If you don't understand the reference of the title then you are too young to be scrolling through this gallery. We're just kidding, of course. Even if you weren't born until after 2000, we hope you can at least learn something about the twentieth century from these memes. 

Check out /r/HistoryMemes for a never-ending supply!

As the nation marks the one-year anniversary of the Pulse Nightclub massacre in Orlando this week, a group of experts on active shooter/hostile incident response will assemble at National Fire Protection Association (NFPA) headquarters to develop NFPA 3000, Standard for Preparedness and Response to Active Shooter and/or Hostile Events. It is expected that the initial standard will be completed by early 2018; then the public will have the opportunity to offer input for immediate review.

I don't think I could have voted for Biden. I held my nose and voted for Harris. I was never going to make a thing of it.  I wasn't going suggest anybody shouldn't vote.  

The thing is, my vote doesn't matter. I mean, yah, there's that chance the election would have come down to the state of Pennsylvania, and the state of Pennsylvania would come down to one vote - mine! - but while we like to imagine these things, they aren't very likely.

Absent mandatory voting, elections depend on lots of people deciding that it does matter if they vote, even though it really doesn't.  Not individually.  

Why did I almost not vote?  No of course I didn't want the bad orange man to win - and ultimately that's why I voted - but also I've been watching a genocide unfold for past year and I've watched Biden's smirking ghouls at State on that subject and I've watched almost the entire Dem-industrial complex go after the people who opposed that genocide, or at best stay silent.

These people are so rotten and so horrible and many of them would be on trial in a just world.  People were put on trial for less. "We" certainly supported putting people on trial for less, instead of opposing it in every way possible.  We went to war - supposedly - over less!

So much for the international rules-based order.

I'm an engaged voter.  I understand the issues.  I understand harm reduction.  I understand that the bad orange man is very bad indeed.  I have no belief in accelerationism or fantasies about third party presidential runs.  I am not a narcissist about this stuff; politics is never going to be centered around my personal desires.

But how dare these fucking people make me vote for this.  How dare almost all of them, at best, stay silent.  What did they want to be in positions of power for?  Vacation homes and new boats?

It is, truly, a problem from hell, Samantha.

This has been trotted out for years, mostly about Afghanistan, and which "Left" are you talking about? There is no "Left" in the NYT (Bouie but it isn't really his beat), the Washington Post, CNN... MSNBC has Hayes and he did!

If you want credit from this unnamed Left, you'd better empower them. The Chapo guys gave you a lot of credit! Then they criticized you for other things! That's how it works!

I’m definitely going to do this again! READ MORE...

Rachel Maddow reminds Americans how Trump told his followers, "You don’t need to vote. I have so many votes." The Republican candidate said multiple times that he had the votes he needed to become president, implicating something other than votes would give him power.

Votes are still being counted in many states, almost one week after the election. Republicans are close to getting control of the U.S. House but Newsweek reports many races are too close to call. I'm not ready to put on a foil hat but isn't it worth looking into some of the odd things surrounding the 2024 election?

I'm not saying the election was "rigged" or unfair. All I am suggesting is that there are strange things about the 2024 election that merit a second look. Since democracy of the free world is at stake, it's worth the trouble.

Trump Doesn't Need Votes and Secret With Moses Mike

As Maddow noted, Trump telling voters he doesn't need their vote is a red flag. The GOP candidate said it multiple times. Trump also made several comments about the "secret" he and Speaker Mike Moses Johnson had about the election.

read more

(Shortlink to this post: https://debbieohi.link/goodnight-ganesha)

I met Nadia Salomon through the SCBWI and am also familiar with her online. I love her enthusiasm, positive outlook, and the support she has shown fellow members of the kidlit community over the years! I was excited to get a sneak peek of GOODNIGHT GANESHA, her debut as a picture book author. The bedtime story celebrates nigthtime rituals as two young children visit their grandparents in India. SUCH gorgeous illustrations by Poonam Mistry. Thanks to both Nadia and Poonam for answering some questions about the book as well as their advice for young writers and illustrators!

