the quiescent genome and transcriptome using deep-sequencing technologies offers an unprecedented view of the global mechanisms governing this reversibly arrested cellular state and its importance for cell identity...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29028288/hypochlorous-acid-is-anti-pruritic-and-anti-inflammatory-in-a-mouse-model-of-atopic-dermatitis
#7
Tomoki Fukuyama, Britta C Martel, Keith Linder, Sarah Ehling, Joy Rachel Ganchingco, Wolfgang Bäumer
BACKGROUND: It has been reported that topical hypochlorous acid (HOCl) formulations lead to relief of itch in human patients with atopic dermatitis, however the specific anti-pruritic mechanism of action remains unclear. OBJECTIVE: To confirm itch relief and reduction of lesions in a mouse model of atopic dermatitis and to elucidate possible HOCl's mode of action. METHODS: In this study, the effects of topical administration of HOCl hydrogel (0...
October 13, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29024712/brief-activation-of-gabaergic-interneurons-initiates-the-transition-to-ictal-events-through-post-inhibitory-rebound-excitation
#8
Michael Chang, Joshua A Dian, Suzie Dufour, Lihua Wang, Homeira Moradi-Chameh, Meera Ramani, Liang Zhang, Peter L Carlen, Thilo Womelsdorf, Taufik A Valiante
Activation of γ-aminobutyric acid (GABAA) receptors have been associated with the onset of epileptiform events. To investigate if a causal relationship exists between GABAA receptor activation and ictal event onset, we activated inhibitory GABAergic networks in the superficial layer (2/3) of the somatosensory cortex during hyperexcitable conditions using optogenetic techniques in mice expressing channelrhodopsin-2 in all GABAergic interneurons. We found that a brief 30ms light pulse reliably triggered either an interictal-like event (IIE) or ictal-like ("ictal") event in the in vitro cortical 4-Aminopyridine (4-AP) slice model...
October 9, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29020623/functional-plasticity-of-odor-representations-during-motherhood
#9
Amit Vinograd, Yael Fuchs-Shlomai, Merav Stern, Diptendu Mukherjee, Yuan Gao, Ami Citri, Ian Davison, Adi Mizrahi
Motherhood is accompanied by new behaviors aimed at ensuring the wellbeing of the offspring. Olfaction plays a key role in guiding maternal behaviors during this transition. We studied functional changes in the main olfactory bulb (OB) of mothers in mice. Using in vivo two-photon calcium imaging, we studied the sensory representation of odors by mitral cells (MCs). We show that MC responses to monomolecular odors become sparser and weaker in mothers. In contrast, responses to biologically relevant odors are spared from sparsening or strengthen...
October 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/29019386/antimicrobial-peptide-polymer-conjugates-with-high-activity-influence-of-polymer-molecular-weight-and-peptide-sequence-on-antimicrobial-activity-proteolysis-and-biocompatibility
#10
Prashant Kumar, Allen Takayesu, Usama Abbasi, Manu Thomas Kalathottukaren, Srinivas Abbina, Jayachandran N Kizhakkedathu, Suzana K Straus
We report the synthesis, characterization, activity and biocompatibility of a novel series of antimicrobial peptide-polymer conjugates. Using the parent peptide aurein 2.2, we designed a peptide array (~100 peptides) with single and multiple W and R mutations and identified antimicrobial peptides (AMPs) with potent activity against S. aureus. These novel AMPs were conjugated to hyperbranched polyglycerol (HPG) of different molecular weights and number of peptides to improve their antimicrobial activity and toxicity...
October 11, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29018970/andersen-s-syndrome-mutants-produce-a-knockdown-of-inwardly-rectifying-k-channel-in-mouse-skeletal-muscle-in-vivo
#11
Dina Simkin, Gaëlle Robin, Serena Giuliano, Ana Vukolic, Pamela Moceri, Nicolas Guy, Kay-Dietrich Wagner, Alain Lacampagne, Bruno Allard, Saïd Bendahhou
Andersen's syndrome (AS) is a rare autosomal disorder that has been defined by the triad of periodic paralysis, cardiac arrhythmia, and developmental anomalies. AS has been directly linked to over 40 different autosomal dominant negative loss-of-function mutations in the KCNJ2 gene, encoding for the tetrameric strong inward rectifying K(+) channel KIR2.1. While KIR2.1 channels have been suggested to contribute to setting the resting membrane potential (RMP) and to control the duration of the action potential (AP) in skeletal and cardiac muscle, the mechanism by which AS mutations produce such complex pathophysiological symptoms is poorly understood...
