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Date: April 27, 2020

As COVID-19 continues to impact communities around the world, people and families everywhere are spending more time at home. In light of this, we’re launching a throwback Doodle series looking back at some of our popular interactive Google Doodle games!

Stay and play at home with today’s featured throwback: 

Our 2017 Doodle game celebrating 50 years of Kids Coding!

 

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Date: April 27, 2020

Today’s Doodle commemorates what is widely revered as the Netherlands’ most popular holiday, King’s Day. Known as Koningsdag in Dutch, today honors the birthday of the first Dutch king in 123 years, His Royal Highness Willem-Alexander.

Depicted in the Doodle artwork, the red, white, and blue tricolor Dutch flag was affirmed in its current form by a royal decree in 1937. With orange as the official color of the day, the flag is often seen with a small orange stripe, or a wimpel, hovering on the top for King’s Day.

Fijne Koningsdag! (Happy King’s Day!)

Location: Netherlands

Tags: national day, National Holiday, independence, history, Netherlands, King's Day

Date: April 28, 2020

As COVID-19 continues to impact communities around the world, people and families everywhere are spending more time at home. In light of this, we’re launching a throwback Doodle series looking back at some of our popular interactive Google Doodle games!

Stay and play at home with today’s featured throwback: 

Our 2017 Doodle game celebrating Cricket!

 

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Date: April 29, 2020

As COVID-19 continues to impact communities around the world, people and families everywhere are spending more time at home. In light of this, we’re launching a throwback Doodle series looking back at some of our popular interactive Google Doodle games!

Stay and play at home with today’s featured throwback: 

Our 2017 Doodle game celebrating Oskar Fischinger!
 

 

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Date: April 30, 2020

As COVID-19 continues to impact communities around the world, people and families everywhere are spending more time at home. In light of this, we’re launching a throwback Doodle series looking back at some of our popular interactive Google Doodle games!

Stay and play at home with today’s featured throwback: 

Our 2016 Doodle game celebrating Clara Rockmore!
 

 

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Date: May 1, 2020

As COVID-19 continues to impact communities around the world, people and families everywhere are spending more time at home. In light of this, we’re launching a throwback Doodle series looking back at some of our popular interactive Google Doodle games!

Stay and play at home with today’s featured throwback: 

Our 2018 Doodle game celebrating Garden Gnomes!
 

 

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Date: May 1, 2020

Also known as May Day or International Workers’ Day, Labour Day is celebrated on May 1st in many countries around the world. Today’s Doodle celebrates the day by illustrating a handful of the many professions across the labor force.

Recognized around the world, Labour Day originated from the 19th-century labour movement. First declared a holiday by trade unions in 1889, Labour Day commemorates worker’s rights and their fight for weekends, better working conditions, and shorter working days. 

Here’s to everyone contributing to the livelihoods of those around them each and every day. 

Happy Labour Day!

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Date: May 4, 2020

As COVID-19 continues to impact communities around the world, people and families everywhere are spending more time at home. In light of this, we’re launching a throwback Doodle series looking back at some of our popular interactive Google Doodle games!

Stay and play at home with today’s featured throwback: 

Our 2016 Doodle game celebrating Wilbur Scoville!
 

 

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Date: May 5, 2020

As COVID-19 continues to impact communities around the world, people and families everywhere are spending more time at home. In light of this, we’re launching a throwback Doodle series looking back at some of our popular interactive Google Doodle games!

Stay and play at home with today’s featured throwback: 

Our 2019 Doodle game celebrating Lotería!
 

 

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Date: May 6, 2020

As COVID-19 continues to impact communities around the world, people and families everywhere are spending more time at home. In light of this, we’re launching a throwback Doodle series looking back at some of our popular interactive Google Doodle games!

Stay and play at home with today’s featured throwback: 

Our 2016 Doodle game celebrating Halloween!
 

 

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Date: May 7, 2020

As COVID-19 continues to impact communities around the world, people and families everywhere are spending more time at home. In light of this, we’re launching a throwback Doodle series looking back at some of our popular interactive Google Doodle games!