Nadia Salomon lives in northern California with her family. Nadia writes picture book, middle-grade, and graphic novel manuscripts with themes of South Asian and Caribbean culture, STEM, non-fiction, and humor. Nadia is the winner of the 2020 SCBWI Service Award and the 2019 SCBWI WOOP Honor Award for work of outstanding progress on her non-fiction, picture book manuscript, MYRLIE: A VOICE OF HOPE. You can find out more about Nadia on her website, Twitter, Facebook, Instagram and YouTube. You can sign up for her newsletter here.

Poonam Mistry is a freelance illustrator living in the UK and graduated in 2010 with a degree in Graphic Design and Illustration at the University of Hertfordshire. Poonam creates her beautifully intricate images by hand using fine liners and then digitally alters them. You can find out more about Poonam on her website, Twitter, and Instagram.

Synopsis of GOODNIGHT GANESHA (Philomel, Aug. 31, 2021):

"As nighttime falls over the city, two children visiting their grandparents in India find there’s so much fun to be had! Whether it’s listening to epic stories or observing rituals in the puja room, there are many moments that make this time together special. In this beautiful, rhyming ode to bedtime, the only thing more universal than getting ready for bed and saying goodnight is the love between children and their grandparents."

Inspiration photo from Poonam Mistry.

Q. What was your path to publication?

Nadia: I'm a #PitMad success story. I landed my amazing agent, Ammi-Joan Paquette, through twitter pitching! That's about three years after joining SCBWI. But my debut, GOODNIGHT GANESHA, is not the story she faved, but instead what I call a 'hot potato' idea inspired by my child. I wrote the draft in October of 2017. I sent it to several editors and agents I had connected with through conferences, but received lots of champagne rejections before shelving it. It was one of 21 manuscripts I shared with my agent in March of 2018. She loved the concept, but asked me to write the story in lyrical prose. After rounds of revisions, in January of 2019, she finally accepted the manuscript. She sent it out on sub. Six months later, in July of 2019, we sold the manuscript to Liza Kaplan, a senior editor at Philomel Books. I am now traditionally published. From concept to release will be 3 years, 10 months, 14 days to be exact.

Q. What interaction did you have with the illustrator, if any, during the process?

Nadia: Poonam and I interacted behind the scenes, but we NEVER discussed GOODNIGHT GANESHA or the art for the book. I trusted her whole-heartedly. All work related communications went through our editor. We became friends behind the scenes - coping through the pandemic, bonding over shared culture, family, and everything else in between, but we NEVER had convos as she worked on the book. The one time was at the end, when Poonam completed the art and asked me, "DID YOU SEE THE FINAL ART YET?" And I was like, "Uhm...NO." She was so excited. She said she put a lot of extra details and hoped I liked it. I was so antsy, but stayed calm. A few days later I received the final art. It was just incredible! We had a good cry messaging back and forth over the final art and what this project meant to each of us. We're about to contribute a piece of Telugu Culture and Kalamkari art into kidlit; we're ecstatic and proud of what we created together.

Q. What was your illustration process for GOODNIGHT GANESHA?

Poonam: For Goodnight Ganesha, I began by actually taking photographs around my parent's house. They have a lot of decorative ornaments and wall hangings all around their home so this was the perfect starting point for the book. Nadia's text is so poetic and beautiful so I sketched the imagery I felt best represented each spread and would really showcase her words- usually I have several versions for each part of the text and pick the ones I like the most. Once this was approved, I sketched out larger versions on thick cartridge paper and used black ink to draw in the designs in neat. This is where I added all the patterns and details. Mostly I took inspiration from traditional Indian art such Kalamkari textiles and Madhubani art. I layered the patterned very much like you would see on sarees and fabrics. After completing the drawing, I used Photoshop to add colour and additional patterns to finish it off. Some of the spreads have a patterned border- this was because I wanted them to look like wall hangings and Kalamkari textile pieces- big pieces of art!

Q. What advice do you have for young writers?

Nadia: Read, read, read. Write your stories. Make writing a habit. Write, write, write. Use the power of storytelling to change the world through joy. Explore your emotions, your memories, and create new classics. There's someone out there, an adult, another child, a pair of hands waiting to read your story that may impact or influence their life. No matter your age, your size, your voice - your words have value.

