Cytoplasmic lipid droplets (LDs) of neutral lipids (triacylglycerols TAGs, sterylesters, etc.) are reserves of high-energy metabolites and other constituents for future needs. They are present in ...diverse cells of eukaryotes and prokaryotes. An LD has a core of neutral lipids enclosed with a monolayer of phospholipids and proteins, which play structural and/or metabolic roles. During the past 3 decades, studies of LDs in diverse organisms have blossomed after they were found to be involved in prevalent human diseases and industrial uses. LDs in plant seeds were studied before those in mammals and microbes, and the latter studies have since moved forward. Plant LDs carry a hallmark protein called oleosin, which has a long hydrophobic hairpin penetrating the TAG core and stabilizing the LD. The oleosin gene first appeared in green algae and has evolved in enhancing promoter strength, tandem repeats, and/or expression specificity, leading to the appearance of new LD organelles, such as tapetosomes in Brassicaceae. The synthesis of LDs occurs with TAG-synthesizing enzymes on the endoplasmic reticulum (ER), and nascent TAGs are sequestered in the acyl moiety region between the bilayers of phospholipids, which results in ER-LD swelling. Oleosin is synthesized on the cytosol side of the ER and extracts the LD from the ER-LD to cytosol. This extraction of LD to the cytosol is controlled solely by the innate properties of oleosin, and modified oleosin can redirect the LD to the ER lumen and then vacuoles. The breakdown of LDs requires lipase associating with core retromer and binding to peroxisomes, which then send the enzyme to LDs via tubular extensions. Two groups of LD-associated proteins, caleosin/dioxygenase/steroleosin and LD/oil body-associated proteins, participate in cellular stress defenses via enzymic activities and binding, respectively. The surface of LDs in all plant cells may be an inert refuge for these and other proteins, which exert functions on diverse cell components. Oleosin-LDs have been explored for commercial applications; successes in their uses will rely on overcoming conceptual and technical difficulties.
Caveolin-1 (Cav1) is an integral membrane, scaffolding protein found in plasma membrane invaginations (caveolae). Cav1 regulates multiple cancer-associated processes. In breast cancer, a tumor ...suppressive role for Cav1 has been suggested; however, Cav1 is frequently overexpressed in aggressive breast cancer subtypes, suggesting an oncogenic function in advanced-stage disease. To further delineate Cav1 function in breast cancer progression, we evaluated its expression levels among a panel of cell lines representing a spectrum of breast cancer phenotypes. In basal-like (the most aggressive BC subtype) breast cancer cells, Cav1 was consistently upregulated, and positively correlated with increased cell proliferation, anchorage-independent growth, and migration and invasion. To identify mechanisms of Cav1 gene regulation, we compared DNA methylation levels within promoter 'CpG islands' (CGIs) with 'CGI shores', recently described regions that flank CGIs with less CG-density. Integration of genome-wide DNA methylation profiles ('methylomes') with Cav1 expression in 30 breast cancer cell lines showed that differential methylation of CGI shores, but not CGIs, significantly regulated Cav1 expression. In breast cancer cell lines having low Cav1 expression (despite promoter CGI hypomethylation), we found that treatment with a DNA methyltransferase inhibitor induced Cav1 expression via CGI shore demethylation. In addition, further methylome assessments revealed that breast cancer aggressiveness associated with Cav1 CGI shore methylation levels, with shore hypermethylation in minimally aggressive, luminal breast cancer cells and shore hypomethylation in highly aggressive, basal-like cells. Cav1 CGI shore methylation was also observed in human breast tumors, and overall survival rates of breast cancer patients lacking estrogen receptor α (ERα) negatively correlated with Cav1 expression. Based on this first study of Cav1 (a potential oncogene) CGI shore methylation, we suggest this phenomenon may represent a new prognostic marker for ERα-negative, basal-like breast cancer.
Chondrosarcoma is the second most common sarcoma in bone malignancy and is characterized by a high metastatic potential. Angiogenesis is essential for the cancer metastasis. Endothelin-1 (ET-1) has ...been implicated in tumor angiogenesis and metastasis. However, the relationship of ET-1 with vascular endothelial growth factor (VEGF) expression and angiogenesis in human chondrosarcoma cells is mostly unknown. Here, we found that the expression of ET-1 and VEGF were correlated with tumor stage and were significantly higher than that in the normal cartilage. Exogenous ET-1 with chondrosarcoma cells promoted VEGF expression and subsequently increased migration and tube formation in endothelial progenitor cells. ET-1 increased VEGF expression and angiogenesis through ETAR, integrin-linked kinase (ILK), Akt and hypoxia-inducible factor-1α (HIF-1α) signaling cascades. Knockdown of ET-1 decreased VEGF expression and also abolished chondrosarcoma conditional medium-mediated angiogenesis in vitro as well as angiogenesis effects in the chick chorioallantoic membrane and Matrigel plug nude mice model in vivo. In addition, in the xenograft tumor angiogenesis model, knockdown of ET-1 significantly reduced tumor growth and tumor-associated angiogenesis. Taken together, these results indicate that ET-1 occurs through ETAR, ILK and Akt, which in turn activates HIF-1α, resulting in the activation of VEGF expression and contributing to the angiogenesis and tumor growth of human chondrosarcoma cells.