Stay and play at home with today’s featured throwback: 

Our 2017 Doodle game celebrating the birth of Hip Hop!
 

 

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Date: May 8, 2020

As COVID-19 continues to impact communities around the world, people and families everywhere are spending more time at home. In light of this, we’re launching a throwback Doodle series looking back at some of our popular interactive Google Doodle games!

Stay and play at home with today’s featured throwback: 

Our 2010 Doodle game celebrating PAC-MAN!
 

 

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The post Reel Review: What’s New with the Shimano Stella SW 2020? appeared first on Ocean Blue Fishing Adventures.

The post New Arrivals: Top Fishing Sunglasses You Can Try this 2020 appeared first on Ocean Blue Fishing Adventures.

We previously established that global deletion of the enhancer of trithorax and polycomb (ETP) gene, Asxl2, prevents weight gain. Because proinflammatory macrophages recruited to adipose tissue are central to the metabolic complications of obesity, we explored the role of ASXL2 in myeloid lineage cells. Unexpectedly, mice without Asxl2 only in myeloid cells (Asxl2ΔLysM) were completely resistant to diet-induced weight gain and metabolically normal despite increased food intake, comparable activity, and equivalent fecal fat. Asxl2ΔLysM mice resisted HFD-induced adipose tissue macrophage infiltration and inflammatory cytokine gene expression. Energy expenditure and brown adipose tissue metabolism in Asxl2ΔLysM mice were protected from the suppressive effects of HFD, a phenomenon associated with relatively increased catecholamines likely due to their suppressed degradation by macrophages. White adipose tissue of HFD-fed Asxl2ΔLysM mice also exhibited none of the pathological remodeling extant in their control counterparts. Suppression of macrophage Asxl2 expression, via nanoparticle-based siRNA delivery, prevented HFD-induced obesity. Thus, ASXL2 controlled the response of macrophages to dietary factors to regulate metabolic homeostasis, suggesting modulation of the cells’ inflammatory phenotype may impact obesity and its complications.

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.

Tumor-associated peptide–human leukocyte antigen complexes (pHLAs) represent the largest pool of cell surface–expressed cancer-specific epitopes, making them attractive targets for cancer therapies. Soluble bispecific molecules that incorporate an anti-CD3 effector function are being developed to redirect T cells against these targets using 2 different approaches. The first achieves pHLA recognition via affinity-enhanced versions of natural TCRs (e.g., immune-mobilizing monoclonal T cell receptors against cancer [ImmTAC] molecules), whereas the second harnesses an antibody-based format (TCR-mimic antibodies). For both classes of reagent, target specificity is vital, considering the vast universe of potential pHLA molecules that can be presented on healthy cells. Here, we made use of structural, biochemical, and computational approaches to investigate the molecular rules underpinning the reactivity patterns of pHLA-targeting bispecifics. We demonstrate that affinity-enhanced TCRs engage pHLA using a comparatively broad and balanced energetic footprint, with interactions distributed over several HLA and peptide side chains. As ImmTAC molecules, these TCRs also retained a greater degree of pHLA selectivity, with less off-target activity in cellular assays. Conversely, TCR-mimic antibodies tended to exhibit binding modes focused more toward hot spots on the HLA surface and exhibited a greater degree of crossreactivity. Our findings extend our understanding of the basic principles that underpin pHLA selectivity and exemplify a number of molecular approaches that can be used to probe the specificity of pHLA-targeting molecules, aiding the development of future reagents.

Organ shortage continues to limit the lives of patients who require liver transplantation. While extending criteria for liver organs provides a needed resource, tissue damage from prolonged ischemic injury can result in early allograft dysfunction and consequent rejection. In this issue of the JCI, Nakamura et al. used a mouse transplantation model with prolonged ex vivo cold storage to explore liver graft protection. The authors found that liver grafts with absent carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) exhibited increased ischemia-reperfusion injury inflammation and decreased function in wild-type recipients. The authors went on to correlate CEACAM1 levels with postreperfusion damage in human liver transplant recipients. Notably, this study identified a potential biomarker for liver transplant donor graft quality.

