Low Carb Brussels Sprouts Alfredo is a creamy and cheesy side dish loaded with bacon which quickly cooks in the Instant Pot pressure cooker.

craving more? check out TasteSpotting

Try some homestyle Chinese with this easy, healthy, and delicious bean sprout stir fry that takes just minutes to put on your dinner table!

craving more? check out TasteSpotting

Politicos watered down earlier efforts, so data defenders will fight to the end

The small group of policy wonks that forced California’s legislature to rush through privacy legislation two years ago are back – and this time they want a ballot.…

'B' is for basic controls that up and disappeared

A study of the UK online advertising market, conducted by global accounting firm PwC, has found that publishers get just half of what advertisers spend, with the other half siphoned off by ad-supply chain intermediaries.…

Things will change forever, nods ex-Facebooker Alex Stamos

Video conferencing software biz Zoom has bought Keybase in a surprise move just weeks after hiring Facebook's one-time CSO.…

We all need to tighten our belts

For the first time in over three decades, BT has suspended its dividend scheme as the former state-owned teleco grapples with the fallout from the novel coronavirus pandemic, and the financial uncertainty that'll inevitably ensue.…

High-frequency audio could be used to stealthily track netizens

Technical folks looking to improve web privacy haven't been able to decide whether sound beyond the range of human hearing poses enough of a privacy risk to merit restriction.…

Update used wrong data type, causing Tinder to Spotify to fall over

A change in the Facebook SDK backend managed to crash many popular iOS apps that integrated the code library, used for implementing various Facebook services.…

If you listen closely, you can hear how the creatures' full-throated call increases in volume when you are on holiday

On Call Friday is here! How is your weekend looking? Same as the last one, and the one before that? Never mind – before breaking into the lockdown lagers, join us for another entry in The Register's tales of those brave souls who are On Call.…

iGiant not only screwed up the wiring, it knew it was shipping dodgy gear, it is claimed

Apple is potentially facing a class-action lawsuit over the failure of displays on its MacBook Pro line.…

Hayabusa 2 expected to return with out-of-this-world material in December

Video Close-up footage of asteroid Ryugu, taken by the Hayabusa 2 spacecraft as it touched down to retrieve a sample, reveals the near-Earth object’s surface may have been torched by the Sun as its orbit changed over time.…

Opposition spokesman on tourism, Dr Wykeham McNeill, is calling for an investigation into allegations that some employers of tourism workers have not been turning over income tax deductions to government.  The situation has resulted in...

A review by Rob Cranley (9). A great flight sim that absorbed many, many hours of my youth

A review by Medio DeCritici (165). A 2020 Review - Aliens Versus Predator (PC, 1999)

A review by Medio DeCritici (165). A 2020 Review - Aliens vs. Predator (PC, 2010)

A review by Medio DeCritici (165). A 2020 Review - Alpha Protocol (PC, 2010)

Компания Meizu провела в Китае мероприятие, на котором анонсировала свою новую флагманскую линейку смартфонов — Meizu 17.

Экспедиционная группа из Китая поднялась на гору Эверест и решила там же протестировать в экстремальных условиях камеры смартфонов.

Tattoo pistols are definitely the devices that are used to create and use tattoos. These pistols are also known as tattoo models. They have been utilized for several years to create stylish and delightful bits of system craft. Right now,… Continue Reading →

“The most difficult part was persuading our children that they had the freedom to make anything they wanted,” writes mom Anam Ahmed at Let Grow. (Click here!) …Like most kids, my children live prescheduled lives (at least they did in “the time before”). At school, someone tells them when to play outside and when to […]

These “cards” are really an excuse for kids to interview their moms and shower them with the ultimate gifts: attention to mom’s quirky uniqueness, gratitude, and offers of help! Here you go — click here! (Mother’s Day is SUNDAY!)

For large electric power storage projects the cost of batteries has plummeted. 2008, when battery prices were 10 times higher than they are today. This advance is timely as photovoltaic electric power prices have dropped so far that in SoCal PV is causing a growing drop in mid-day demand and therefore a much bigger spike in evening demand. Therefore there's a growing need for a cheaper way to store power generated in mid day and deliver it in the evening. You can see how much solar power output surges each day in California by clicking on some of the Daily Renewables Watch links at the Cal ISO site (the organization that manages California's electric grid). The growing supply of wind...

Keep calm, and stay geeky people!

Date: April 25, 2020

As COVID-19 continues to impact communities around the world, people are coming together to help one another now more than ever. We’re launching a Doodle series to recognize and honor many of those on the front lines.

Today, we’d like to say: 

To all coronavirus helpers, thank you.
 

