Białko CTRP3 zwiększa wrażliwość na insulinę adipocytów 3T3-L1 przez hamowanie procesu zapalnego i poprawę przekazywania sygnału insulinowego

 Introduction: C1q/TNF-related Protein-3 (CTRP3) is a novel adipokine with multiple effects such as lowering glucose levels, inhibiting glyconeogenesis in the liver, and increasing angiogenesis and anti-inflammation. But little is known about the effects of CTRP3 on insulin resistance in adipose tissue. This study aims to investigate the effects and mechanisms of CTRP3 on the insulin sensitivity of 3T3-L1 adipocytes.Material and methods: Insulin resistant 3T3-L1 adipocytes were induced by palmic acid cultivation. Such adipocytes were treated with recombinant CTRP3 protein at different concentrations (0, 10, 50, 1,250 ng/mL）for 12 hours, and at a concentration of 250 ng/mL for differing times (2, 6, 12, and 24h). Another group was pre-treated with wortmannin, the special inhibitor of phosphatidylinositol-4,5- bisphosphate 3-kinase (PI3K), for 20 minutes before the treatment with 250 ng/mL CTRP3. The glucose consumption, the glucose uptake, the expression and release of tumour necrosis factor α (TNF-α) and interleukin-6(IL-6) in supernatant, and the protein relative expression of PI3K and protein kinase B (PKB)(ser437) were detected.Results: Compared to the control group, glucose consumption in the CTRP3 intervention group at concentrations of 10, 50, 250, and 1,250 ng/mL was increased by 22.1%, 42.9%, 76.6% and 80.5% respectively (all P < 0.01); the glucose uptake was increased by 39.0%, 68.0%, 108.0% and 111.0% respectively (all P < 0.01); the content of TNF-α in the culture media of CTRP3 (10, 50, 250 ng/mL) intervention group was decreased by 7.6% (P > 0.05), 13.0% (P < 0.05) and 17.4% (P < 0.01) respectively; the content of IL-6 was decreased by 7.1%, 12.4% and 17.1% respectively (all P < 0.01); the protein relative expression of PI3K was increased by 0.63-, 1.00- and 1.36-fold respectively (all P < 0.01), and PKB(ser437) increased by 0.65-, 1.61- and 1.93-fold respectively (all P < 0.01); the mRNA relative expression of GLUT-4 was increased by 23.0%, 47.0% and 62.0% respectively (all P < 0.01). After the treatment with wortmannin, glucose consumption, glucose uptake, PI3K and PKB(ser437) protein relative expression, as well as GLUT-4 mRNA relative expression, was decreased by 53.2%, 44.7%, 43.4%, 56.1 and 30.9% respectively (all P < 0.01).Conclusions: CTRP3 could improve insulin sensitivity of insulin resistant 3T3-L1 adipocytes by decreasing inflammation and ameliorating insulin signalling transduction, indicating that CTRP3 may be a new target for the prevention and cure of insulin resistance and type 2 diabetes. (Endokrynol Pol 2014; 65 (4): 252–258) Wstęp: Białko związane z C1q/TNF typu 3 (CTRP3, C1q/TNF-related Protein-3) jest nowo odkrytą adipokiną o wielorakim działaniu obejmującym obniżenie stężenia glukozy we krwi, hamowanie glukoneogenezy w wątrobie, pobudzanie angiogenezy i działanie przeciwzapalne, Niewiele jednak wiadomo na temat wpływu CTRP3 na insulinooporność komórek tłuszczowych. Badanie to przeprowadzono w celu oceny mechanizmów działania tej adipokiny i jej wpływu na wrażliwość na insulinę adipocytów 3T3-L1.Materiał i metody: Insulinooporne adipocyty 3T3-L1 uzyskano poprzez dodanie do hodowli tych komórek kwasu palmitynowego. Następnie adipocyty te poddano działaniu rekombinowanego białka CTRP3 w różnych stężeniach (0, 10, 50, 1250 ng/ml przez 12 godzin oraz w stężeniu 250 ng/ml przez różny czas (2, 6, 12, 24 godz.). Inną grupę hodowli komórkowych przed dodaniem CTRP3 w stężeniu 250 ng/ml inkubowano wstępnie z wortmaniną, inhibitorem kinazy fosfatydyloinozytolu-4,5 (PI3K, phosphatidylinositol-4,5- bisphosphate 3-kinase) przez 20 minut. Określono zużycie glukozy, wychwyt glukozy, ekspresję i uwalnianie czynnika martwicy nowotworów typu alfa (TNF-α, tumor necrosis factor α) i interleukiny 6 (IL-6, interleukin-6,) w supernatancie oraz ekspresję PI3K i kinazy białkowej B (PKB, protein kinase B) (ser437).Wyniki: Zużycie glukozy w hodowlach poddanych działaniu CTRP3 w stężeniach 10, 50, 250, 1250 ng/ml było większe niż w hodowli kontrolnej odpowiednio o 22,1%, 42,9%, 76,6% i 80,5% (dla wszystkich porównań p < 0,01). Wychwyt glukozy był większy o 39,0%, 68,0%, 108,0% i 111,0% (dla wszystkich porównań p < 0,01) Zawartości TNF-α w medium hodowli komórkowej z dodatkiem CTRP3 (10, 50, 250 ng/ml) były mniejsze odpowiednio o 7,6% (p > 0,05), 13,0% (p < 0,05) i 17,4% (p < 0,01), a zawartości IL-6 były mniejsze o odpowiednio 7,1%, 12,4% i 17,1% (dla wszystkich porównań p < 0,01). Związana z białkami ekspresja PI3K stanowiła odpowiednio 0,63-, 1,00- i 1,36-krotność wartości uzyskanej w hodowli kontrolnej (dla wszystkich porównań p < 0,01), a ekspresja PKB(ser437) stanowiła odpowiednio 0,65-, 1,61- i 1,93-krotność (dla wszystkich porównań p < 0,01); Względna ekspresja mRNA GLUT-4 była większa odpowiednio o 23,0%, 47,0% i 62,0% (dla wszystkich porównań p < 0,01). W hodowlach poddanych wstępnie działaniu wortmaniny zużycie glukozy, signifiwychwyt glukozy, ekspresja PI3K i PKB(ser437) oraz ekspresja mRNA GLUT-4 były mniejsze odpowiednio o 53,2%, 44,7%, 43,4%, 56,1% i 30,9% (dla wszystkich porównań p < 0,01).Wnioski: Białko CTRP3 może powodować zwiększenie wrażliwości na insulinę insulinoopornych adipocytów 3T3-L1 przez hamowanie procesu zapalnego i poprawę przewodzenia sygnałów insulinowych, co wskazuje, że białko to może być nowym celem w zapobieganiu i leczeniu insulinooporności i cukrzycy typu 2. (Endokrynol Pol 2014; 65 (4): 253–258)

FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures overlaying anti-N-methyl-D-aspartate receptor encephalitis: a case report and literature review

BackgroundFLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) has been identified increasingly frequently in recent years. However, this rare MOG antibody disease may coexist with anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARe), in an overlap syndrome with unknown clinical features and prognosis.MethodsWe report a new case of this overlap syndrome and present a systematic review of similar cases in the literature to provide information on the clinical presentation, MRI features, EGG abnormalities, treatment, and prognosis of patients with this rare syndrome.ResultsA total of 12 patients were analyzed in the study. The most common clinical manifestations of FLAMES overlaid with anti-NMDARe were epilepsy (12/12), headache (11/12), and fever (10/12). Increases in intracranial pressure (median: 262.5 mmH2O, range: 150–380 mmH2O), cerebrospinal fluid (CSF) leukocyte count (median: 128×106/L, range: 1-610×106/L), and protein level (median: 0.48 g/L) were also observed. The median CSF anti-NMDAR antibody titer was 1:10 (1:1–1:32), while the median serum MOG antibody titer was 1:32 (1:10–1:1024). Seven cases exhibited unilateral cortical FLAIR hyperintensity, and five cases (42%) had bilateral cortical FLAIR hyperintensity, including four cases involving the bilateral medial frontal lobes. Of the 12 patients, five showed lesions at other sites (e.g., the brainstem, corpus callosum, or frontal orbital gyrus) before or after the development of cortical encephalitis. EEG showed slow waves in four cases, spike–slow waves in two cases, an epileptiform pattern in one case, and normal waves in two cases. The median number of relapses was two. Over a mean follow-up period of 18.5 months, only one patient experienced residual visual impairment, while the remaining 11 patients had good prognoses.ConclusionFLAMES alone is difficult to distinguish from overlap syndrome based on clinical features. However, FLAMES with bilateral medial frontal lobe involvement suggests the presence of the overlap syndrome

