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It's hard to keep up with the Zoomers!

Helping you manage those out-of-control feelings!

Contes de fées aux enfants - Bonne route, les amis !.

Contes de fées aux enfants - L'histoire de Jack le fermier.

It’s not everyday we regurgitate a few old (and new!) chemistry jokes. How often do we tell them? Periodically. We told one the other day, but there was no reaction. Hahaha! Wait? How come nobody else is laughing? Ehem… well, anyways, here are a few more: When I first heard oxygen and magnesium got together […]

The post Top 20 Chemistry Jokes of Some Time appeared first on Funny & Jokes.

---------------------------------------------------[Sat Nov 26 15:25:44 2016]--
From: (S) ease of well-being  (steph)

Subject: Optimism or denial as mental self-defence

A few things recently have given me cause to consider my response to bad things
happening, and my reactions to other people's responses.  First, there's
Trump's election in the US which is undesirable and directly or indirectly
likely to cause some people harm (although I doubt it'll have any effect on me
personally).  I agree that he's not the best or even a good candidate and I
agree that he has incited prejudiced people to show and act on their
prejudices: people are being hurt.  However, I do not like the stream of
articles saying he's a white supremacist or a Nazi or California should secede
or the Electoral College should choose Clinton, or whatever.  Part of this is
doubtless my contrary streak, but part of it is something different.  I observe
that I am semi-consciously adopting a position that `things will turn out all
right' or `it won't be that bad' because countenancing the opposite is not good
for my mental health.

The other thing is some changes in the wider organisation for which I work;
basically there has been a botched reorganisation which has left most people
unhappy and from what I hear from numerous sources with good reason.  This
doesn't currently affect me much and I don't expect it to because of political
realities.  However, even just having the argument with someone closer to the
failing department (and more likely to feel its direct effects) seems to be
followed by my feeling anxious and depressed.  Again, adopting a constructive
positive attitude (which may appear to others pollyannaish, naive, optimistic,
or just in denial) seems to be a defence I've learned here and I suspect it
helps.  But there's more obviously a risk when I'm more involved than I am in
the US case, namely that my optimism will blind me to dangers that will be to
my detriment.

Does my ornery nature come to the rescue, though?  Perhaps because I'm at heart
a bit of a grumpy sod and only respect authorities when I think they deserve it
my tendency to want to probe and prod and query and dig my heels in may
counteract the defensive optimism.  Or alternatively, I'm optimistic in a
different sense: perhaps I just have confidence that I'll win?

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.

Familial dysautonomia (FD) is the most prevalent form of hereditary sensory and autonomic neuropathy (HSAN). In FD, a germline mutation in the Elp1 gene leads to Elp1 protein decrease that causes sympathetic neuron death and sympathetic nervous system dysfunction (dysautonomia). Elp1 is best known as a scaffolding protein within the nuclear hetero-hexameric transcriptional Elongator protein complex, but how it functions in sympathetic neuron survival is very poorly understood. Here, we identified a cytoplasmic function for Elp1 in sympathetic neurons that was essential for retrograde nerve growth factor (NGF) signaling and neuron target tissue innervation and survival. Elp1 was found to bind to internalized TrkA receptors in an NGF-dependent manner, where it was essential for maintaining TrkA receptor phosphorylation (activation) by regulating PTPN6 (Shp1) phosphatase activity within the signaling complex. In the absence of Elp1, Shp1 was hyperactivated, leading to premature TrkA receptor dephosphorylation, which resulted in retrograde signaling failure and neuron death. Inhibiting Shp1 phosphatase activity in the absence of Elp1 rescued NGF-dependent retrograde signaling, and in an animal model of FD it rescued abnormal sympathetic target tissue innervation. These results suggest that regulation of retrograde NGF signaling in sympathetic neurons by Elp1 may explain sympathetic neuron loss and physiologic dysautonomia in patients with FD.

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.

