ResearchPad - 38 https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Nucleoplasmin is a limiting component in the scaling of nuclear size with cytoplasmic volume]]> https://www.researchpad.co/article/elastic_article_15327 How nuclear size is regulated relative to cell size is a fundamental cell biological question. Reductions in both cell and nuclear sizes during Xenopus laevis embryogenesis provide a robust scaling system to study mechanisms of nuclear size regulation. To test if the volume of embryonic cytoplasm is limiting for nuclear growth, we encapsulated gastrula-stage embryonic cytoplasm and nuclei in droplets of defined volume using microfluidics. Nuclei grew and reached new steady-state sizes as a function of cytoplasmic volume, supporting a limiting component mechanism of nuclear size control. Through biochemical fractionation, we identified the histone chaperone nucleoplasmin (Npm2) as a putative nuclear size effector. Cellular amounts of Npm2 decrease over development, and nuclear size was sensitive to Npm2 levels both in vitro and in vivo, affecting nuclear histone levels and chromatin organization. We propose that reductions in cell volume and the amounts of limiting components, such as Npm2, contribute to developmental nuclear size scaling.

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<![CDATA[Cell polarity–dependent centrosome separation in the <i>C. elegans</i> embryo]]> https://www.researchpad.co/article/elastic_article_15326 In animal cells, faithful chromosome segregation depends on the assembly of a bipolar spindle driven by the timely separation of the two centrosomes. Here we took advantage of the highly stereotypical cell divisions in Caenorhabditis elegans embryos to identify new regulators of centrosome separation. We find that at the two-cell stage, the somatic AB cell initiates centrosome separation later than the germline P1 cell. This difference is strongly exacerbated by the depletion of the kinesin-13 KLP-7/MCAK, resulting in incomplete centrosome separation at NEBD in AB but not P1. Our genetic and cell biology data indicate that this phenotype depends on cell polarity via the enrichment in AB of the mitotic kinase PLK-1, which itself limits the cortical localization of the dynein-binding NuMA orthologue LIN-5. We postulate that the timely separation of centrosomes is regulated in a cell type–dependent manner.

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<![CDATA[Vimentin protects cells against nuclear rupture and DNA damage during migration]]> https://www.researchpad.co/article/elastic_article_15324 Mammalian cells frequently migrate through tight spaces during normal embryogenesis, wound healing, diapedesis, or in pathological situations such as metastasis. Nuclear size and shape are important factors in regulating the mechanical properties of cells during their migration through such tight spaces. At the onset of migratory behavior, cells often initiate the expression of vimentin, an intermediate filament protein that polymerizes into networks extending from a juxtanuclear cage to the cell periphery. However, the role of vimentin intermediate filaments (VIFs) in regulating nuclear shape and mechanics remains unknown. Here, we use wild-type and vimentin-null mouse embryonic fibroblasts to show that VIFs regulate nuclear shape and perinuclear stiffness, cell motility in 3D, and the ability of cells to resist large deformations. These changes increase nuclear rupture and activation of DNA damage repair mechanisms, which are rescued by exogenous reexpression of vimentin. Our findings show that VIFs provide mechanical support to protect the nucleus and genome during migration.

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<![CDATA[Glial SIK3: A central player in ion and volume homeostasis in <i>Drosophila</i> peripheral nerves]]> https://www.researchpad.co/article/elastic_article_15313 The electrical properties of neuronal cells rely on gradients of ions across their membranes and the extracellular fluid (ECF) in which they are bathed. Little is known regarding how the ECF volume and content is maintained. In this issue, Li et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201907138) identify the kinase SIK3 in glia as a key signal transduction regulator in ion and volume homeostasis in Drosophila peripheral nerves.

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<![CDATA[TGFβ-like DAF-7 acts as a systemic signal for autophagy regulation in <i>C. elegans</i>]]> https://www.researchpad.co/article/elastic_article_15306 In response to stress conditions, autophagy activity in multicellular organisms is systemically modulated to ensure maintenance of cellular homeostasis at an organismal level. Very little is known about the intercellular signals that elicit the long-range organism-wide autophagy response. Here we showed that during Caenorhabditis elegans development, loss of cuticle annular furrow collagens elicits autophagy in the hypodermis, intestine, and muscle. The cilia of sensory neurons with cuticle-localized endings are essential for triggering this systemic response. The TGFβ-like molecule DAF-7, which is secreted in part from a specific pair of ciliated neurons, acts as a systemic factor that activates a canonical TGFβ signaling pathway in distant tissues to induce autophagy. We also showed that AAK-2/AMPK and the STAT-like protein STA-2 act differentially in different tissues for autophagy activation. Our study reveals a circuit that senses and transduces the signal from the damaged cuticle to activate systemic autophagy during animal development.

