The internet went crazy today when a rumor seemed to break through about the always-destined Harry Potter television show — specifically that while no series is actually in the works, WB is now officially shopping for writers and pitches for an HBO Max event. We did a quick-and-dirty reaction pod with our three hosts and our good friend Proma Khosla, a longtime LeakyCon staffer and Mashable entertainment reporter, to break down the news, what it means for the franchise, and what the fandom does now. 

Basically, we decided the fandom just needs to get a trillion dollars together and buy the franchise from JKR. 

You can follow Proma on Twitter at @promawhatup  and read her Mashable articles here!

~*~

Don't forget to follow us on @pottercast on Twitter and @pottercastpod on Instagram!

Join our patreon! patreon.com/pottercast - Now, you can also join our Discord community there!

You can also buy PotterCast-related merch at mischiefmerch.com!

For a second time, Kari Lake has been denied a win in an election.  First, it was for governor of Arizona, which was clearly due to election and voter fraud.  Now, it appears something similar occurred in her race against Ruben Gallego.  Now, the head of her campaign is speaking out and saying that there …

World leaders and officials sent their best wishes to President Trump and First Lady Melania Trump on Friday for a swift recovery after he announced early Friday morning that the First couple tested positive for COVID-19. Israeli Prime Minister Benjamin Netanyahu tweeted that he and his wife Sara, along with “millions of Israelis” are wishing […]

The post World Leaders React To Trump’s COVID-19 Diagnosis appeared first on Hispolitica.

A nuclear-powered aircraft carrier, like American carriers, would be a major jump for China, giving its navy a global reach.

If Trump's proposed 60% tariff against China is enacted and the country responds aggressively, it could pressure some of America's largest companies.

Google is investing in the development of the next generation of nuclear power, backing a company that’s building small modular reactors and agreeing to purchase energy once the sites start supplying US grids.

Instant Reaction: CPI, August 14, 2024

Instant Reaction: Mortgage Rates, August 15, 2024

Instant Reaction: Mortgage Rates, August 29, 2024

Instant Reaction: Mortgage Rates, September 5, 2024

Instant Reaction: Jobs, September 6, 2024

Republican primary opponents like Ron DeSantis said that every time they announced another indictment, his poll numbers got better. They should have known better. But they were blinded by hate.

The post BOOM: Trump Prosecutors React To New Post-Election Realities… Here’s Their Plan appeared first on Clash Daily.

Amelia C. Peterson
Nov 1, 2012; 11:1475-1488
Technological Innovation and Resources

Leigh Anderson
Apr 1, 2006; 5:573-588
Research

Philip L. Ross
Dec 1, 2004; 3:1154-1169
Research

G Lepage
Jan 1, 1986; 27:114-120
Articles

John A. Glomset
Mar 1, 1968; 9:155-167
Reviews

A. Kh. Khachatryan, Kh. A. Khachatryan and A. Zh. Narimanyan
Trans. Moscow Math. Soc. 83 (), 183-200.
Abstract, references and article information

Proteins in the α-macroglobulin (αM) superfamily use thiol esters to form covalent conjugation products upon their proteolytic activation. αM protease inhibitors use theirs to conjugate proteases and preferentially react with primary amines (e.g. on lysine side chains), whereas those of αM complement components C3 and C4B have an increased hydroxyl reactivity that is conveyed by a conserved histidine residue and allows conjugation to cell surface glycans. Human α2-macroglobulin–like protein 1 (A2ML1) is a monomeric protease inhibitor but has the hydroxyl reactivity–conveying histidine residue. Here, we have investigated the role of hydroxyl reactivity in a protease inhibitor by comparing recombinant WT A2ML1 and the A2ML1 H1084N mutant in which this histidine is removed. Both of A2ML1s' thiol esters were reactive toward the amine substrate glycine, but only WT A2ML1 reacted with the hydroxyl substrate glycerol, demonstrating that His-1084 increases the hydroxyl reactivity of A2ML1's thiol ester. Although both A2ML1s conjugated and inhibited thermolysin, His-1084 was required for the conjugation and inhibition of acetylated thermolysin, which lacks primary amines. Using MS, we identified an ester bond formed between a thermolysin serine residue and the A2ML1 thiol ester. These results demonstrate that a histidine-enhanced hydroxyl reactivity can contribute to protease inhibition by an αM protein. His-1084 did not improve A2ML1's protease inhibition at pH 5, indicating that A2ML1's hydroxyl reactivity is not an adaption to its acidic epidermal environment.

