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https://www.readbyqxmd.com/read/28079384/hypoxia-and-h2o2-dual-sensitive-vesicles-for-enhanced-glucose-responsive-insulin-delivery
#1
Jicheng Yu, Chenggen Qian, Yuqi Zhang, Zheng Cui, Yong Zhu, Qundong Shen, Frances S Ligler, John B Buse, Zhen Gu
A glucose-responsive closed-loop insulin delivery system mimicking pancreas activity without long-term side effect has the potential to improve diabetic patients' health and quality of life. Here, we developed a novel glucose-responsive insulin delivery device using a painless microneedle-array patch containing insulin-loaded vesicles. Formed by self-assembly of hypoxia and H2O2 dual-sensitive diblock copolymer, the glucose-responsive polymersome-based vesicles (d-GRPs) can disassociate and subsequently release insulin triggered by H2O2 and hypoxia generated during glucose oxidation catalyzed by glucose specific enzyme...
January 12, 2017: Nano Letters
https://www.readbyqxmd.com/read/28057699/glucagon-like-peptide-1-and-its-analogues-act-in-the-dorsal-raphe-and-modulate-central-serotonin-to-reduce-appetite-and-body-weight
#2
Rozita H Anderberg, Jennifer E Richard, Kim Eerola, Lorena Lopez Ferreras, Elin Banke Nordbeck, Caroline Hansson, Hans Nissbrandt, Filip Berqquist, Fiona M Gribble, Frank Reimann, Ingrid Wernstedt-Asterholm, Christophe Lamy, Karolina P Skibicka
Glucagon-like peptide-1 (GLP-1) and serotonin play critical roles in energy balance regulation. Both systems are exploited clinically as anti-obesity strategies. Surprisingly whether they interact in order to regulate energy balance is poorly understood. Here we investigated mechanisms by which GLP-1 and serotonin interact at the level of the CNS. Serotonin depletion impaired the ability of exendin-4, a clinically utilized GLP-1 analogue, to reduce body weight in rats, suggesting serotonin is a critical mediator of the energy balance impact of GLP-1R activation...
January 5, 2017: Diabetes
https://www.readbyqxmd.com/read/28009968/the-dielectrophoretic-disassociation-of-chloride-ions-and-the-influence-on-diamagnetic-anisotropy-in-cell-membranes
#3
Marcy C Purnell, Terence J Skrinjar
Chloride channels represent ubiquitously expressed proteins that regulate fundamental cellular processes including membrane potential, maintenance of intracellular pH, and regulation of cell volume. However, mechanisms to modulate this large family of ion channels have remained elusive to date. This large chloride channel family does not appear to operate with selectivity similar to the sodium and potassium channels. These unique channels appear to be bi-directional cotransporters of two or more different molecules or ions across a bilayer phospholipid membrane...
November 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27967292/the-role-of-p53-in-myelodysplastic-syndromes-and-acute-myeloid-leukemia-molecular-aspects-and-clinical-implications
#4
Ling Zhang, Kathy L McGraw, David A Sallman, Alan F List
TP53 gene mutations occurring in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are associated with high-risk karyotypes including 17p abnormalities, monosomal and complex cytogenetics. TP53 mutations in these disorders portend rapid disease progression and resistance to conventional therapeutics. Notably, the size of the TP53 mutant clone as measured by mutation allele burden is directly linked to overall survival (OS) confirming the importance of p53 as a negative prognostic variable...
December 14, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27965026/disentangling-stimulus-plausibility-and-contextual-congruency-electro-physiological-evidence-for-differential-cognitive-dynamics
#5
Moreno I Coco, Susana Araujo, Karl Magnus Petersson
Expectancy mechanisms are routinely used by the cognitive system in stimulus processing and in anticipation of appropriate responses. Electrophysiology research has documented negative shifts of brain activity when expectancies are violated within a local stimulus context (e.g., reading an implausible word in a sentence) or more globally between consecutive stimuli (e.g., a narrative of images with an incongruent end). In this EEG study, we examine the interaction between expectancies operating at the level of stimulus plausibility and at more global level of contextual congruency to provide evidence for, or against, a disassociation of the underlying processing mechanisms...
