Excessive lipid deposition is a hallmark of nonalcoholic fatty liver disease (NAFLD). Although much has been learned about the enzymes and metabolites involved in NAFLD, few studies have focused on the role of long non-coding RNAs (lncRNAs) in hepatic lipid accumulation. Here, using in vitro and in vivo models of NAFLD, we found that the lncRNA Gm15622 is highly expressed in the liver of obese mice fed a high-fat diet (HFD) and in murine liver (AML-12) cells treated with free fatty acids. Investigating the molecular mechanism in the liver-enriched expression of Gm15622 and its effects on lipid accumulation in hepatocytes and on NAFLD pathogenesis, we found that Gm15622 acts as a sponge for the microRNA miR-742-3p. This sponging activity increased the expression of the transcriptional regulator sterol regulatory element–binding transcription factor 1c (SREBP-1c) and promoted lipid accumulation in the liver of the HFD mice and AML-12 cells. Moreover, further results indicated that metformin suppresses Gm15622 and alleviates NAFLD-associated lipid deposition in mice. In conclusion, we have identified an lncRNA Gm15622–miR-742-3p–SREBP-1c regulatory circuit associated with NAFLD in mice, a finding that significantly advances our insight into how lipid metabolism and accumulation are altered in this metabolic disorder. Our results also suggest that Gm15622 may be a potential therapeutic target for managing NAFLD.

Contact between inflammatory cells and endothelial cells (ECs) is a crucial step in vascular inflammation. Recently, we demonstrated that the cell-surface level of endomucin (EMCN), a heavily O-glycosylated single-transmembrane sialomucin, interferes with the interactions between inflammatory cells and ECs. We have also shown that, in response to an inflammatory stimulus, EMCN is cleared from the cell surface by an unknown mechanism. In this study, using adenovirus-mediated overexpression of a tagged EMCN in human umbilical vein ECs, we found that treatment with tumor necrosis factor α (TNF-α) or the strong oxidant pervanadate leads to loss of cell-surface EMCN and increases the levels of the C-terminal fragment of EMCN 3- to 4-fold. Furthermore, treatment with the broad-spectrum matrix metalloproteinase inhibitor batimastat (BB94) or inhibition of ADAM metallopeptidase domain 10 (ADAM10) and ADAM17 with two small-molecule inhibitors, GW280264X and GI254023X, or with siRNA significantly reduced basal and TNFα-induced cell-surface EMCN cleavage. Release of the C-terminal fragment of EMCN by TNF-α treatment was blocked by chemical inhibition of ADAM10 alone or in combination with ADAM17. These results indicate that cell-surface EMCN undergoes constitutive cleavage and that TNF-α treatment dramatically increases this cleavage, which is mediated predominantly by ADAM10 and ADAM17. As endothelial cell-surface EMCN attenuates leukocyte–EC interactions during inflammation, we propose that EMCN is a potential therapeutic target to manage vascular inflammation.

Pediatric thrombocytopenia has a wide differential diagnosis, and recently, genetic testing to identify its etiology has become more common. We present a case of a 16-year-old boy with a history of chronic moderate thrombocytopenia, who later developed constitutional symptoms and bilateral hand edema with cold exposure. Laboratory evaluation revealed evidence both of inflammation and elevated muscle enzymes. These abnormalities persisted over months. His thrombocytopenia was determined to be immune mediated. Imaging revealed lymphadenopathy and asplenia, and a muscle biopsy was consistent with tubular aggregate myopathy. Ophthalmology evaluation noted photosensitivity, pupillary miosis, and iris hypoplasia. Genetic testing demonstrated a pathogenic variant in STIM1 consistent with autosomal dominant Stormorken syndrome. Our case is novel because of the overlap of phenotypes ascribed to both gain-of-function and loss-of-function pathogenic variants in STIM1, thereby blurring the distinctions between these previously described syndromes. Pediatricians should consider checking muscle enzymes when patients present with thrombocytopenia and arthralgia, myalgia, and/or muscle weakness. Our case highlights the importance of both multidisciplinary care and genetic testing in cases of chronic unexplained thrombocytopenia. By understanding the underlying genetic mechanism to a patient’s thrombocytopenia, providers are better equipped to make more precise medical management recommendations.