IL-17–producing RORγt+ γδ T cells (γδT17 cells) are innate lymphocytes that participate in type 3 immune responses during infection and inflammation. Herein, we show that γδT17 cells rapidly proliferate within neonatal lymph nodes and gut, where, upon entry, they upregulate T-bet and coexpress IL-17, IL-22, and IFN-γ in a STAT3- and retinoic acid–dependent manner. Neonatal expansion was halted in mice conditionally deficient in STAT5, and its loss resulted in γδT17 cell depletion from all adult organs. Hyperactive STAT5 mutant mice showed that the STAT5A homolog had a dominant role over STAT5B in promoting γδT17 cell expansion and downregulating gut-associated T-bet. In contrast, STAT5B preferentially expanded IFN-γ–producing γδ populations, implying a previously unknown differential role of STAT5 gene products in lymphocyte lineage regulation. Importantly, mice lacking γδT17 cells as a result of STAT5 deficiency displayed a profound resistance to experimental autoimmune encephalomyelitis. Our data identify that the neonatal microenvironment in combination with STAT5 is critical for post-thymic γδT17 development and tissue-specific imprinting, which is essential for infection and autoimmunity.

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.

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.

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.

Approximately half of the world’s population is infected with the stomach pathogen Helicobacter pylori. Infection with H. pylori is the main risk factor for distal gastric cancer. Bacterial virulence factors, such as the oncoprotein CagA, augment cancer risk. Yet despite high infection rates, only a fraction of H. pylori–infected individuals develop gastric cancer. This raises the question of defining the specific host and bacterial factors responsible for gastric tumorigenesis. To investigate the tumorigenic determinants, we analyzed gastric tissues from human subjects and animals infected with H. pylori bacteria harboring different CagA status. For laboratory studies, well-defined H. pylori strain B128 and its cancerogenic derivative strain 7.13, as well as various bacterial isogenic mutants were employed. We found that H. pylori compromises key tumor suppressor mechanisms: the host stress and apoptotic responses. Our studies showed that CagA induces phosphorylation of XIAP E3 ubiquitin ligase, which enhances ubiquitination and proteasomal degradation of the host proapoptotic factor Siva1. This process is mediated by the PI3K/Akt pathway. Inhibition of Siva1 by H. pylori increases survival of human cells with damaged DNA. It occurs in a strain-specific manner and is associated with the ability to induce gastric tumor.

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.

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 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).

The editors of JCI and JCI Insight are revisiting our editorial processes in light of the strain that the COVID-19 pandemic places on the worldwide scientific community. Here, we discuss adjustments to our decision framework in light of restrictions placed on laboratory working conditions for many of our authors.

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.

Brown and beige adipose tissues contain thermogenic fat cells that can be activated by β3-adrenergic receptor agonists. In rodents, such drugs both diminish obesity and improve glucose homeostasis. In this issue of the JCI, O’Mara et al. and Finlin and Memetimin et al. report that chronic administration of the approved β3 agonist mirabegron to human subjects was without effect on body weight or fat mass, but improved several measures of glucose homeostasis. Though the mechanisms mediating these metabolic effects are uncertain, the data suggest that β3 agonists could have therapeutic utility in disorders of glucose homeostasis.