Help stop the spread of COVID-19 by following these steps.  

Learn more here about the latest ways we’re responding, and how our products can help people stay connected during this time.

Location: Global

Tags: covid, Current Event, covid-19, appreciation, helpers, coronavirus

Date: May 4, 2020

Happy US Teacher Appreciation Week!

Today (and everyday!), we honor teachers across the nation, who continue to work tirelessly to shape our future generations, even in the midst of the unprecedented COVID-19 pandemic.

Today’s Doodle was created by Doodler Kevin Laughlin who collaborated with the 54 2020 State Teachers of the Year during their visit to Google this past February. 

Below, Kevin shares more on his experience working with the teachers on today’s Doodle!

I know from firsthand experience how much of a positive impact a teacher can have on a young person's life. I can't express how happy I am to have had the opportunity to be a part of the Teacher Appreciation project this year.

When I met these teachers on campus in February, I was so inspired by their love of teaching and dedication to their students, which I felt each minute I spent with them. As they presented their own Doodle designs, they shared anecdotes about their classrooms, advocated for their students, and spoke passionately about educational equity. 

I am glad to see their work represented in the final Doodle on Google’s homepage today celebrating these often unsung heroes. To every teacher, thank you times infinity! 

Learn more about the many ways Google is celebrating and supporting teachers, in classrooms or at home.

See some of the teacher concepts that inspired today’s Doodle below:

...and all of the concepts from our 54 2020 State Teachers of the Year:

Photos from the Doodle brainstorming session at the 2020 National Teacher of the Year Program

Location: U.S. Virgin Islands, United States

Tags: teachers’ day, National Holiday, education, teaching

The post The Angler’s Code: What are the Best Practices for a Better Fishing Future? appeared first on Ocean Blue Fishing Adventures.

Ничто так не подчёркивает важность достоверных новостей, как кризис. Однако пандемия сovid-19 переворачивает вверх дном журналистику и меняет условия труда. Нельзя недооценивать возникающий в результате стресс для психического здоровья работников СМИ.

Hearing loss caused by the death of sensory hair cells of the inner ear is an unfortunate side effect for many patients treated with aminoglycoside antibiotics or platinum-containing chemotherapy agents. In animal models, induction of heat shock confers substantial otoprotection against aminoglycoside- and cisplatin-induced hair cell death. In this issue of the JCI, Breglio et al. demonstrate that inner ear tissue released exosomes carrying heat shock protein 70 (HSP70) in response to heat stress. HSP70 acted by a paracrine mechanism that engaged the Toll-like receptor 4 (TLR4) on hair cells to protect them from death. Exosomes and the HSP70/TLR4 pathway could thus provide treatment targets for the protection of hair cells from chemically induced death or from other insults, such as noise.

Hair cells, the mechanosensory receptors of the inner ear, are responsible for hearing and balance. Hair cell death and consequent hearing loss are common results of treatment with ototoxic drugs, including the widely used aminoglycoside antibiotics. Induction of heat shock proteins (HSPs) confers protection against aminoglycoside-induced hair cell death via paracrine signaling that requires extracellular heat shock 70-kDa protein (HSP70). We investigated the mechanisms underlying this non–cell-autonomous protective signaling in the inner ear. In response to heat stress, inner ear tissue releases exosomes that carry HSP70 in addition to canonical exosome markers and other proteins. Isolated exosomes from heat-shocked utricles were sufficient to improve survival of hair cells exposed to the aminoglycoside antibiotic neomycin, whereas inhibition or depletion of exosomes from the extracellular environment abolished the protective effect of heat shock. Hair cell–specific expression of the known HSP70 receptor TLR4 was required for the protective effect of exosomes, and exosomal HSP70 interacted with TLR4 on hair cells. Our results indicate that exosomes are a previously undescribed mechanism of intercellular communication in the inner ear that can mediate nonautonomous hair cell survival. Exosomes may hold potential as nanocarriers for delivery of therapeutics against hearing loss.