Q. What advice do you have for young illustrators?

Poonam: My biggest piece of advice is to do art that is true to yourself. My style is a real reflection of the things I love and what makes me who I am. It is my visual voice. Also always keep drawing and be experimental in the media you use. Although my work is mostly digital, I love painting in my style!

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For more insights from book creators, see my Inkygirl Interview Archives.

It all starts with the anything-but-smooth introduction...

Social media users have spread a quote attributed to Democratic Rep. Jamie Raskin, claiming he said "we won’t be certifying the election" if former President Donald Trump wins. Raskin responded, saying the quote is "100% fabricated" and that "America is having a free and fair election and Congress will certify the winner." The origin of the posts appears to be a misleading account of Raskin's comments in February.

The post Raskin Didn’t Say He ‘Won’t Be Certifying the Election’ appeared first on FactCheck.org.

Nearly every Wednesday of the semester, The Mossavar-Rahmini Center for Iran and Persian Gulf Studies invites a scholar to speak on their area of study. Topics relate to Iran and the Persian Gulf area while employing an interdisciplinary lens. To view the details of upcoming seminar topics, please visit iran.princeton.edu/upcoming-events.

Nearly every Wednesday of the semester, The Mossavar-Rahmini Center for Iran and Persian Gulf Studies invites a scholar to speak on their area of study. Topics relate to Iran and the Persian Gulf area while employing an interdisciplinary lens. To view the details of upcoming seminar topics, please visit iran.princeton.edu/upcoming-events.

Not everything that crosses a supermassive black hole’s accretion disc gets spaghettified, astrophysicists say.

The oldest DNA ever retrieved, preserved in sediments in northern Greenland, reveals that Arctic and temperate species once commingled in an ecosystem unlike anything that exists today.

Having lived in London for four years, American Kassondra Cloos thought a trip see her adopted city as imagined by the Wizarding World of Harry Potter in Orlando would be fairly pointless – but instead she finds a home from home that’s suited to even grown-up kids

The following article, Maybe Tim Walz Shouldn’t Bring Up ‘That Gay Guy’, was first published on The Black Sphere.

Tim Walz is no stranger to controversy. After lying about his military record and China, people are wondering what else is he lying about...

Continue reading Maybe Tim Walz Shouldn’t Bring Up ‘That Gay Guy’ ...

"Customers must be able to reevaluate their willingness to have their genome data shared outside the original intent.”

The post Patronis Questions DNA Testing Companies’ User Confidentiality appeared first on Shark Tank.

Today is election day, the day that will decide who is president for the next four years, and which political party will control Congress and most state legislatures. Polls are now open in most of the country, so you can vote today if you haven’t already. But all voters have already voted in one small […]

The post Today is Election Day; Harris and Trump tie in Dixville Notch midnight vote to kick off Election Day appeared first on Liberty Unyielding.

Kamala Harris spent over a billion dollars on her campaign to succeed Joe Biden after he dropped out of the presidential race on July 21. She hobnobbed with famous celebrities, and spent millions on events aimed at reaching low-information voters. But millions of Americans didn’t realize Harris was even on the ballot prior to election […]

The post Millions of Americans didn’t know Harris had replaced Biden appeared first on Liberty Unyielding.

Latest scorecard from the Women's Big Bash League match between Sydney Thunder and Perth Scorchers at Sydney's Drummoyne Oval.

Manchester City weighing up defensive duo, Jonathan David sets wage demands, Joshua Zirkzee loan interests Juventus, plus more.

The country is set to experience varied weather conditions, with several impact-based warnings issued across various provinces, according to the South African Weather Service.

Ryan Lawler notes in his Contentinople blog that CBS's high definition stream of the NCAA men's basketball tournament has been a great success.

CBS Sports reported that traffic to its NCAA March Madness on Demand site on the first day of the tourney increased 56 percent year-over-year, to 2.7 million unique users yesterday from 1.75 million uniques a year ago.

If there is a conclusion to be drawn, I do not think it is that internet video can or should compete with television. In this case, I believe the draw is a combination of the fact that watching television on Thursday afternoon is not an option for people with a day job, and that there are many games going on simultaneously and CBS television does not always cut to the game that the individual user wants to see.

