2,205 research outputs found
Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects
(E)-1-[2-HyÂdroxy-4,6-bisÂ(methÂoxyÂmethÂoxy)phenÂyl]-3-[3-methÂoxy-4-(methÂoxyÂmethÂoxy)phenÂyl]prop-2-en-1-one
The title compound, C22H26O9, crystallizes with two independent molÂecules in the asymmetric unit in which the dihedral angles between the two benzene rings are 21.4â
(2) and 5.1â
(2)°. An intraÂmolecular OâHâŻO hydrogen bond occurs in each molÂecule. InterÂmolecular CâHâŻO hydrogen bonds stabilize the crystal structure
O-GlcNAcylation of core components of the translation initiation machinery regulates protein synthesis
Protein synthesis is essential for cell growth, proliferation, and survival. Protein synthesis is a tightly regulated process that involves multiple mechanisms. Deregulation of protein synthesis is considered as a key factor in the development and progression of a number of diseases, such as cancer. Here we show that the dynamic modification of proteins by O-linked ÎČ-N-acetyl-glucosamine (O-GlcNAcylation) regulates translation initiation by modifying core initiation factors eIF4A and eIF4G, respectively. Mechanistically, site-specific O-GlcNAcylation of eIF4A on Ser322/323 disrupts the formation of the translation initiation complex by perturbing its interaction with eIF4G. In addition, O-GlcNAcylation inhibits the duplex unwinding activity of eIF4A, leading to impaired protein synthesis, and decreased cell proliferation. In contrast, site-specific O-GlcNAcylation of eIF4G on Ser61 promotes its interaction with poly(A)-binding protein (PABP) and poly(A) mRNA. Depletion of eIF4G O-GlcNAcylation results in inhibition of protein synthesis, cell proliferation, and soft agar colony formation. The differential glycosylation of eIF4A and eIF4G appears to be regulated in the initiation complex to fine-tune protein synthesis. Our study thus expands the current understanding of protein synthesis, and adds another dimension of complexity to translational control of cellular proteins
Quantitative Proteomic Study of Human Lung Squamous Carcinoma and Normal Bronchial Epithelial Acquired by Laser Capture Microdissection
Objective. To investigate the differential protein profile of human lung squamous carcinoma (HLSC) and normal bronchial epithelium (NBE) and provide preliminary results for further study to explore the carcinogenic mechanism of HLSC. Methods. Laser capture microdissection (LCM) was used to purify the target cells from 10 pairs of HLSC tissues and their matched NHBE, respectively. A stable-isotope labeled strategy using iTRAQ, followed by 2D-LC/Q-STAR mass spectrometry, was performed to separate and identify the differential expression proteins. Results. A total of 96 differential expression proteins in the LCM-purified HLSC and NBE were identified. Compared with NBE, 49 proteins were upregulated and 47 proteins were downregulated in HLSC. Furthermore, the expression levels of the differential proteins including HSPB1, CKB, SCCA1, S100A8, as well as S100A9 were confirmed by western blot and tissue microarray and were consistent with the results of quantitative proteomics. Conclusion. The different expression proteins in HLSC will provide scientific foundation for further study to explore the carcinogenic mechanism of HLSC
Plasmofluidic Disk Resonators
Waveguide-coupled silicon ring or disk resonators have been used for optical signal processing and sensing. Large-scale integration of optical devices demands continuous reduction in their footprints, and ultimately they need to be replaced by silicon-based plasmonic resonators. However, few waveguide-coupled silicon-based plasmonic resonators have been realized until now. Moreover, fluid cannot interact effectively with them since their resonance modes are strongly confined in solid regions. To solve this problem, this paper reports realized plasmofluidic disk resonators (PDRs). The PDR consists of a submicrometer radius silicon disk and metal laterally surrounding the disk with a 30-nm-wide channel in between. The channel is filled with fluid, and the resonance mode of the PDR is strongly confined in the fluid. The PDR coupled to a metal-insulator-silicon-insulator-metal waveguide is implemented by using standard complementary metal oxide semiconductor technology. If the refractive index of the fluid increases by 0.141, the transmission spectrum of the waveguide coupled to the PDR of radius 0.9 mu m red-shifts by 30 nm. The PDR can be used as a refractive index sensor requiring a very small amount of analyte. Plus, the PDR filled with liquid crystal may be an ultracompact intensity modulator which is effectively controlled by small driving voltageopen
Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay
The decay channel
is studied using a sample of events collected
by the BESIII experiment at BEPCII. A strong enhancement at threshold is
observed in the invariant mass spectrum. The enhancement can be fit
with an -wave Breit-Wigner resonance function with a resulting peak mass of
and a
narrow width that is at the 90% confidence level.