Three years after the launch of the M10, Leica is bringing a black-and-white Monochrom version to market, with an all-new 40MP imager and the classic M rangefinder design.

The Smart Tab M10 switches between a tablet and a smart display, while the Smart Frame looks to better display your photos with ambient sensors.

Elon Musk for his sheer audacity of dreaming unabashedly and then making those impossible dreams come true, says Ajit Andhare, COO, Viacom18 Studios.

In Delhi, the comparison made from the second week of March (before lockdown) to first week of April (April 6), reduction in PM2.5 was found to be by 62 per cent, PM10 by 57 per cent and NOx by 50 per cent,  the latest SAFAR data accessed by PTI showed.

In its report, the CPCB said, "Significant reduction in PM2.5, PM10 and NO2 levels observed. Overall, 46 per cent reduction in PM2.5 and 50 per cent reduction in PM10 concentration observed during the lockdown period."

The IC6.1.8 ISR10 and ICADVM18.1 ISR10 production releases are now available for download.(read more)

Cisco M1070 Content Security Management Appliance IronPort remote host header injection exploit.

DM160232 SWI Evaluation Kit GUI

PIC32CM1216MC00048

Objective

To describe the clinical and molecular genetic findings in a family segregating a novel mutation in the AIFM1 gene on the X chromosome.

Contact between inflammatory cells and endothelial cells (ECs) is a crucial step in vascular inflammation. Recently, we demonstrated that the cell-surface level of endomucin (EMCN), a heavily O-glycosylated single-transmembrane sialomucin, interferes with the interactions between inflammatory cells and ECs. We have also shown that, in response to an inflammatory stimulus, EMCN is cleared from the cell surface by an unknown mechanism. In this study, using adenovirus-mediated overexpression of a tagged EMCN in human umbilical vein ECs, we found that treatment with tumor necrosis factor α (TNF-α) or the strong oxidant pervanadate leads to loss of cell-surface EMCN and increases the levels of the C-terminal fragment of EMCN 3- to 4-fold. Furthermore, treatment with the broad-spectrum matrix metalloproteinase inhibitor batimastat (BB94) or inhibition of ADAM metallopeptidase domain 10 (ADAM10) and ADAM17 with two small-molecule inhibitors, GW280264X and GI254023X, or with siRNA significantly reduced basal and TNFα-induced cell-surface EMCN cleavage. Release of the C-terminal fragment of EMCN by TNF-α treatment was blocked by chemical inhibition of ADAM10 alone or in combination with ADAM17. These results indicate that cell-surface EMCN undergoes constitutive cleavage and that TNF-α treatment dramatically increases this cleavage, which is mediated predominantly by ADAM10 and ADAM17. As endothelial cell-surface EMCN attenuates leukocyte–EC interactions during inflammation, we propose that EMCN is a potential therapeutic target to manage vascular inflammation.

Liling Niu, Fuyun Wu, Kaili Li, Jing Li, Shenyuan L. Zhang, Junjie Hu, and Qian Wang

Store-operated Ca²⁺ entry (SOCE) is critical for numerous Ca²⁺-related processes. The activation of SOCE requires engagement between stromal interaction molecule 1 (STIM1) molecules on the endoplasmic reticulum and Ca²⁺ release-activated channel (CRAC) Orai on the plasma membrane. However, the molecular details of their interactions remain elusive. Here, we analyzed STIM1-Orai interactions using synthetic peptides derived from the N- and C-termini of Orai channels (Orai-NT and Orai-CT, respectively) and purified fragments of STIM1. The binding of STIM1 to Orai-NT is hydrophilic based, whereas binding to the Orai-CT is mostly hydrophobic. STIM1 decreases its affinity for Orai-CT when Orai-NT is present, supporting a stepwise interaction. Orai3-CT exhibits stronger binding to STIM1 than Orai1-CT, largely due to the shortness of one helical turn. The role of newly identified residues was confirmed by co-immunoprecipitation and Ca²⁺ imaging using full-length molecules. Our results provide important insight into CRAC gating by STIM1.

