Curing HIV infection will require the elimination of a reservoir of infected CD4+ T cells that persists despite HIV-specific cytotoxic T cell (CTL) responses. Although viral latency is a critical factor in this persistence, recent evidence also suggests a role for intrinsic resistance of reservoir-harboring cells to CTL killing. This resistance may have contributed to negative outcomes of clinical trials, where pharmacologic latency reversal has thus far failed to drive reductions in HIV reservoirs. Through transcriptional profiling, we herein identified overexpression of the prosurvival factor B cell lymphoma 2 (BCL-2) as a distinguishing feature of CD4+ T cells that survived CTL killing. We show that the inducible HIV reservoir was disproportionately present in BCL-2hi subsets in ex vivo CD4+ T cells. Treatment with the BCL-2 antagonist ABT-199 was not sufficient to drive reductions in ex vivo viral reservoirs when tested either alone or with a latency-reversing agent (LRA). However, the triple combination of strong LRAs, HIV-specific T cells, and a BCL-2 antagonist uniquely enabled the depletion of ex vivo viral reservoirs. Our results provide rationale for novel therapeutic approaches targeting HIV cure and, more generally, suggest consideration of BCL-2 antagonism as a means of enhancing CTL immunotherapy in other settings, such as cancer.

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.

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.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. Although gene-environment interactions have been implicated in the etiology of several disorders, the impact of paternal and/or maternal metabolic syndrome on the clinical phenotypes of offspring and the underlying genetic and epigenetic contributors of NAFLD have not been fully explored. To this end, we used the liver-specific insulin receptor knockout (LIRKO) mouse, a unique nondietary model manifesting 3 hallmarks that confer high risk for the development of NAFLD: hyperglycemia, insulin resistance, and dyslipidemia. We report that parental metabolic syndrome epigenetically reprograms members of the TGF-β family, including neuronal regeneration–related protein (NREP) and growth differentiation factor 15 (GDF15). NREP and GDF15 modulate the expression of several genes involved in the regulation of hepatic lipid metabolism. In particular, NREP downregulation increases the protein abundance of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and ATP-citrate lyase (ACLY) in a TGF-β receptor/PI3K/protein kinase B–dependent manner, to regulate hepatic acetyl-CoA and cholesterol synthesis. Reduced hepatic expression of NREP in patients with NAFLD and substantial correlations between low serum NREP levels and the presence of steatosis and nonalcoholic steatohepatitis highlight the clinical translational relevance of our findings in the context of recent preclinical trials implicating ACLY in NAFLD progression.

Infection with the Gram-negative bacterium Helicobacter pylori remains the most important modifiable risk factor for the development of gastric cancer, a leading cause of cancer-related deaths worldwide. How the interactions between H. pylori and its host shape the gastric environment during chronic infection warrants further investigation. In this issue of the JCI, Palrasu et al. used human cell lines and mouse models to provide mechanistic insight into H. pylori’s ability to delay apoptosis in gastric epithelial cells by actively driving the degradation of a proapoptotic factor, SIVA1. Their findings suggest that promoting the survival of gastric epithelial cells has implications not only for H. pylori pathogenesis but for host tumorigenesis.

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.

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.

Systemic sclerosis (SSc) is an autoimmune fibrotic disease whose pathogenesis is poorly understood and lacks effective therapies. We undertook quantitative analyses of T cell infiltrates in the skin of 35 untreated patients with early diffuse SSc and here show that CD4+ cytotoxic T cells and CD8+ T cells contribute prominently to these infiltrates. We also observed an accumulation of apoptotic cells in SSc tissues, suggesting that recurring cell death may contribute to tissue damage and remodeling in this fibrotic disease. HLA-DR–expressing endothelial cells were frequent targets of apoptosis in SSc, consistent with the prominent vasculopathy seen in patients with this disease. A circulating effector population of cytotoxic CD4+ T cells, which exhibited signatures of enhanced metabolic activity, was clonally expanded in patients with systemic sclerosis. These data suggest that cytotoxic T cells may induce the apoptotic death of endothelial and other cells in systemic sclerosis. Cell loss driven by immune cells may be followed by overly exuberant tissue repair processes that lead to fibrosis and tissue dysfunction.