December 10, 2016: Neuropsychologia
https://www.readbyqxmd.com/read/27957567/rapid-capillary-mixing-experiments-for-the-analysis-of-hydrophobic-membrane-complexes-directly-from-aqueous-lipid-bilayer-solutions
#6
John W Patrick, Breanna Zerfas, Jianmin Gao, David H Russell
In this study the gas-phase conformer preferences of Gramicidin A (GA), a linear antimicrobial pentadecapeptide, were investigated directly from aqueous solutions of lipid vesicle bilayers using a mixing tee-electrospray ionization (MT-ESI) setup coupled with ion mobility mass spectrometry (IM-MS). The required time for GA sample preparation was decreased by approximately 50% using MT-ESI when compared to previously reported methods which required freeze-drying of samples. Using an MT-ESI approach to analyze samples of GA associated with POPC (16:0, 18:1 PC) and DEPC (22:1 PC) lipid bilayers yielded dimer conformer preferences comparable to results obtained using more lengthy protocols...
December 13, 2016: Analyst
https://www.readbyqxmd.com/read/27940163/synergistic-antitumor-efficacy-of-redox-and-ph-dually-responsive-micelleplexes-for-co-delivery-of-camptothecin-and-genes
#7
Maohua Chen, Yun Zhang, Zhoujiang Chen, Songzhi Xie, Xiaoming Luo, Xiaohong Li
: Challenges remain to load and deliver two or multiple drugs of complementary effects for synergistic cancer therapies. In the current study, multiarmed amphiphilic copolymers of 4-arm poly(ethylene glycol) (PEG) and polyaspartate (PAsp) are created for conjugation of camptothecin (CPT) and condensation with tumor necrosis factor-α (TNF) plasmids. Diethylenetriamine (DET) is grafted on PAsp, and CPT is conjugated onto PAsp(DET) by disulfide linkages to form hydrophobic cores of micelles, followed by condensation with TNF plasmids to form micelleplexes...
December 7, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27939957/time-course-of-disassociation-of-bone-formation-signals-with-bone-mass-and-bone-strength-in-sclerostin-antibody-treated-ovariectomized-rats
#8
Yanfei L Ma, Matthew Hamang, Jonathan Lucchesi, Nicoletta Bivi, Qianqiang Zeng, Mary D Adrian, Sarah E Raines, Jiliang Li, Stuart A Kuhstoss, Victor Obungu, Henry U Bryant, Venkatesh Krishnan
Sclerostin antibodies increase bone mass by stimulating bone formation. However, human and animal studies show that bone formation increases transiently and returns to pre-treatment level despite ongoing antibody treatment. To understand its mechanism of action, we studied the time course of bone formation, correlating the rate and extent of accrual of bone mass and strength after sclerostin antibody treatment. Ovariectomized (OVX) rats were treated with a sclerostin-antibody (Scle-ab) at 20mg/kg sc once weekly and sacrificed at baseline and 2, 3, 4, 6, and 8weeks post-treatment...
December 8, 2016: Bone
https://www.readbyqxmd.com/read/27919079/receptor-usage-dictates-hiv-1-restriction-by-human-trim5%C3%AE-in-dendritic-cell-subsets
#9
Carla M S Ribeiro, Ramin Sarrami-Forooshani, Laurentia C Setiawan, Esther M Zijlstra-Willems, John L van Hamme, Wikky Tigchelaar, Nicole N van der Wel, Neeltje A Kootstra, Sonja I Gringhuis, Teunis B H Geijtenbeek
The most prevalent route of HIV-1 infection is across mucosal tissues after sexual contact. Langerhans cells (LCs) belong to the subset of dendritic cells (DCs) that line the mucosal epithelia of vagina and foreskin and have the ability to sense and induce immunity to invading pathogens. Anatomical and functional characteristics make LCs one of the primary targets of HIV-1 infection. Notably, LCs form a protective barrier against HIV-1 infection and transmission. LCs restrict HIV-1 infection through the capture of HIV-1 by the C-type lectin receptor Langerin and subsequent internalization into Birbeck granules...