The global ionospheric response to a stratospheric sudden warming (SSW) is studied using three‐dimensional electron density maps derived from radio occultation observations of FORMOSAT‐3/COSMIC ...during the 2009 SSW periods. Results show that the ionospheric electron density at EIA crests exhibit a morning/early afternoon increase followed by an afternoon decrease and an evening increase, indicative of a semidiurnal component during the SSW period, which is consistent with recent studies. The latitude‐altitude electron density slice maps show that the SSW related modifications of the equatorial plasma fountain interact with the existing summer‐to‐winter neutral winds and resulting in a north–south asymmetry. The global ionospheric response shows a clear longitudinal dependence in the equatorial plasma fountain enhancement during morning/early afternoon, inferred from the duration of the equatorial ionization anomaly (EIA) enhancement. Following the enhancement, prominent global EIA reductions resulting from the equatorial plasma fountain weakening in the afternoon sector are seen. The ionospheric response to the 2009 SSW event is also compared with the usual seasonal variation during January–February 2007. Instead of showing the electron density increase in the northern hemisphere and decrease in the southern hemisphere as the usual seasonal variation does, the SSW period ionosphere shows prominent global electron density reductions in the afternoon period during the 2009 SSW event.
Key Points
Longitudinal variations of the ionospheric response to SSW are observed
The global electron densities show prolonged reductions in the afternoon during SSW
The study aimed to determine the long-term Staphylococcus aureus colonization patterns and strain relatedness, and the association between maternal and infant colonization in infancy.
A birth cohort ...study was conducted from January 2012 to November 2014. Nasopharyngeal swabs for S. aureus detection were collected from infants at the age of 1, 2, 4, 6 and 12 months and from mothers when their children were 1-month-old.
In total, 254 samples were collected at each planned visit during the first 12-month study. The prevalence of S. aureus colonization decreased in the first year of life, ranging from 61.0% (155/254) at the age of 1 month to 12.2% (31/254) at 12 months. Persistent colonization, defined as a positive culture on four or five occasions, was detected in only 13.8% (35/254) of carriers. Most of the persistent carriers were colonized with methicillin-resistant S. aureus (MRSA) only, and among persistent MRSA carriers, 61.1% (11/18) had indistinguishable genotypes. Of the mothers with MRSA colonization, 77.1% (27/35) had infants who were concomitantly colonized at the age of 1 month; 70.4% (19/27) of the infant–mother paired isolates belonged to indistinguishable or related subtypes, which suggests that surrounding carriers, probably their mothers, may be the possible source for MRSA acquisition in early infancy.
Staphylococcus aureus colonization including MRSA was commonly observed in our cohort. Strains of persistent MRSA among infant–mother pairs were usually of indistinguishable genotypes. Therefore, horizontal spread within households is possibly an important factor related to infant MRSA colonization.
Summary
We hypothesized that the aberrant expression of microRNAs (miRNAs) in rheumatoid arthritis (RA) T cells was involved in the pathogenesis of RA. The expression profile of 270 human miRNAs in T ...cells from the first five RA patients and five controls were analysed by real‐time polymerase chain reaction. Twelve miRNAs exhibited potentially aberrant expression in RA T cells compared to normal T cells. After validation with another 22 RA patients and 19 controls, miR‐223 and miR‐34b were over‐expressed in RA T cells. The expression levels of miR‐223 were correlated positively with the titre of rheumatoid factor (RF) in RA patients. Transfection of Jurkat cells with miR‐223 mimic suppressed insulin‐like growth factor‐1 receptor (IGF‐1R) and transfection with miR‐34b mimic suppressed cAMP response element binding protein (CREB) protein expression by Western blotting. The protein expression of IGF‐1R but not CREB was decreased in RA T cells. The addition of recombinant IGF‐1‐stimulated interleukin (IL)‐10 production by activated normal T cells, but not RA T cells. The transfection of miR‐223 mimic impaired IGF‐1‐mediated IL‐10 production in activated normal T cells. The expression levels of SCD5, targeted by miR‐34b, were decreased in RA T cells after microarray analysis. In conclusion, both miR‐223 and miR‐34b were over‐expressed in RA T cells, but only the miR‐223 expression levels were correlated positively with RF titre in RA patients. Functionally, the increased miR‐223 expression could impair the IGF‐1‐mediated IL‐10 production in activated RA T cells in vivo, which might contribute to the imbalance between proinflammatory and anti‐inflammatory cytokines.