ABSTRACT

Aspergillus flavus, a ubiquitous and saprophytic fungus, is the second most common cause of aspergillosis worldwide. Several mechanisms contribute to the establishment of the fungal infection. Extracellular vesicles (EVs) have been described as "virulence factor delivery bags" in several fungal species, demonstrating a crucial role during the infection. In this study, we evaluated production of A. flavus EVs and their immunomodulatory functions. We verified that A. flavus EVs induce macrophages to produce inflammatory mediators, such as nitric oxide, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-1β. Furthermore, the A. flavus EVs enhance phagocytosis and killing by macrophages and induce M1 macrophage polarization in vitro. In addition, a prior inoculation of A. flavus EVs in Galleria mellonella larvae resulted in a protective effect against the fungal infection. Our findings suggest that A. flavus EVs are biologically active and affect the interaction between A. flavus and host immune cells, priming the innate immune system to eliminate the fungal infection. Collectively, our results suggest that A. flavus EVs play a crucial role in aspergillosis.

IMPORTANCE Immunocompromised patients are susceptible to several fungal infections. The genus Aspergillus can cause increased morbidity and mortality. Developing new therapies is essential to understand the fungal biology mechanisms. Fungal EVs carry important virulence factors, thus playing pivotal roles in fungal pathophysiology. No study to date has reported EV production by Aspergillus flavus, a fungus considered to be the second most common cause of aspergillosis and relevant food contaminator found worldwide. In this study, we produced A. flavus EVs and evaluated the in vitro immunomodulatory effects of EVs on bone marrow-derived macrophages (BMDMs) and in vivo effects in a Galleria mellonella model.

Follow our live updates here Coronavirus: the symptoms

Government advice continues to state that only journeys which are absolutely essential should be undertaken, and anyone travelling in the area should expect disruption and a longer journey time, with the road expected to remain closed for some time.

MORNING BRIEFING: Commuters and HSC students have been advised to avoid the M1 at Berowra after a road worker was hit by a utility early this morning, causing lane closures, and a man dies in a blaze at a Maitland home.

MORNING BRIEFING: Eastern suburb residents are particularly at risk after smoke haze blankets Sydney, and a north-bound lane on M1 remains closed after four trucks caught fire after a collision

Washington DC (UPI) Apr 29, 2020
FN America and Colt's Manufacturing received a $383.3 million, five-year contract to manufacture M16A4 rifles for Afghanistan, Grenada, Iraq, Lebanon and Nepal through the Pentagon's foreign military sales program. The M16A4 is the fourth generation of the M16 series of military rifles. The Marine Corps began phasing out the M16 in favor of the M4 carbine in 2015. In 2008 the Sta

