N-Glycosylation of ß4 Integrin Controls the Adhesion and Motility of Keratinocytes

α6ß4 integrin is an essential component of hemidesmosomes and modulates cell migration in wound healing and cancer invasion. To elucidate the role of N-glycosylation on ß4 integrin, we investigated keratinocyte adhesion and migration through the re-expression of wild-type or N-glycosylation-defective ß4 integrin (ΔNß4) in ß4 integrin null keratinocytes. N-glycosylation of ß4 integrin was not essential for the heterodimer formation of ß4 integrin with α6 integrin and its expression on a cell surface, but N-glycosylation was required for integrin-mediated cell adhesion and migration. Concomitantly with the reduction of ß4 integrin in the membrane microdomain, the intracellular signals of Akt and ERK activation were decreased in cells expressing ΔNß4 integrin. Forced cross-linking of ß4 integrin rescued the decreased ERK activation in ΔNß4 integrin-expressing cells to a similar extent in wild-type ß4 integrin-expressing cells. Surprisingly, compared with cells expressing wild-type ß4 integrin, an alternation in N-glycan structures expressed on epidermal growth factor receptor (EGFR), and the induction of a stronger association between EGFR and ß4 integrin were observed in ΔNß4 integrin-expressing cells. These results clearly demonstrated that N-glycosylation on ß4 integrin plays an essential role in keratinocyte cellular function by allowing the appropriate complex formation on cell surfaces

First spectroscopic observations of the galaxies that reionized the Universe

Low-mass galaxies in the early universe are believed to be the building blocks of present-day galaxies. These fledgling systems likely played a pivotal role in cosmic reionization, a major phase transition from neutral Hydrogen to ionized plasma around 600-800 Myr after the Big Bang. However, these galaxies have eluded comprehensive spectroscopic studies owing to their extreme faintness. Here we report the first spectroscopic analysis of 8 ultra-faint galaxies during the epoch of reionization with absolute magnitudes between M$_{\rm UV}$ $\sim -17$ to $-15$ mag (down to 0.005 $L^{\star}$). The combination of ultra-deep NIRSpec (Near-Infrared Spectrograph) observations and the strong gravitational lensing boost of Abell~2744 allow us to derive the first spectroscopic constraints on the prevalence of faint galaxies and their ionizing properties during the Universe's first billion years. We find that faint galaxies are prodigious producers of ionizing photons with log($\xi_{\rm ion}$/ Hz erg$^{-1}$) =$25.8\pm 0.05$, a factor of 4 larger than canonical values. This means that the total rate of ionizing photons produced by galaxies exceeds that needed for reionization, even for modest values of escape fraction ($f_{\rm esc}$ =5%). These findings provide robust evidence that faint galaxies were the main drivers of cosmic reionization at $z\sim7$.Comment: 29 pages, 7 figures, 2 table

The DEAD-box RNA Helicase DDX6 is Required for Efficient Encapsidation of a Retroviral Genome

Viruses have to encapsidate their own genomes during the assembly process. For most RNA viruses, there are sequences within the viral RNA and virion proteins needed for high efficiency of genome encapsidation. However, the roles of host proteins in this process are not understood. Here we find that the cellular DEAD-box RNA helicase DDX6 is required for efficient genome packaging of foamy virus, a spumaretrovirus. After infection, a significant amount of DDX6, normally concentrated in P bodies and stress granules, re-localizes to the pericentriolar site where viral RNAs and Gag capsid proteins are concentrated and capsids are assembled. Knockdown of DDX6 by siRNA leads to a decreased level of viral nucleic acids in extracellular particles, although viral protein expression, capsid assembly and release, and accumulation of viral RNA and Gag protein at the assembly site are little affected. DDX6 does not interact stably with Gag proteins nor is it incorporated into particles. However, we find that the ATPase/helicase motif of DDX6 is essential for viral replication. This suggests that the ATP hydrolysis and/or the RNA unwinding activities of DDX6 function in moderating the viral RNA conformation and/or viral RNA-Gag ribonucleoprotein complex in a transient manner to facilitate incorporation of the viral RNA into particles. These results reveal a unique role for a highly conserved cellular protein of RNA metabolism in specifically re-locating to the site of viral assembly for its function as a catalyst in retroviral RNA packaging

A shot in the Dark (Ages): a faint galaxy at z=9.76z=9.76 confirmed with JWST

The appearance of galaxies over the first billion years after the Big Bang is believed to be responsible for the last dramatic change in the state of the Universe. Ultraviolet photons from galaxies within this time period - the Epoch of Reionization - ionized intergalactic Hydrogen, rendering the Universe transparent to UV radiation and ending the so-called cosmic Dark Ages, sometime after redshift $z\sim8$. The majority of ionizing photons in the first few hundred Myrs of cosmic history are thought to derive from galaxies significantly fainter than the characteristic luminosity $L^{*}$. These faint galaxies are thought to be surrounded by sufficient neutral gas to prevent the escape of the Lyman-$\alpha$ photons that would allow confirmation with current observatories. Here we demonstrate the power of the recently commissioned James Webb Space Telescope to transform our understanding of the sources of reionization, by reporting the first spectroscopic confirmation of a very low luminosity ($\sim0.05 L^{*}$) galaxy at $z=9.76$, observed 480 Myr after the Big Bang, via the detection of the Lyman-break and redward continuum with the NIRSpec and NIRCam instruments. The galaxy JD1 is gravitationally magnified by a factor of $\mu\sim13$ by the foreground cluster A2744. The power of JWST and lensing allows us to peer deeper than ever before into the cosmic Dark Ages, revealing the compact ($\sim$150 pc) and complex morphology and physical properties of an ultrafaint galaxy ($M_{\rm UV}=-17.45$).Comment: Submitted to Nature. 34 pages, 4 main figures, 1 supplementary figure, 2 supplementary tables. Comments are welcom

Root growth and crop performance of soybean under chemical, physical, and biological changes after subsoiling.