Intrinsically disordered protein domains often have multiple binding partners. It is plausible that the strength of pairing with specific partners evolves from an initial low affinity to a higher affinity. However, little is known about the molecular changes in the binding mechanism that would facilitate such a transition. We previously showed that the interaction between two intrinsically disordered domains, NCBD and CID, likely emerged in an ancestral deuterostome organism as a low-affinity interaction that subsequently evolved into a higher-affinity interaction before the radiation of modern vertebrate groups. Here we map native contacts in the transition states of the low-affinity ancestral and high-affinity human NCBD/CID interactions. We show that the coupled binding and folding mechanism is overall similar but with a higher degree of native hydrophobic contact formation in the transition state of the ancestral complex and more heterogeneous transient interactions, including electrostatic pairings, and an increased disorder for the human complex. Adaptation to new binding partners may be facilitated by this ability to exploit multiple alternative transient interactions while retaining the overall binding and folding pathway.

Identification of antibody-binding epitopes is crucial to understand immunological mechanisms. It is of particular interest for allergenic proteins with high cross-reactivity as observed in the lipid transfer protein (LTP) syndrome, which is characterized by severe allergic reactions. Art v 3, a pollen LTP from mugwort, is frequently involved in this cross-reactivity, but no antibody-binding epitopes have been determined so far. To reveal human IgE-binding regions of Art v 3, we produced three murine high-affinity mAbs, which showed 70–90% coverage of the allergenic epitopes from mugwort pollen–allergic patients. As reliable methods to determine structural epitopes with tightly interacting intact antibodies under native conditions are lacking, we developed a straightforward NMR approach termed hydrogen/deuterium exchange memory (HDXMEM). It relies on the slow exchange between the invisible antigen-mAb complex and the free 15N-labeled antigen whose 1H-15N correlations are detected. Due to a memory effect, changes of NH protection during antibody binding are measured. Differences in H/D exchange rates and analyses of mAb reactivity to homologous LTPs revealed three structural epitopes: two partially cross-reactive regions around α-helices 2 and 4 as well as a novel Art v 3–specific epitope at the C terminus. Protein variants with exchanged epitope residues confirmed the antibody-binding sites and revealed strongly reduced IgE reactivity. Using the novel HDXMEM for NMR epitope mapping allowed identification of the first structural epitopes of an allergenic pollen LTP. This knowledge enables improved cross-reactivity prediction for patients suffering from LTP allergy and facilitates design of therapeutics.

War in Ukraine: The world reaction - Brazil and Africa Audio NCapeling 9 June 2022

The ninth episode of our podcast mini-series examines perspectives from Brazil and the Africa region and the impact on their relations with Russia.

How have Brazil and Africa reacted to the war in Ukraine? With impending elections in Brazil, how is President Bolsonaro’s relationship with Putin received by the public? How will food insecurity affect African nations’ response to the war?

This episode was produced by David Dargahi and Anouk Millet of Earshot Strategies on behalf of Chatham House.