Money Supply M1 in Burundi increased to 1382397 BIF Million in June from 1339556.70 BIF Million in May of 2019. Money Supply M1 in Burundi averaged 617768.37 BIF Million from 2008 until 2019, reaching an all time high of 1382397 BIF Million in June of 2019 and a record low of 236399.10 BIF Million in January of 2008. This page provides - Burundi Money Supply M1- actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in Brunei increased to 4578.39 BND Million in October from 4447.11 BND Million in September of 2019. Money Supply M1 in Brunei averaged 4430.94 BND Million from 2011 until 2019, reaching an all time high of 5758 BND Million in January of 2012 and a record low of 3323 BND Million in July of 2011. This page provides - Brunei Money Supply M1- actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in Cyprus increased to 4429 EUR Thousand in December from 4209 EUR Thousand in November of 2007. Money Supply M1 in Cyprus averaged 1780.44 EUR Thousand from 1993 until 2007, reaching an all time high of 4429 EUR Thousand in December of 2007 and a record low of 792 EUR Thousand in February of 1993. This page provides - Cyprus Money Supply M1 - actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in Maldives decreased to 14557.80 MVR Million in December from 14777.60 MVR Million in November of 2019. Money Supply M1 in Maldives averaged 8997.14 MVR Million from 2004 until 2019, reaching an all time high of 15312.50 MVR Million in May of 2018 and a record low of 2347.60 MVR Million in October of 2004. This page provides - Maldives Money Supply M1- actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in Argentina increased to 1942902.30 ARS Million in December from 1686438 ARS Million in November of 2019. Money Supply M1 in Argentina averaged 251460.85 ARS Million from 1990 until 2019, reaching an all time high of 1942902.30 ARS Million in December of 2019 and a record low of 440.30 ARS Million in January of 1990. This page provides - Argentina Money Supply M1 - actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in Macedonia increased to 175684.63 MKD Million in December from 159560 MKD Million in November of 2019. Money Supply M1 in Macedonia averaged 69439.09 MKD Million from 2003 until 2019, reaching an all time high of 175684.63 MKD Million in December of 2019 and a record low of 23381.70 MKD Million in March of 2003. This page provides - Macedonia Money Supply M1- actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in China increased to 57510 CNY Billion in March from 55270 CNY Billion in February of 2020. Money Supply M1 in China averaged 11605.21 CNY Billion from 1978 until 2020, reaching an all time high of 57600.92 CNY Billion in December of 2019 and a record low of 74.51 CNY Billion in June of 1978. This page provides - China Money Supply M1 - actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in South Korea increased to 973571.40 KRW Billion in February from 939624.90 KRW Billion in January of 2020. Money Supply M1 in South Korea averaged 206861.94 KRW Billion from 1970 until 2020, reaching an all time high of 973571.40 KRW Billion in February of 2020 and a record low of 260.40 KRW Billion in January of 1970. This page provides - South Korea Money Supply M1 - actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in Brazil increased to 419431.85 BRL Million in March from 401833.81 BRL Million in February of 2020. Money Supply M1 in Brazil averaged 121190.66 BRL Million from 1980 until 2020, reaching an all time high of 434632.72 BRL Million in December of 2019 and a record low of 0 BRL Million in February of 1980. This page provides - Brazil Money Supply M1 - actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in Italy increased to 1277319 EUR Million in February from 1257326 EUR Million in January of 2020. Money Supply M1 in Italy averaged 471571.56 EUR Million from 1980 until 2020, reaching an all time high of 1282775 EUR Million in November of 2019 and a record low of 65564 EUR Million in February of 1980. This page provides - Italy Money Supply M1 - actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in Indonesia increased to 1505490.50 IDR Billion in February from 1484402.60 IDR Billion in January of 2020. Money Supply M1 in Indonesia averaged 282145.38 IDR Billion from 1972 until 2020, reaching an all time high of 1565327.50 IDR Billion in December of 2019 and a record low of 317.90 IDR Billion in January of 1972. This page provides - Indonesia Money Supply M1 - actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in Gambia decreased to 23819.60 GMD Million in February from 24091.70 GMD Million in January of 2020. Money Supply M1 in Gambia averaged 5315.70 GMD Million from 1992 until 2020, reaching an all time high of 24195.90 GMD Million in December of 2019 and a record low of 