BACKGROUND Glucose-6-phosphate dehydrogenase (G6PD) deficiency decreases the ability of red blood cells (RBCs) to withstand oxidative stress. Refrigerated storage of RBCs induces oxidative stress. We hypothesized that G6PD-deficient donor RBCs would have inferior storage quality for transfusion as compared with G6PD-normal RBCs.METHODS Male volunteers were screened for G6PD deficiency; 27 control and 10 G6PD-deficient volunteers each donated 1 RBC unit. After 42 days of refrigerated storage, autologous 51-chromium 24-hour posttransfusion RBC recovery (PTR) studies were performed. Metabolomics analyses of these RBC units were also performed.RESULTS The mean 24-hour PTR for G6PD-deficient subjects was 78.5% ± 8.4% (mean ± SD), which was significantly lower than that for G6PD-normal RBCs (85.3% ± 3.2%; P = 0.0009). None of the G6PD-normal volunteers (0/27) and 3 G6PD-deficient volunteers (3/10) had PTR results below 75%, a key FDA acceptability criterion for stored donor RBCs. As expected, fresh G6PD-deficient RBCs demonstrated defects in the oxidative phase of the pentose phosphate pathway. During refrigerated storage, G6PD-deficient RBCs demonstrated increased glycolysis, impaired glutathione homeostasis, and increased purine oxidation, as compared with G6PD-normal RBCs. In addition, there were significant correlations between PTR and specific metabolites in these pathways.CONCLUSION Based on current FDA criteria, RBCs from G6PD-deficient donors would not meet the requirements for storage quality. Metabolomics assessment identified markers of PTR and G6PD deficiency (e.g., pyruvate/lactate ratios), along with potential compensatory pathways that could be leveraged to ameliorate the metabolic needs of G6PD-deficient RBCs.TRIAL REGISTRATION ClinicalTrials.gov NCT04081272.FUNDING The Harold Amos Medical Faculty Development Program, Robert Wood Johnson Foundation grant 71590, the National Blood Foundation, NIH grant UL1 TR000040, the Webb-Waring Early Career Award 2017 by the Boettcher Foundation, and National Heart, Lung, and Blood Institute grants R01HL14644 and R01HL148151.

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.

BACKGROUND Mirabegron is a β3-adrenergic receptor (β3-AR) agonist approved only for the treatment of overactive bladder. Encouraging preclinical results suggest that β3-AR agonists could also improve obesity-related metabolic disease by increasing brown adipose tissue (BAT) thermogenesis, white adipose tissue (WAT) lipolysis, and insulin sensitivity.METHODS We treated 14 healthy women of diverse ethnicities (27.5 ± 1.1 years of age, BMI of 25.4 ± 1.2 kg/m2) with 100 mg mirabegron (Myrbetriq extended-release tablet, Astellas Pharma) for 4 weeks in an open-label study. The primary endpoint was the change in BAT metabolic activity as measured by [18F]-2-fluoro-d-2-deoxy-d-glucose (18F-FDG) PET/CT. Secondary endpoints included resting energy expenditure (REE), plasma metabolites, and glucose and insulin metabolism as assessed by a frequently sampled intravenous glucose tolerance test.RESULTS Chronic mirabegron therapy increased BAT metabolic activity. Whole-body REE was higher, without changes in body weight or composition. Additionally, there were elevations in plasma levels of the beneficial lipoprotein biomarkers HDL and ApoA1, as well as total bile acids. Adiponectin, a WAT-derived hormone that has antidiabetic and antiinflammatory capabilities, increased with acute treatment and was 35% higher upon completion of the study. Finally, an intravenous glucose tolerance test revealed higher insulin sensitivity, glucose effectiveness, and insulin secretion.CONCLUSION These findings indicate that human BAT metabolic activity can be increased after chronic pharmacological stimulation with mirabegron and support the investigation of β3-AR agonists as a treatment for metabolic disease.TRIAL REGISTRATION Clinicaltrials.gov NCT03049462.FUNDING This work was supported by grants from the Intramural Research Program of the NIDDK, NIH (DK075112, DK075116, DK071013, and DK071014).

Lipid-rich myelin forms electrically insulating, axon-wrapping multilayers that are essential for neural function, and mature myelin is traditionally considered metabolically inert. Surprisingly, we discovered that mature myelin lipids undergo rapid turnover, and quaking (Qki) is a major regulator of myelin lipid homeostasis. Oligodendrocyte-specific Qki depletion, without affecting oligodendrocyte survival, resulted in rapid demyelination, within 1 week, and gradually neurological deficits in adult mice. Myelin lipids, especially the monounsaturated fatty acids and very-long-chain fatty acids, were dramatically reduced by Qki depletion, whereas the major myelin proteins remained intact, and the demyelinating phenotypes of Qki-depleted mice were alleviated by a high-fat diet. Mechanistically, Qki serves as a coactivator of the PPARβ-RXRα complex, which controls the transcription of lipid-metabolism genes, particularly those involved in fatty acid desaturation and elongation. Treatment of Qki-depleted mice with PPARβ/RXR agonists significantly alleviated neurological disability and extended survival durations. Furthermore, a subset of lesions from patients with primary progressive multiple sclerosis were characterized by preferential reductions in myelin lipid contents, activities of various lipid metabolism pathways, and expression level of QKI-5 in human oligodendrocytes. Together, our results demonstrate that continuous lipid synthesis is indispensable for mature myelin maintenance and highlight an underappreciated role of lipid metabolism in demyelinating diseases.

