Endorepellin, the C-terminal fragment of the heparan sulfate proteoglycan perlecan, influences various signaling pathways in endothelial cells by binding to VEGFR2. In this study, we discovered that soluble endorepellin activates the canonical stress signaling pathway consisting of PERK, eIF2α, ATF4, and GADD45α. Specifically, endorepellin evoked transient activation of VEGFR2, which, in turn, phosphorylated PERK at Thr980. Subsequently, PERK phosphorylated eIF2α at Ser51, upregulating its downstream effector proteins ATF4 and GADD45α. RNAi-mediated knockdown of PERK or eIF2α abrogated the endorepellin-mediated up-regulation of GADD45α, the ultimate effector protein of this stress signaling cascade. To functionally validate these findings, we utilized an ex vivo model of angiogenesis. Exposure of the aortic rings embedded in 3D fibrillar collagen to recombinant endorepellin for 2–4 h activated PERK and induced GADD45α vis à vis vehicle-treated counterparts. Similar effects were obtained with the established cellular stress inducer tunicamycin. Notably, chronic exposure of aortic rings to endorepellin for 7–9 days markedly suppressed vessel sprouting, an angiostatic effect that was rescued by blocking PERK kinase activity. Our findings unravel a mechanism by which an extracellular matrix protein evokes stress signaling in endothelial cells, which leads to angiostasis.

State-of-the-art electron microscopy reveals the large-scale organization of the proteins that regulate neurotransmitter release

This spectacular image – which took the best part of a year to create – shows the fine structure of a nerve terminal at high resolution, revealing, for the very first time, an intricate network of fine filaments that controls the movements of synaptic vesicles.

The brain is soft and wet, with the consistency of a lump of jelly. Yet, it is the most complex and highly organized structure that we know of, containing hundreds of billions of neurons and glial cells, and something on the order of one quadrillion synaptic connections, all of which are arranged in a very specific manner.

Related: 3D model of a nerve terminal in atomic detail | Mo Costandi

Related: Blowing up the brain to reveal its finer details

The decrease in WiFi usage can also be attributed to people staying at homes.

Airtel emerged on the top in terms of latency experience with an average response time of 54.1 milliseconds, followed by Jio at 56.3 ms.

Business leaders have an important decision to make this year: to continue operating under the status quo or to join the list of successful companies creating a more sustainable future by contracting or investing in renewable energy and making a positive impact on their brand, customers, employees and bottom line.

Master signal integrity and ensure data quality

China's central bank said on Sunday it will step up counter-cyclical adjustments to support the economy and make monetary policy more flexible to fend off financial risks.

"The persistence of the drought conditions, in the Colorado River basin especially, is essentially unprecedented in human history," John Fleck, author of "Water is for Fighting Over," said.

The outlook for the global steel market has become more uncertain, according to industry and government officials at the OECD’s Steel Committee meeting in Paris on 5-6 2011 . Policies to support open markets for raw materials are key, they said.

The role of international organisations (IOs) is critical in the development of rules and standards that can help advance the well-being of citizens in an increasingly globalised world.

This scoping document brings forward relevant in vitro and ex vivo thyroid assays to the attention of OECD member countries, and provide recommendations for their further development/use, and also, to identify aspects of the thyroid signalling pathway that are not covered and would require further attention

Due to the COVID-19 pandemic and nationwide lockdown, all film and television shoots in the country had come to a complete halt in March. However, according to the latest development, the Karnataka government has now granted permission for Kannada Television shows to

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Archives, Room Use Only - UG573.U78 1901

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Archives, Room Use Only - UG603.A76 1912

Archives, Room Use Only - TK5741.T74 1902

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Archives, Room Use Only - UG573.U56 1916