December 15, 2016: Nature
https://www.readbyqxmd.com/read/27899394/stress-activated-kinase-mkk7-governs-epigenetics-of-cardiac-repolarization-for-arrhythmia-prevention
#10
Sanjoy K Chowdhury, Wei Liu, Min Zi, Yatong Li, Shunyao Wang, Hoyee Tsui, Sukhpal Prehar, Simon J Castro, Henggui Zhang, Yong Ji, Xiuqin Zhang, Rui-Ping Xiao, Rongli Zhang, Ming Lei, Lukas Cyganek, Kaomei Guan, Catherine B Millar, Xudong Liao, Mukesh K Jain, Mark R Boyett, Elizabeth J Cartwright, Holly A Shiels, Xin Wang
BACKGROUND: -Ventricular arrhythmia is a leading cause of cardiac mortality. Most antiarrhythmics present paradoxical pro-arrhythmic side effects, culminating in a greater risk of sudden death. METHODS: -We describe a new regulatory mechanism linking mitogen-activated kinase kinase-7 (MKK7) deficiency with increased arrhythmia vulnerability in hypertrophied and failing hearts using mouse models harbouring MKK7 knockout or overexpression. The human relevance of this arrhythmogenic mechanism is evaluated in human induced pluripotent stem cells-derived cardiomyocytes (iPSC-CMs)...
November 29, 2016: Circulation
https://www.readbyqxmd.com/read/27893218/measuring-response-styles-in-likert-items
#11
Ulf Böckenholt
The recently proposed class of item response tree models provides a flexible framework for modeling multiple response processes. This feature is particularly attractive for understanding how response styles may affect answers to attitudinal questions. Facilitating the disassociation of response styles and attitudinal traits, item response tree models can provide powerful process tests of how different response formats may affect the measurement of substantive traits. In an empirical study, 3 response formats were used to measure the 2-dimensional Personal Need for Structure traits...
November 28, 2016: Psychological Methods
https://www.readbyqxmd.com/read/27847360/parvovirus-capsid-structures-required-for-infection-mutations-controlling-receptor-recognition-and-protease-cleavages
#12
Heather M Callaway, Kurtis H Feng, Donald W Lee, Andrew B Allison, Melissa Pinard, Robert McKenna, Mavis Agbandje-McKenna, Susan Hafenstein, Colin R Parrish
: Parvovirus capsids are small but complex molecular machines responsible for undertaking many of the steps of cell infection, genome packing, and cell-to-cell as well as host-to-host transfer. The details of parvovirus infection of cells are still not fully understood, but the processes must involve small changes in the capsid structure that allow the endocytosed virus to escape from the endosome, pass through the cell cytoplasm, and deliver the ssDNA genome to the nucleus where viral replication occurs...
November 9, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27829411/-i-wish-someone-watched-me-interview-medical-student-insight-into-observation-and-feedback-as-a-method-for-teaching-communication-skills-during-the-clinical-years
#13
Heather Schopper, Marcy Rosenbaum, Rick Axelson
BACKGROUND: Experts suggest observation and feedback is a useful tool for teaching and evaluating medical student communication skills during the clinical years. Failing to do this effectively risks contributing to deterioration of students' communication skills during the very educational period in which they are most important. While educators have been queried about their thoughts on this issue, little is known about what this process is like for learners and if they feel they get educational value from being observed...
November 9, 2016: BMC Medical Education
https://www.readbyqxmd.com/read/27821763/design-of-a-molecular-support-for-cryo-em-structure-determination
#14
Thomas G Martin, Tanmay A M Bharat, Andreas C Joerger, Xiao-Chen Bai, Florian Praetorius, Alan R Fersht, Hendrik Dietz, Sjors H W Scheres
Despite the recent rapid progress in cryo-electron microscopy (cryo-EM), there still exist ample opportunities for improvement in sample preparation. Macromolecular complexes may disassociate or adopt nonrandom orientations against the extended air-water interface that exists for a short time before the sample is frozen. We designed a hollow support structure using 3D DNA origami to protect complexes from the detrimental effects of cryo-EM sample preparation. For a first proof-of-principle, we concentrated on the transcription factor p53, which binds to specific DNA sequences on double-stranded DNA...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27802571/aquerium-a-web-application-for-comparative-exploration-of-domain-based-protein-occurrences-on-the-taxonomically-clustered-genome-tree
#15
Ogun Adebali, Igor B Zhulin
Gene duplication and loss are major driving forces in evolution. While many important genomic resources provide information on gene presence, there is a lack of tools giving equal importance to presence and absence information as well as web platforms enabling easy visual comparison of multiple domain-based protein occurrences at once. Here, we present Aquerium, a platform for visualizing genomic presence and absence of biomolecules with a focus on protein domain architectures. The web server offers advanced domain organization querying against the database of pre-computed domains for ∼26,000 organisms and it can be utilized for identification of evolutionary events, such as fusion, disassociation, duplication, and shuffling of protein domains...