Johannes Griss
Dec 1, 2020; 19:2115-2124
Technological Innovation and Resources

Daphne E.C. Boer
Dec 23, 2020; 0:jlr.RA120001043v1-jlr.RA120001043
Research Articles

Deficiency of glucocerebrosidase (GBA), a lysosomal β-glucosidase, causes Gaucher disease. The enzyme hydrolyzes β-glucosidic substrates and transglucosylates cholesterol to cholesterol-β-glucoside. Here we show that recombinant human GBA also cleaves β-xylosides and transxylosylates cholesterol. The xylosyl-cholesterol formed acts as acceptor for subsequent formation of di-xylosyl-cholesterol. Common mutant forms of GBA from patients with Gaucher disease with reduced β-glucosidase activity were similarly impaired in β-xylosidase, transglucosidase and transxylosidase activities, except for a slightly reduced xylosidase/glucosidase activity ratio of N370S GBA and a slightly reduced transglucosylation/glucosidase activity ratio of D409H GBA. XylChol was found to be reduced in spleen from Gaucher disease patients. The origin of newly identified XylChol in mouse and human tissues was investigated. Cultured human cells exposed to exogenous β-xylosides generated XylChol in a manner dependent on active lysosomal GBA but not the cytosol-facing β-glucosidase GBA2. We later sought an endogenous β-xyloside acting as donor in transxylosylation reactions, identifying xylosylated ceramide (XylCer) in cells and tissues that serve as donor in the formation of XylChol. UDP-glucosylceramide synthase (GCS) was unable to synthesize XylChol but could catalyse formation of XylCer. Thus, food-derived β-D-xyloside and XylCer are potential donors for the GBA-mediated formation of XylChol in cells. The enzyme GCS produces XylCer at a low rate. Our findings point to further catalytic versatility of GBA and prompt a systematic exploration of the distribution and role of xylosylated lipids.

Pathway analyses are key methods to analyze 'omics experiments. Nevertheless, integrating data from different 'omics technologies and different species still requires considerable bioinformatics knowledge.

Here we present the novel ReactomeGSA resource for comparative pathway analyses of multi-omics datasets. ReactomeGSA can be used through Reactome's existing web interface and the novel ReactomeGSA R Bioconductor package with explicit support for scRNA-seq data. Data from different species is automatically mapped to a common pathway space. Public data from ExpressionAtlas and Single Cell ExpressionAtlas can be directly integrated in the analysis. ReactomeGSA greatly reduces the technical barrier for multi-omics, cross-species, comparative pathway analyses.

We used ReactomeGSA to characterize the role of B cells in anti-tumor immunity. We compared B cell rich and poor human cancer samples from five of the Cancer Genome Atlas (TCGA) transcriptomics and two of the Clinical Proteomic Tumor Analysis Consortium (CPTAC) proteomics studies. B cell-rich lung adenocarcinoma samples lacked the otherwise present activation through NFkappaB. This may be linked to the presence of a specific subset of tumor associated IgG+ plasma cells that lack NFkappaB activation in scRNA-seq data from human melanoma. This showcases how ReactomeGSA can derive novel biomedical insights by integrating large multi-omics datasets.

Protein tyrosine kinases (PTKs) play key roles in cellular signal transduction, cell cycle regulation, cell division, and cell differentiation. Dysregulation of PTK-activated pathways, often by receptor overexpression, gene amplification, or genetic mutation, is a causal factor underlying numerous cancers. In this study, we have developed a parallel reaction monitoring (PRM)-based assay for quantitative profiling of 83 PTKs. The assay detects 308 proteotypic peptides from 54 receptor tyrosine kinases and 29 nonreceptor tyrosine kinases in a single run. Quantitative comparisons were based on the labeled reference peptide method. We implemented the assay in four cell models: 1) a comparison of proliferating versus epidermal growth factor (EGF)-stimulated A431 cells, 2) a comparison of SW480Null (mutant APC) and SW480APC (APC restored) colon tumor cell lines, and 3) a comparison of 10 colorectal cancer cell lines with different genomic abnormalities, and 4) lung cancer cell lines with either susceptibility (11-18) or acquired resistance (11-18R) to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib. We observed distinct PTK expression changes that were induced by stimuli, genomic features or drug resistance, which were consistent with previous reports. However, most of the measured expression differences were novel observations. For example, acquired resistance to erlotinib in the 11-18 cell model was associated not only with previously reported upregulation of MET, but also with upregulation of FLK2 and downregulation of LYN and PTK7. Immunoblot analyses and shotgun proteomics data were highly consistent with PRM data. Multiplexed PRM assays provide a targeted, systems-level profiling approach to evaluate cancer-related proteotypes and adaptations. Data are available through Proteome eXchange Accession PXD002706.