Optical orbital-angular-momentum-multiplexed data transmission under high scattering

Multiplexing multiple orbital angular momentum (OAM) channels enables high-capacity optical communication. However, optical scattering from ambient microparticles in the atmosphere or mode coupling in optical fibers significantly decreases the orthogonality between OAM channels for demultiplexing and eventually increases crosstalk in communication. Here, we propose a novel scattering-matrix-assisted retrieval technique (SMART) to demultiplex OAM channels from highly scattered optical fields and achieve an experimental crosstalk of –13.8 dB in the parallel sorting of 24 OAM channels after passing through a scattering medium. The SMART is implemented in a self-built data transmission system that employs a digital micromirror device to encode OAM channels and realize reference-free calibration simultaneously, thereby enabling a high tolerance to misalignment. We successfully demonstrate high-fidelity transmission of both gray and color images under scattering conditions at an error rate of <0.08%. This technique might open the door to high-performance optical communication in turbulent environments

A‐to‐I RNA editing in Klebsiella pneumoniae regulates quorum sensing and affects cell growth and virulence

Millions of adenosine (A) to inosine (I) RNA editing events are reported and well-studied in eukaryotes; however, many features and functions remain unclear in prokaryotes. By combining PacBio Sequel, Illumina whole-genome sequencing, and RNA Sequencing data of two Klebsiella pneumoniae strains with different virulence, a total of 13 RNA editing events are identified. The RNA editing event of badR is focused, which shows a significant difference in editing levels in the two K. pneumoniae strains and is predicted to be a transcription factor. A hard-coded Cys is mutated on DNA to simulate the effect of complete editing of badR. Transcriptome analysis identifies the cellular quorum sensing (QS) pathway as the most dramatic change, demonstrating the dynamic regulation of RNA editing on badR related to coordinated collective behavior. Indeed, a significant difference in autoinducer 2 activity and cell growth is detected when the cells reach the stationary phase. Additionally, the mutant strain shows significantly lower virulence than the WT strain in the Galleria mellonella infection model. Furthermore, RNA editing regulation of badR is highly conserved across K. pneumoniae strains. Overall, this work provides new insights into posttranscriptional regulation in bacteria

Optical orbital-angular-momentum-multiplexed data transmission under high scattering

Multiplexing multiple orbital angular momentum (OAM) channels enables high-capacity optical communication. However, optical scattering from ambient microparticles in the atmosphere or mode coupling in optical fibers significantly decreases the orthogonality between OAM channels for demultiplexing and eventually increases crosstalk in communication. Here, we propose a novel scattering-matrix-assisted retrieval technique (SMART) to demultiplex OAM channels from highly scattered optical fields and achieve an experimental crosstalk of –13.8 dB in the parallel sorting of 24 OAM channels after passing through a scattering medium. The SMART is implemented in a self-built data transmission system that employs a digital micromirror device to encode OAM channels and realize reference-free calibration simultaneously, thereby enabling a high tolerance to misalignment. We successfully demonstrate high-fidelity transmission of both gray and color images under scattering conditions at an error rate of <0.08%. This technique might open the door to high-performance optical communication in turbulent environments

Distributed quantum computing over 7.0 km

Distributed quantum computing provides a viable approach towards scalable quantum computation, which relies on nonlocal quantum gates to connect distant quantum nodes, to overcome the limitation of a single device. However, such an approach has only been realized within single nodes or between nodes separated by a few tens of meters, preventing the target of harnessing computing resources in large-scale quantum networks. Here, we demonstrate distributed quantum computing between two nodes spatially separated by 7.0 km, using stationary qubits based on multiplexed quantum memories, flying qubits at telecom wavelengths, and active feedforward control based on field-deployed fiber. Specifically, we illustrate quantum parallelism by implementing Deutsch-Jozsa algorithm and quantum phase estimation algorithm between the two remote nodes. These results represent the first demonstration of distributed quantum computing over metropolitan-scale distances and lay the foundation for the construction of large-scale quantum computing networks relying on existing fiber channels.Comment: 6 pages, 3 figure