BACKGROUND The live attenuated BPZE1 vaccine candidate induces protection against B. pertussis and prevents nasal colonization in animal models. Here we report on the responses in humans receiving a single intranasal administration of BPZE1.METHODS We performed multiple assays to dissect the immune responses induced in humans (n = 12) receiving BPZE1, with particular emphasis on the magnitude and characteristics of the antibody responses. Such responses were benchmarked to adolescents (n = 12) receiving the complete vaccination program of the currently used acellular pertussis vaccine (aPV). Using immunoproteomics analysis, potentially novel immunogenic B. pertussis antigens were identified.RESULTS All BPZE1 vaccinees showed robust B. pertussis–specific antibody responses with regard to significant increase in 1 or more of the following parameters: IgG, IgA, and memory B cells to B. pertussis antigens. BPZE1–specific T cells showed a Th1 phenotype, and the IgG exclusively consisted of IgG1 and IgG3. In contrast, all aPV vaccines showed a Th2-biased response. Immunoproteomics profiling revealed that BPZE1 elicited broader and different antibody specificities to B. pertussis antigens as compared with the aPV that primarily induced antibodies to the vaccine antigens. Moreover, BPZE1 was superior at inducing opsonizing antibodies that stimulated ROS production in neutrophils and enhanced bactericidal function, which was in line with the finding that antibodies against adenylate cyclase toxin were only elicited by BPZE1.CONCLUSION The breadth of the antibodies, the Th1-type cellular response, and killing mechanisms elicited by BPZE1 may hold prospects of improving vaccine efficacy and protection against B. pertussis transmission.TRIAL REGISTRATION ClinicalTrials.gov NCT02453048, NCT00870350.FUNDING ILiAD Biotechnologies, Swedish Research Council (Vetenskapsrådet), Swedish Heart-Lung Foundation.

It’s no secret that I love Japan. I mean, I really, really love Japan. I felt more at home in Tokyo than I ever have anywhere else, and I think about going back all. the. time. I’m even thinking about it right now. You’re probably reading this right now because, at the very least, some tiny part of you is curious about whether you should do it. It might be the tiiiiiiiniest little part, but I’m sure it’s there. Maybe you don’t want to admit it because it seems pretty impossible, and yeah, I will admit that if you have a job that you don’t want to leave, strong family ties, kids, pets, or no money (among other things), it must seem like a distant what-if that will never happen. Here’s the thing. If you’re really, honestly interested, then make it happen. Because guess what? You freaking can make it happen, and don’t let anybody tell you no. If you’re coming up with a “But…” right now, I’ll stop you right there! “But I have kids/pets…” Figure out how to take them with you, because you can! “But I don’t want to leave my job…” Take a sabbatical for a year, look into transfers to a branch abroad, look for a better job in the same field in Japan, or look into whether this job is really worth giving up on this dream (maybe it isn’t). “But I can’t speak the language…” So? I moved to Japan and didn’t speak a word. Some people learn before they go, some people learn while they’re there (me), and some people never learn (I don’t recommend this). I could go on forever, but the whole world is at your fingers if you really want it! I seriously believe that. It’s not always easy, but if you want something badly enough, don’t you owe it to yourself to at least try? Anyways, let me give you the top reasons why I think that you should give living in Japan a try! 1. Living in a different culture opens your eyes. This especially is true if you immerse yourself in as much of the culture as you can. Make Japanese friends, learn about what people do on a daily basis and what they believe in. Try doing things in ways that are new to you. Try new foods! Mochi is the schiz, by the way! Once you’ve experienced doing new things, it will change how you do things even if you return back home. I will always have a no-shoes policy in my house (it’s so much cleaner!), I absolutely CRAVE a train system (if only!), and I have a newfound respect for walking and cycling. I never did this when I was little, but now, if I can, I walk! 2. You’ll have a fresh start. In your new home in Japan, you won’t have any of the drama that surrounded you in your old one. Thanks to the internet, we can still keep in touch with friends and family, but being a few thousand miles away from them will keep a lot of the drama to a minimum. Take a chance to stretch your wings and see what kind of person you are when you have the freedom to be you without their judgement. Trust me, it takes a weight off being in a new place where nobody knows who you used to be (or who they thought you used to be). Oh, and you know what? I bet that you will love yourself more than you ever did before. 3. Japan is a magical place! Seriously. Cherry blossoms, gorgeous temples and “castles” (I wouldn’t call them castles, but they’re called that nonetheless, and they’re really cool anyway), a rich history filled with Samurai and ninjas (who doesn’t love ninjas?), seasonal treats, and an entire culture that grew up reading manga. How does this not sound like an amazing place to live?!  And no offense to any other country, but Japanese trains come quickly, go almost everywhere, are extremely punctual, and pretty clean, which makes them (Tokyo especially) easily #1 in the world in public transportation. Now that sounds magical to me. 4. Universal Health Care. If you’re American like me, this will make a HUGE difference in your life. Trust me. If you come from pretty much any other 1st world nation, it probably won’t matter as much, though. But at least it’s good! 5. Japan is safer than where you came from. There’s no gun violence. There’s very low crime in general. You can walk in the dead of night in the seediest parts of town, as a woman, alone, and still feel perfectly safe from other people. From earthquakes is another matter, but you’ll get used to them really fast, and Japan is built to withstand all but the biggest. 6. Wa. There is a concept called wa in Japanese society, which essentially promotes practicing peace and harmony in your daily life. Wa is obvious in everything from traditional architecture and decor to the way that people act around each other– courteousness, quiet, and respect are what you expect most from your neighbors. You’re never going to wake up to your neighbors blaring music at 3am having a raucous party. Even drunken people wandering the street are more polite than not (although most of them just sort of stumble home or sit down where they are for the night– but remember, Japan is safe so they only thing they have to worry about is getting chilly). We could all use a little bit of harmony in our lives, and that’s something that Japan taught me to value. I’m surprised that yoga isn’t more popular, since they’re pretty in tune with each other. 7. All the new gadgets, and all of the old culture. Sure, Silicon Valley is where a lot of new apps are coming out, but if you want lots of little weird but useful gadgets to make your life easier (or more interesting), take a stroll through Akihabara. Plus, there are tons of cheap versions of what you’re used to, like large-capacity flash drives and SD cards. And I would be remiss in not mentioning the used electronics! Smartphones! Right next to small neighborhood temples, btw. It’s the only place to find Ayanami Rei in a kimono, wandering the street. The best of both worlds! 8. MANGA AND ANIME EVERYWHERE. This should be your main reason. This should be enough of a reason. Not only is it available everywhere, but events abound. If you wanted, you could go to an anime-related event every weekend of the year. Also, let’s not forget that it’s the only place to see all of the anime movies released in the theater, go to the official events (like Jump Festa, Comicket, World Cosplay Summit, and Anime Japan, among others), and see the musicals, seiyuu radio shows, and stage plays. If this isn’t reason enough, you’re probably in the wrong place. 9. It’s cheaper than you think. I lived in Tokyo, and then I moved back to the US, thinking that because I was living in a place often called “The Most Expensive City In The World,” it would be cheaper here. Nope.. Apartment rents, even in small cities, are at least the price that I was paying in Tokyo (~$600/mo). And try finding that in LA. So far I haven’t had any luck, and especially not in the areas that are actually sort-of-kind-of safe. Food is also about on-par with the US, especially domestic food. Considering that it’s an island, it’s actually really, really cheap. Food in Hawaii cost sometimes 3-4 times what I was able to get it for in Japan. Then, when you factor in healthcare, which is pretty cheap (what you pay for the insurance is based on your income, and then it covers 80% of all your bills — this is a simplification, but generally holds true), and transportation costs (you don’t need a car, therefore no gas, no insurance, no car maintenance fees), it’s downright cheap. Even living in Tokyo. 10. You will never run out of things to do. In nearly a decade, I never ran out of cool things to do. Can you say the same about the city that you live in now? Thought so. Ah man, I kinda feel ready to jump back on a plane and move across the ocean… three cats and all! Somebody hold me back… resistance is fading……………….  