366.16 GMD Million in August of 1994. This page provides - Gambia Money Supply M1- actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in Japan increased to 830310.10 JPY Billion in March from 819689 JPY Billion in February of 2020. Money Supply M1 in Japan averaged 236259.57 JPY Billion from 1960 until 2020, reaching an all time high of 830310.10 JPY Billion in March of 2020 and a record low of 3921 JPY Billion in February of 1960. This page provides - Japan Money Supply M1 - actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in the United States increased to 4267.60 USD Billion in March from 4019.30 USD Billion in February of 2020. Money Supply M1 in the United States averaged 1041.76 USD Billion from 1959 until 2020, reaching an all time high of 4267.60 USD Billion in March of 2020 and a record low of 138.90 USD Billion in January of 1959. This page provides - United States Money Supply M1 - actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in Malawi decreased to 609603.10 MWK Million in February from 615700 MWK Million in January of 2020. Money Supply M1 in Malawi averaged 78849.04 MWK Million from 1975 until 2020, reaching an all time high of 628800 MWK Million in December of 2019 and a record low of 56.40 MWK Million in February of 1976. This page provides - Malawi Money Supply M1- actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in Rwanda decreased to 1146.10 RWF Billion in January from 1147.50 RWF Billion in December of 2019. Money Supply M1 in Rwanda averaged 442.40 RWF Billion from 2003 until 2020, reaching an all time high of 1147.50 RWF Billion in December of 2019 and a record low of 79.50 RWF Billion in January of 2003. This page provides - Rwanda Money Supply M1- actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in Botswana increased to 19688.87 BWP Million in November from 19167.64 BWP Million in October of 2019. Money Supply M1 in Botswana averaged 12525.02 BWP Million from 2008 until 2019, reaching an all time high of 19688.87 BWP Million in November of 2019 and a record low of 6522.55 BWP Million in October of 2009. This page provides - Botswana Money Supply M1 - actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in Switzerland increased to 691015 CHF Million in March from 674223 CHF Million in February of 2020. Money Supply M1 in Switzerland averaged 296339.57 CHF Million from 1984 until 2020, reaching an all time high of 691015 CHF Million in March of 2020 and a record low of 89321 CHF Million in August of 1985. This page provides - Switzerland Money Supply M1 - actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in Poland increased to 1224779.80 PLN Million in March from 1152635.43 PLN Million in February of 2020. Money Supply M1 in Poland averaged 396912.14 PLN Million from 1996 until 2020, reaching an all time high of 1224779.80 PLN Million in March of 2020 and a record low of 63625.70 PLN Million in February of 1997. This page provides - Poland Money Supply M1 - actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in Portugal decreased to 145735.80 EUR Million in February from 145901.50 EUR Million in January of 2020. Money Supply M1 in Portugal averaged 72599.48 EUR Million from 1997 until 2020, reaching an all time high of 145901.50 EUR Million in January of 2020 and a record low of 29718 EUR Million in October of 1997. This page provides - Portugal Money Supply M1 - actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in Namibia increased to 58403.90 NAD Million in January from 56966.10 NAD Million in December of 2019. Money Supply M1 in Namibia averaged 19140.82 NAD Million from 1993 until 2020, reaching an all time high of 58403.90 NAD Million in January of 2020 and a record low of 1181.60 NAD Million in January of 1994. This page provides - Namibia Money Supply M1 - actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in Israel decreased to 431512 ILS Million in February from 434271 ILS Million in January of 2020. Money Supply M1 in Israel averaged 78298.42 ILS Million from 1981 until 2020, reaching an all time high of 434271 ILS Million in January of 2020 and a record low of 8 ILS Million in April of 1981. This page provides - Israel Money Supply M1 - actual values, historical data, forecast, chart, statistics, economic calendar and news.

Money Supply M1 in Germany increased to 2444 EUR Billion in March from 2348.20 EUR Billion in February of 2020. Money Supply M1 in Germany averaged 628.71 EUR Billion from 1973 until 2020, reaching an all time high of 2444 EUR Billion in March of 2020 and a record low of 65.40 EUR Billion in January of 1973. This page provides the latest reported value for - Germany Money Supply M1 - plus previous releases, historical high and low, short-term forecast and long-term prediction, economic calendar, survey consensus and news.