BACKGROUND Beige adipose tissue is associated with improved glucose homeostasis in mice. Adipose tissue contains β3-adrenergic receptors (β3-ARs), and this study was intended to determine whether the treatment of obese, insulin-resistant humans with the β3-AR agonist mirabegron, which stimulates beige adipose formation in subcutaneous white adipose tissue (SC WAT), would induce other beneficial changes in fat and muscle and improve metabolic homeostasis.METHODS Before and after β3-AR agonist treatment, oral glucose tolerance tests and euglycemic clamps were performed, and histochemical analysis and gene expression profiling were performed on fat and muscle biopsies. PET-CT scans quantified brown adipose tissue volume and activity, and we conducted in vitro studies with primary cultures of differentiated human adipocytes and muscle.RESULTS The clinical effects of mirabegron treatment included improved oral glucose tolerance (P < 0.01), reduced hemoglobin A1c levels (P = 0.01), and improved insulin sensitivity (P = 0.03) and β cell function (P = 0.01). In SC WAT, mirabegron treatment stimulated lipolysis, reduced fibrotic gene expression, and increased alternatively activated macrophages. Subjects with the most SC WAT beiging showed the greatest improvement in β cell function. In skeletal muscle, mirabegron reduced triglycerides, increased the expression of PPARγ coactivator 1 α (PGC1A) (P < 0.05), and increased type I fibers (P < 0.01). Conditioned media from adipocytes treated with mirabegron stimulated muscle fiber PGC1A expression in vitro (P < 0.001).CONCLUSION Mirabegron treatment substantially improved multiple measures of glucose homeostasis in obese, insulin-resistant humans. Since β cells and skeletal muscle do not express β3-ARs, these data suggest that the beiging of SC WAT by mirabegron reduces adipose tissue dysfunction, which enhances muscle oxidative capacity and improves β cell function.TRIAL REGISTRATION Clinicaltrials.gov NCT02919176.FUNDING NIH: DK112282, P30GM127211, DK 71349, and Clinical and Translational science Awards (CTSA) grant UL1TR001998.

I’ve been to Forks and La Push, where the Twilight book series takes place, but I’ve never been to the actual filming locations from the movies! That’s because while the director wanted to film in Forks, when he came to scout the town he realized there was just not enough infrastructure to support an entire film crew– there were literally not enough places to house and feed all of the people who would be working on the movie, and there was no other large town within driving distance! (Yeah, Forks is really far out there) Enter Halloweento— I mean, St. Helens, Oregon! St. Helens stands in for most of Forks in the movies, and a few places in nearby Portland, Oregon make up most of the rest. I ended up nearby by complete accident, as it was only when I picked up a brochure at Halloweentown that I learned that Bella’s house was just on the other side of town! LUCKY!!!  So, we took a short break to drive over to the locations that were still standing, and made a special detour to Portland because how could we leave the Cullen house behind?! I WANTED TO GO INSIDE SO BADLY! It is a real house with real people that live there, and although they encouraged taking photos from outside (according both to a brochure from City Hall and a sign in front of the house), the inside was off-limits. Honestly, it’s not Bella that I particularly love. I didn’t care for her portrayal by Kristen Stewart (sorry!), or her melancholy, passive attitude in the book. Actually, I didn’t care for Edward, either. It was the idea of a love so strong that forces of  nature were pulling you together. It’s the idea of fitting together so perfectly that you can’t do anything without the other that I am a complete sucker for! I said it on my old Livejournal years ago, but Twilight is just a big Mary Sue anyway, so I like to imagine myself as Bella, with a gorgeous (female) Edward out there waiting for me. ???? Like I said, it’s the love, not the characters themselves. I’ll fight you on this (just kidding). ???? Here is where Edward rescued Bella from some catcallers, complete with the mural that the movie crew painted (!) on the building. And the theater that they drove past, that you can’t really see well in the movie but hey, it was on the map!! This is Jilly’s, which supplied all of the dresses in the shop when Bella went to pick out something with her friends for prom. Oddly enough, they had this sign outside but no actual merchandise inside. Go figure. ???? This place, which is a private house now, was the bookstore where Bella went to find out more information about the Quileute myths. And then, though we only had a little bit of time, we drove over to Portland and checked out Edward’s house. I have to say…. THIS HOUSE WAS GORGEOUS. Whew! I would LOVE to live there. LOVE LOVE LOVE! I would also have loved a tour, but it is a private residence, and therefore we kept our distance. Mmm, but it sure is gorgeous! Twilight brings back a lot of memories for me, and it’s special because I grew up (mostly) in Washington. It’s also not the only book series to claim that there are werewolves living amongst the local residents. The town that I spent most of my childhood in also has a series revolving around it! I’m planning to take a trip over there to see my old friends and photograph all of the wolfy places of interest, so I’ll post about it then! Love ya, and see ya tomorrow!