October 10, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29018244/bioengineering-of-functional-human-induced-pluripotent-stem-cell-derived-intestinal-grafts
#12
Kentaro Kitano, Dana M Schwartz, Haiyang Zhou, Sarah E Gilpin, Gregory R Wojtkiewicz, Xi Ren, Cesar A Sommer, Amalia V Capilla, Douglas J Mathisen, Allan M Goldstein, Gustavo Mostoslavsky, Harald C Ott
Patients with short bowel syndrome lack sufficient functional intestine to sustain themselves with enteral intake alone. Transplantable vascularized bioengineered intestine could restore nutrient absorption. Here we report the engineering of humanized intestinal grafts by repopulating decellularized rat intestinal matrix with human induced pluripotent stem cell-derived intestinal epithelium and human endothelium. After 28 days of in vitro culture, hiPSC-derived progenitor cells differentiate into a monolayer of polarized intestinal epithelium...
October 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29017919/whole-cell-biopanning-with-a-synthetic-phage-display-library-of-nanobodies-enabled-the-recovery-of-follicle-stimulating-hormone-receptor-inhibitors
#13
Ronan Crepin, Gianluca Veggiani, Selma Djender, Anne Beugnet, François Planeix, Christophe Pichon, Sandrine Moutel, Sebastian Amigorena, Franck Perez, Nicolae Ghinea, Ario de Marco
Antibodies are essential reagents that are increasingly used in diagnostics and therapy. Their specificity and capacity to recognize their native antigen are critical characteristics for their in vivo application. Follicle-stimulating hormone receptor is a GPCR protein regulating ovarian follicular maturation and spermatogenesis. Recently, its potentiality as a cancer biomarker has been demonstrated but no antibody suitable for in vivo tumor targeting and treatment has been characterized so far. In this paper we describe the first successful attempt to recover recombinant antibodies against the FSHR and that: i) are directly panned from a pre-immune library using whole cells expressing the target receptor at their surface; ii) show inhibitory activity towards the FSH-induced cAMP accumulation; iii) do not share the same epitope with the natural binder FSH; iv) can be produced inexpensively as mono- or bivalent functional molecules in the bacterial cytoplasm...
October 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28992202/kr%C3%A3-ppel-like-factors-and-vascular-wall-homeostasis
#14
Yanbo Fan, Haocheng Lu, Wenying Liang, Wenting Hu, Jifeng Zhang, Y Eugene Chen
Cardiovascular diseases (CVDs) are major causes of death worldwide. Identification of promising targets for prevention and treatment of CVDs is paramount in the cardiovascular field. Numerous transcription factors regulate cellular function through modulation of specific genes and thereby are involved in the physiological and pathophysiological processes of CVDs. Although Krüppel-like factors (KLFs) have a similar protein structure with a conserved zinc finger domain, they possess distinct tissue and cell distribution patterns as well as biological functions...
August 23, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28990786/longitudinal-monitoring-of-antibody-responses-against-tumor-cells-using-magneto-nanosensors-with-a-nanoliter-of-blood
#15
Jung-Rok Lee, Carmel T Chan, Daniel Ruderman, Hui-Yen Chuang, Richard S Gaster, Michelle Atallah, Parag Mallick, Scott W Lowe, Sanjiv S Gambhir, Shan X Wang
Each immunoglobulin isotype has unique immune effector functions. The contribution of these functions in the elimination of pathogens and tumors can be determined by monitoring quantitative temporal changes in isotype levels. Here, we developed a novel technique using magneto-nanosensors based on the effect of giant magnetoresistance (GMR) for longitudinal monitoring of total and antigen-specific isotype levels with high precision, using as little as 1 nL of serum. Combining in vitro serologic measurements with in vivo imaging techniques, we investigated the role of the antibody response in the regression of firefly luciferase (FL)-labeled lymphoma cells in spleen, kidney and lymph nodes in a syngeneic Burkitt's lymphoma mouse model...
