The Dual Meissner Effect and Magnetic Displacement Currents

The dual Meissner effect is observed without monopoles in quenched $SU (2)$ QCD with Landau gauge-fixing. Magnetic displacement currents which are time-dependent Abelian magnetic fields play a role of solenoidal currents squeezing Abelian electric fields. Monopoles are not always necessary to the dual Meissner effect. The squeezing of the electric flux means the dual London equation and the massiveness of the Abelian electric fields as an asymptotic field. The mass generation of the Abelian electric fields is related to a gluon condensate $\neq 0$ of mass dimension 2.Comment: 4 pages, 5 Postscript figures, title modified, some references added, minor changes made ; Accepted for publication in Phys.Rev.Let

A microRNA (mmu-miR-124) prevents Sox9 expression in developing mouse ovarian cells

In mammals, sex differentiation depends on gonad development, which is controlled by two groups of sex-determining genes that promote one gonadal sex and antagonize the opposite one. SOX9 plays a key role during testis development in all studied vertebrates, whereas it is kept inactive in the XX gonad at the critical time of sex determination, otherwise, ovary-to-testis gonadal sex reversal occurs. However, molecular mechanisms underlying repression of Sox9 at the beginning of ovarian development, as well as other important aspects of gonad organogenesis, remain largely unknown. Because there is indirect evidence that micro-RNAs (miRNA) are necessary for testicular function, the possible involvement of miRNAs in mammalian sex determination deserved further research. Using microarray technology, we have identified 22 miRNAs showing sex-specific expression in the developing gonads during the critical period of sex determination. Bioinformatics analyses led to the identification of miR-124 as the candidate gene for ovarian development. We knocked down or overexpressed miR-124 in primary gonadal cell cultures and observed that miR-124 is sufficient to induce the repression of both SOX9 translation and transcription in ovarian cells. Our results provide the first evidence of the involvement of a miRNA in the regulation of the gene controlling gonad development and sex determination. The miRNA microarray data reported here will help promote further research in this field, to unravel the role of other miRNAs in the genetic control of mammalian sex determination

Testicular somatic cell-like cells derived from embryonic stem cells induce differentiation of epiblasts into germ cells

Regeneration of the testis from pluripotent stem cells is a real challenge, reflecting the complexity of the interaction of germ cells and somatic cells. Here we report the generation of testicular somatic cell-like cells (TesLCs) including Sertoli cell-like cells (SCLCs) from mouse embryonic stem cells (ESCs) in xeno-free culture. We find that Nr5a1/SF1 is critical for interaction between SCLCs and PGCLCs. Intriguingly, co-culture of TesLCs with epiblast-like cells (EpiLCs), rather than PGCLCs, results in self-organised aggregates, or testicular organoids. In the organoid, EpiLCs differentiate into PGCLCs or gonocyte-like cells that are enclosed within a seminiferous tubule-like structure composed of SCLCs. Furthermore, conditioned medium prepared from TesLCs has a robust inducible activity to differentiate EpiLCs into PGCLCs. Our results demonstrate conditions for in vitro reconstitution of a testicular environment from ESCs and provide further insights into the generation of sperm entirely in xeno-free culture

Downregulation of Histone H3 Lysine 9 Methyltransferase G9a Induces Centrosome Disruption and Chromosome Instability in Cancer Cells

Modifications of the histone amino-terminal tails affect access of regulatory factors and complexes to chromatin and thereby influence biological processes. Cancer cells are characterized by prominent epigenetic dysregulation, including histone modifications. However, the functional roles of the histone methyltransferases (HMT) in cancer remain unclear.We studied RNAi-based inhibition (knockdown, KD) of 2 different H3K9 HMTs, SUV39H1 and G9a. Knockdown of the 2 HMTs in PC3 cancer cell line markedly inhibited cell growth and caused profound morphological changes with loss of telomerase activity and shortened telomeres. SUV39H1 KD cells showed substantial increase in G2/M fraction. G9a KD cells showed increased DNA content (1.7-fold in 2 independent clones) compared with FACS analyses to control. Karyotype analyses showed that this was due to an increased number of chromosomes (from 61 to 102) in G9a KD cells compared to parental PC3. Intriguingly, we found abnormal centrosome morphology and number in about 25% of the G9a KD cells, while centrosomes were morphologically normal in control cells. Microarray analyses after KD of SUV39H1 or G9a showed very few genes up-regulated among the 39,000 genes. The silenced tumor-suppressor genes p16 and RASSF1A were not activated in KD cells.These data suggest that the 2 HMTs, SUV39H1 and G9a are required to perpetuate the malignant phenotype. Furthermore, G9a plays a critical role in regulating centrosome duplication presumably through chromatin structure rather than through affecting gene expression in cancer cells. Targeting these histone methyltransferases may be of therapeutic benefit in cancers

Ionospheric Response to the Total Solar Eclipse of 22 July 2009 as Deduced from VLBI and GPS Data

A total solar eclipse occurred over China at latitudes of about 30 N on the morning of 22 July 2009, providing a unique opportunity to investigate the influence of the sun on the earth's upper ionosphere. GPS observations from Shanghai GPS Local Network and VLBI observations from stations Shanghai, Urumqi, and Kashima were used to observe the response of TEC to the total solar eclipse. From the GPS data reduction, the sudden decrease of TEC at the time of the eclipse, amounting to 2.8 TECU, and gradual increase of TEC after the eclipse were found by analyzing the diurnal variations. More distinctly, the variations of TEC were studied along individual satellite passes. The delay in reaching the minimum level of TEC with the maximum phase of eclipse was 5-10 min. Besides, we also compared the ionospheric activity derived from different VLBI stations with the GPS results and found a strong correlation between them