Cats. Cats are the best, and I can’t seem to settle down in any one place for too long, so my cats (possibly to their dismay) have had to move around with my silly butt. I don’t own a boat that can cross the Pacific Ocean, so that means taking them on a plane. BUT! While it’s no fun for anyone, it’s not really as hard as you think! Really really! My cats are my family, and if you’re here then you probably also have furry family members, and you are worried about flying with them. I’ve both taken my cats in the cabin and had to check them into the pet cargo hold (to my terror), but they not only survived, they are all flourishing wonderfully. While things do happen (and if something happens, raise a ruckus and make sure that whomever hurt your baby knows it), for the most part, flying is actually pretty safe for cats. Not that you want to take them. It’s just that sometimes you have to. So read on for my personal tips on how to make the flight go as smoothly as possible for all of you! Trust me, you’ll want it to be this way. My cats at the vet for their checkups and vaccinations. 1. Do Your Homework. This might seem obvious, but that being said, let’s put it out there anyway. Know your stuff! There are two things that you’re going to need to find out as soon as you decide to fly with your pets:      a) What paperwork does the airline require for me to bring my cat on the plane?      b) What does my arrival location require for me to bring my cat into the country/state? Usually, a) is the easiest part. It’s usually just a health certificate from your vet, issued less than a week before travel. Just book an appointment at your vet for less than a week before departure, and tell them that you’re flying to (wherever). All of my vets, even my one in Japan, either knew what they needed, or looked it up beforehand. Check your airline’s webpage (my absolute favorite for flying with pets is Alaska Air, btw. You can take two in the cabin by yourself, and it’s the only airline I know of that allows this!), and follow the instructions. I keep all of my paperwork with my passport while flying, so that I can show it to the ticketing agent or anyone else that asks (sometimes, nobody has, but at least I had it). In all of the cases where I’ve flown, my plane required a current health certificate to board, and when I left Japan, they required an inspection from the on-site team, which I just asked for when I arrived in Narita. b) can be easy, or it can be hard. In order to enter the US from Japan, I had to check the US Customs website for the country’s official regulations, and Washington State for its regulations.  The US didn’t have any regulations at the time, but Washington state required a health certificate (same as the plane), and current rabies vaccination, both of which I had done within the week before I left. Funny enough, nobody checked my paperwork after I landed, since it was the 4th of July and the Agricultural Inspections office was closed. When I went to Hawaii, it was another story. It was a long, long, long process (more than 6 months) to get all of my testing and paperwork done for Sansa to enter the state, but I did it, kept all of my paperwork in order, and was able to leave the airport in Hawaii with her in my arms without any fuss! There was a lot to do, but I just made sure that I knew what I needed, did it, and had the documentation, and things were pretty smooth sailing afterward! You should always check the official government pages to make sure that you have the correct information. In Hawaii’s case, it can be found here. All of my cats reacted differently to being examined. 2. Get your stuff in order! Once you have your list of things that you need (vaccinations, health checks, etc), then CALL the airline to make your reservations (you always need to call them in order to add pets to your tickets. They usually cost a little bit extra, and try to get them in the cabin if you can). Then, check your airline’s website to find out what kind of carrier you will need, and whether you will need anything else. When I flew to Washington the first time, and to Hawaii, I only had one cat, so I didn’t need any food (I brought some anyway, and a little bowl in my carryon just in case), and a soft-sided carrier that would fit in the dimensions they specified on their websites (it’s usually in the pet section or the carry-on section, and every airline is different). When I flew to Washington again, it was with three cats, so I needed two large hard carriers that met certain criteria for my babies flying underneath, and one soft-sided one for the baby going in the cabin. The website for the airline was very specific, but it was easy to find what I needed at Petco. Check, check, and check. I had my carriers, my paperwork, and I was ready! When your cat isn’t too happy about getting her shots. 3. Getting ready for the flight. A week or so before my flight (or days in my last case), I set all of my pet carriers out in the living room and set them up how I was going to have them for the flight — I lined the bottoms with puppy training pads (in case there was an accident in-flight), then a towel for absorbency (in the large hard carriers only), and finally, on top of that, a blanket that I had been using a lot (so that it had our scents on it, and would comfort the cats). I sprayed the interior of all of the carriers with Feliway, and left them out for the cats to get used to them. The carriers sitting out for the curious kitties to explore. They all took turns exploring the carriers, and after a few days, got comfortable with them and would lounge around inside, play with them, and rub up against the sides. This was all in order to reduce the stress of travel on them as much as possible. I continued to spray them with Feliway at least once a day until we left. There is no hard and fast rule on this, but I took away my cats’ food and water the morning of the trip, and waited until just before we left to toss out the litter boxes. There was some satisfaction in being able to stuff those nasty things in a giant garbage bag and haul them to the trash without scooping! Hey, take pleasure while you can– you’re about to undertake something pretty stressful! After I called my Uber, I rounded up the cats one by one and deposited them in their carriers. Nobody was particularly happy about this, but just be patient. Two of my babies at the airport waiting for inspection. All of them were champs! 4. The Flight Be calm, patient, and as rational as possible. I know that it’s pretty scary (terrifying, to me) to let your precious babies our of your sight, but once the porter had helped me to the ticket counters (I actually needed two the last time, and I tipped them very well), I just reminded myself that it would all be over soon, and that the calmer I was, the better the kitties would feel. In order to pass through security, you will need to remove the cats one-by-one from their carriers and hold them while the crew puts your carrier through the scanner, or manually scans by hand (two of mine were too large to fit). Sometimes, they will let you do all of this in a separate room so that the cats are calmer, but there isn’t always one available (it will say that you can do this on most websites, but I wasn’t allowed a separate room the last time and had to hold three wiggly cats in the middle of the airport). BRING A HARNESS FOR THIS. I can’t stress this enough. My cats don’t like harnesses, but I fastened one to them before I brought them out of the carrier, and removed it right after, and it brought me a lot of peace of mind. None of my cats tried to run, but I have heard that some cats do, and you don’t want to take that chance. Look for a harness like this one— thick and really hard to pull out of. Better safe than sorry. I only brought one harness for three cats, since I would only need to take out one cat at a time. By the next morning, everyone was already claiming “our” new bed as their own. And that’s it!  Once you’re on the flight, it’s mostly a waiting game. I honestly am not sure whether the cats or I were more stressed about the trip, and they were certainly shaken and scared when they arrived at our new home. However, within a few days, my cats were all behaving as if they’d never lived anywhere else. They rebound quickly as long as you shower them with love and affection. ???? Well, those are my tips for making the smoothest ride possible! It helps to have litter and litter pans, food, etc, sent to your new place before you arrive, as well, so that everything will be easy to set up for you. Make sure that your kitties are confined to one room for at least a few hours, and let them hide for as long as they need to. They’ll get curious and hungry and come out on their own. I hope this helps someone! If I did it, anyone can! Remember, I took three cats on a flight overseas BY MYSELF! Nobody to even drop my off at the airport but an UberXL driver! =^-^=