I think the focus should be on the success of delivering a high quality video experience to a large audience, many of whom were at work. This is just another step in the direction of enterprise video becoming an essential element of the workplace experience.

A.F. Branco Cartoon – Democrats, the party of child genital mutilation and late-term abortion, are outraged at Trump for his comments alluding to..

Mitochondria are specialized compartments that produce requisite ATP to fuel cellular functions and serve as centers of metabolite processing, cellular signaling, and apoptosis. To accomplish these roles, mitochondria rely on the genetic information in their small genome (mitochondrial DNA) and the nucleus. A growing appreciation for mitochondria's role in a myriad of human diseases, including inherited genetic disorders, degenerative diseases, inflammation, and cancer, has fueled the study of biochemical mechanisms that control mitochondrial function. The mitochondrial transcriptional machinery is different from nuclear machinery. The in vitro re-constituted transcriptional complexes of Saccharomyces cerevisiae (yeast) and humans, aided with high-resolution structures and biochemical characterizations, have provided a deeper understanding of the mechanism and regulation of mitochondrial DNA transcription. In this review, we will discuss recent advances in the structure and mechanism of mitochondrial transcription initiation. We will follow up with recent discoveries and formative findings regarding the regulatory events that control mitochondrial DNA transcription, focusing on those involved in cross-talk between the mitochondria and nucleus.

RecQ family helicases are highly conserved from bacteria to humans and have essential roles in maintaining genome stability. Mutations in three human RecQ helicases cause severe diseases with the main features of premature aging and cancer predisposition. Most RecQ helicases shared a conserved domain arrangement which comprises a helicase core, an RecQ C-terminal domain, and an auxiliary element helicase and RNaseD C-terminal (HRDC) domain, the functions of which are poorly understood. In this study, we systematically characterized the roles of the HRDC domain in E. coli RecQ in various DNA transactions by single-molecule FRET. We found that RecQ repetitively unwinds the 3'-partial duplex and fork DNA with a moderate processivity and periodically patrols on the ssDNA in the 5'-partial duplex by translocation. The HRDC domain significantly suppresses RecQ activities in the above transactions. In sharp contrast, the HRDC domain is essential for the deep and long-time unfolding of the G4 DNA structure by RecQ. Based on the observations that the HRDC domain dynamically switches between RecA core- and ssDNA-binding modes after RecQ association with DNA, we proposed a model to explain the modulation mechanism of the HRDC domain. Our findings not only provide new insights into the activities of RecQ on different substrates but also highlight the novel functions of the HRDC domain in DNA metabolisms.

A. I. Aptekarev and M. L. Yattselev
Trans. Moscow Math. Soc. 83 (), 251-268.
Abstract, references and article information

Simão Correia
Proc. Amer. Math. Soc. 152 (), 5117-5136.
Abstract, references and article information

Bacterial low-copy-number plasmids require partition (par) systems to ensure their stable inheritance by daughter cells. In general, these systems consist of three components: a centromeric DNA sequence, a centromere-binding protein and a nucleotide hydrolase that polymerizes and functions as a motor. Type III systems, however, segregate plasmids using three proteins: the FtsZ/tubulin-like GTPase TubZ, the centromere-binding protein TubR and the MerR-like transcriptional regulator TubY. Although the TubZ filament is sufficient to transport the TubR-centromere complex in vitro, TubY is still necessary for the stable maintenance of the plasmid. TubY contains an N-terminal DNA-binding helix-turn-helix motif and a C-terminal coiled-coil followed by a cluster of lysine residues. This study determined the crystal structure of the C-terminal domain of TubY from the Bacillus cereus pXO1-like plasmid and showed that it forms a tetrameric parallel four-helix bundle that differs from the typical MerR family proteins with a dimeric anti-parallel coiled-coil. Biochemical analyses revealed that the C-terminal tail with the conserved lysine cluster helps TubY to stably associate with the TubR-centromere complex as well as to nonspecifically bind DNA. Furthermore, this C-terminal tail forms an amphipathic helix in the presence of lipids but must oligomerize to localize the protein to the membrane in vivo. Taken together, these data suggest that TubY is a component of the nucleoprotein complex within the partitioning machinery, and that lipid membranes act as mediators of type III systems.

