Karen Sepko is a seasoned entrepreneur specializing in real estate sales, hospitality management, and investment properties

Pradipta "PK" Kanjilal's achievements including overseeing a successful merger of two airlines

Is Known for Championing Accessible and Inclusive Learning

PakStyle.pk has been a go-to destination for fashion enthusiasts in Pakistan. With a wide range of dressing options, they cater to every occasion from bridal wear to formals and party wear dresses, and their latest collection 2024 is no exception.

Maria uses a half pumpkin to make a Fall door decoration!

It's not too late to decorate your porch for Halloween...this quick and easy Halloween pumpkin diorama will make a great weekend project!

Autumn Harvest Grown widely around the world on every continent except Antarctica, pumpkins or squash are reputed to have originated in North America. Seeds dating back to 7000 and 5500 BC have been found in Mexico. Technically speaking, pumpkins, or winter squash … Continue reading →

ASIA PKI Consortium signs MoU with ETSI

Sophia Antipolis, 2 December 2021

During the ETSI General Assembly, ASIA PKI and ETSI signed a Memorandum of Understanding (MoU) to structure and strengthen the relationship between both organizations and foster a closer relationship.

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PKI Consortium signs MoU with ETSI

Sophia Antipolis, 1 February 2022

On 26 January PKI Consortium and ETSI signed a Memorandum of Understanding (MoU) to structure and strengthen the relationship between both organizations and foster a closer relationship.

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Integrated proteomics reveals autophagy landscape and an autophagy receptor controlling PKA-RI complex homeostasis in neurons  Nature.com

The Army has awarded Repkon USA a contract worth up to $435 million to build a new TNT production facility in Graham, Kentucky, the service said on Friday. The contract […]

Joshua Davies discusses TLS, PKI vulnerabilities in the PKI, and the evolution of the PKI to make it more secure, with host Robert Blumen.

Press Packers Martha and Greta visit a farm to find out what happens to leftover crops.

WASHINGTON, D.C. – The National Association of Broadcasters (NAB) announced today that trade show veteran Karen Chupka will succeed Chris Brown as managing director and executive vice president, Global Connections and Events, effective January 1, 2024. Brown announced in July that he is transitioning out of NAB following the 2024 NAB Show, after 25 years of service to the organization.

In a personal interview with Dr. Linda Livingstone, Paul Hopkins, Chairman of the Board of Farmers Group, Inc. and Chairman of the Americas of Zurich Financial Services, talks about his career at Farmers and the business culture that has developed there.

Paul Hopkins, Chairman of the Board of Farmers Group, Inc. and Chairman of the Americas of Zurich Financial Services, presents on the values of leadership and ingredients for success. (Part 1 of 2)

Paul Hopkins, Chairman of the Board of Farmers Group, Inc. and Chairman of the Americas of Zurich Financial Services, sits down for an interview with Dr. Linda Livingstone, Dean of the Graziadio School of Business and Management. Paul also answers various questions from audience members. (Part 2 of 2)

"All things are possible..." Netflix has revealed an official trailer for a movie called Mary, yet another new take on the birth of Jesus story. This is ready for streaming in December already. Directed by DJ Caruso (Disturbia, Eagle Eye, I Am Number Four, Redeeming Love), Mary reveals a side of the icon we’ve never seen or even imagined before. Noa Cohen (from the series "Infinity", "8200") stars as Mary in this coming-of-age biblical epic tale in which Mary is shunned following a miraculous conception and forced into hiding. When King Herod ignites a murderous pursuit for her newborn baby Jesus, Mary and Joseph go on the run – bound by faith and driven by courage – to save his life at all costs. The ensemble cast includes Ido Tako, Stephanie Nur, Susan Brown, Ori Pfeffer, Eamon Farren, Hilla Vidor, Mili Avital, Gudmundur Thorvaldsson, Dudley O'Shaughnessy, and Keren Tzur, with Anthony Hopkins. So they made an action thriller about Mary? They must be really hoping to get more religious viewers tuning in. Look good? Here's the official trailer (+ two posters) for DJ Caruso's film Mary, direct from Netflix's YouTube: Through Mary's eyes, this coming-of-age biblical epic is the story […]

The FSU alum, who also won LIV Golf Singapore this year, picked up his fifth career victory since the Saudi-funded league began in June 2022.

The start of the PGA Tour’s postseason had tense moments at the top of the leaderboard and on the bubble to determine the top 50 players in the FedEx Cup who advanced.