You read that right. Joanne and I visited a Masonic Cemetary. Alone. It was one of the most calming experiences of my life. We were kind of invited, by the town, and when we arrived, we were definitely welcomed by the residents. This all started when, in the brochure listing the “town attractions” that we received in St. Helens, were two cemeteries. The addresses as well as short descriptions were listed, as well as a short missive asking us to please be respectful and not make loud noises. It sounded really creepy and really interesting, so both of us jumped at the chance to drive out there right before sunset. They weren’t what I expected at all… Well, the first one was actually roped off with a “no trespassing” sign hanging from it, so we didn’t go inside. It was right alongside the highway in Oregon, across some old train tracks, visible from the road, and named and marked on a tourist map, yet they didn’t want visitors. I wonder what happened there. In any case, we headed for the other cemetery. This one was removed from the main road, and rumored to be a lot larger. It was also known to be haunted, but visitors were welcome as long as they were respectful. Off the map it was, but when we arrived, it was also gated off. A sad Joanne looks through the gate at the second destination that was cut off from us. Ah, but unlike the other cemetery, this one didn’t have a “no tresspassing” sign. There was a clear path around the sides of the gate, the ground bare of grass and obviously well-traversed. Apparently a lot of people walked around the gate. Maybe they just didn’t want us to drive. We decided to walk. There was even a sign. And a long, winding, steep road through the forest.  It was quite a hike to reach the top of the large hill where the cemetery was supposedly located, but the view was breathtaking. It took us a good ten or fifteen minutes to reach the top, and the road was quite steep. For some reason, to the immediate right of the trail, someone had been excavating land for quite some time, and there was a deep quarry. Why someone would dig a quarry next to a burial ground is beside me. I don’t doubt that the residents were unhappy about it. I wondered if maybe I would feel some spirits, but I didn’t expect what really happened to me. As soon as I stepped off of the road and onto the grass, a calm unlike anything I’ve ever felt descended upon me. It enveloped me in a warm cocoon, and Joanne and I immediately separated and wandered quietly alone between the gravestones. I know, 100%, that not only was I welcomed, but that the residents were happy to have me there. I talked a bit with some of the gravestones, but mostly wandered about, amazed at how much serenity I felt. We must have spent around a half hour wandering quietly alone, together, before we left in order to return to the festivities in town. But I’ll never forget the experience. It was something really, really special. I took some video footage too, but I’m not sure yet whether I want to use it. We’ll see! Someday, I’ll set up a tripod and get a shot of me walking like this. But for now, have Joanne instead. ???? <3