Hepatocellular carcinoma (HCC) is clearly age-related and represents one of the deadliest cancer types worldwide. As a result of globally increasing risk factors including metabolic disorders, the incidence rates of HCC are still rising. However, the molecular hallmarks of HCC remain poorly understood. Neuropeptide Y (NPY) and NPY receptors represent a highly conserved, stress-activated system involved in diverse cancer-related hallmarks including aging and metabolic alterations, but its impact on liver cancer had been unclear. Here, we observed increased expression of NPY5 receptor (Y5R) in HCC, which correlated with tumor growth and survival. Furthermore, we found that its ligand NPY was secreted by peritumorous hepatocytes. Hepatocyte-derived NPY promoted HCC progression by Y5R activation. TGF-β1 was identified as a regulator of NPY in hepatocytes and induced Y5R in invasive cancer cells. Moreover, NPY conversion by dipeptidylpeptidase 4 (DPP4) augmented Y5R activation and function in liver cancer. The TGF-β/NPY/Y5R axis and DPP4 represent attractive therapeutic targets for controlling liver cancer progression.

An in-depth understanding of immune escape mechanisms in cancer is likely to lead to innovative advances in immunotherapeutic strategies. However, much remains unknown regarding these mechanisms and how they impact immunotherapy resistance. Using several preclinical tumor models as well as clinical specimens, we identified a mechanism whereby CD8+ T cell activation in response to programmed cell death 1 (PD-1) blockade induced a programmed death ligand 1/NOD-, LRR-, and pyrin domain–containing protein 3 (PD-L1/NLRP3) inflammasome signaling cascade that ultimately led to the recruitment of granulocytic myeloid-derived suppressor cells (PMN-MDSCs) into tumor tissues, thereby dampening the resulting antitumor immune response. The genetic and pharmacologic inhibition of NLRP3 suppressed PMN-MDSC tumor infiltration and significantly augmented the efficacy of anti–PD-1 antibody immunotherapy. This pathway therefore represents a tumor-intrinsic mechanism of adaptive resistance to anti–PD-1 checkpoint inhibitor immunotherapy and is a promising target for future translational research.

Lymph node stromal cells (LNSCs) regulate immunity through constructing lymphocyte niches. LNSC-produced laminin α5 (Lama5) regulates CD4+ T cells but the underlying mechanisms of its functions are poorly understood. Here we show that depleting Lama5 in LNSCs resulted in decreased Lama5 protein in the LN cortical ridge (CR) and around high endothelial venules (HEVs). Lama5 depletion affected LN structure with increased HEVs, upregulated chemokines, and cell adhesion molecules, and led to greater numbers of Tregs in the T cell zone. Mouse and human T cell transendothelial migration and T cell entry into LNs were suppressed by Lama5 through the receptors α6 integrin and α-dystroglycan. During immune responses and allograft transplantation, depleting Lama5 promoted antigen-specific CD4+ T cell entry into the CR through HEVs, suppressed T cell activation, and altered T cell differentiation to suppressive regulatory phenotypes. Enhanced allograft acceptance resulted from depleting Lama5 or blockade of T cell Lama5 receptors. Lama5 and Lama4/Lama5 ratios in allografts were associated with the rejection severity. Overall, our results demonstrated that stromal Lama5 regulated immune responses through altering LN structures and T cell behaviors. This study delineated a stromal Lama5–T cell receptor axis that can be targeted for immune tolerance modulation.