XSTR-PKIS - Current and new challenges for public-key infrastructure standardization

Multipurpose Smart ID Card with PKI (Bio Digital Signature with Smart Card + e-ID + Credit Card)
Source: SG 17 Chairman
Study Questions: Q9/17

UPU-ITU mini workshop: Multipurpose Smart ID Card with PKI (Bio Digital Signature with Smart Card + e-ID + Credit Card)"
Source: TSB
Study Questions: Q9/17

China's Xiaomi had complained to the Competition Commission of India (CCI) that the report - which found Flipkart, some of its sellers, and smartphone players in violation of competition laws - contained commercial secrets that should have been redacted, Reuters reported in September.

The action is related to the financial transactions being done by some of the "preferred" vendors and sellers who do business through Amazon and Flipkart like e-commerce platforms.

E-commerce platform Flipkart's logistics arm reported a more than five times surge in its net losses to Rs 1,718.4 crore last fiscal (FY24), compared to Rs 324.6 crore in the previous fiscal (FY23).

The planned action signals growing regulatory scrutiny of Walmart-owned Flipkart and Amazon when their sales are rapidly growing in India's $70 billion e-commerce market. An antitrust investigation also found the two companies breached laws by favouring select sellers, Reuters has reported.

In August, Flipkart senior vice president of category and marketplace Amitesh Jha joined Swiggy as the chief executive of Instamart, while Dhruvish Thakkar, a senior director at Flipkart Epharma, moved to Swiggy the following month as assistant vice-president of Dineout – its dining out vertical.

The strategic adoption of EVs has resulted in substantial operational efficiencies, lowering the cost per order at the hub level and improving the last-mile delivery speed by 20 per cent, compared to conventional delivery vehicles, Flipkart said.

We may think about food all the time, but when is the last time you thought about what your food sounded like?

Today, we get an update on the 'Golden Gate 26'. Then, it's time again to celebrate all things pumpkin! And, a new musical shows how enslaved Black people sought freedom in Mexico.

Here are five especially delicious options for the week ahead and those to come.

Caleb Ingham and his La Salle men’s swimming and diving teammates hosted their second straight competition at Kirk Pool, this time competing against the Johns Hopkins Blue Jays. Ingham and his teammates fell by a score of 161 – 126. Ingham swam the anchor leg for the La Salle men’s 400 yard medley relay C […]

[Updated with video] Bermuda cyclists Kaden Hopkins and Conor White competed in the elite men’s time-trial at the UCI World Cycling Championships in Zurich, Switzerland, today [September 22]. Hopkins, who competes in the road race next weekend, finished 32nd and White 39th in a field of 59 riders. Belgium’s Remco Evenepoel won the race in […]

City Hall [US, Frederick Wiseman, 4] The latest of Wiseman’s distinctive epic-length observational documentaries studies the quotidian, procedural and human moments of human life as seen through the processes of municipal government in Boston, as held together by the thoughtful charisma of Mayor Martin Walsh. Improbably absorbing as always, this institutional cross-section offers a beguiling vision of an oasis of good government in the USA.

In a normal year I’d wait for the four and a half hour Wiseman documentary to arrive on television rather than taking up two time slots to watch it from the confines of a cinema seat at TIFF. But this is not such a year and with a digital screening you get a pause button when you need it. This is bound for PBS and due to the breadth of its subject matter will serve as an excellent introduction to those unfamiliar with this pillar of the documentary form. Or track down 2017’s Ex Libris, about the New York Public Library. In North America Wiseman’s filmography can be found on the Kanopy platform, which you may be able to access through your public library system.

The Father [UK, Florian Zeller, 4] Retired engineer (Anthony Hopkins) struggles to piece together the confusing reality of his living circumstances as his daughter (Olivia Colman) copes with his progressing dementia. Impeccably performed stage play adaptation puts the viewer inside the contradictory shifts of the protagonist’s subjective viewpoint.

Forget Draculas and Cthulhus. This is the real terror.

Summer of 85 [France, Francois Ozon, 4] Love between two young men in a French beach town leads to a bizarre crime. Teen emotions run high in a sunlit melodrama of Eros and Thanatos.

We've featured the work of Ray Villafane before here on WIN, but today we have another of the pumpkin sculptures that made him famous. This time, it's his largest piece ever, unveiled at the New York Botanical gardens this last weekend. The piece is made of several pumpkins, with different sections carved and then held together with rods and adhesive. Check for more in the gallery below!

ZombieGeisha says: "My guinea pig, Spooky, making a mess of his orange snack."

Now Spooky, who is going to take you seriously when you can't even bother to wipe your chin?

Do you have a squee pet that you want to share with the world? Send us your pet pictures and stories, and they could end up on Daily Squee!

Hot’s Bad Boy debuts Nov. 21, joined by Daum's Life is a Difficult Age, Crystal’s Before, and Armageddon Time on Netflix.

A selection of the week's best photos from across the African continent and beyond.