Being back in a cold and rainy climate reminds me of Tokyo. No, seriously. Washington has four seasons, just like Tokyo did, and just like Hawaii didn’t. I suppose that’s what has been making me feel really nostalgic these days. I’m in a place with the weather of Japan, but way less awesome. I have seriously owned around seventeen kajillion books about Japan in my lifetime, and I’ve given away, donated, or sold back almost the same amount. Some of them I bought, some of them were given to me, and I even found one or two. But the thing is that I have moved so many times that the only ones I’ve kept are those that I absolutely, positively, do not want to live without. (Well, maybe I could live without them, but then would I really be living?) Anyays! Right now, I only own three books in English about Japan, and these are them, and here is why I really like them:   1. The Otaku Encyclopedia: An Insider’s Guide to the Subculture of Cool Japan Disclaimer: A friend of mine wrote this, but that’s not why I’m recommending it.  Pat has written a bunch of books and papers, and they’re all great, but this is the one that I wish that every single otaku in the world could have. What is it? It’s seriously a dictionary, but not the kind of dictionary that we used when I was a little kid to look up stuff for our school essays. I never had a dictionary like this. You probably know what Hatsune Miku is, but do you know what a Heta-uma is? How about a kuchi-paku? Guess where you can find all of that information that you didn’t know that you needed to have? In this freaking book. I know a fair amount about Otaku culture. I lived and breathed it in Japan for almost a whole decade. But I didn’t know half of the stuff that Patrick wrote about in his book, and that’s why you need it. Plus, it’s got a lot of color, a cute mascot, and some really cool exclusive interviews. You can even learn about Tenimyu!   2. Tokyo on Foot So. I saw this book in the book store in Japan, even though it’s written in English. Maybe that’s because although there is a story in it, it’s mostly drawings and you don’t need to be able to read to get the gist of it. It was written/drawn by an artist that came to stay in Tokyo while his girlfriend was there for an internship. He spent almost every day of his six months there wandering the city with colored pencils and a pad of paper and drawing what he saw. Not only are his drawings aces, I absolutely love his little comments about places and people and things. Right after I bought this book (years ago), I was so enamored that I tried emulating his style with less than stellar results. Me and colored pencils don’t mix, which kind of makes this book even more cool (somehow)! Part of the reason that I really enjoyed this book was because it made me nostalgic for my own first days in Tokyo. I remembered thinking a lot of the same things. I just wish that I’d been good with colored pencils (and had enough confidence to write a book). You can read about my first year here on my blog, though! Honestly, I don’t think that this book is as much a must-have for otaku as the other two, but if art and impressions of Japan is your thing, I think you will love it as much as I do. I seriously only brought two English-language books back with me when I moved out of Japan, and this was one. The other was an ancient copy of The Mysterious Island that my father got when he was a kid and passed on to me.   3. Tokyo Geek’s Guide Aaaaalright. I was really, really skeptical about this one. I’ve seen a hundred other “guides to Tokyo” for otaku, but I didn’t keep any of them. This one, though? I am not only keeping it forever, I am going to give a copy to any of my friends traveling to Japan on their own to go otaku-shopping. Holy cow, I wish this book had existed when I first moved to Japan, because it covers things that it took me years of living there to find on my own! It’s a bona-fide travel guide, minus all of the generic stuff that you can find in a normal travel guide. It doesn’t focus on hotels or nice restaurants. Instead, it lists maid cafes, anime shops, and AWESOME stuff like Swallowtail (don’t know what that is? You need to get this book and find out because it is awesome!). The book is split into districts of Tokyo, and lists otaku-related info about each area along with detailed maps and how to get to all of these places. It’s kind of big and heavy for a travel guide, but it’s seriously the only one that I’m interested in having with me next time that I travel to Tokyo. There are places in it that I haven’t even been to. Oh, and bonus? There is a whole section in the latter part of the book talking about Geeky festivals like Comicket and JUMP Festa. I REALLY, REALLY WISH THAT THIS HAD BEEN AROUND WHEN I MOVED TO JAPAN. It’s 14 years too late for that, but not too late for my next trip, and not too late for yours! It’s also in full color. If you’re reading this, I think that you will probably want this book. GO BUY IT.   This has absolutely NOT been a paid advertisement. I am just a geeky girl honestly recommending things that she likes to you that she thinks you need. :3 See you again soon la la la!