BACKGROUND Preclinical experiments have shown that donor blood cells, modified in vitro by an alkylating agent (modified immune cells [MICs]), induced long-term specific immunosuppression against the allogeneic donor.METHODS In this phase I trial, patients received either 1.5 × 106 MICs per kg BW on day –2 (n = 3, group A), or 1.5 × 108 MICs per kg BW on day –2 (n = 3, group B) or day –7 (n = 4, group C) before living donor kidney transplantation in addition to post-transplantation immunosuppression. The primary outcome measure was the frequency of adverse events (AEs) until day 30 (study phase) with follow-up out to day 360.RESULTS MIC infusions were extremely well tolerated. During the study phase, 10 treated patients experienced a total of 69 AEs that were unlikely to be related or not related to MIC infusion. No donor-specific human leukocyte antigen Abs or rejection episodes were noted, even though the patients received up to 1.3 × 1010 donor mononuclear cells before transplantation. Group C patients with low immunosuppression during follow-up showed no in vitro reactivity against stimulatory donor blood cells on day 360, whereas reactivity against third-party cells was still preserved. Frequencies of CD19+CD24hiCD38hi transitional B lymphocytes (Bregs) increased from a median of 6% before MIC infusion to 20% on day 180, which was 19- and 68-fold higher, respectively, than in 2 independent cohorts of transplanted controls. The majority of Bregs produced the immunosuppressive cytokine IL-10. MIC-treated patients showed the Immune Tolerance Network operational tolerance signature.CONCLUSION MIC administration was safe and could be a future tool for the targeted induction of tolerogenic Bregs.TRIAL REGISTRATION EudraCT number: 2014-002086-30; ClinicalTrials.gov identifier: NCT02560220FUNDING Federal Ministry for Economic Affairs and Technology, Berlin, Germany, and TolerogenixX GmbH, Heidelberg, Germany.

Regenerative pain medicine, which seeks to harness the body’s own reparative capacity, is rapidly emerging as a field within pain medicine and orthopedics. It is increasingly appreciated that common analgesic mechanisms for these treatments depend on neuroimmune modulation. In this Review, we discuss recent progress in mechanistic understanding of nociceptive sensitization in chronic pain with a focus on neuroimmune modulation. We also examine the spectrum of regenerative outcomes, including preclinical and clinical outcomes. We further distinguish the analgesic mechanisms of regenerative therapies from those of cellular replacement, creating a conceptual and mechanistic framework to evaluate future research on regenerative medicine.

Facioscapulohumeral muscular dystrophy (FSHD) results from expression of the full-length double homeobox 4 (DUX4-FL) retrogene in skeletal muscle. However, even in cases of severe FSHD the presence of DUX4 is barely detectable. In this issue of the JCI, Bosnakovski et al. used an inducible, muscle-specific human DUX4 to reproduce the low-level, sporadic DUX4 expression of human FSHD muscle as well the myopathology seen in human FSHD disease. Notably, dysregulated fibroadipogenic progenitors accumulated in affected muscles, thus providing a mechanism for the replacement of muscle by fibrosis and fat.

Fibroblasts are key effector cells in tissue remodeling. They remain persistently activated in fibrotic diseases, resulting in progressive deposition of extracellular matrix. Although fibroblast activation may be initiated by external factors, prolonged activation can induce an “autonomous,” self-maintaining profibrotic phenotype in fibroblasts. Accumulating evidence suggests that epigenetic alterations play a central role in establishing this persistently activated pathologic phenotype of fibroblasts. We demonstrated that in fibrotic skin of patients with systemic sclerosis (SSc), a prototypical idiopathic fibrotic disease, TGF-β induced the expression of DNA methyltransferase 3A (DNMT3A) and DNMT1 in fibroblasts in a SMAD-dependent manner to silence the expression of suppressor of cytokine signaling 3 (SOCS3) by promoter hypermethylation. Downregulation of SOCS3 facilitated activation of STAT3 to promote fibroblast-to-myofibroblast transition, collagen release, and fibrosis in vitro and in vivo. Reestablishment of the epigenetic control of STAT3 signaling by genetic or pharmacological inactivation of DNMT3A reversed the activated phenotype of SSc fibroblasts in tissue culture, inhibited TGF-β–dependent fibroblast activation, and ameliorated experimental fibrosis in murine models. These findings identify a pathway of epigenetic imprinting of fibroblasts in fibrotic disease with translational implications for the development of targeted therapies in fibrotic diseases.