Chemical, physical and biological soil attributes can facilitate soybean root growth in greater volume and depth in the soil, which can minimize yield reduction caused by water deficit. Soil management can contribute positively or negatively to these soil attributes. The aim of this work was to evaluate the root growth and crop performance of soybean, in response to chemical, physical and biological changes after subsoiling at different depths. At the R5 phenological stage, trenches were made for sampling and soil collection for chemical, physical and biological analysis and root growth was carried out. At V5, V7, R2 and R5 stages, plants were collected to evaluate height, leaf area and dry mass. At V5, stage number and dry mass of the nodules were evaluated. Subsoiling increased pH and Ca, and decreased Al in the soil, resulted in higher relative density and did not affect in mechanical penetration resistance compared to non-subsoiled soil. Basal respiration and soybean nodulation were higher in the subsoiled soil. Up to 15 cm depth, there were 87.91% of the total root dry mass and 78.79% of the total root volume. Initial and final plant growth were the same in subsoiled and non-subsoiled soil. Number of nodules in the subsoiled soil was 28% higher than in the non-subsoiled soil. Under these study conditions, subsoiling provides lower root growth but benefits grain yield

The Promigratory Activity of the Matricellular Protein Galectin-3 Depends on the Activation of PI-3 Kinase

Expression of galectin-3 is associated with sarcoma progression, invasion and metastasis. Here we determined the role of extracellular galectin-3 on migration of sarcoma cells on laminin-111. Cell lines from methylcholanthrene-induced sarcomas from both wild type and galectin-3−/− mice were established. Despite the presence of similar levels of laminin-binding integrins on the cell surface, galectin-3−/− sarcoma cells were more adherent and less migratory than galectin-3+/+ sarcoma cells on laminin-111. When galectin-3 was transiently expressed in galectin-3−/− sarcoma cells, it inhibited cell adhesion and stimulated the migratory response to laminin in a carbohydrate-dependent manner. Extracellular galectin-3 led to the recruitment of SHP-2 phosphatase to focal adhesion plaques, followed by a decrease in the amount of phosphorylated FAK and phospho-paxillin in the lamellipodia of migrating cells. The promigratory activity of extracellular galectin-3 was inhibitable by wortmannin, implicating the activation of a PI-3 kinase dependent pathway in the galectin-3 triggered disruption of adhesion plaques, leading to sarcoma cell migration on laminin-111

UNCOVER: A NIRSpec Identification of a Broad-line AGN at z = 8.50

Deep observations with the James Webb Space Telescope (JWST) have revealed an emerging population of red pointlike sources that could provide a link between the postulated supermassive black hole seeds and observed quasars. In this work, we present a JWST/NIRSpec spectrum from the JWST Cycle 1 UNCOVER Treasury survey of a massive accreting black hole at z = 8.50 displaying a clear broad-line component as inferred from the Hβ line with FWHM = 3439 ± 413 km s−1, typical of the broad-line region of an active galactic nucleus (AGN). The AGN nature of this object is further supported by high ionization, as inferred from emission lines, and a point-source morphology. We compute a black hole mass of log 10 ( M BH / M ⊙ ) = 8.17 ± 0.42 and a bolometric luminosity of L bol ∼ 6.6 × 1045 erg s−1. These values imply that our object is accreting at ∼40% of the Eddington limit. Detailed modeling of the spectral energy distribution in the optical and near-infrared, together with constraints from ALMA, indicate an upper limit on the stellar mass of log 10 ( M * / M ⊙ ) < 8.7 , which would lead to an unprecedented ratio of black hole to host mass of at least ∼30%. This is orders of magnitude higher compared to the local QSOs but consistent with recent AGN studies at high redshift with JWST. This finding suggests that a nonnegligible fraction of supermassive black holes either started out from massive seeds and/or grew at a super-Eddington rate at high redshift. Given the predicted number densities of high-z faint AGN, future NIRSpec observations of larger samples will allow us to further investigate galaxy-black hole coevolution in the early Universe

Galectin-3 alters the lateral mobility and clustering of beta 1-integrin receptors

Glycoprotein receptors are influenced by myriad intermolecular interactions at the cell surface. Specific glycan structures may interact with endogenous lectins that enforce or disrupt receptor-receptor interactions. Glycoproteins bound by multivalent lectins may form extended oligomers or lattices, altering the lateral mobility of the receptor and influencing its function through endocytosis or changes in activation. In this study, we have examined the interaction of Galectin-3 (Gal-3), a human lectin, with adhesion receptors. We measured the effect of recombinant Gal-3 added exogenously on the lateral mobility of the alpha 5 beta 1 integrin on HeLa cells. Using single-particle tracking (SPT) we detected increased lateral mobility of the integrin in the presence of Gal-3, while its truncated C-terminal domain (Gal-3C) showed only minor reductions in lateral mobility. Treatment of cells with Gal-3 increased beta 1-integrin mediated migration with no apparent changes in viability. In contrast, Gal-3C decreased both cell migration and viability. Fluorescence microscopy allowed us to confirm that exogenous Gal-3 resulted in reorganization of the integrin into larger clusters. We used a proteomics analysis to confirm that cells expressed endogenous Gal-3, and found that addition of competitive oligosaccharide ligands for the lectin altered the lateral mobility of the integrin. Together, our results are consistent with a Gal-3-integrin lattice model of binding and confirm that the lateral mobility of integrins is natively regulated, in part, by galectins