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<![CDATA[Two <i>S. pombe</i> septation phases differ in ingression rate, septum structure, and response to F-actin loss]]> https://www.researchpad.co/article/elastic_article_15305 In fission yeast, cytokinesis requires a contractile actomyosin ring (CR) coupled to membrane and septum ingression. Septation proceeds in two phases. In anaphase B, the septum ingresses slowly. During telophase, the ingression rate increases, and the CR becomes dispensable. Here, we explore the relationship between the CR and septation by analyzing septum ultrastructure, ingression, and septation proteins in cells lacking F-actin. We show that the two phases of septation correlate with septum maturation and the response of cells to F-actin removal. During the first phase, the septum is immature and, following F-actin removal, rapidly loses the Bgs1 glucan synthase from the membrane edge and fails to ingress. During the second phase, the rapidly ingressing mature septum can maintain a Bgs1 ring and septum ingression without F-actin, but ingression becomes Cdc42 and exocyst dependent. Our results provide new insights into fungal cytokinesis and reveal the dual function of CR as an essential landmark for the concentration of Bgs1 and a contractile structure that maintains septum shape and synthesis.

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<![CDATA[Par-1 controls the composition and growth of cortical actin caps during <i>Drosophila</i> embryo cleavage]]> https://www.researchpad.co/article/elastic_article_15303 Cell structure depends on the cortex, a thin network of actin polymers and additional proteins underlying the plasma membrane. The cell polarity kinase Par-1 is required for cells to form following syncytial Drosophila embryo development. This requirement stems from Par-1 promoting cortical actin caps that grow into dome-like metaphase compartments for dividing syncytial nuclei. We find the actin caps to be a composite material of Diaphanous (Dia)-based actin bundles interspersed with independently formed, Arp2/3-based actin puncta. Par-1 and Dia colocalize along extended regions of the bundles, and both are required for the bundles and for each other’s bundle-like localization, consistent with an actin-dependent self-reinforcement mechanism. Par-1 helps establish or maintain these bundles in a cortical domain with relatively low levels of the canonical formin activator Rho1-GTP. Arp2/3 is required for displacing the bundles away from each other and toward the cap circumference, suggesting interactions between these cytoskeletal components could contribute to the growth of the cap into a metaphase compartment.

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<![CDATA[Analysing and optimizing the electrolysis efficiency of a lithium cell based on the electrochemical and multiphase model]]> https://www.researchpad.co/article/Ndcd4e658-410c-459a-b2e7-c2622a65d27d

Based on an electrochemical multiphysical simulation, a method for analysing electrolysis efficiency has been presented that considers the energy consumption required to produce a single kilogram of lithium and for the production of lithium, rather than the voltage in various parts. By adopting them as the criteria for analysing electrolysis efficiency in the lithium cell, several structural parameters have been optimized, such as the anode radius and anode–cathode distance. These parameters strongly affect the cell voltage and the velocity field distribution, which has a significant impact on the concentration distribution. By integrating the concentration distribution, the lithium production and energy consumption per kilogram, lithium is computed. By appointing the minimum of the chlorine and lithium concentration as the secondary reaction intensity, it is clear where the secondary reaction intensity is strong in the cell. The structure of a lithium electrolysis cell has been optimized by applying an orthogonal design approach, with the energy consumption notably decreasing from 35.0 to 28.3 kWh (kg Li)−1 and the lithium production successfully increasing by 0.17 mol.

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<![CDATA[Correction to ‘Organic matter removal from mother liquor of gas field wastewater by electro-Fenton process with the addition of H2O2: effect of initial pH’]]> https://www.researchpad.co/article/N3eef130c-63c1-4544-a5ad-d082b766f783 ]]> <![CDATA[Dynamic inferential NOx emission prediction model with delay estimation for SCR de-NOx process in coal-fired power plants]]> https://www.researchpad.co/article/Nd9906310-a1f9-4420-a449-a3d55d7a4735

The selective catalytic reduction (SCR) decomposition of nitrogen oxide (de-NOx) process in coal-fired power plants not only displays nonlinearity, large inertia and time variation but also a lag in NOx analysis; hence, it is difficult to obtain an accurate model that can be used to control NH3 injection during changes in the operating state. In this work, a novel dynamic inferential model with delay estimation was proposed for NOx emission prediction. First, k-nearest neighbour mutual information was used to estimate the time delay of the descriptor variables, followed by reconstruction of the phase space of the model data. Second, multi-scale wavelet kernel partial least square was used to improve the prediction ability, and this was followed by verification using benchmark dataset experiments. Finally, the delay time difference method and feedback correction strategy were proposed to deal with the time variation of the SCR de-NOx process. Through the analysis of the experimental field data in the steady state, the variable state and the NOx analyser blowback process, the results proved that this dynamic model has high prediction accuracy during state changes and can realize advance prediction of the NOx emission.