October 9, 2017: Nano Letters
https://www.readbyqxmd.com/read/28988851/ablation-of-c-fibers-decreases-quantal-size-of-gabaergic-synaptic-transmission-in-the-insular-cortex
#16
Shota Murayama, Kiyofumi Yamamoto, Mari Kaneko, Bunnai Ogiso, Masayuki Kobayashi
The primary sensory cortex exhibits neuroplastic changes responding to sensory disturbances, and GABAergic synaptic transmission plays a critical role in the regulation of plasticity. The insular cortex (IC) integrates orofacial nociceptive signals conveyed via myelinated Aδ- and unmyelinated C-fibers. However, it has been unknown whether a disturbance of nociceptive inputs, such as a deletion of the peripheral nerves, alters GABAergic local circuit in IC. The present study elucidated GABAergic synaptic transmission in the model rat whose C-fibers were ablated by capsaicin injection 1-2 days after birth...
October 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/28987182/tauopathies
#17
Gabor G Kovacs
Tauopathies are neurodegenerative disorders characterized by the deposition of abnormal tau protein in the brain. The spectrum of tau pathologies expands beyond the traditionally discussed disease forms like Pick disease, progressive supranuclear palsy, corticobasal degeneration, and argyrophilic grain disease. Emerging entities and pathologies include globular glial tauopathies, primary age-related tauopathy, which includes neurofibrillary tangle dementia, chronic traumatic encephalopathy (CTE), and aging-related tau astrogliopathy...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28986995/biocatalytic-conversion-of-cycloalkanes-to-lactones-using-an-in-vivo-cascade-in-pseudomonas-taiwanensis-vlb120
#18
Rohan Karande, Diego Salamanca, Andreas Schmid, Katja Buehler
Chemical synthesis of lactones from cycloalkanes is a multi-step process challenged by limitations in reaction efficiency (conversion and yield), atom economy (by-products) and environmental performance. A heterologous pathway comprising novel enzymes with compatible kinetics was designed in Pseudomonas taiwanensis VLB120 enabling in-vivo cascade for synthesizing lactones from cycloalkanes. The respective pathway included cytochrome P450 monooxygenase (CHX), cyclohexanol dehydrogenase (CDH), and cyclohexanone monooxygenase (CHXON) from Acidovorax sp...
October 7, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28986785/genome-wide-cell-type-specific-mapping-of-in-vivo-chromatin-protein-binding-using-an-flp-inducible-damid-system-in-drosophila
#19
Alexey V Pindyurin
A thorough study of the genome-wide binding patterns of chromatin proteins is essential for understanding the regulatory mechanisms of genomic processes in eukaryotic nuclei, including DNA replication, transcription, and repair. The DNA adenine methyltransferase identification (DamID) method is a powerful tool to identify genomic binding sites of chromatin proteins. This method does not require fixation of cells and the use of specific antibodies, and has been used to generate genome-wide binding maps of more than a hundred different proteins in Drosophila tissue culture cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28985235/a-bayesian-approach-to-modelling-heterogeneous-calcium-responses-in-cell-populations
#20
Agne Tilūnaitė, Wayne Croft, Noah Russell, Tomas C Bellamy, Rüdiger Thul
Calcium responses have been observed as spikes of the whole-cell calcium concentration in numerous cell types and are essential for translating extracellular stimuli into cellular responses. While there are several suggestions for how this encoding is achieved, we still lack a comprehensive theory. To achieve this goal it is necessary to reliably predict the temporal evolution of calcium spike sequences for a given stimulus. Here, we propose a modelling framework that allows us to quantitatively describe the timing of calcium spikes...
October 6, 2017: PLoS Computational Biology
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