SUN proteins in higher eukaryotes, "structural bridges" connecting the nuclear interior with the cytoskeleton

The nucleus is separated from the cytoplasm by a selective structural barrier - the nuclear envelope in eukaryotic cells. The nuclear envelope is composed of inner and outer nuclear membranes (INM and ONM) separated by a perinuclear space (PNS). The specific INM integral proteins interact with the nuclear lamina and are associated with a variety of human diseases, collectively termed nuclear envelopathies. In eukaryotes the SUN domain proteins form a conserved family, the majority of which localize to the INM. UNC-84, which is the first SUN domain protein discovered in Caenorhabditis elegans, has been well studied and shown to be involved in nuclear anchorage and migration. Sun1, a novel INM protein, is the closest homolog to Caenorhabditis elegans UNC-84 in mammals. We show that Sun1 is broadly expressed in various mouse tissues. It spans the inner nuclear membrane three times via transmembrane domains with the N-terminus facing the nucleoplasm and the C-terminus residing in the perinuclear space. Like other inner nuclear membrane proteins Sun1 interacts with chromatin. Sun1 proteins are able to form homo-oligomers with a reduced lateral mobility, which are further stabilized by disulfide bonds. Sun1 can also oligomerize with Sun2, another SUN domain paralogous mammalian protein, at the nuclear envelope. The Sun1 C-terminus directly interacts with the KASH domain of Nesprins. These nuclear spectrin repeat containing proteins are able to bind directly to the actin cytoskeleton. Furthermore, we demonstrated that Sun1 is required for the proper nuclear envelope localization of Nesprin-1 and -2 by RNA interference and dominant negative interference studies. Together these data support a model in which SUN proteins tether Nesprins at the envelope via interactions inside the perinuclear space. In this way, SUN proteins and Nesprins form a physical link between the nucleoskeleton and cytoskeleton. We propose that SUN domain proteins by serving as mechanical adaptors and nuclear envelope receptors allow the physical integration and signaling interplay of cytoplasmic and nucleoplasmic compartments

A study of correlation between permeability and pore space based on dilation operation

CO2 and fracturing liquid injection into tight and shale gas reservoirs induces reactivity between minerals and injected materials, which results in porosity change and thus permeability change. In this paper, the dilation operation is used to simulate the change of the porosity and the corresponding change of permeability based on Lattice-Boltzmann is studied. Firstly we obtain digital images of a real core from CT experiment. Secondly the pore space of digital cores is expanded by dilation operation which is one of basic mathematical morphologies. Thirdly, the distribution of pore bodies and pore throats is obtained from the pore network modeling extracted by maximal ball method. Finally, the correlation between network modeling parameters and permeabilities is analyzed. The result is that the throat change leads to exponential change of permeability and that the big throats significantly influence permeability.Cited as: Zha, W., Yan, S., Li, D., et al. A study of correlation between permeability and pore space based on dilation operation. Advances in Geo-Energy Research, 2017, 1(2): 93-99, doi: 10.26804/ager.2017.02.0

HIV associated cell death: Peptide-induced apoptosis restricts viral transmission.

The human immunodeficiency virus (HIV) is still a global pandemic and despite the successful use of anti-retroviral therapy, a well-established cure remains to be identified. Viral modulation of cell death has a significant role in HIV pathogenesis. Here we sought to understand the major mechanisms of HIV- induced death of lymphocytes and the effects on viral transmission. Flow cytometry analysis of lymphocytes from five latent HIV-infected patients, and HIV IIIB-infected MT2 cells demonstrated both necrosis and apoptosis to be the major mechanisms of cell death in CD4+ and CD4-/CD8- lymphocytes. Significantly, pro-apoptotic tumor necrosis factor (TNF) peptide (P13) was found to inhibit HIV-related cell death and reduced viral transmission. Whereas pro-necrotic TNF peptide (P16) had little effect on HIV-related cell death and viral transmission. Understanding mechanisms by which cell death can be manipulated may provide additional drug targets to reduce the loss of CD4+ cells and the formation of a viral reservoir in HIV infection

An equivalent single-phase flow for oil-water two-phase flow and its potential application in well test

