Harpist Yolanda Kondonassis’ newest album “dreams, soars and levitates” through an intricately flowing compositional architecture with the inclusion of a newly commissioned harp concerto by Pulitzer Prize-winning composer Jennifer Higdon . “The idea was the interplay and the precociousness, and the childlike wonder,” Kondonassis elaborates on how Higdon encompassed her emotions in the composition. “She really impressed upon us that this is fluid and full of wonder, rather than the somnambulant kind of experience.” Kondonassis’ album “American Rapture” expands upon how North American compositions have developed through three generations and features the Rochester Philharmonic Orchestra, directed by Ward Stare. Listen to the full interview between Kondonassis, Stare and Of Note’s Katy Henriksen with the streaming link above.

The possibilities of artistic expression are limitless with every piece of music, but composer and pianist Craig Swanson took it to another level with the release of his album “The French Suite Kit.” Swanson was inspired by pianist Glenn Gould to create multiple unique variations of Bach’s French Suite No. 4 in Eb Major , giving listeners more control over how they prefer to hear Bach expressed. “Part of the joy of music is its improvisatory nature, and trying to find all of the potential expressions that are worthwhile in your music,” Swanson says. “It seemed to me that there was a wealth of possibility not limiting yourself to one particular way or one particular approach.” Listen to the full interview between Swanson and Of Note’s Katy Henriksen with the streaming link above.

DJ techno/trance mixes - good. Swiss train driver pov videos - good. Swiss train driver pov videos set to techno mixes - double plus good! From Thomas H.

This is too good to leave on the cutting room floor. Dr. Art Markman explains new research on how dogs read human facial expressions and what it could tell us about how they think.

Shares of American Express Co. (AXP) are declining almost 3 percent or $2.50 in Monday's morning trade at $5.82 despite no stock-specific news. The stock has traded in a range of $67.00 to $138.13 in the past 52 weeks.

One of the original uses of networking tech were attempts at racial profiling and predictive policing, author Charlton McIlwain says.

In a new doc, the Canadian actress takes a searing look at injustices in her home province.

Indigenous dancers from three states gather on the banks of the Darling River to honour a waterway that's underpinned their cultures for millennia.

Regional Express Airlines has warned the folding of its services to some regional and remote communities could effectively shut residents off from the rest of Australia, as the company waits hopefully for vital federal government funding.

WA Liberal MPs distance themselves from their new leader's policy direction, including contentious moves to abandon the Western Power sale and steer away from supporting deregulated trading hours, after strong criticism from the business lobby.

Regional Express Airlines says a video of what is claimed to be a rusty propeller shaft on one of its planes does not actually show corrosion, with CASA saying it had "no current issues" with the safety of Rex aircraft.

IBM Business Partners can put the power of advertising behind their sales efforts. Take advantage of the 1Q Express Advantage advertising campaign now airing in select U.S. cities. Includes print, radio, Web banners, demand generation, mobile and search.

(United States Fifth Circuit) - Held that the First Amendment's commercial speech protections entitled a company to operate automotive service centers under the name "Tire Engineers," even though a state board that licenses engineers objected to the use of the profession's occupational title. Reversed and rendered summary judgment in favor of the company, in this declaratory judgment action.

(United States Fifth Circuit) - Vacated and remanded. A $2.8 million verdict in a car accident and injury case was vacated because there was no evidence to support an award for future mental anguish or future pain and suffering.

(United States Supreme Court) - The US Supreme Court held that American Express (Amex) anti-steering provisions, in its agreement with merchants to prohibit merchants who take Amex cards from discouraging customers from using their cards in order for the merchant to avoid paying Amex a fee, do not violate the Sherman Antitrust Act.

(United States Second Circuit) - Held that a bunker (marine fuel) supplier was potentially entitled to assert a maritime lien against certain vessels to which it had physically provided marine fuel for which it was not paid, under an exception to the usual subcontractor rule. The exception allows maritime liens to be asserted by subcontractors whose selection was controlled or directed by a vessel's owner/charterer. Vacated and remanded on this issue.