Yi-Han Lin
Dec 1, 2020; 19:2030-2046
Research

Ji Eun Kim
Dec 20, 2020; 0:RA120.002159v1-mcp.RA120.002159
Research

We have observed overexpression of PACS-1, a cytosolic sorting protein in primary cervical tumors. Absence of exonic mutations and overexpression at the RNA level suggested a transcriptional and/or posttranscriptional regulation. University of California Santa Cruz genome browser analysis of PACS-1 micro RNAs (miR), revealed two 8-base target sequences at the 3' terminus for hsa-miR-34a and hsa-miR-449a. Quantitative RT-PCR and Northern blotting studies showed reduced or loss of expression of the two microRNAs in cervical cancer cell lines and primary tumors, indicating dysregulation of these two microRNAs in cervical cancer. Loss of PACS-1 with siRNA or exogenous expression of hsa-miR-34a or hsa-miR-449a in HeLa and SiHa cervical cancer cell lines resulted in DNA damage response, S-phase cell cycle arrest, and reduction in cell growth. Furthermore, the siRNA studies showed that loss of PACS-1 expression was accompanied by increased nuclear γH2AX expression, Lys382-p53 acetylation, and genomic instability. PACS-1 re-expression through LNA-hsa-anti-miR-34a or -449a or through PACS-1 cDNA transfection led to the reversal of DNA damage response and restoration of cell growth. Release of cells post 24-h serum starvation showed PACS-1 nuclear localization at G1-S phase of the cell cycle. Our results therefore indicate that the loss of hsa-miR-34a and hsa-miR-449a expression in cervical cancer leads to overexpression of PACS-1 and suppression of DNA damage response, resulting in the development of chemo-resistant tumors.

Mitochondrial DNA (mtDNA) encodes proteins and RNAs that support the functions of mitochondria and thereby numerous physiological processes. Mutations of mtDNA can cause mitochondrial diseases and are implicated in aging. The mtDNA within cells is organized into nucleoids within the mitochondrial matrix, but how mtDNA nucleoids are formed and regulated within cells remains incompletely resolved. Visualization of mtDNA within cells is a powerful means by which mechanistic insight can be gained. Manipulation of the amount and sequence of mtDNA within cells is important experimentally and for developing therapeutic interventions to treat mitochondrial disease. This review details recent developments and opportunities for improvements in the experimental tools and techniques that can be used to visualize, quantify, and manipulate the properties of mtDNA within cells.

Mutations in the GUCY2D gene coding for the dimeric human retinal membrane guanylyl cyclase (RetGC) isozyme RetGC1 cause various forms of blindness, ranging from rod dysfunction to rod and cone degeneration. We tested how the mutations causing recessive congenital stationary night blindness (CSNB), recessive Leber's congenital amaurosis (LCA1), and dominant cone–rod dystrophy-6 (CORD6) affected RetGC1 activity and regulation by RetGC-activating proteins (GCAPs) and retinal degeneration-3 protein (RD3). CSNB mutations R666W, R761W, and L911F, as well as LCA1 mutations R768W and G982VfsX39, disabled RetGC1 activation by human GCAP1, -2, and -3. The R666W and R761W substitutions compromised binding of GCAP1 with RetGC1 in HEK293 cells. In contrast, G982VfsX39 and L911F RetGC1 retained the ability to bind GCAP1 in cyto but failed to effectively bind RD3. R768W RetGC1 did not bind either GCAP1 or RD3. The co-expression of GUCY2D allelic combinations linked to CSNB did not restore RetGC1 activity in vitro. The CORD6 mutation R838S in the RetGC1 dimerization domain strongly dominated the Ca2+ sensitivity of cyclase regulation by GCAP1 in RetGC1 heterodimer produced by co-expression of WT and the R838S subunits. It required higher Ca2+ concentrations to decelerate GCAP-activated RetGC1 heterodimer—6-fold higher than WT and 2-fold higher than the Ser838-harboring homodimer. The heterodimer was also more resistant than homodimers to inhibition by RD3. The observed biochemical changes can explain the dominant CORD6 blindness and recessive LCA1 blindness, both of which affect rods and cones, but they cannot explain the selective loss of rod function in recessive CSNB.