Time for a break is here - the new Weekday Escape arrived! This week we get typical escape games only - four rooms with firmly closed door. The first comes Amajeto who locked you in their nice living room and... Tagged as: amajeto, blog, browser, escape, free, gotmail, japanese, pixelkobo, pointandclick, puzzle, rating-g, smartcode, spiceapp, weekday-escape

Hi, it's escaping time! With Amajeto's light and fresh room we move closer to spring and all the cute tiny birds support that feeling. TomoLaSiDo reached us a bit late for Valentine, but never mind it's fun - actually, it's... Tagged as: amajeto, blog, browser, escape, free, japanese, pixelkobo, pointandclick, puzzle, rating-g, rinnogogo, tomolasido, weekday-escape

Another escape Wednesday is here! Very retro Ariyoshi's game is quite short but fun, with refreshing approach to the genre. TomoLaSiDo locked you in their room on the day with special calendar date and you need to gather several outlets... Tagged as: ariyoshi, blog, browser, escape, free, japanese, nicolet, pixelkobo, pointandclick, puzzle, rating-g, tomolasido, weekday-escape

Welcome, this week it's retro time again! Vitamin Hana wants you to escape from an unusual place - from an oceanarium. Then you get locked in Yomino Kagura's prettily decorated room, and then it's time for No1game 's short adventure... Tagged as: blog, browser, escape, escapemen, free, fuwayura, japanese, no1game, pointandclick, puzzle, rating-g, vitaminhana, weekday-escape, yominokagura

Hi! The week is over and the brand new Weekday Escape here! Amajeto helps you to enjoy your stay at home and suggests some activities like looking for lost remote controller in coded drawers and finding ways how to open... Tagged as: amajeto, blog, browser, escape, free, japanese, masa, pixelkobo, pointandclick, puzzle, rating-g, rinnogogo, weekday-escape

Hi, it's time for a break, it's escaping time! Selfdefiant wants you to escape a desert temple which is, very conveniently, placed next to a stream so no worries of dehydration in case you stay here longer than expected. TomoLaSiDo... Tagged as:

Hello - the new WE is here! Wishing you beautiful spring and happy playing during this quarantine time! Amajeto is definitely back and has changed remarkably, the latest game is bigger and feels more like their older escapes. Very nice.... Tagged as: blog, browser, escape, free, gotmail, japanese, nicolet, pointandclick, puzzle, rating-g, selfdefiant, spiceapp, tomolasido, weekday-escape

Hi, it's time to have some fun from the past! This Weekday Escape is retro! Vitamin Hana wants you to escape a room - no surprise - but also to redecorate it. Yomino Kagura isn't so demanding, their escape is... Tagged as: blog, browser, esc-forest, escape, escapemen, free, japanese, no1game, pointandclick, puzzle, rating-g, vitaminhana, weekday-escape, yominokagura

It's Wednesday, it's escape time! Amajeto locked you in their room and wants you to escape, and TomoLaSiDo as well. Puzzles aren't hard so it doesn't take long to leave to enjoy the lovely weather outside. In Spiceapp's escape you... Tagged as: amajeto, blog, browser, escape, free, gotmail, japanese, masa, pointandclick, puzzle, rating-g, spiceapp, tomolasido, weekday-escape

Hi, hope your week is fine so far - now even better with new Weekday Escape! From Amajeto's room you'll escape easily with all the practice you have. Then you get locked in Akatsuki no Yado's one, a bit complicated... Tagged as: akatsukinoyado, amajeto, blog, browser, escape, free, gotmail, japanese, nicolet, pointandclick, puzzle, rating-g, spiceapp, weekday-escape

Hope you’re having a wonderful summer or winter, depending on where you live. I’m hard at work on new books for you, and wanted to quickly let you know about a Kindle Countdown Deal on Amazon US and UK! (Amazon only does these deals in the US and UK–sadly it is out of my control. […]

You can grab four steamy and sweet MM holiday romances in one box set for a major discount! This new collection is only $6.99 or you can borrow it in KU. I’m also very excited that these novellas are available in print for the first time! ???? Buy the ebook box set exclusively at Amazon […]

“Looking for a fun and sweet holiday romance with dual POV, some heat, a humorous caper, and a wonderful HEA ending? Look no further!” ~ Gay Book Reviews Fa-la-la-la-la! My new holiday romance is now available to buy or borrow in KU! You’ve got fake boyfriends, bisexual exploration, found family, a single dad in desperate need […]

My figure skating romance has a new (old) title! Misha and Dev’s story was originally two novellas published through Loose Id called Cold War and Holding the Edge. I later combined them into one volume to give you more bang for your buck. To avoid confusion, I called the book The Winning Edge. However, Cold War is frankly just a much better […]

Hello! Hope you and yours are all well and safe during these stressful times. If you need an action-packed adventure to escape with, Ends of the Earth is on sale this week only for $0.99! On a Montana camping trip, single dad Jason is surprised by his attraction to Ben, an older park ranger. But when Jason’s daughter is kidnapped, […]

iFixit hasn't yet done a full teardown of the new Magic Keyboard designed for the new iPad Pro models, but the repair site today partnered with x-ray company Creative Electron to create Magic Keyboard x-rays that give us a view of just what's inside.