Эксперты из DxOMark протестировали камеры новых смартфонов iPhone 11 Pro и 11 Pro Max, и в результате испытаний новинки от компании Apple оказались недостаточно хороши, чтобы возглавить рейтинг. В общ...

Microsoft plans to add trackpad and mouse support to its Word, Excel, and PowerPoint apps for iPad by the fall, according to TechCrunch and The Verge.

iPadOS 13.4 introduced trackpad and mouse support on all iPad models released in the past four to five years. Keyboards with trackpads include Apple's Magic Keyboard and Brydge's Pro+ for the iPad Pro and Logitech's Combo for the 10.2-inch iPad and the 10.5-inch iPad Air.

When using a trackpad, the cursor displays as a circle on the screen, popping up only when you have a finger on the trackpad. The circle then morphs into various other shapes when hovering over app icons, text fields, or other on-screen elements.

After the bumper here, the review will get into spoiler territory. I will say that if you are a Sonic fan this movie will give you a sense of pride as it is far better than it should have had any right in being. Taking the franchise’s lore and resetting it to tell its own story, but retaining the strong characterization and quip heavy personalities of Sonic and Robotnik that makes their rivalry such a strong one. It also keeps the first entry simple with the hedgehog and doctor being the only two characters from the universe being in the film. This makes the story stronger since it can develop those two far more and not have to worry about any other kind of side character fan service for now.

Hey, at least now Sonic fans can brag to Mario ones that Mario may still be the king of games, but Sonic blew the plumber’s cinematic pieces out of the water. Not that that was a high bar I suppose. Then again, having better quality games than Sonic these days isn’t one either (the author quips while using a quote from Sonic Forces for his review’s headline).

In the video game Sonic the Hedgehog, timing is everything. While at the heart of the game is a fast paced platformer, its foundation has always been learning the layout of a level and timing your actions appropriately. In a twist, the timing of this film and its release had quite a bit of impact on my view of it.

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As governments restrict gatherings of people, furry conventions are being postponed or canceled. Here's a quick run down of events in April, May, and June and their status as of May 5 17:28 EDT (UTC-4) in response to the COVID-19 pandemic - updates to come.

A new section has been added for past events impacted for historical purposes.

Links go to statements if available, or to their Twitter feed or site. See also: Furry Fandom and the Internet forced back to roots by viral outbreak

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Erowid Exp113948

Cornel West and Tavis Smiley criticize President Barack Obama for being to the right of even President Richard Nixon. Continue reading →

Thinking of using TurboTax to file your tax returns? Think again. The Minnesota Department of Revenue advises against using Intuit software to file tax returns! It found unacceptable errors in Intuit tax software, including TurboTax, ProSeries, Lacerte, and Intuit online. Continue reading →

The Berlin police department is looking to build a new facility, but some residents don't think spending $21 million should even be considered. Continue reading →

A year ago this month the U.S. Department of Justice announced that the banking giant JPMorgan Chase would avoid criminal charges by agreeing to pay $13 billion to settle claims that it had routinely overstated the quality of mortgages it … Continue reading →

Online criminals have been systematically targeting TurboTax, filing fraudulent tax returns of individuals, and diverting their tax refunds to prepaid debit, cards, stealing their personal information, and using and impairing their credit ratings. Continue reading →

Bernie Sanders offers a real deal to the middle class and not the raw deal of Hillary Clinton Continue reading →

Senator Bernie Sanders does not think that Hillary Clinton can stand up and fight for the middle class. Continue reading →