(California Court of Appeal) - Held that the trial court erred in denying class certification to truck drivers bringing wage and hour claims against their employer. Reversed and remanded for further proceedings, explaining that errors were made in analyzing whether predominantly common issues existed.

(United States Supreme Court) - The US Supreme Court held that American Express (Amex) anti-steering provisions, in its agreement with merchants to prohibit merchants who take Amex cards from discouraging customers from using their cards in order for the merchant to avoid paying Amex a fee, do not violate the Sherman Antitrust Act.

The stars of the 2019 BET Awards jam to "Black Is Love."

The rapper was seen acting bizarre in a series of videos.

The stars of the 2019 BET Awards jam to "Black Is Love."

Although CEACAM1 (CC1) glycoprotein resides at the interface of immune liver injury and metabolic homeostasis, its role in orthotopic liver transplantation (OLT) remains elusive. We aimed to determine whether/how CEACAM1 signaling may affect hepatic ischemia-reperfusion injury (IRI) and OLT outcomes. In the mouse, donor liver CC1 null mutation augmented IRI-OLT (CC1-KO→WT) by enhancing ROS expression and HMGB1 translocation during cold storage, data supported by in vitro studies where hepatic flush from CC1-deficient livers enhanced macrophage activation in bone marrow–derived macrophage cultures. Although hepatic CC1 deficiency augmented cold stress–triggered ASK1/p-p38 upregulation, adjunctive ASK1 inhibition alleviated IRI and improved OLT survival by suppressing p-p38 upregulation, ROS induction, and HMGB1 translocation (CC1-KO→WT), whereas ASK1 silencing (siRNA) promoted cytoprotection in cold-stressed and damage-prone CC1-deficient hepatocyte cultures. Consistent with mouse data, CEACAM1 expression in 60 human donor liver biopsies correlated negatively with activation of the ASK1/p-p38 axis, whereas low CC1 levels associated with increased ROS and HMGB1 translocation, enhanced innate and adaptive immune responses, and inferior early OLT function. Notably, reduced donor liver CEACAM1 expression was identified as one of the independent predictors for early allograft dysfunction (EAD) in human OLT patients. Thus, as a checkpoint regulator of IR stress and sterile inflammation, CEACAM1 may be considered as a denominator of donor hepatic tissue quality, and a target for therapeutic modulation in OLT recipients.

The mechanisms by which prostate cancer shifts from an indolent castration-sensitive phenotype to lethal castration-resistant prostate cancer (CRPC) are poorly understood. Identification of clinically relevant genetic alterations leading to CRPC may reveal potential vulnerabilities for cancer therapy. Here we find that CUB domain-containing protein 1 (CDCP1), a transmembrane protein that acts as a substrate for SRC family kinases (SFKs), is overexpressed in a subset of CRPC. Notably, CDCP1 cooperates with the loss of the tumor suppressor gene PTEN to promote the emergence of metastatic prostate cancer. Mechanistically, we find that androgens suppress CDCP1 expression and that androgen deprivation in combination with loss of PTEN promotes the upregulation of CDCP1 and the subsequent activation of the SRC/MAPK pathway. Moreover, we demonstrate that anti-CDCP1 immunoliposomes (anti–CDCP1 ILs) loaded with chemotherapy suppress prostate cancer growth when administered in combination with enzalutamide. Thus, our study identifies CDCP1 as a powerful driver of prostate cancer progression and uncovers different potential therapeutic strategies for the treatment of metastatic prostate tumors.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by loss of repression of the DUX4 gene; however, the DUX4 protein is rare and difficult to detect in human muscle biopsies, and pathological mechanisms are obscure. FSHD is also a chronic disease that progresses slowly over decades. We used the sporadic, low-level, muscle-specific expression of DUX4 enabled by the iDUX4pA-HSA mouse to develop a chronic long-term muscle disease model. After 6 months of extremely low sporadic DUX4 expression, dystrophic muscle presented hallmarks of FSHD histopathology, including muscle degeneration, capillary loss, fibrosis, and atrophy. We investigated the transcriptional profile of whole muscle as well as endothelial cells and fibroadiopogenic progenitors (FAPs). Strikingly, differential gene expression profiles of both whole muscle and, to a lesser extent, FAPs, showed significant overlap with transcriptional profiles of MRI-guided human FSHD muscle biopsies. These results demonstrate a pathophysiological similarity between disease in muscles of iDUX4pA-HSA mice and humans with FSHD, solidifying the value of chronic rare DUX4 expression in mice for modeling pathological mechanisms in FSHD and highlighting the importance FAPs in this disease.