Lamin A is a component of the inner nuclear membrane that, together with epigenetic factors, organizes the genome in higher order structures required for transcriptional control. Mutations in the lamin A/C gene cause several diseases belonging to the class of laminopathies, including muscular dystrophies. Nevertheless, molecular mechanisms involved in the pathogenesis of lamin A–dependent dystrophies are still largely unknown. The polycomb group (PcG) of proteins are epigenetic repressors and lamin A interactors, primarily involved in the maintenance of cell identity. Using a murine model of Emery-Dreifuss muscular dystrophy (EDMD), we show here that lamin A loss deregulated PcG positioning in muscle satellite stem cells, leading to derepression of non–muscle-specific genes and p16INK4a, a senescence driver encoded in the Cdkn2a locus. This aberrant transcriptional program caused impairment in self-renewal, loss of cell identity, and premature exhaustion of the quiescent satellite cell pool. Genetic ablation of the Cdkn2a locus restored muscle stem cell properties in lamin A/C–null dystrophic mice. Our findings establish a direct link between lamin A and PcG epigenetic silencing and indicate that lamin A–dependent muscular dystrophy can be ascribed to intrinsic epigenetic dysfunctions of muscle stem cells.

Seizures often herald the clinical appearance of gliomas or appear at later stages. Dissecting their precise evolution and cellular pathogenesis in brain malignancies could inform the development of staged therapies for these highly pharmaco-resistant epilepsies. Studies in immunodeficient xenograft models have identified local interneuron loss and excess glial glutamate release as chief contributors to network disinhibition, but how hyperexcitability in the peritumoral microenvironment evolves in an immunocompetent brain is unclear. We generated gliomas in WT mice via in utero deletion of key tumor suppressor genes and serially monitored cortical epileptogenesis during tumor infiltration with in vivo electrophysiology and GCAMP7 calcium imaging, revealing a reproducible progression from hyperexcitability to convulsive seizures. Long before seizures, coincident with loss of inhibitory cells and their protective scaffolding, gain of glial glutamate antiporter xCT expression, and reactive astrocytosis, we detected local Iba1+ microglial inflammation that intensified and later extended far beyond tumor boundaries. Hitherto unrecognized episodes of cortical spreading depolarization that arose frequently from the peritumoral region may provide a mechanism for transient neurological deficits. Early blockade of glial xCT activity inhibited later seizures, and genomic reduction of host brain excitability by deleting MapT suppressed molecular markers of epileptogenesis and seizures. Our studies confirmed xenograft tumor–driven pathobiology and revealed early and late components of tumor-related epileptogenesis in a genetically tractable, immunocompetent mouse model of glioma, allowing the complex dissection of tumor versus host pathogenic seizure mechanisms.

Immunosuppression continues to be a necessary component of transplantation, despite its association with a multitude of adverse effects. Numerous efforts have been made to circumvent the need for immunosuppression by using various techniques to achieve donor hyporesponsiveness. In this issue of the JCI, Morath et al. take this endeavor forward. Prior to transplantation, the researchers infused recipients with donor-modified immune cells and achieved immunologic hyporesponsiveness. This successful phase I trial also provides a possible avenue for achieving transplantation without the requisite immunosuppression.

Hypoxia-inducible factor (HIF) is strikingly upregulated in many types of cancer, and there is great interest in applying inhibitors of HIF as anticancer therapeutics. The most advanced of these are small molecules that target the HIF-2 isoform through binding the PAS-B domain of HIF-2α. These molecules are undergoing clinical trials with promising results in renal and other cancers where HIF-2 is considered to be driving growth. Nevertheless, a central question remains as to whether such inhibitors affect physiological responses to hypoxia at relevant doses. Here, we show that pharmacological HIF-2α inhibition with PT2385, at doses similar to those reported to inhibit tumor growth, rapidly impaired ventilatory responses to hypoxia, abrogating both ventilatory acclimatization and carotid body cell proliferative responses to sustained hypoxia. Mice carrying a HIF-2α PAS-B S305M mutation that disrupts PT2385 binding, but not dimerization with HIF-1β, did not respond to PT2385, indicating that these effects are on-target. Furthermore, the finding of a hypomorphic ventilatory phenotype in untreated HIF-2α S305M mutant mice suggests a function for the HIF-2α PAS-B domain beyond heterodimerization with HIF-1β. Although PT2385 was well tolerated, the findings indicate the need for caution in patients who are dependent on hypoxic ventilatory drive.