THE AMERICAN PEOPLE IN THIS PARTICULAR MOMENT IN OUR HISTORY MUST MAKE A VERY FUNDAMENTAL DECISION, AND THAT DECISION IS DO WE CONTINUE THE STATUS QUO WHICH INCLUDES A 40-YEAR DECLINE OF OUR MIDDLE CLASS AND A HUGE AND GROWING GAP BETWEEN THE VERY, VERY RICH AND EVERYONE ELSE, OR DO WE FIGHT FOR A BOLD AND MEANINGFUL ECONOMIC AGENDA THAT CREATES JOBS, RAISES WAGES, PROTECTS OUR ENVIRONMENT AND PROVIDES HEALTH CARE FOR EVERY AMERICAN Continue reading →

Sen. Bernie Sanders (I-Vt.) warns not to underestimate him in the 2016 Democratic race for the White House. Sanders, who is formally launching his campaign Tuesday, said he has a strong message. Continue reading →

“Thank you all very much for being here and for all the support that you have given me over the years: as the mayor of this great city, as Vermont’s only congressman and now as a U.S. senator. Thanks also … Continue reading →

Chuck Todd tells Andrea Mitchell that Hillary Clinton will win the African-American and Hispanic vote in spite of the intellectual appeal of Bernie Sanders to liberal white voters Continue reading →

An Offer in Compromise is an agreement between the taxpayer and the government that settles a tax liability for payment of less than the full amount owed. The Internal Revenue Service will generally accept an Offer in Compromise when it … Continue reading →

Noor asks Hedges how the presidential nominees should respond to these types of terrorist attacks in the U.S. “Their response should be the end of the occupation in the Middle East and the cessation of saturation bombing by drones and military aircrafts and missiles in parts of Iraq and Syria and Pakistan and Yemen and Somalia,” Hedges responds. He goes on to explain how decades of foreign policy decisions made by both parties have created the circumstances for terrorist attacks. Continue reading →

Questions surrounding Hillary Clinton and the Clinton Foundation continue to grow. On Sunday, Democratic National Committee interim chairperson Donna Brazile defended Clinton’s meetings as secretary of state with Clinton Foundation donors, saying, "When Republicans meet with their donors, with their supporters, their activists, they call it a meeting. When Democrats do that, they call it a conflict." Donna Brazile’s comments come in response to an Associated Press investigation revealing that while Hillary Clinton served as secretary of state, more than half of the private citizens she met with during the reporting period had donated to the Clinton Foundation. The AP investigation comes after a three-year battle to gain access to State Department calendars. The analysis shows that at least 85 of 154 people Hillary Clinton had scheduled phone or in-person meetings with were foundation donors. We speak to Pulitzer Prize-winning journalist Glenn Greenwald of The Intercept. His most recent piece is headlined "Why Did the Saudi Regime and Other Gulf Tyrannies Donate Millions to the Clinton Foundation?" Continue reading →

The middle class needs to vote for Donald Trump in order to oppose the elites, Corporate America, Wall Street, the career politicians, and the media, who have all conspired to destroy the middle class. Donald Trump is the Molotov cocktail, the human hand grenade, that every beaten-down, nameless, forgotten working stiff who used to be part of what was called the middle class can legally throw into the system that stole their lives from them. Continue reading →

The Democratic National Committee is controlled by its big corporate donors. Tom Perez was recruited to defeat progressive Keith Ellison to keep the Democratic Party in the coffers of its corporate donors. Ellison's defeat as head of the DNC was a hit job by the corporate machine within the DNC. Continue reading →

NEWS 8 IS YOUR LOCAL ELECTION HEADQUARTERS…. AND TONIGHT…VOODOO ECONOMICS! CHIEF POLITICAL CORRESPONDENT MARK DAVIS TELLING US HOW REPEALING THE STATE INCOME TAX IS THE LATEST HEATED TOPIC BETWEEN THE CANIDATES FOR GOVERNOR.   DEMOCRAT NED LAMONT IS OPENING A … Continue reading →