Exploring the potential of blended learning to promote retention and achievement in higher education professional study programs

In this paper, we present a blended learning model designed for a university professional study program attended by full-time professional workers, i.e. in-service teachers studying in the field of School Administration. The model integrates four main instructional strategies at the program level: mentoring; participation in an online community of professional learning and practice; collaborative concept-mapping with an object-typed knowledge modeling software, and face-to-face seminars in a work setting. Based on interview and observation data collected during two successive small-scale experimentations of the model, we explored potential factors that could have had an impact on students’ academic retention and achievement. Four types of factors were identified: personal, professional, institutional and pedagogical. We found that pedagogical and professional factors, which are insufficiently considered in theoretical models of student retention, are of primary concern for students who work full-time as professionals. A blended learning model designed at the program level and strongly “situated” in the professional practice of the students is a promising avenue to adjust to their career constraints and aspirations and, thus, promoting their academic retention and achievement

Interaction between Maternal Passive Smoking during Pregnancy and CYP1A1 and GSTs Polymorphisms on Spontaneous Preterm Delivery

Objective: The present study aimed to examine the association between maternal passive smoking during pregnancy and the risk of spontaneous PTD and to explore the potential interaction of the single or joint gene polymorphism of CYP1A1 and GSTs with maternal passive smoking on the risk of spontaneous PTD. Method: We investigated whether the association between maternal passive smoking and PTD can be modified by 2 metabolic genes, i.e. cytochrome P4501A1 (CYP1A1) and glutathione S-transferases (GSTs), in a case-control study with 198 spontaneous preterm and 524 term deliveries in Shenzhen and Foshan, China. We used logistic regression to test gene-passive smoking interaction, adjusting for maternal socio-demographics and prepregnancy body mass index. Results: Overall, maternal passive smoking during pregnancy was associated with higher risk of PTD (adjusted odds ratio = 2.20 [95% confidence interval: 1.56–3.12]). This association was modified by CYP1A1 and GSTs together, but not by any single genotype. For cross-categories of CYP1A1 Msp I and GSTs, maternal passive smoking was associated with higher risk of PTD among those women with CYP1A1 “TC/CC”+ GSTs “null”, but not among women with other genotypes; and this interaction was significant (OR = 2.66 [95% CI: 1.19–5.97]; P-value: 0.017). For cross-categories of CYP1A1 BsrD I and GSTs, maternal passive smoking was associated with higher risk of PTD only among those women with CYP1A1“AG/GG”+ GSTs “null”, but not among women with other genotypes; and this interaction was significant (OR = 3.00 [95% CI: 1.17–7.74]; P-value: 0.023). Conclusions: Our findings suggest that the combined genotypes of CYP1A1 and GSTs can help to identify vulnerable pregnant women who are subject to high risk of spontaneous PTD due to passive smoking

Direct Reprogramming of Mouse Fibroblasts to Neural Stem Cells by Small Molecules

Copyright © 2016 Yan-Chuang Han et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Although it is possible to generate neural stem cells (NSC) from somatic cells by reprogramming technologies with transcription factors, clinical utilization of patient-specific NSC for the treatment of human diseases remains elusive. The risk hurdles are associated with viral transduction vectors induced mutagenesis, tumor formation from undifferentiated stem cells, and transcription factors-induced genomic instability. Here we describe a viral vector-free and more efficient method to induce mouse fibroblasts into NSC using small molecules. The small molecule-induced neural stem (SMINS) cells closely resemble NSC in morphology, gene expression patterns, self-renewal, excitability, and multipotency. Furthermore, the SMINS cells are able to differentiate into astrocytes, functional neurons, and oligodendrocytes in vitro and in vivo. Thus, we have established a novel way to efficiently induce neural stem cells (iNSC) from fibroblasts using only small molecules without altering the genome. Such chemical induction removes the risks associated with current techniques such as the use of viral vectors or the induction of oncogenic factors. This technique may, therefore, enable NSC to be utilized in various applications within clinical medicine