Increased microvascular permeability to plasma proteins and neutrophil emigration are hallmarks of innate immunity and key features of numerous inflammatory disorders. Although neutrophils can promote microvascular leakage, the impact of vascular permeability on neutrophil trafficking is unknown. Here, through the application of confocal intravital microscopy, we report that vascular permeability–enhancing stimuli caused a significant frequency of neutrophil reverse transendothelial cell migration (rTEM). Furthermore, mice with a selective defect in microvascular permeability enhancement (VEC-Y685F-ki) showed reduced incidence of neutrophil rTEM. Mechanistically, elevated vascular leakage promoted movement of interstitial chemokines into the bloodstream, a response that supported abluminal-to-luminal neutrophil TEM. Through development of an in vivo cell labeling method we provide direct evidence for the systemic dissemination of rTEM neutrophils, and showed them to exhibit an activated phenotype and be capable of trafficking to the lungs where their presence was aligned with regions of vascular injury. Collectively, we demonstrate that increased microvascular leakage reverses the localization of directional cues across venular walls, thus causing neutrophils engaged in diapedesis to reenter the systemic circulation. This cascade of events offers a mechanism to explain how local tissue inflammation and vascular permeability can induce downstream pathological effects in remote organs, most notably in the lungs.

This isn’t in the photos, but it’s foggy and cold this morning in western Washington. It’s the weirdest summer I’ve ever experienced — foggy, frigid mornings, cool days, and then freezing nights! It’s not very pleasant for a desert creature like myself, but it’s quite nice to sit inside and write in my blog a least. I have to say, it sure is weird, though. It’s August and I wear a sweater or sweatshirt most of the time and then I’m still cold! ^^; There are a few sunny days here and there, though. I get out on those days, into the wilderness and bright blue beyond. Sometimes, I just drive and drive in my still-unnamed yellow bug, and other times I find something that not a lot of people know about. This is about one of them. ^^ I love to wander, to find all of the nooks and crannies of wherever I happen to be. Tourist sites? Well, they’re usually cool and I want to see them, but it’s the little, hidden things off the beaten trail that really get my soul revving. So, Johns River (no apostrophe, it was named back when apostrophes weren’t used on maps) was one of those things. I found out about it by googling and googling, thinking that someone, somewhere, must have written about something other than the two really traveled trails in Grays Harbor. I mean, this area is the gateway to the wild peninsula of Washington, where according to Stephanie Meyer and Patricia Briggs, vampires and werewolves run wild. I also loooooooove mountain meadows. Johns river is not in the mountains, so I suppose that it mostly qualifies as grassland surrounded by trees? It’s just a little concrete path, and it’s not even a mile (0.6 miles one way) long, but with the river on one side and a huge expanse of pasture to the other side, it took my breath away.   Just look at this. Elk supposedly graze around here a lot, and I didn’t see any since I went during midday, but I bet it’s really a sight at sunset. It’s not far, so I will definitely have to come back. Can’t you just imagine little river sprites lounging on the bank, cleaning themselves? And little fairies flitting through the air? I bet this is a really magical place at sunset.   The little shack in the distance is off the trail. It’s supposedly for hunters (YUCK) and photographers. It would make a wonderful place to watch the sprites from. This shack is at the very end of the trail, and the same thing. It’s boring inside. I didn’t see any geldings, but I saw a few mosquitoes and a spider. If you’re lucky enough to have a horse that loves to take you along on its adventures, you can continue. I was wearing shorts, so I didn’t go, because ticks! But I will come back. Yes, I will come back. :3 Road to nowhere. Ignore the buildings. They’re only there for magical curse removal. Here’s a panorama of wildness. I’m feeling really magical today, can’t you tell? I think it’s because I have Daniel Waples playing in the background, and it’s all foggy outside. That reminds me that I want a handpan so badly. I need to find a handpan that I can afford soooooo badly, because I think it’s a music that speaks to my inner essence. Does anyone know what these gorgeous purple flowers are? They’re not lavender. The River People watch over this creek. Be careful to please them. It’s me. Sometimes I wear bright colors, sometimes I wear pastels. I don’t think that a magical being has to stick to  neutrals. (That hand thing is a shaka, a very cool gesture that I learned during my time in Hawaii that means “hang loose.” I like to think that it also means that you should be yourself and follow your instincts.) I think that I’ll go research handpans again. I should write down how much they cost so that I can be sure to stock my Airstream with one when I get it. ???? Here’s to the future! Excelsior! (Is that a good “to infinity, and beyond!!” kind of quote? If not, what should I use instead? I feel like “banzai!” is overused) Oh, and I’ve been arting on my Tumblr lately. I’ve been writing a serial ficiton that is mysterious connected to my soon-to-come comic, Denkiki on my other tumblr. Go check them out!  I’m going to start using my mailing list soon, too, to keep people updated, so stay tuned and I’ll post the link soon! Or make it a popup, I’m not sure. But I want to offer something cool for when people sign up. ???? Chaoness!