A high O3 episode was detected in urban Shanghai, a typical city in the Yangtze River Delta (YRD) region in August 2010. The CMAQ integrated process rate method is applied to account for the ...contribution of different atmospheric processes during the high pollution episode. The analysis shows that the maximum concentration of ozone occurs due to transport phenomena, including vertical diffusion and horizontal advective transport. Gas-phase chemistry producing O3 mainly occurs at the height of 300–1500 m, causing a strong vertical O3 transport from upper levels to the surface layer. The gas-phase chemistry is an important sink for O3 in the surface layer, coupled with dry deposition. Cloud processes may contribute slightly to the increase of O3 due to convective clouds or to the decrease of O3 due to scavenging. The horizontal diffusion and heterogeneous chemistry contributions are negligible during the whole episode. Modeling results show that the O3 pollution characteristics among the different cities in the YRD region have both similarities and differences. During the buildup period, the O3 starts to appear in the city regions of the YRD and is then transported to the surrounding areas under the prevailing wind conditions. The O3 production from photochemical reaction in Shanghai and the surrounding area is most significant, due to the high emission intensity in the large city; this ozone is then transported out to sea by the westerly wind flow, and later diffuses to rural areas like Chongming island, Wuxi and even to Nanjing. The O3 concentrations start to decrease in the cities after sunset, due to titration of the NO emissions, but ozone can still be transported and maintain a significant concentration in rural areas and even regions outside the YRD region, where the NO emissions are very small.
The objective of this study was to determine the usefulness of augmented reality (AR) in teaching. An experiment was conducted to examine children's learning performances, which included the number ...of errors they made, their ability to remember the content of what they had read and their satisfaction with the three types of teaching materials, including a picture book, physical interactions and an AR graphic book. The three teaching materials were aimed to respectively demonstrate the characteristics of six bacteria with 2D graphics, 3D physical objects, and 3D virtual objects. Seventy‐two fifth‐grade children were randomly selected to participate in the study, and they were divided into three groups, each of which used the assigned teaching material to learn the name of the six different bacteria in intervals of 1, 2 and 3 min. Results showed that the AR graphic book offers a practical and hands‐on way for children to explore and learn about the bacteria. Follow‐up interviews indicated that the children liked the AR graphic book the most, and they preferred it to the other materials.
Lay Description
What is currently known about Augmented Reality and learning?
Augmented reality (AR) provides a new perspective for learning by allowing learners to visualize complex spatial relationships and concepts.
What the paper adds to the subject matter?
AR improves learning performances to a similar extent as the most used teaching materials (both picture books and physical interactions) do.
AR not only facilitates learning but also increases learning motivations better than conventional teaching materials do.
The implications of study findings for practitioners.
If children feel bored about reading textbooks, give them AR (because AR effectively enhances learning and children are more motivated when using AR).
AR teaching material is a good alternative to conventional picture book and physical interactions.
Essentials
ARHGEF10 single‐nucleotide polymorphism provides risk of ischemic and atherothrombotic stroke.
The role of ARHGEF10 in platelet function was examined using ARHGEF10 knockout mice.
ARHGEF10 ...deficiency inhibits platelet function and arterial thrombus formation.
ARHGEF10 knockout protects mice from stroke‐induced infarction.
Summary
Background
ARHGEF10, a member of the Rho guanine nucleotide exchange factor (GEF) family, stimulates Rho GTPases. Rho GTPases have been reported to regulate a variety of cellular behaviors, such as cell polarity, cytoskeletal organization, and gene transcription. ARHGEF10 single‐nucleotide polymorphisms are linked to the risk of ischemic stroke. However, the role of ARHGEF10 in platelet function remains unknown.
Objective
To examine the role of ARHGEF10 in platelet function.
Methods
ARHGEF10−/−were generated. We examined the in vitro and in vivo effects of ARHGEF10 knockout on platelet function and arterial thrombosis formation.
Results
ARHGEF10−/− mice had normal platelet counts, but showed altered aggregation in response to thrombin, collagen, ADP, protease‐activated receptor‐4 peptide, and U46619 stimulation. ARHGEF10 knockout influenced platelet spreading on fibrinogen‐coated surfaces, and caused the platelets to show less lamellipodia‐like extension than wild‐type platelets. ARHGEF10 knockout also inhibited platelet clot retraction induced by thrombin stimulation. ARHGEF10 knockout resulted in prolonged tail bleeding time and inhibited the stable thrombus formation induced by FeCl3 in the carotid artery.
Conclusions
ARHGEF10 serves as an important regulator in platelet shape change, spreading, and aggregation. Moreover, ARHGEF10 also plays an important role in arterial thrombosis formation.
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