These results are consistent with published BESII results. These mass and width
values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics
MAPping out distribution routes for kinesin couriers
In the crowded environment of eukaryotic cells, diffusion is an inefficient distribution mechanism for cellular components. Long-distance active transport is required and is performed by molecular motors including kinesins. Furthermore, in highly polarized, compartmentalized and plastic cells such as neurons, regulatory mechanisms are required to ensure appropriate spatio-temporal delivery of neuronal components. The kinesin machinery has diversified into a large number of kinesin motor proteins as well as adaptor proteins that are associated with subsets of cargo. However, many mechanisms contribute to the correct delivery of these cargos to their target domains. One mechanism is through motor recognition of subdomain-specific microtubule (MT) tracks, sign-posted by different tubulin isoforms, tubulin post-translational modifications (PTMs), tubulin GTPase activity and MT associated proteins (MAPs). With neurons as a model system, a critical review of these regulatory mechanisms is presented here, with particular focus on the emerging contribution of compartmentalised MAPs. Overall, we conclude that â especially for axonal cargo â alterations to the MT track can influence transport, although in vivo, it is likely that multiple track-based effects act synergistically to ensure accurate cargo distribution
Differences in cerebral response to esophageal acid stimuli and psychological anticipation in GERD subtypes - An fMRI study
<p>Abstract</p> <p>Background</p> <p>To evaluate whether there are differences in the cerebral response to intraesophageal acid and psychological anticipation stimuli among subtypes of gastroesophageal reflux disease (GERD).</p> <p>Methods</p> <p>Thirty nine patients with GERD and 11 healthy controls were enrolled in this study after gastroscopy and 24 hr pH monitoring. GERD subjects were divided into four subgroups: RE (reflux esophagitis), NERD+ (non-erosive reflux disease with excessive acid reflux), NERD-SI+ (normal acid exposure and positive symptom index) and NERD-SI+ (normal acid exposure and negative symptom index, but responded to proton pump inhibitor trial). Cerebral responses to intraesophageal acid and psychological anticipation were evaluated with fMRI.</p> <p>Results</p> <p>During intraesophageal acid stimulation, the prefrontal cortex (PFC) region was significantly activated in all subgroups of GERD; the insular cortex (IC) region was also activated in RE, NERD+ and NERD-SI- groups; the anterior cingulated cortex (ACC) region was activated only in RE and NERD-SI- groups. The RE subgroup had the shortest peak time in the PFC region after acid was infused, and presented the greatest change in fMRI signals in the PFC and ACC region (<it>P </it>= 0.008 and <it>P </it>= 0.001, respectively). During psychological anticipation, the PFC was significantly activated in both the control and GERD groups. Activation of the IC region was found in the RE, NERD-SI+ and NERD-SI- subgroups. The ACC was activated only in the NERD-SI+ and NERD-SI- subgroups. In the PFC region, the NERD-SI- subgroup had the shortest onset time (<it>P </it>= 0.008) and peak time (<it>P </it>< 0.001). Compared with actual acid infusion, ACC in RE and IC in NERD+ were deactivated while additional areas including the IC and ACC were activated in the NERD-SI+ group; and in NERD-SI- group, onset-time and peak time in the PFC and IC areas were obviously shorter in induced anticipation than in actual acid infusion.</p> <p>Conclusions</p> <p>The four subgroups of GERD patients and controls showed distinctly different activation patterns and we therefore conclude GERD patients have different patterns of visceral perception and psychological anticipation. Psychological factors play a more important role in NERD-SI+ and NERD-SI- groups than in RE and NERD+ groups.</p
Observation of decays into vector meson pairs , , and
Decays of to vector meson pairs , and
are observed for the first time using
\psip events accumulated at the BESIII detector at the BEPCII
collider. The branching fractions are measured to be , , and , for , , and ,
respectively. The observation of decays into a pair of vector
mesons , and indicates that the hadron
helicity selection rule is significantly violated in decays. In
addition, the measurement of gives the rate of doubly
OZI-suppressed decay. Branching fractions for and
decays into other vector meson pairs are also measured with improved precision.Comment: 4 pages, 2 figure
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