Chiara Pavanello
Dec 1, 2020; 61:1784-1788
Patient-Oriented and Epidemiological Research

Familial LCAT deficiency (FLD) is a rare genetic disorder of HDL metabolism, caused by loss-of-function mutations in the LCAT gene and characterized by a variety of symptoms including corneal opacities and kidney failure. Renal disease represents the leading cause of morbidity and mortality in FLD cases. However, the prognosis is not known and the rate of deterioration of kidney function is variable and unpredictable from patient to patient. In this article, we present data from a follow-up of the large Italian cohort of FLD patients, who have been followed for an average of 12 years. We show that renal failure occurs at the median age of 46 years, with a median time to a second recurrence of 10 years. Additionally, we identify high plasma unesterified cholesterol level as a predicting factor for rapid deterioration of kidney function. In conclusion, this study highlights the severe consequences of FLD, underlines the need of correct early diagnosis and referral of patients to specialized centers, and highlights the urgency for effective treatments to prevent or slow renal disease in patients with LCAT deficiency.

Voltage-gated Cav1 and Cav2 Ca2+ channels are comprised of a pore-forming α1 subunit (Cav1.1-1.4, Cav2.1-2.3) and auxiliary β (β1-4) and α2δ (α2δ−1−4) subunits. The properties of these channels vary with distinct combinations of Cav subunits and alternative splicing of the encoding transcripts. Therefore, the impact of disease-causing mutations affecting these channels may depend on the identities of Cav subunits and splice variants. Here, we analyzed the effects of a congenital stationary night blindness type 2 (CSNB2)-causing mutation, I745T (IT), in Cav1.4 channels typical of those in human retina: Cav1.4 splice variants with or without exon 47 (Cav1.4+ex47 and Cav1.4Δex47, respectively), and the auxiliary subunits, β2X13 and α2δ-4. We find that IT caused both Cav1.4 splice variants to activate at significantly more negative voltages and with slower deactivation kinetics than the corresponding WT channels. These effects of the IT mutation, along with unexpected alterations in ion selectivity, were generally larger in channels lacking exon 47. The weaker ion selectivity caused by IT led to hyperpolarizing shifts in the reversal potential and large outward currents that were evident in channels containing the auxiliary subunits β2X13 and α2δ-4 but not in those with β2A and α2δ-1. We conclude that the IT mutation stabilizes channel opening and alters ion selectivity of Cav1.4 in a manner that is strengthened by exclusion of exon 47 and inclusion of β2X13 and α2δ-4. Our results reveal complex actions of IT in modifying the properties of Cav1.4 channels, which may influence the pathological consequences of this mutation in retinal photoreceptors.

Sepsis-induced acute kidney injury (S-AKI) is the most common complication in hospitalized and critically ill patients, highlighted by a rapid decline of kidney function occurring a few hours or days after sepsis onset. Systemic inflammation elicited by microbial infections is believed to lead to kidney damage under immunocompromised conditions. However, although AKI has been recognized as a disease with long-term sequelae, partly because of the associated higher risk of chronic kidney disease (CKD), the understanding of kidney pathophysiology at the molecular level and the global view of dynamic regulations in situ after S-AKI, including the transition to CKD, remains limited. Existing studies of S-AKI mainly focus on deriving sepsis biomarkers from body fluids. In the present study, we constructed a mid-severity septic murine model using cecal ligation and puncture (CLP), and examined the temporal changes to the kidney proteome and phosphoproteome at day 2 and day 7 after CLP surgery, corresponding to S-AKI and the transition to CKD, respectively, by employing an ultrafast and economical filter-based sample processing method combined with the label-free quantitation approach. Collectively, we identified 2,119 proteins and 2950 phosphosites through multi-proteomics analyses. Among them, we identified an array of highly promising candidate marker proteins indicative of disease onset and progression accompanied by immunoblot validations, and further denoted the pathways that are specifically responsive to S-AKI and its transition to CKD, which include regulation of cell metabolism regulation, oxidative stress, and energy consumption in the diseased kidneys. Our data can serve as an enriched resource for the identification of mechanisms and biomarkers for sepsis-induced kidney diseases.