ICMR teams up with Bharat Biotech to develop COVID-19 vaccine  The Financial ExpressView Full coverage on Google News

An attractive rewards credit card for frequent Delta flyers. While some American Express rewards cards offer great perks, like complimentary access to its exclusive network of airport lounges, you won’t get that perk with the (lounge access costs $39 per visit). However, you will get attractive rewards rates on several types of travel-related purchases along with other valuable travel benefits. This card offers you the highest reward rate when you make purchases with Delta or spend on hotel bookings, which […]

The post Delta SkyMiles® Platinum American Express Card Review appeared first on The Simple Dollar.

A top-shelf rewards credit card with luxury travel perks. The gives you access to coveted airport lounges, which is a unique benefit that will be highly attractive to some. Only a few American Express rewards cards will get you into the 10 Centurion Lounges around the world. Additionally, the card offers a number of other travel benefits, including access to Delta Sky Clubs and a free checked bag on Delta flights. Like any credit card, it does come with some […]

The post Delta SkyMiles® Reserve American Express Card Review appeared first on The Simple Dollar.

Total debts at nearly AUD7 billion

Microsoft's free web editor is a sophisticated WYSIWYG web editor with many features usually only found in commercial offerings (and no wonder, since it was previously something you had to buy). This tutorial series takes you through the process of designing a fully functional multi-page website with Expression Web.

Find out how you can insert a video into your web page with the free Microsoft Expression Web editor. The video, in this case, will be placed on your website itself (ie, self-hosted) and not on a video sharing site.

McDonald’s knows exactly where its beef is. The fast food chain’s CEO on Thursday expressed full confidence in the burger joint’s meat supply.

Brooklyn Borough President Eric Adams called Saturday for all New York supermarkets to offer express lane treatment for those heroic New Yorkers on the front lines of the coronavirus pandemic.

Angels pitcher Andrew Heaney struggled against the Houston Astros in 2018, and he's irate not only at the sign stealing but because players haven't apologized.

McDonald’s knows exactly where its beef is. The fast food chain’s CEO on Thursday expressed full confidence in the burger joint’s meat supply.

One man wore plastic gloves and a face mask as he pulled up in a pickup to receive school-packed meals for his children.

Several University of California regents expressed deep skepticism about the use of SAT and ACT tests in admissions decisions, signaling the standardized tests may be headed for elimination as an application requirement.

ON MAY 7, 1945, General Alfred Jodl, the commander of German forces in western Europe, walked into a technical college in the city of Reims which served as General Eisenhower's HQ in France.

Known as “My Special Aflac Duck,” the robot is merging play with tools that help doctors do their jobs.

Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.