PRELP secreted from mural cells protects the function of blood brain barrier through regulation of endothelial cell-cell integrity

INTRODUCTION: Proline/arginine-rich end leucine-rich repeat protein (PRELP), is a small secreted proteoglycan expressed by pericytes and vascular smooth muscle cells surrounding the brain vasculature of adult mouse. METHODS: We utilised a Prelp knockout (Prelp−/−) mouse model to interrogate vasculature integrity in the brain alongside performing in vitro assays to characterise PRELP application to endothelial cells lines. Our findings were supplemented with RNA expression profiling to elucidate the mechanism of how PRELP maintains neurovasculature function. RESULTS: Prelp−/− mice presented with neuroinflammation and reducedneurovasculature integrity, resulting in IgG and dextran leakage in the cerebellum and cortex. Histological analysis of Prelp−/− mice revealed reducedcell-cell integrity of the blood brain barrier, capillary attachment of pericytes andastrocyte end-feet. RNA-sequencing analysis found that cell-cell adhesion andinflammation are affected in Prelp−/− mice and gene ontology analysis as well as gene set enrichment analysis demonstrated that inflammation related processes and adhesion related processes such as epithelial-mesenchymal transition and apical junctions were significantly affected, suggesting PRELP is a regulator of cell-cell adhesion. Immunofluorescence analysis showed that adhesion junction protein expression levels of cadherin, claudin-5, and ZO-1, was suppressed in Prelp−/− mice neurovasculature. Additionally, in vitro studies revealed that PRELP application to endothelial cells enhances cell-cell integrity, induces mesenchymal-endothelial transition and inhibits TGF-β mediated damage to cell-cell adhesion. DISCUSSION: Our study indicates that PRELP is a novel endogenous secreted regulator of neurovasculature integrity and that PRELP application may be a potential treatment for diseases associated with neurovascular damage

Global e-VLBI observations of the gamma-ray narrow line Seyfert 1 PMN J0948+0022

There is growing evidence of relativistic jets in radio-loud narrow-line Seyfert 1 (RL-NLS1) galaxies. We constrain the observational properties of the radio emission in the first RL-NLS1 galaxy ever detected in gamma-rays, PMN J0948+0022, i.e., its flux density and structure in total intensity and in polarization, its compactness, and variability. We performed three real-time e-VLBI observations of PMN J0948+0022 at 22 GHz, using a global array including telescopes in Europe, East Asia, and Australia. These are the first e-VLBI science observations ever carried out with a global array, reaching a maximum baseline length of 12458 km. The observations were part of a large multiwavelength campaign in 2009. The source is detected at all three epochs. The structure is dominated by a bright component, more compact than 55 microarcsec, with a fainter component at a position angle theta~ 35deg. Relativistic beaming is required by the observed brightness temperature of 3.4x10^11 K. Polarization is detected at a level of about 1%. The parameters derived by the VLBI observations, in addition to the broad-band properties, confirm that PMN J0948+0022 is similar to flat spectrum radio quasars. Global e-VLBI is a reliable and promising technique for future studies.Comment: Accepted for publication as a Letter in Astronomy and Astrophysic

Germ cell sex determination in mammals

One of the major decisions that germ cells make during their development is whether to differentiate into oocytes or sperm. In mice, the germ cells’ decision to develop as male or female depends on sex-determining signalling molecules in the embryonic gonadal environment rather than the sex chromosome constitution of the germ cells themselves. In response to these sex-determining cues, germ cells in female embryos initiate oogenesis and enter meiosis, whereas germ cells in male embryos initiate spermatogenesis and inhibit meiosis until after birth. However, it is not clear whether the signalling molecules that mediate germ cell sex determination act in the developing testis or the developing ovary, or what these signalling molecules might be. Here, we review the evidence for the existence of meiosis-inducing and meiosis-preventing substances in the developing gonad, and more recent studies aimed at identifying these molecules in mice. In addition, we discuss the possibility that some of the reported effects of these factors on germ cell development may be indirect consequences of impairing sexual differentiation of gonadal somatic cells or germ cell survival. Understanding the molecular mechanisms of germ cell sex determination may provide candidate genes for susceptibility to germ cell tumours and infertility in humans

Sex reversal following deletion of a single distal enhancer of Sox9

Cell fate decisions require appropriate regulation of key genes. Sox9, a direct target of SRY, is pivotal in mammalian sex determination. In vivo high-throughput chromatin accessibility techniques, transgenic assays, and genome editing revealed several novel gonadal regulatory elements in the 2-megabase gene desert upstream of Sox9. Although others are redundant, enhancer 13 (Enh13), a 557–base pair element located 565 kilobases 5′ from the transcriptional start site, is essential to initiate mouse testis development; its deletion results in XY females with Sox9 transcript levels equivalent to those in XX gonads. Our data are consistent with the time-sensitive activity of SRY and indicate a strict order of enhancer usage. Enh13 is conserved and embedded within a 32.5-kilobase region whose deletion in humans is associated with XY sex reversal, suggesting that it is also critical in humans