The human cardiovascular system has adapted to function optimally in Earth's 1G gravity, and microgravity conditions cause myocardial abnormalities, including atrophy and dysfunction. However, the underlying mechanisms linking microgravity and cardiac anomalies are incompletely understood. In this study, we investigated whether and how calpain activation promotes myocardial abnormalities under simulated microgravity conditions. Simulated microgravity was induced by tail suspension in mice with cardiomyocyte-specific deletion of Capns1, which disrupts activity and stability of calpain-1 and calpain-2, and their WT littermates. Tail suspension time-dependently reduced cardiomyocyte size, heart weight, and myocardial function in WT mice, and these changes were accompanied by calpain activation, NADPH oxidase activation, and oxidative stress in heart tissues. The effects of tail suspension were attenuated by deletion of Capns1. Notably, the protective effects of Capns1 deletion were associated with the prevention of phosphorylation of Ser-345 on p47phox and attenuation of ERK1/2 and p38 activation in hearts of tail-suspended mice. Using a rotary cell culture system, we simulated microgravity in cultured neonatal mouse cardiomyocytes and observed decreased total protein/DNA ratio and induced calpain activation, phosphorylation of Ser-345 on p47phox, and activation of ERK1/2 and p38, all of which were prevented by calpain inhibitor-III. Furthermore, inhibition of ERK1/2 or p38 attenuated phosphorylation of Ser-345 on p47phox in cardiomyocytes under simulated microgravity. This study demonstrates for the first time that calpain promotes NADPH oxidase activation and myocardial abnormalities under microgravity by facilitating p47phox phosphorylation via ERK1/2 and p38 pathways. Thus, calpain inhibition may be an effective therapeutic approach to reduce microgravity-induced myocardial abnormalities.

In addition to their well-known role in the control of cellular proliferation and cancer, cell cycle regulators are increasingly identified as important metabolic modulators. Several GWAS have identified SNPs near CDKN2A, the locus encoding for p16INK4a (p16), associated with elevated risk for cardiovascular diseases and type-2 diabetes development, two pathologies associated with impaired hepatic lipid metabolism. Although p16 was recently shown to control hepatic glucose homeostasis, it is unknown whether p16 also controls hepatic lipid metabolism. Using a combination of in vivo and in vitro approaches, we found that p16 modulates fasting-induced hepatic fatty acid oxidation (FAO) and lipid droplet accumulation. In primary hepatocytes, p16-deficiency was associated with elevated expression of genes involved in fatty acid catabolism. These transcriptional changes led to increased FAO and were associated with enhanced activation of PPARα through a mechanism requiring the catalytic AMPKα2 subunit and SIRT1, two known activators of PPARα. By contrast, p16 overexpression was associated with triglyceride accumulation and increased lipid droplet numbers in vitro, and decreased ketogenesis and hepatic mitochondrial activity in vivo. Finally, gene expression analysis of liver samples from obese patients revealed a negative correlation between CDKN2A expression and PPARA and its target genes. Our findings demonstrate that p16 represses hepatic lipid catabolism during fasting and may thus participate in the preservation of metabolic flexibility.

Alison M. Kurimchak
Dec 1, 2020; 19:2068-2089
Research

Autophagy plays critical roles in the maintenance of endothelial cells in response to cellular stress caused by blood flow. There is growing evidence that both cell adhesion and cell detachment can modulate autophagy, but the mechanisms responsible for this regulation remain unclear. Immunoglobulin and proline-rich receptor-1 (IGPR-1) is a cell adhesion molecule that regulates angiogenesis and endothelial barrier function. In this study, using various biochemical and cellular assays, we demonstrate that IGPR-1 is activated by autophagy-inducing stimuli, such as amino acid starvation, nutrient deprivation, rapamycin, and lipopolysaccharide. Manipulating the IκB kinase β activity coupled with in vivo and in vitro kinase assays demonstrated that IκB kinase β is a key serine/threonine kinase activated by autophagy stimuli and that it catalyzes phosphorylation of IGPR-1 at Ser220. The subsequent activation of IGPR-1, in turn, stimulates phosphorylation of AMP-activated protein kinase, which leads to phosphorylation of the major pro-autophagy proteins ULK1 and Beclin-1 (BECN1), increased LC3-II levels, and accumulation of LC3 punctum. Thus, our data demonstrate that IGPR-1 is activated by autophagy-inducing stimuli and in response regulates autophagy, connecting cell adhesion to autophagy. These findings may have important significance for autophagy-driven pathologies such cardiovascular diseases and cancer and suggest that IGPR-1 may serve as a promising therapeutic target.