Arterial cardiovascular events are the leading cause of death in patients with JAK2V617F myeloproliferative neoplasms (MPNs). However, their mechanisms are poorly understood. The high prevalence of myocardial infarction without significant coronary stenosis or atherosclerosis in patients with MPNs suggests that vascular function is altered. The consequences of JAK2V617F mutation on vascular reactivity are unknown. We observe here increased responses to vasoconstrictors in arteries from Jak2V617F mice resulting from a disturbed endothelial NO pathway and increased endothelial oxidative stress. This response was reproduced in WT mice by circulating microvesicles isolated from patients carrying JAK2V617F and by erythrocyte-derived microvesicles from transgenic mice. Microvesicles of other cellular origins had no effect. This effect was observed ex vivo on isolated aortas, but also in vivo on femoral arteries. Proteomic analysis of microvesicles derived from JAK2V617F erythrocytes identified increased expression of myeloperoxidase as the likely mechanism accounting for their effect. Myeloperoxidase inhibition in microvesicles derived from JAK2V617F erythrocytes suppressed their effect on oxidative stress. Antioxidants such as simvastatin and N-acetyl cysteine improved arterial dysfunction in Jak2V617F mice. In conclusion, JAK2V617F MPNs are characterized by exacerbated vasoconstrictor responses resulting from increased endothelial oxidative stress caused by circulating erythrocyte-derived microvesicles. Simvastatin appears to be a promising therapeutic strategy in this setting.

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 renaissance of complement diagnostics and therapeutics has introduced precision medicine into a widened field of complement-mediated diseases. In particular, complement-mediated diseases (or complementopathies) with ongoing or published clinical trials of complement inhibitors include paroxysmal nocturnal hemoglobinuria, cold agglutinin disease, hemolytic uremic syndrome, nephropathies, HELLP syndrome, transplant-associated thrombotic microangiopathy, antiphospholipid antibody syndrome, myasthenia gravis, and neuromyelitis optica. Recognizing that this field is rapidly expanding, we aim to provide a state-of-the-art review of (a) current understanding of complement biology for the clinician, (b) novel insights into complement with potential applicability to clinical practice, (c) complement in disease across various disciplines (hematology, nephrology, obstetrics, transplantation, rheumatology, and neurology), and (d) the potential future of precision medicine. Better understanding of complement diagnostics and therapeutics will not only facilitate physicians treating patients in clinical practice but also provide the basis for future research toward precision medicine in this field.

Elevated pressure in the pancreatic gland is the central cause of pancreatitis following abdominal trauma, surgery, endoscopic retrograde cholangiopancreatography, and gallstones. In the pancreas, excessive intracellular calcium causes mitochondrial dysfunction, premature zymogen activation, and necrosis, ultimately leading to pancreatitis. Although stimulation of the mechanically activated, calcium-permeable ion channel Piezo1 in the pancreatic acinar cell is the initial step in pressure-induced pancreatitis, activation of Piezo1 produces only transient elevation in intracellular calcium that is insufficient to cause pancreatitis. Therefore, how pressure produces a prolonged calcium elevation necessary to induce pancreatitis is unknown. We demonstrate that Piezo1 activation in pancreatic acinar cells caused a prolonged elevation in intracellular calcium levels, mitochondrial depolarization, intracellular trypsin activation, and cell death. Notably, these effects were dependent on the degree and duration of force applied to the cell. Low or transient force was insufficient to activate these pathological changes, whereas higher and prolonged application of force triggered sustained elevation in intracellular calcium, leading to enzyme activation and cell death. All of these pathological events were rescued in acinar cells treated with a Piezo1 antagonist and in acinar cells from mice with genetic deletion of Piezo1. We discovered that Piezo1 stimulation triggered transient receptor potential vanilloid subfamily 4 (TRPV4) channel opening, which was responsible for the sustained elevation in intracellular calcium that caused intracellular organelle dysfunction. Moreover, TRPV4 gene–KO mice were protected from Piezo1 agonist– and pressure-induced pancreatitis. These studies unveil a calcium signaling pathway in which a Piezo1-induced TRPV4 channel opening causes pancreatitis.

Treating neuropathic pain is challenging and novel non–opioid-based medicines are needed. Using unbiased receptomics, transcriptomic analyses, immunofluorescence, and in situ hybridization, we found that the expression of the orphan GPCR Gpr160 and GPR160 increased in the rodent dorsal horn of the spinal cord following traumatic nerve injury. Genetic and immunopharmacological approaches demonstrated that GPR160 inhibition in the spinal cord prevented and reversed neuropathic pain in male and female rodents without altering normal pain response. GPR160 inhibition in the spinal cord attenuated sensory processing in the thalamus, a key relay in the sensory discriminative pathways of pain. We also identified cocaine- and amphetamine-regulated transcript peptide (CARTp) as a GPR160 ligand. Inhibiting endogenous CARTp signaling in spinal cord attenuated neuropathic pain, whereas exogenous intrathecal CARTp evoked painful hypersensitivity through GPR160-dependent ERK and cAMP response element–binding protein (CREB). Our findings de-orphanize GPR160, identify it as a determinant of neuropathic pain and potential therapeutic target, and provide insights into its signaling pathways. CARTp is involved in many diseases including depression and reward and addiction; de-orphanization of GPR160 is a major step forward understanding the role of CARTp signaling in health and disease.