January 2017: Proteins
https://www.readbyqxmd.com/read/27795702/motor-imagery-classification-using-mu-and-beta-rhythms-of-eeg-with-strong-uncorrelating-transform-based-complex-common-spatial-patterns
#16
Youngjoo Kim, Jiwoo Ryu, Ko Keun Kim, Clive C Took, Danilo P Mandic, Cheolsoo Park
Recent studies have demonstrated the disassociation between the mu and beta rhythms of electroencephalogram (EEG) during motor imagery tasks. The proposed algorithm in this paper uses a fully data-driven multivariate empirical mode decomposition (MEMD) in order to obtain the mu and beta rhythms from the nonlinear EEG signals. Then, the strong uncorrelating transform complex common spatial patterns (SUTCCSP) algorithm is applied to the rhythms so that the complex data, constructed with the mu and beta rhythms, becomes uncorrelated and its pseudocovariance provides supplementary power difference information between the two rhythms...
2016: Computational Intelligence and Neuroscience
https://www.readbyqxmd.com/read/27771715/er-stress-via-chop-pathway-is-involved-in-fk506-induced-apoptosis-in-rat-fibroblasts
#17
Jian Tang, Yingbin Ge, Lei Yang, Xinyu Xu, Tao Sui, Dawei Ge, Jun Que, Xiaojian Cao
BACKGROUND/AIMS: Hypertrophic scars (HS) formation results from reduced apoptosis and increased proliferation of fibroblasts. Therefore, apoptosis of fibroblasts is a key target for the development of novel therapeutic strategies for HS. Previous reports demonstrated that FK506 could attenuate scar formation in vivo and FK506 could also induce endoplasmic reticulum stress (ER stress). However, the effects of FK506 on ER stress-mediated apoptosis in fibroblasts remain unclear. METHODS: Rat skin fibroblasts were used in the study...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27765863/characterization-of-11c-gsk1482160-for-targeting-the-p2x7-receptor-as-a-biomarker-for-neuroinflammation
#18
Paul R Territo, Jill A Meyer, Jonathan S Peters, Amanda A Riley, Brian P McCarthy, Mingzhang Gao, Min Wang, Mark A Green, Qi-Huang Zheng, Gary D Hutchins
BACKGROUND: The P2X7 receptor represents a novel molecular target for imaging neuroinflammation via PET. GSK1482160, a potent P2X7 receptor antagonist, has high receptor affinity, blood-brain barrier penetration, and has been recently radiolabel ((11)C-GSK1482160). Therefore, we report the initial physical and biological characterization of this novel ligand. METHODS: (11)C-GSK1482160 synthesis was according to published methods. Cell density studies were performed in human embryonic kidney cell lines expressing human P2X7 receptors (HEK293-hP2X7R) and analyzed by western blot analysis, immuno-fluorescence assay (IFA), and radiologic-immunohistochemistry (RIHC) using P2X7R polyclonal antibodies...
October 20, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27739609/disassociation-between-brain-activation-and-executive-function-in-fragile-x-premutation-females
#19
Annie L Shelton, Kim Cornish, Meaghan Clough, Sanuji Gajamange, Scott Kolbe, Joanne Fielding
Executive dysfunction has been demonstrated among premutation (PM) carriers (55-199 CGG repeats) of the Fragile X mental retardation 1 (FMR1) gene. Further, alterations to neural activation patterns have been reported during memory and comparison based functional magnetic resonance imaging (fMRI) tasks in these carriers. For the first time, the relationships between fMRI neural activation during an interleaved ocular motor prosaccade/antisaccade paradigm, and concurrent task performance (saccade measures of latency, accuracy and error rate) in PM females were examined...
October 14, 2016: Human Brain Mapping
https://www.readbyqxmd.com/read/27733607/stimulation-of-ppc-affects-the-mapping-between-motion-and-force-signals-for-stiffness-perception-but-not-motion-control
#20
Raz Leib, Firas Mawase, Amir Karniel, Opher Donchin, John Rothwell, Ilana Nisky, Marco Davare
: How motion and sensory inputs are combined to assess an object's stiffness is still unknown. Here, we provide evidence for the existence of a stiffness estimator in the human posterior parietal cortex (PPC). We showed previously that delaying force feedback with respect to motion when interacting with an object caused participants to underestimate its stiffness. We found that applying theta-burst transcranial magnetic stimulation (TMS) over the PPC, but not the dorsal premotor cortex, enhances this effect without affecting movement control...
October 12, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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