Elucidating the structural dynamics of small molecules and proteins in the liquid solution phase is essential to ensure a fundamental understanding of their reaction mechanisms. In this regard, time-resolved X-ray solution scattering (TRXSS), also known as time-resolved X-ray liquidography (TRXL), has been established as a powerful technique for obtaining the structural information of reaction intermediates and products in the liquid solution phase and is expected to be applied to a wider range of molecules in the future. A TRXL experiment is generally performed at the beamline of a synchrotron or an X-ray free-electron laser (XFEL) to provide intense and short X-ray pulses. Considering the limited opportunities to use these facilities, it is necessary to verify the plausibility of a target experiment prior to the actual experiment. For this purpose, a program has been developed, referred to as S-cube, which is short for a Solution Scattering Simulator. This code allows the routine estimation of the shape and signal-to-noise ratio (SNR) of TRXL data from known experimental parameters. Specifically, S-cube calculates the difference scattering curve and the associated quantum noise on the basis of the molecular structure of the target reactant and product, the target solvent, the energy of the pump laser pulse and the specifications of the beamline to be used. Employing a simplified form for the pair-distribution function required to calculate the solute–solvent cross term greatly increases the calculation speed as compared with a typical TRXL data analysis. Demonstrative applications of S-cube are presented, including the estimation of the expected TRXL data and SNR level for the future LCLS-II HE beamlines.

A mysterious X-ray signal has been found in a detailed study of galaxy clusters using NASA’s Chandra X-ray Observatory and ESA’s XMM-Newton. One intriguing possibility […]

The post Mysterious X-ray signal from space appeared first on Smithsonian Insider.

When it’s time for a meal of katydids, bats use their ears. When hunting and eating male katydids, different bat species locate their prey by […]

The post To hunt, bats listen for signals in prey mating calls appeared first on Smithsonian Insider.

When astronomers study protoplanetary disks of gas and dust that surround young stars, they sometimes spot a dark gap like the Cassini division in Saturn’s […]

The post Disk Gaps Don’t Always Signal Planets appeared first on Smithsonian Insider.

Scott J. Neal, Qingxiang Zhou, and Francesca Pignoni

The specification of organs, tissues and cell types results from cell fate restrictions enacted by nuclear transcription factors under the control of conserved signaling pathways. The progenitor epithelium of the Drosophila compound eye, the eye imaginal disc, is a premier model for the study of such processes. Early in development, apposing cells of the eye disc are established as either retinal progenitors or support cells of the peripodial epithelium (PE), in a process whose genetic and mechanistic determinants are poorly understood. We have identified Protein Phosphatase 2A (PP2A), and specifically a STRIPAK-PP2A complex that includes the scaffolding and substrate-specificity components Cka, Strip and SLMAP, as a critical player in the retina-PE fate choice. We show that these factors suppress ectopic retina formation in the presumptive PE and do so via the Hippo signaling axis. STRIPAK-PP2A negatively regulates Hpo kinase, and consequently its substrate Wts, to release the transcriptional co-activator Yki into the nucleus. Thus, a modular higher-order PP2A complex refines the activity of this general phosphatase to act in a precise specification of cell fate.

Olivia R. Grafinger, Genya Gorshtein, Tyler Stirling, Megan I. Brasher, and Marc G. Coppolino

Malignant cancer cells can invade extracellular matrix (ECM) through the formation of F-actin-rich subcellular structures termed invadopodia. ECM degradation at invadopodia is mediated by matrix metalloproteinases (MMPs), and recent findings indicate that membrane-anchored membrane type 1-matrix metalloproteinase (MT1-MMP) has a primary role in this process. Maintenance of an invasive phenotype is dependent on internalization of MT1-MMP from the plasma membrane and its recycling to sites of ECM remodeling. Internalization of MT1-MMP is dependent on its phosphorylation, and here we examine the role of β1 integrin-mediated signaling in this process. Activation of β1 integrin using the antibody P4G11 induced phosphorylation and internalization of MT1-MMP and resulted in increased cellular invasiveness and invadopodium formation in vitro. We also observed phosphorylation of Src and epidermal growth factor receptor (EGFR) and an increase in their association in response to β1 integrin activation, and determined that Src and EGFR promote phosphorylation of MT1-MMP on Thr⁵⁶⁷. These results suggest that MT1-MMP phosphorylation is regulated by a β1 integrin-Src-EGFR signaling pathway that promotes recycling of MT1-MMP to sites of invadopodia formation during cancer cell invasion.