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<![CDATA[Telemedicine assessment of long-term cognitive and functional status in anti-leucine-rich, glioma-inactivated 1 encephalitis]]> https://www.researchpad.co/article/N3fbbce8f-a3b6-489f-969f-64e343f95b34

Objective

To assess the feasibility of a structured telephone interview examining the long-term cognitive and functional status in anti–leucine-rich, glioma-inactivated 1 (LGI1) encephalitis.

Methods

Telephone interviews were conducted with 37 patients after a median follow-up of 87 months from disease onset and 23 healthy controls matched for age and sex. Cognitive status was assessed with the telephone Mini-Mental State Examination (t-MMSE) and 3 tests exploring verbal memory, fluency, and executive function. Functional status was evaluated with the Functional Activities Questionnaire and the modified Rankin Scale (mRS). Patients were classified as normal, with mild cognitive impairment (MCI), or with dementia based on cognitive and functional status. Assessment of the cognitive reserve was performed with a structured questionnaire. Logistic regression analysis was applied to identify predictors of cognitive impairment.

Results

Telephone interviews were successful in 36/37 (97%) patients. Cognitive impairment was detected in 27 (75%) including 17 with MCI and 10 with dementia. Eight (29%) patients would have been misclassified using only the t-MMSE. Twenty-six (72%) patients were functionally independent according to the mRS, but only 9 (35%) were cognitively normal. Independent predictors for long-term cognitive impairment were a low cognitive reserve (OR = 1.36, 95% CI: 1.05–1.76; p = 0.02) and bilateral hippocampal hyperintensity at initial MRI (OR = 27.03, 95% CI: 1.87–390; p = 0.02).

Conclusions

Telemedicine is a feasible tool to assess the cognitive and functional outcome in patients with anti-LGI1 encephalitis. Cognitive impairment is often missed if only functional scales are used. Premorbid cognitive reserve and MRI with bilateral hippocampal hyperintensity were predictors for long-term cognitive impairment.

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<![CDATA[The RNA exosome nuclease complex regulates human embryonic stem cell differentiation]]> https://www.researchpad.co/article/Ne8da9728-a5df-4d19-b6d8-4a6e659197f5

This work shows that the exosome modulates the levels of LINE-1 retrotransposons and specific miRNAs, lncRNAs, and mRNAs that encode developmental regulators or affect their expression. The exosome restrains stem cell differentiation in part by degrading transcripts encoding FOXH1, a transcription factor crucial for mesendoderm formation.

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<![CDATA[The amino acid transporter SLC-36.1 cooperates with PtdIns3P 5-kinase to control phagocytic lysosome reformation]]> https://www.researchpad.co/article/Ndbf67ba1-f075-4531-9ced-7a6bcdd2ef63

How lysosomes reform following phagolysosomal digestion of apoptotic cells is poorly understood. Gan et al. reveal that the amino acid transporter SLC-36.1 cooperates with PtdIns3P 5-kinase to control phagocygtic lysosome reformation in Caenorhabditis elegans embryos and autophagic lysosome reformation in adult animals.

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<![CDATA[Yorkie controls tube length and apical barrier integrity during airway development]]> https://www.researchpad.co/article/N8510fe64-1ef6-4de2-b892-e6d4e824e187

Skouloudaki et al. identify an alternative role of the transcriptional coactivator Yorkie (Yki) in controlling water impermeability and tube size of developing Drosophila airways. Tracheal impermeability is triggered by Yki-mediated transcriptional regulation of δ-aminolevulinate synthase (Alas), whereas tube elongation is controlled by binding of Yki to the actin-severing factor Twinstar.

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<![CDATA[Developmentally regulated GTP-binding protein 1 modulates ciliogenesis via an interaction with Dishevelled]]> https://www.researchpad.co/article/Nbcb3b40a-fa2f-4210-a1a2-470a83bd2c8d

Our study reveals Drg1 as a new binding partner of Dishevelled. The Drg1–Dishevelled association regulates Daam1 and RhoA interactions and activity, leading to polymerization and stability of the actin cytoskeleton, a process that is essential for proper multiciliation.