The Magic Keyboard uses scissor switch keys instead of butterfly keys, which have now been effectively eliminated from Apple's product lineup. The scissor switch mechanism is clearly visible in the x-ray view, and iFixit calls it the simplest mechanism in the accessory, but the biggest improvement compared to the Smart Keyboard.

Below the keyboard, there are metal plates that iFixit believes are for reinforcing the keyboard's body against bending, and the trackpad is a new design that's different from MacBook trackpads.

There appear to be multiple buttons under the trackpad to capture presses, while the MacBook Trackpads have no buttons and simulate presses with haptic feedback.


There are at least two spring loaded hinge designs at the folding point, featuring both a small coil and a larger coil, plus there are two cables for connecting the Smart Connector to the keyboard for power and data transfer.

Lots and lots of magnets are visible in the x-ray, with the magnets used to hold the Magic Keyboard on the ‌iPad Pro‌. There's a whole ring of tiny magnets around the camera cutout, which iFixit said was a "lot of little polarized bits" to line up, space out, and configure with the ‌iPad Pro‌ components.

According to iFixit, there's more going on in the Magic Keyboard than there is in many laptops, which could explain its price point. Apple charges $299 for the 11-inch Magic Keyboard and $349 for the 12.9-inch version.

This article, "An X-Ray View of Apple's Magic Keyboard for iPad Pro" first appeared on MacRumors.com

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Popular journaling app Day One today updated to version 4.13, adding support for trackpad navigation on iPad, a new Day View interface, and other improvements.


This release comes after the launch of iOS and iPadOS 13.4, which added support for trackpads and mice on ‌‌iPad‌‌.

After updating, Day One users on ‌iPad‌ can use various trackpad actions to interact with the app, including two-finger swipe down to dismiss, and two-finger horizontal swipe to open and close the journal drawer.

• How to Use a Bluetooth Mouse or Trackpad With Your iPad

The new Day View offers quicker access to daily entries by tapping on or clicking dates in the calendar or the timeline.

Also in this update, Daily Reminders now include additional information like the number of photos taken and locations visited on a given day, and the Settings pages now provide links to Day One feature documents.

Elsewhere, several bugs have been fixed, including one that caused video thumbnails not to display in the media timeline, and one that prevented photos in the activity feed from showing location or calendar events.

Day One is a free download for iPhone and ‌iPad‌ from the App Store with in-app purchases for premium features. [Direct Link]
This article, "Day One Journaling App Update Adds iPad Trackpad Support, New Day View, and More" first appeared on MacRumors.com

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Apple today announced that it will begin reopening its retail stores in Germany on May 11, nearly two months after they were closed due to the global health crisis.


In a statement shared with German website Macerkopf, Apple said the stores will initially be focusing on Genius Bar service and support. Enhanced health and safety measures will be implemented, such as body temperature checks prior to entry, limits on how many customers can be in the store at once, social distancing, and reduced hours of operation.

Apple operates 15 retail stores in Germany and will be posting specific hours of operation for each location on its website.

Apple closed all of its retail stores outside of the Greater China region in mid-March. The company has since started to reopen some locations, including in South Korea, Austria, and Australia. All locations in the United States remain closed.

This article, "Apple Stores in Germany to Begin Reopening May 11 With Enhanced Health and Safety Measures" first appeared on MacRumors.com

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Amazon is taking up to $100 off the Apple Watch Series 5 this week, with prices starting at $299.99 for the 40mm GPS models. Only the Gold Aluminum Case with Pink Sport Band is available at this price. If you order today, the Apple Watch should arrive sometime next week.

Note: MacRumors is an affiliate partner with Amazon. When you click a link and make a purchase, we may receive a small payment, which helps us keep the site running.

The Apple Watch Series 5 was released in September 2019 with a new OLED screen that supports an always-on feature, which represents the biggest change to the Series 5 models. The newest Apple Watch is available in 40mm and 44mm sizes, and it has the overall same design as the Series 4 models.

$100 OFF

Apple Watch S5 (40mm, GPS) for $299.99

If you're shopping for a cellular model, there are also a few solid discounts on Amazon for these devices. You can get the Gold Aluminum Case with Pink Sport Band (40mm) for $399.00, down from $499.00. Likewise, the Silver Aluminum Case with White Sport Band (40mm) is $399.00 right now.

For the 44mm cellular models, a solid deal is the Space Gray Aluminum Case with Black Sport Band at $429.00, down from $529.00. You'll find the same price on the Silver Aluminum Case with White Sport Band and the Gold Aluminum Case with Pink Sport Band.

Across the board, these sales are either new low prices on the Apple Watch Series 5, or they're matching previous low prices seen on these models on Amazon. There are a few other deals going on for different Series 5 models as well, including numerous 44mm cellular devices that are about $50 off Apple's original prices. Be sure to head to Amazon to check out the full sale before these prices expire, or the retailer runs out of stock.

Keep up with all of this week's best discounts on Apple products and related accessories in our dedicated Apple Deals roundup.
This article, "Deals: Apple Watch Series 5 Models Discounted by Up to $100 on Amazon" 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.
This article, "Apple Arcade's Latest Game Combines Turn-Based RPG With Strategy Board Game" first appeared on MacRumors.com

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