We're still waiting to hear news about Apple Card's performance relative to the major card issuers, but that hasn't stopped Samsung from announcing plans to launch an "innovative" debit card as part of a new mobile-first money management platform the company has been developing over the last year.


Announced on Thursday in a blog post by Samsung Pay vice-president Sang Ahn, the forthcoming debit card is in partnership with finance company SoFi and will be backed by a cash management account.

"In 2020, Samsung Pay will be expanding our service from being a rewarding way to shop and pay, to also being a rewarding way to manage money," writes Ahn. "Over the past year we have been busy developing a mobile-first money management platform. Our vision is to help consumers better manage their money so that they can achieve their dreams and goals. Now more than ever, mobile financial services and money management tools will play an even bigger role in our daily lives while also opening up new possibilities."

The debit card is scheduled to launch this summer. Other than that, Samsung hasn't offered any details on how it will work, but expect it to integrate with Samsung's existing mobile payment system.

Launched in August 2019, ‌Apple Card‌ is a credit card linked to Apple Pay and built into the Wallet app on iPhone. Apple partnered with Goldman Sachs to launch the card, and in October the investment bank hailed it as "the most successful credit-card launch ever." Nine months later, neither Apple nor Goldman Sachs has offered any concrete details on its performance.

During the global health crisis, Apple has introduced an ‌Apple Card‌ Assistance Program that allows ‌‌Apple Card‌‌ holders to skip their March and April payments without incurring interest charges for that billing cycle. For more details on how the card works, check out our comprehensive Apple Card guide.
This article, "Samsung Announces 'Innovative' Debit Card Launching this Summer" first appeared on MacRumors.com

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Apple's plan to release an updated version of AirPods later this year has been delayed due to the global health crisis, according to the Nikkei Asian Review.


This lines up with a recent report from analyst Ming-Chi Kuo, who said that mass production of third-generation AirPods will begin in the first half of 2021, followed by mass production of second-generation AirPods Pro between the fourth quarter of 2021 and the first quarter of 2022. Kuo also expects Apple's rumored high-end over-ear headphones to enter mass production at some point in mid-2020.

Kuo did acknowledge rumors of new AirPods coming in the second half of 2020, but he said they are "more likely to be the new Beats model." Last month, leaker Jon Prosser claimed that Apple was planning to release so-called "AirPods X" around September or October with a BeatsX-like design for sports and running.

Apple's second-generation AirPods launched in March 2019, while the AirPods Pro were released at the end of October.

This article, "Apple's Plan to Introduce New AirPods Later This Year Reportedly Delayed" first appeared on MacRumors.com

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The Label's "The_Otherside" is this week's addition to Apple Arcade on the iPhone, iPad, and Apple TV. The game is described as both a turn-based RPG and a strategy board game:

Otherside is a turn based RPG and strategy board game where you will control four survivors who hope to push back the shadowy threat. Make your way through each level solving puzzles, fighting monsters, and destroying the spirit anchors that threaten our dimension.

Do you have what it takes to restore the town back to normal and save the day?