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<![CDATA[Microtubules promote intercellular contractile force transmission during tissue folding]]> https://www.researchpad.co/article/N2bc9b7b1-9221-4873-aaa4-29095195955f

During morphogenesis, how intercellular contractile force transmission is maintained in the face of tension is not well understood. Ko et al. describe polarized, noncentrosomal microtubules that promote the attachment of actomyosin to cell junctions for proper tissue-wide force integration.

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<![CDATA[The Oncology Data Network (ODN): A Collaborative European Data‐Sharing Platform to Inform Cancer Care]]> https://www.researchpad.co/article/N489f0c71-803a-4859-9f2f-c5d4affc57ae

The rise of precision oncology has made clinical decision making more complex than ever before. The Oncology Data Network was established to enable the clinical community to efficiently access potentially practice‐changing insights from an extended network of cancer centers. This article describes the progress to date and calls for greater collaboration.

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<![CDATA[Difference in adsorbable organic halogen formation between phenolic and non-phenolic lignin model compounds in chlorine dioxide bleaching]]> https://www.researchpad.co/article/N3d6a1ba2-190b-4ad6-aafe-2aa1b63345ca

Adsorbable organic halogen (AOX) is generally formed by the reaction of residual lignin in pulps with chlorine dioxide during bleaching. Lignin has a complex structure. Different functional groups and bonds are present in lignin structures. Phenolic hydroxyl is one of the important functional groups in lignin, and it significantly influences the chemical properties and reactivity. To study the effect of phenolic hydroxyl on AOX formation, vanillyl alcohol (VA) was selected as the phenolic lignin model compound, and veratryl alcohol (VE) was selected as the non-phenolic lignin model compound in this study. The kinetics of AOX formation by the reaction of VA or VE with chlorine dioxide was studied. The effects of pH, chlorine dioxide, lignin model compound concentration and reaction temperature on AOX formation are discussed. The activation energies of the reaction of VA and VE with chlorine dioxide are 16 242.47 J mol−1 and 281.34 J mol−1, respectively. Thus, we found that the non-phenolic lignin can react with chlorine dioxide to form AOX more easily than phenolic lignin.

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<![CDATA[Acceptability of Routine Evaluations Using Patient‐Reported Outcomes of Common Terminology Criteria for Adverse Events and Other Patient‐Reported Symptom Outcome Tools in Cancer Outpatients: Princess Margaret Cancer Centre Experience]]> https://www.researchpad.co/article/Neb7f2fdc-96dd-41ba-a953-ffd1b838a5d2

regorafenib dosing in patients with metastatic or recurrent gastrointestinal stromal tumors after failure of imatinib and sunitinib.

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<![CDATA[Responses of apoptosis and matrix metabolism of annulus fibrosus cells to different magnitudes of mechanical tension in vitro]]> https://www.researchpad.co/article/5c94bd6dd5eed0c484613215

Background: Annulus fibrosus (AF) is important to confine disc nucleus pulposus (NP) tissue during mechanical load experience. However, the knowledge on AF cell biology under mechanical load is much limited compared with disc NP. Objective: The present study aimed to investigate responses of apoptosis and matrix metabolism of AF cells to different magnitudes of mechanical tension in vitro. Methods: Rat AF cells were subjected to different magnitudes (5, 10, and 20% elongations at a frequency of 1.0 Hz for 6 h per day) of mechanical tension for 7 days. Control AF cells were cultured without mechanical tension. Cell apoptosis ratio, caspase-3 activity, gene/protein expression of apoptosis-related molecules (Bcl-2, Bax, caspase-3/cleaved caspase-3 and cleaved PARP), matrix macromolecules (aggrecan and collagen I) and matrix metabolism-related enzymes (TIMP-1, TIMP-3, MMP-3, and ADAMTS-4) were analyzed. Results: Compared with 5% tension group and control group, 10 and 20% tension groups significantly increased apoptosis ratio, caspase-3 activity, up-regulated gene/protein expression of Bax, caspase-3/cleaved caspase-3, cleaved PARP, MMP-3, and ADAMTS-4, whereas down-regulated gene/protein expression of Bcl-2, aggrecan, collagen I, TIMP-1, and TIMP-3. No significant difference was found in these parameters apart from Bcl-2 expression between the control group and 5% tension group. Conclusion: High mechanical tension promotes AF cell apoptosis and suppresses AF matrix synthesis compared with low mechanical tension. The present study indirectly indicates how mechanical overload induces disc degeneration through affecting AF biology.

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