In this work an equivalent single-phase flow model is proposed based on the oil-water two-phase flow equation with saturation-dependent parameters such as equivalent viscosity and equivalent formation volume factor. The equivalent viscosity is calculated from the oil-water relative permeability curves and oil-water viscosity. The equivalent formation volume factor is obtained by the fractional flow of the water phase. In the equivalent single-phase flow model, the equivalent viscosity and phase saturation are interdependent when the relative permeability curves are known. Four numerical experiments based on PEBI grids show that equivalent single-phase flow has a good agreement with the oil-water two-phase flow, which shows that the equivalent single-phase flow model can be used to interpret oil-water two-phase pressure data measured in the wellbore during the buildup period. Because numerical solution of single-phase flow model is several times faster than that of the two-phase flow model, whether the new model interprets the pressure data directly or offers good initial values for the true oil-water two-phase pressure data interpretation, it will obviously improve the efficiency of the interpretation of oil-water pressure data and decrease the burden of engineers.Cited as: Zha, W., Li, D., Lu, Z., Jia, B. An equivalent single-phase flow for oil-water two-phase flow and its potential application in well test. Advances in Geo-Energy Research, 2018, 2(2): 218-227, doi: 10.26804/ager.2018.02.0

Small RNA zippers lock miRNA molecules and block miRNA function in mammalian cells.

MicroRNAs (miRNAs) loss-of-function phenotypes are mainly induced by chemically modified antisense oligonucleotides. Here we develop an alternative inhibitor for miRNAs, termed \u27small RNA zipper\u27. It is designed to connect miRNA molecules end to end, forming a DNA-RNA duplex through a complementary interaction with high affinity, high specificity and high stability. Two miRNAs, miR-221 and miR-17, are tested in human breast cancer cell lines, demonstrating the 70∼90% knockdown of miRNA levels by 30-50 nM small RNA zippers. The miR-221 zipper shows capability in rescuing the expression of target genes of miR-221 and reversing the oncogenic function of miR-221 in breast cancer cells. In addition, we demonstrate that the miR-221 zipper attenuates doxorubicin resistance with higher efficiency than anti-miR-221 in human breast cancer cells. Taken together, small RNA zippers are a miRNA inhibitor, which can be used to induce miRNA loss-of-function phenotypes and validate miRNA target genes

Effect of Asafoetida Extract on Growth and Quality of Pleurotus ferulic

Different concentrations of asafoetida extract were added to the medium of Pleurotus ferulic and the effects of the extract on growth of P. ferulic mycelium and fruiting bodies was observed. As the amount of asafoetida extract additive was increased, the growth of Pleurotus mycelium was faster, the time formation of buds was shorter and that yield of fruiting bodies was stimulated. However, overdosing of asafoetida extract hampered the growth of Pleurotus ferulic. The amino acid composition and volatile components in three kinds of pleurotus’ were contrasted, including wild pleurotus (WP), cultivated pleurotus with asafoetida extract (CPAE) and cultivated pleurotus without asafoetida extract (CP). CPAE with 2.3 g/100 g asafoetida extract addition had the highest content of total amino acids, as well as essential amino acids. WP had a higher content of total amino acids and essential amino acids than CP. In addition, CPAE with 2.3 g/100 g had the highest score of protein content of pleurotus fruiting bodies, while WP had a higher score than CP. In the score of essential amino acid components of pleurotus fruiting bodies, CP had the highest score, while CPAE was higher than WP. Asafoetida extract influenced the volatile components of Pleurotus ferulic greatly, making the volatile components of cultivated pleurotus more similar to those of wild pleurotus (WP)

MUC1 Contributes to BPDE-Induced Human Bronchial Epithelial Cell Transformation through Facilitating EGFR Activation

Although it is well known that epidermal growth factor receptor (EGFR) is involved in lung cancer progression, whether EGFR contributes to lung epithelial cell transformation is less clear. Mucin 1 (MUC1 in human and Muc1 in animals), a glycoprotein component of airway mucus, is overexpressed in lung tumors; however, its role and underlying mechanisms in early stage lung carcinogenesis is still elusive. This study provides strong evidence demonstrating that EGFR and MUC1 are involved in bronchial epithelial cell transformation. Knockdown of MUC1 expression significantly reduced transformation of immortalized human bronchial epithelial cells induced by benzo[a]pyrene diol epoxide (BPDE), the active form of the cigarette smoke (CS) carcinogen benzo(a)pyrene (BaP)s. BPDE exposure robustly activated a pathway consisting of EGFR, Akt and ERK, and blocking this pathway significantly increased BPDE-induced cell death and inhibited cell transformation. Suppression of MUC1 expression resulted in EGFR destabilization and inhibition of the BPDE-induced activation of Akt and ERK and increase of cytotoxicity. These results strongly suggest an important role for EGFR in BPDE-induced transformation, and substantiate that MUC1 is involved in lung cancer development, at least partly through mediating carcinogen-induced activation of the EGFR-mediated cell survival pathway that facilitates cell transformation