Prostate cancer (PCa) cells heavily rely on an active androgen receptor (AR) pathway for their survival. Enzalutamide (MDV3100) is a second-generation antiandrogenic drug that was approved by the Food and Drug Administration in 2012 to treat patients with castration-resistant prostate cancer (CRPC). However, emergence of resistance against this drug is inevitable, and it has been a major challenge to develop interventions that help manage enzalutamide-resistant CRPC. Erythropoietin-producing human hepatocellular (Eph) receptors are targeted by ephrin protein ligands and have a broad range of functions. Increasing evidence indicates that this signaling pathway plays an important role in tumorigenesis. Overexpression of EPH receptor B4 (EPHB4) has been observed in multiple types of cancer, being closely associated with proliferation, invasion, and metastasis of tumors. Here, using RNA-Seq analyses of clinical and preclinical samples, along with several biochemical and molecular methods, we report that enzalutamide-resistant PCa requires an active EPHB4 pathway that supports drug resistance of this tumor type. Using a small kinase inhibitor and RNAi-based gene silencing to disrupt EPHB4 activity, we found that these disruptions re-sensitize enzalutamide-resistant PCa to the drug both in vitro and in vivo. Mechanistically, we found that EPHB4 stimulates the AR by inducing proto-oncogene c-Myc (c-Myc) expression. Taken together, these results provide critical insight into the mechanism of enzalutamide resistance in PCa, potentially offering a therapeutic avenue for enhancing the efficacy of enzalutamide to better manage this common malignancy.

pncRNA-D is an irradiation-induced 602-nt long noncoding RNA transcribed from the promoter region of the cyclin D1 (CCND1) gene. CCND1 expression is predicted to be inhibited through an interplay between pncRNA-D and RNA-binding protein TLS/FUS. Because the pncRNA-D–TLS interaction is essential for pncRNA-D–stimulated CCND1 inhibition, here we studied the possible role of RNA modification in this interaction in HeLa cells. We found that osmotic stress induces pncRNA-D by recruiting RNA polymerase II to its promoter. pncRNA-D was highly m6A-methylated in control cells, but osmotic stress reduced the methylation and also arginine methylation of TLS in the nucleus. Knockdown of the m6A modification enzyme methyltransferase-like 3 (METTL3) prolonged the half-life of pncRNA-D, and among the known m6A recognition proteins, YTH domain-containing 1 (YTHDC1) was responsible for binding m6A of pncRNA-D. Knockdown of METTL3 or YTHDC1 also enhanced the interaction of pncRNA-D with TLS, and results from RNA pulldown assays implicated YTHDC1 in the inhibitory effect on the TLS–pncRNA-D interaction. CRISPR/Cas9-mediated deletion of candidate m6A site decreased the m6A level in pncRNA-D and altered its interaction with the RNA-binding proteins. Of note, a reduction in the m6A modification arrested the cell cycle at the G0/G1 phase, and pncRNA-D knockdown partially reversed this arrest. Moreover, pncRNA-D induction in HeLa cells significantly suppressed cell growth. Collectively, these findings suggest that m6A modification of the long noncoding RNA pncRNA-D plays a role in the regulation of CCND1 gene expression and cell cycle progression.

The arrangement of functionally-related genes in operons is a fundamental element of how genetic information is organized in prokaryotes. This organization ensures coordinated gene expression by co-transcription. Often, however, alternative genetic responses to specific stress conditions demand the discoordination of operon expression. During cold temperature stress, accumulation of the gene encoding the sole Asp–Glu–Ala–Asp (DEAD)-box RNA helicase in Synechocystis sp. PCC 6803, crhR (slr0083), increases 15-fold. Here, we show that crhR is expressed from a dicistronic operon with the methylthiotransferase rimO/miaB (slr0082) gene, followed by rapid processing of the operon transcript into two monocistronic mRNAs. This cleavage event is required for and results in destabilization of the rimO transcript. Results from secondary structure modeling and analysis of RNase E cleavage of the rimO–crhR transcript in vitro suggested that CrhR plays a role in enhancing the rate of the processing in an auto-regulatory manner. Moreover, two putative small RNAs are generated from additional processing, degradation, or both of the rimO transcript. These results suggest a role for the bacterial RNA helicase CrhR in RNase E-dependent mRNA processing in Synechocystis and expand the known range of organisms possessing small RNAs derived from processing of mRNA transcripts.

Tamar Geiger
Mar 1, 2012; 11:M111.014050-M111.014050
Special Issue: Prospects in Space and Time

Timothy J. Griffin
Apr 1, 2002; 1:323-333
Research