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.

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.

Video from Thabo Meerkat, transcribed

Welcome to another edition of Digging Up Positivity! This episode is dedicated to the many volunteers that make all those amazing conventions and charities possible. But besides them, we are covering some animation news and other (maybe otter?) tidbits!

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Are you a taxpreparer who is unsatisfied with the quality of Intuit's ProSeries tax software program? I am not a happy user of ProSeries tax software. Choose your tax software carefully. I will be searching for an alternative tax software vendor for the year 2014. Continue reading →

TurboTax’s Anti-Fraud Efforts Under Scrutiny Two former security employees at Intuit — the makers of the popular tax preparation software and service TurboTax – allege that the company has made millions of dollars knowingly processing state and federal tax refunds filed … Continue reading →

Accountants CPA Hartford Connecticut LLC:  This transcript may contain errors. The Willis Report:  And tonight’s stunning accusation against Intuit, the maker of Turbotax, the popular tax preparation software.  Two whistleblowers claim that Intuit knew that criminals used its tax software … Continue reading →

This is one of the best interviews on American politics ever to be broadcasted. Ralph Nader and Jill Stein discuss our corrupt government and corrupt media controlled by corporations, and explain how we no longer have a democracy but corporate tyranny. Continue reading →

"And you know, we have to stop looking beyond this election cycle and see that this corporate driven ideology, you know, this commodification of the culture, this constant extracting of blood from us as citizens to pay what in essence were private debts of the banks which engaged in casino capitalism, has political consequences. History has taught us that. And Hillary Clinton is only going to further that process." 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 Brainwashing Of Hillary Voters Is Complete. Hillary Clinton voters are either getting paid or have been brainwashed into defending her pro-corporate status quo policies. Jimmy Dore breaks it down on his broadcast, October 20, 2016. Continue reading →

There's got to be a reason for the Democrats to suppose to exist. And the reason the Democrats are supposed to exist is to be an opposition party to the Republicans. If you're in bed with the same people, taking money from the same people, you're no longer an opposition party. There's no reason for you to exist. And guess what? Don't be surprised that people don't vote for you. Continue reading →

Emmy Nominee Leslye Headland to write, produce, and serve as showrunner for new untitled Star Wars series for Disney+.

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Expect evil ravens, hipsters performing pun-magic and John getting drunker than you’ve ever seen him before. Fun. -- Si Spurrier

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