"The_Otherside" is available on the App Store with an Apple Arcade subscription. The service provides iPhone, iPad, Apple TV, and Mac users with access to over 100 games with no in-app purchases or ads for $4.99 per month.
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A nationwide class action lawsuit filed against Apple in Northern California court this week accuses the company of knowingly concealing a defect with a display-related flex cable on recent 13-inch and 15-inch MacBook Pro models.


As discovered by repair website iFixit last year, some MacBook Pro models released in 2016 and 2017 have experienced issues with uneven backlighting caused by a delicate flex cable that can wear out and break after repeated opening and closing of the display. Impacted notebooks can exhibit uneven lighting at the bottom of the screen, which has been described as a "stage light" effect, and the backlighting system can eventually fail entirely.

Since the issue often takes time to manifest, the affected ‌MacBook Pro‌ units can be outside of Apple's one-year warranty period when they start exhibiting symptoms, resulting in an out-of-warranty repair fee of up to $850.

"Imagine spending more than $2,500 on a laptop only for it to fail shortly after the manufacturer's warranty expires," said PARRIS Law Firm attorney R. Rex Parris. "What's even more appalling is Apple requiring customers to spend an additional $600 to $850 to replace the screen."

Apple seemingly fixed the issue by extending the length of the flex cable by 2mm in the 2018 MacBook Pro. It also launched a free repair program in May 2019, but the program only applies to 13-inch MacBook Pro models released in 2016.

iFixit found the 2018 MacBook Pro flex cable on the left to be 2mm longer
The class action lawsuit seeks restitution for all costs attributable to replacing or replacing the affected MacBook Pro units, and calls for Apple to expand its repair program to cover the 15-inch MacBook Pro. The proposed class is defined as all persons within the United States who purchased a 2016 or newer MacBook Pro.

Related Guide: "Flexgate" Display Issues Affecting 2016 MacBook Pro and Later
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Apple's next-generation Apple Watch and watchOS 7 will focus on new mental health capabilities, according to leaker Jon Prosser who recently spoke on the Geared Up podcast. The mention of new ‌Apple Watch‌ features comes towards the end of the podcast.


The next-generation version of the ‌Apple Watch‌, the ‌Apple Watch‌ Series 6, has been rumored to include a blood oxygen sensor, which Prosser says Apple will take advantage of to implement new mental health-related features, such as detecting panic attacks.

What their biggest focus on is right now and I hope it comes this year, it might come next year, but I hope it's coming to WWDC is mental health capabilities. Where they can take the oxygen levels in your blood with your heart rate and determine if you're hyperventilating.

They can identify a panic attack before it happens and warn you on your watch. Especially if you're driving, they'll ask you to pull over and they'll offer breathing exercises once you get pulled over.

Prosser says that while he hopes the feature is released this year, "it might come next year." He also says he hopes for a WWDC unveiling, but if the new feature relies on a blood oxygen sensor in an unreleased version of the ‌Apple Watch‌, it's not likely Apple will unveil the capability until the fall when new ‌Apple Watch‌ models that support it are released.

There is, however, a possibility that it will be revealed at WWDC if older ‌Apple Watch‌ models have a latent ability to detect blood oxygen level, which is not clear at this time, or if the feature does not involve blood oxygen monitoring.

The panic attack detecting rumor was first shared by EverythingApplePro and leaker Max Weinbach back in April, who said that the ‌Apple Watch‌ will also be able to determine when a user is experiencing high levels of stress. Weinbach and EverythingApplePro did not suggest the feature would rely on blood oxygen monitoring, however, and said that it would be available on the ‌Apple Watch‌ Series 4 or later.

Hints that blood oxygen tracking capabilities are coming to a future version of the ‌Apple Watch‌ were found in a leaked version of iOS 14. Blood oxygen monitoring is an important feature because a drop in blood oxygen levels can suggest a serious respiratory or cardiac problem that requires immediate medical attention.

Multiple prior rumors from Bloomberg and other sources have also indicated that the next-generation ‌Apple Watch‌ and watchOS 7 will include sleep tracking features, allowing the ‌Apple Watch‌ to measure sleep quality, length, and other metrics.
This article, "Rumor Claims watchOS 7 Will Have 'Mental Health Capabilities' to Detect Panic Attacks" first appeared on MacRumors.com

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