Texas Longhorns fans were very happy after the second edition of the College Football Playoff rankings were released Tuesday.

Jennifer L. Zamanian
May 2, 2012; 32:6391-6410
Neurobiology of Disease

Sleep is known to drive the consolidation of motor memories. During nonrapid eye movement (NREM) sleep, the close temporal proximity between slow oscillations (SOs) and spindles ("nesting" of SO-spindles) is known to be essential for consolidation, likely because it is closely associated with the reactivation of awake task activity. Interestingly, recent work has found that spindles can occur in temporal clusters or "trains." However, it remains unclear how spindle trains are related to the nesting phenomenon. Here, we hypothesized that spindle trains are more likely when SOs co-occur in the prefrontal and motor cortex. We conducted simultaneous neural recordings in the medial prefrontal cortex (mPFC) and primary motor cortex (M1) of male rats training on the reach-to-grasp motor task. We found that intracortically recorded M1 spindles are organized into distinct temporal clusters. Notably, the occurrence of temporally precise SOs between mPFC and M1 was a strong predictor of spindle trains. Moreover, reactivation of awake task patterns is much more persistent during spindle trains in comparison with that during isolated spindles. Together, our work suggests that the precise coupling of SOs across mPFC and M1 may be a potential driver of spindle trains and persistent reactivation of motor memory during NREM sleep.

Head coach Corey Mace, quarterback Trevor Harris and linebacker Jameer Thurman talk about coming up short in the CFL West Final. The Roughriders lost the the Winnipeg Blue Bombers 38-22 sending the Bombers to their fifth straight Grey Cup.

CBC Sports sat down with Hockey Hall of Famer Mats Sundin, showing him video of some of the biggest moments of his career.

Creactive Design uses 3D CAD software to design products for global brands like Black & Decker, Fujitsu, Nokia, and Pfizer

Voice assistants (VAs) like Alexa and Siri continue to gain popularity in households and on personal devices. According to digital trends research company Emarketer, the number of VA users will surpass 150 million in 2025. Despite the ubiquity, companies haven’t been able to work around users’ strong negative reactions to advertising on these applications. A research team, including scholars from Penn State, may have a solution.

India has ambitious plans to set up nuclear reactors across the country, especially in states where thermal power plants have either completed its life, or where access to coal is a challenge.

India has ambitious plans to set up nuclear reactors across the country, especially in states where thermal power plants have either completed its life, or where access to coal is a challenge.

Signal has been updated with Call Links, a feature that enables users to initiate a group call with multiple participants without the need to form a separate group chat. Additional updates include a "raise hand" button, emoji reactions, and a dedicated calls tab on Signal.

The Great Indian Kapil Show episode featuring Navjot Singh Sidhu will premiere on Netflix on Saturday, November 16 

Shraddha dropped a string of sweaty face and head slamming emojis

"So humbled and honoured our film is getting the love," Kareena Kapoor wrote in her post

Soan Papdi Viral Video: Just after Diwali, an unexpected video of the making process of Soan Papdi surfaced online

In early October, Deepinder Goyal shared a post showing various moments from their day as delivery agents

A light-hearted video showing leftover Diwali faral (Maharashtrian snacks) being eaten with tea has got foodies talking on Instagram.

Shilpa Shetty's unapologetic foodie side shines through in her latest Instagram reel. "My food is my food, and none of your food!" she declared.

The topical features Amul’s mascot dressed as Kareena Kapoor’s character, Jameet Bhamra, enjoying a meal

In the viral video, Jennifer also mentioned that "Cooking outside gives a totally different comfort and feeling. Just took me back to India."

The Delaware Office of Highway Safety (OHS) is reactivating its SoberLift program and bringing awareness to the negative consequences of driving under the influence. In addition, OHS is continuing to partner with State and local law enforcement to conduct DUI patrols through March 19th.  If your plans for the holiday include alcohol, make sure you plan for a sober driver.