Kristina Drizyte-Miller, Jing Chen, Hong Cao, Micah B. Schott, and Mark A. McNiven

Epithelial cells such as liver-resident hepatocytes rely heavily on the Rab family of small GTPases to perform membrane trafficking events that dictate cell physiology and metabolism. Not surprisingly, disruption of several Rabs can manifest in metabolic diseases or cancer. Rab32 is expressed in many secretory epithelial cells but its role in cellular metabolism is virtually unknown. In this study, we find that Rab32 associates with lysosomes and regulates proliferation and cell size of Hep3B hepatoma and HeLa cells. Specifically, we identify that Rab32 supports mTORC1 signaling under basal and amino acid stimulated conditions. Consistent with inhibited mTORC1, an increase in nuclear TFEB localization and lysosome biogenesis is also observed in Rab32-depleted cells. Finally, we find that Rab32 interacts with mTOR kinase and that loss of Rab32 reduces the association of mTOR and mTORC1 pathway proteins with lysosomes, suggesting that Rab32 regulates lysosomal mTOR trafficking. In summary, these findings suggest that Rab32 functions as a novel regulator of cellular metabolism through supporting mTORC1 signaling.

Thomas O'Loughlin, Antonina J. Kruppa, Andre L. R. Ribeiro, James R. Edgar, Abdulaziz Ghannam, Andrew M. Smith, and Folma Buss

Optineurin (OPTN) is a multifunctional protein involved in autophagy, secretion as well as NF-B and IRF3 signalling and OPTN mutations are associated with several human diseases. Here we show that, in response to viral RNA, OPTN translocates to foci in the perinuclear region, where it negatively regulates NF-B and IRF3 signalling pathways and downstream pro-inflammatory cytokine secretion. These OPTN foci consist of a tight cluster of small membrane vesicles, which are positive for ATG9A. Disease mutations linked to POAG cause aberrant foci formation in the absence of stimuli, which correlates with the ability of OPTN to inhibit signalling. Using proximity labelling proteomics, we identify the LUBAC complex, CYLD and TBK1 as part of the OPTN interactome and show that these proteins are recruited to this OPTN-positive perinuclear compartment. Our work uncovers a crucial role for OPTN in dampening NF-B and IRF3 signalling through the sequestration of LUBAC and other positive regulators in this viral RNA-induced compartment leading to altered pro-inflammatory cytokine secretion.

When the Signal Editor is saving data, the indicator that the save is occurring does not appear.  You might notice a delay when saving large data files.This bug exists in the following release(s):
R2020a

Interested in Upgrading?

Kristina Drizyte-Miller
Apr 15, 2020; 0:jcs.236661v1-jcs.236661
Articles

California Governor Gavin Newsom speaks to the press in the spin room after the sixth Democratic primary debate of the 2020 presidential campaign season co-hosted by PBS NewsHour & Politico at Loyola Marymount University in Los Angeles, California on December 19, 2019. ; Credit: AGUSTIN PAULLIER/AFP via Getty Images

After nearly two months of “safer at home” during the COVID-19 outbreak, the state of California appears to be taking its first steps towards reopening businesses and restarting the economy.

Governor Gavin Newsom announced on Monday during the daily press briefing he has held since the start of the outbreak that California will be entering the first phase of its four-stage plan and allowing certain retail businesses like bookstores, music stores, sporting goods stores and florists to reopen for pickup as early as Friday. Manufacturing and logistics can start in the retail supply chain again as well. There are also local control measures in effect that allow certain municipalities to decide themselves whether to move farther ahead in the process and reopen certain things like restaurant dining rooms, though anyone deciding to do so would have to submit “containment plans” to the state. Two cities in Orange County, which has been involved in a back-and-forth with Sacramento over his order last week closing all state and local beaches in OC, have been cleared to reopen their beaches after they submitted plans to the state last week for how they’d reopen the beaches while safely controlling crowds.

Guests:

Erika Ritchie, reporter for the Orange County Register covering South Orange County Coastal Communities; she tweets @lagunaini

Donald Wagner, Orange County Supervisor, 3rd District, which includes Anaheim Hills, Irvine, Orange, Tustin, and the unincorporated canyons; former Mayor of Irvine (2016-2019); tweets @DonWagnerCA 

Bob Whalen, mayor of Laguna Beach

Karen Farrer, mayor of the City of Malibu

Robert Garcia, mayor of Long Beach; he tweets @LongBeachMayor

This content is from Southern California Public Radio. View the original story at SCPR.org.

Today I decided to revisit a topic I covered a few years ago: loading discrete signals in a simulation.... read more >>

Zillow web traffic on for-sale listings and requests to connect with Premier Agents have ticked up recently after slowing in the early days of the U.S. coronavirus pandemic in mid-March