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism that phosphorylates a wide range of proteins to maintain cellular homeostasis. AMPK consists of three subunits: α, β, and γ. AMPKα and β are encoded by two genes, the γ subunit by three genes, all of which are expressed in a tissue-specific manner. It is not fully understood, whether individual isoforms have different functions. Using RNA-Seq technology, we provide evidence that the loss of AMPKβ1 and AMPKβ2 lead to different gene expression profiles in human induced pluripotent stem cells (hiPSCs), indicating isoform-specific function. The knockout of AMPKβ2 was associated with a higher number of differentially regulated genes than the deletion of AMPKβ1, suggesting that AMPKβ2 has a more comprehensive impact on the transcriptome. Bioinformatics analysis identified cell differentiation as one biological function being specifically associated with AMPKβ2. Correspondingly, the two isoforms differentially affected lineage decision toward a cardiac cell fate. Although the lack of PRKAB1 impacted differentiation into cardiomyocytes only at late stages of cardiac maturation, the availability of PRKAB2 was indispensable for mesoderm specification as shown by gene expression analysis and histochemical staining for cardiac lineage markers such as cTnT, GATA4, and NKX2.5. Ultimately, the lack of AMPKβ1 impairs, whereas deficiency of AMPKβ2 abrogates differentiation into cardiomyocytes. Finally, we demonstrate that AMPK affects cellular physiology by engaging in the regulation of hiPSC transcription in an isoform-specific manner, providing the basis for further investigations elucidating the role of dedicated AMPK subunits in the modulation of gene expression.

Nicholas D. LeBlond
Dec 1, 2020; 61:1697-1706
Research Articles

Natalie Bruiners
Dec 1, 2020; 61:1617-1628
Research Articles

Stacey N Keenan
Dec 17, 2020; 0:jlr.RA120001126v1-jlr.RA120001126
Research Articles

Perilipin (PLIN) 5 is a lipid droplet-associated protein that coordinates intracellular lipolysis in highly oxidative tissues and is thought to regulate lipid metabolism in response to phosphorylation by protein kinase A (PKA). We sought to identify PKA phosphorylation sites in PLIN5 and assess their functional relevance in cultured cells and the livers of mice. We detected phosphorylation on S155, S161 and S163 of recombinant PLIN5 by PKA in vitro and identified S155 as a functionally important site for lipid metabolism. Expression of phosphorylation-defective PLIN5 S155A in Plin5 null cells resulted in decreased rates of lipolysis and triglyceride-derived fatty acid oxidation compared with cells expressing wildtype PLIN5. These differences in lipid metabolism were not associated with differences in the cellular distribution of PLIN5. Rather, FLIM-FRET analysis of protein-protein interactions showed that PLIN5 S155 phosphorylation regulates PLIN5 interaction with adipose triglyceride lipase (ATGL) at the lipid droplet, but not with the co-activator of ATGL, α-β hydrolase domain-containing 5 (ABHD5). Re-expression of PLIN5 S155A in the liver of Plin5 liver-specific null mice reduced lipolysis when compared to mice with wildtype PLIN5 re-expression, but was not associated with other changes in hepatic lipid metabolism, such as fatty acid oxidation, de novo lipogenesis and triglyceride secretion. Furthermore, glycemic control was impaired in mice with expression of PLIN5 S155A compared with mice expressing PLIN5. Together, these studies demonstrate that PLIN5 S155 is required for PKA-mediated lipolysis and builds on the body of evidence demonstrating a critical role for PLIN5 in coordinating lipid and glucose metabolism

The dysregulation of myeloid-derived cell metabolism can drive atherosclerosis. AMP-activated protein kinase (AMPK) controls various aspects of macrophage dynamics and lipid homeostasis, which are important during atherogenesis. Using LysM-Cre to drive the deletion of both the α1 and α2 catalytic subunits (MacKO), we aimed to clarify the role of myeloid-specific AMPK signaling in male and female mice made acutely atherosclerotic by injection of AAV vector encoding a gain-of-function mutant PCSK9 (PCSK9-AAV) and WD feeding. After 6 weeks of WD feeding, mice received a daily injection of either the AMPK activator A-769662 or a vehicle control for an additional 6 weeks. Following this (12 weeks total), we assessed myeloid cell populations and differences between genotype or sex were not observed. Similarly, aortic sinus plaque size, lipid staining, and necrotic area did not differ in male and female MacKO mice compared with their littermate floxed controls. Moreover, therapeutic intervention with A-769662 showed no treatment effect. There were also no observable differences in the amount of circulating total cholesterol or triglyceride, and only minor differences in the levels of inflammatory cytokines between groups. Finally, CD68+ area and markers of autophagy showed no effect of either lacking AMPK signaling or AMPK activation. Our data suggest that while defined roles for each catalytic AMPK subunit have been identified, complete deletion of myeloid AMPK signaling does not significantly impact atherosclerosis. Additionally, these findings suggest that intervention with the first-generation AMPK activator A-769662 is not able to stem the progression of atherosclerosis.