Effect of Matrix-Wellbore Flow and Porosity on Pressure Transient Response in Shale Formation Modeling by Dual Porosity and Dual Permeability System

A mathematical dual porosity and dual permeability numerical model based on perpendicular bisection (PEBI) grid is developed to describe gas flow behaviors in shale-gas reservoirs by incorporating slippage corrected permeability and adsorbed gas effect. Parametric studies are conducted for a horizontal well with multiple infinite conductivity hydraulic fractures in shale-gas reservoir to investigate effect of matrix-wellbore flow, natural fracture porosity, and matrix porosity. We find that the ratio of fracture permeability to matrix permeability approximately decides the bottom hole pressure (BHP) error caused by omitting the flow between matrix and wellbore and that the effect of matrix porosity on BHP is related to adsorption gas content. When adsorbed gas accounts for large proportion of the total gas storage in shale formation, matrix porosity only has a very small effect on BHP. Otherwise, it has obvious influence. This paper can help us understand the complex pressure transient response due to existence of the adsorbed gas and help petroleum engineers to interpret the field data better

12(S)‐hydroxyeicosatetraenoic acid impairs vascular endothelial permeability by altering adherens junction phosphorylation levels and affecting the binding and dissociation of its components in high glucose‐induced vascular injury

Abstract Aims/Introduction Diabetes is an important risk factor for atherosclerotic disease. The initiating factor of atherosclerosis is local endothelial cell injury. The arachidonic acid metabolite, 12(S)‐hydroxyeicosatetraenoic acid (12[S]‐HETE), might be involved in this process. In recent years, some studies have discussed the effect of 12(S)‐HETE on vascular endothelial cell function. In the present study, we investigated the effect of 12(S)‐HETE on vascular endothelial cell function in high‐glucose conditions and the mechanisms involved. Materials and Methods Human umbilical vein endothelial cells were cultured in conventional M199 medium and high‐glucose M199 medium. Human umbilical vein endothelial cells were stimulated with 12(S)‐HETE and cinnamyl‐3,4‐dihydroxy‐α‐cyanocinnamate (a 12/15‐lipoxygenases inhibitor). A type 1 diabetes mellitus model was established in C57BL/6 or 12/15‐lipoxygenases knockout mice with streptozotocin. Aortic tissue was harvested for subsequent testing. The transmembrane transport of dextran and human acute monocytic leukaemia cell line (THP‐1) cells was measured. The adherens junction protein, IkBα, nuclear factor kappa Bp65 (P65), intercellular adhesion molecule 1 and vascular cell adhesion protein 1 expression and phosphorylation, and the binding/dissociation of endothelial cell components were observed. Results Transendothelial migration of dextran and THP‐1 cells was significantly increased by stimulation of human umbilical vein endothelial cell monolayers with high glucose and 12(S)‐HETE (P < 0.05). High glucose and 12(S)‐HETE altered the vascular endothelial cadherin and β‐catenin phosphorylation level, and promoted the dissociation of β‐catenin and vascular endothelial cadherin. Expression levels of P‐Ikbα, P‐P65, intercellular adhesion molecule 1 and vascular cell adhesion protein 1 were elevated in high glucose and 12(S)‐HETE treated cells and diabetic mice compared with controls (P < 0.05). Conclusions The lipoxygenases metabolite, 12(S)‐HETE, can impair vascular endothelial permeability by altering adherens junction phosphorylation levels, and affecting the binding and dissociation of its components in high‐glucose conditions

Alginate Hydrogel-Embedded Capillary Sensor for Quantitative Immunoassay with Naked Eye

We have developed an alginate hydrogel-embedded capillary sensor (AHCS) for naked eye-based quantification of immunoassay. Alkaline phosphatase (ALP) can modulate gel-sol transformation to increase the permeability of Cu2+-cross-linked alginate hydrogel film in the AHCS, followed by solution exchange into the capillary. Through measuring the length of the liquid phase of the microfluidics in the capillary at a given time, the concentration of the ALP could be quantified with the naked eye. Since ALP is widely applied as a signal reporter for immunoassays, the AHCS could easily accommodate conventional immune sensing platforms. We justify the practicality of AHCS with hepatitis B virus surface antigen (HBsAg) in serum samples and got comparable results with commercialized immunoassay. This AHCS is easy to make and use, effective in cost, and robust in quantification with the naked eye, showing great promise for next generation point-of-care testing