El periodista se ha dedicado a coleccionar elementos relacionados a las novelas del mundo, en especial, las de Colombia.

The American author of Pew spoke with Eleanor Wachtel about writing a novel that examines faith, forgiveness and identity politics.

How protests in Iran threaten the country's regime; Chinese police have set up outposts in Canada; Kelly Clarkson's best Kellyoke covers; Becky Toyne reviews Iain Reid's new thriller, We Spread; The Linda Lindas drop by for an after-school hangout; and more.

Itamar Ben-Gvir's journey from far-right extremist to political power-broker; why Vladimir Putin wanted the bones of 18th-century Russian leader Grigory Potemkin; Becky Toyne reviews Pulitzer Prize winner Cormac McCarthy's first new novels in 16 years; Haiti's political and economic crisis is fueling a public health disaster for women; five U.S. states get ready to vote on whether to close a loophole that allows for slavery in 2022; and more.

Marian Engel’s Bear is one of Canada’s most controversial novels. But experts say it’s also one of the most daring and enduring.

We've also got three other book reviews of regional interest this week.

Writing a novel may appear to be difficult, but if you follow the basic steps, you can write a novel on your own. Begin by brainstorming and selecting a topic for your novel, then try to construct a story for your novel. Decide on your characters and a point of view, as well as the ... Read more

The post How Do You Write A Novel? first appeared on Storytellers Unplugged.

"I use music as a way into writing; it's a bit of Pavlovian self-programming, and particularly handy if you've got a full day and only narrow windows in which to write. You teach yourself that a particular piece of music means work, and your brain will generally go along. It makes the transition from shopping list to fiction much faster and smoother, at least for me."

"Lines is my fifth novel, and it is the most formally challenging work I've written."

"Every song is a portal into the past, a chance to connect with countless mundane moments from before: where you were, what you felt, who you were with when you happened to be listening to the same thing."

"I didn’t listen to music while writing the manuscript, but I was attuned to its musicality. "

"The Berlin Trilogy of Bowie albums (Low, “Heroes,” and Lodger) were a huge thematic and aesthetic influence on these books, especially his nods back to early 20th century futurism."

"...while I’m writing I need total silence, but even so, the music shares such a similar landscape with the text it’s hard to believe it wasn’t present from the beginning."

"My characters are real to me somewhere out there in the world and this is the soundtrack to their life."

Paperback, Hardcover, Kindle, Audiobook – January 1, 2009

Author-illustrator Ken Lamug has created award-winning picture books and graphic novels. Born in the Philippines, Ken moved to the US with his entire family during his teenage years. His debut middle grade graphic series, MISCHIEF AND MAYHEM #1: BORN TO BE BAD, launched this week from Katherine Tegen Books / HarperCollins!

Mischief and Mayhem is about Missy and her cat Gizmo. They were kicked out of superhero bootcamp. Now it's time for some super-villainy! I love the plot twist that the main character, Missy, decides she doesn't really fit into the labels the world she lives in has created; she's not really a villain, nor is she a superhero.  

Links where you can find out more: MischiefBook.com, Ken on Twitter, Facebook and Instagram. His website: Rabbleboy.com.

Q. I read that MISCHIEF AND MAYHEM started as a 32-page picture book story. How did it end up as a graphic novel?

Yep! The idea for Mischief and Mayhem started as a 32-page picture book - originally titled "Mischief the Supervillain". At the time, I was focused on my picture book ideas and wasn't even considering graphic novels. I had experience illustrating books, so I knew it was just a matter of time until something clicked for me. I went through the steps book creators are familiar with: writing the manuscript, creating dummies, and many rounds of revisions.

The dummy went through the submission process and even hopped to another agent (when I switched to a new one). We received a few rejections and a few interesting comments. One of the more resounding comments was that the idea was cool and needed to be expanded. But the picture book format limited what we could do.

We finally received an acceptance offer along with a caveat... turn it into a graphic novel! Yikes!

A few things scared me about this: it would have to be in full color, and at least 240+ pages. How does one turn a 32-page picture book into something that big?

And before anything was signed, I had to give the editorial team a few things: a fully illustrated first chapter, and a full outline for the book. This would give them a better idea of the story and my comic style. So I added new characters, expanded the moments from the story, and added a lot of jokes!

Once the editorial team gave the thumbs up, I was off to the races to get my debut graphic novel complete.

EXTRA: You can find out more about Ken's process as well as sample sketches in his Q&A with We Need Diverse Books.

Q. I've been thinking about a graphic novel middle grade project, but am intimidated by the amount of time the ART could take. Do you have any tips? How much time did MISCHIEF AND MAYHEM TAKE YOU in total? Were you working on anything else at the same time?

No kidding. Graphic novels ARE a lot of work. I've easily spent 1000 hours on Mischief and Mayhem (including creating marketing materials, videos, etc.). I also have a day job, so most of my after-hours are spent working on the book (typically around 5 hours on the weekdays). I basically stare at the computer screen all day!

During this time, I was also creating art for a picture book. And since the schedule for picture books are a bit more relaxed, I was able to squeeze it in without much problem.

Here are some tips I hope you'll find useful:

1. Working digitally has helped increase my productivity. It's easier to create dummies, inking, make revisions, and get feedback.

2. Scheduling and planning are very important. Find out the deadline, how many pages you can complete per day, and do the math.

In my case, I've determined that I am inking(outlining) about 1 page per hour. This means it will take me roughly 250 hours to outline a 250-page book. Based on that number, I can then determine if my deadline is a realistic goal. I know, it's a lot of math but it does help and you will be able to strategize how you approach the project.

3. Streamlining your art style. This varies depending on your abilities and time. Some artists are blessed enough to work full-time on their books and with longer deadlines. But if you're not one of them, then I would suggest streamlining the look of your characters, your drawing techniques so you can work faster and efficiently. Some artists are able to also hire a team to help support the rest of the task such as coloring, inking, letter, etc., but a majority of graphic creators are one-person operations.

4. Don't forget to take a break and enjoy life.

Q. What advice do you have for young graphic novel writers and illustrators?

Start small. You don't have to create a big "novel" length book right away. I started my comic book journey when I submitted a 4-page comic to an anthology. After I gained some confidence, I started creating 24-page comic one-shots (single issues). And it just kept growing from there.

Comics should be fun for both the creator and the reader, so make sure to enjoy the process and don't stress out about getting it right the first time.

Q. What's next for you?

I just finished illustrating a picture book called FAMILY BUSINESS (by Lenore Appelhans). It's about a raccoon family who seems to always get into trouble. I'm excited for that to come out (no dates yet).

I'm also in the middle of Mischief and Mayhem book 2. As I write this my hand is hurting from illustrating a "Where's Waldo-Esque" spread. Ha! But I'm proud to say the art has improved and the story is even bigger than the first one.

I've never really had a big plan for my drawing/art career. It's all a blessing and a humbling experience. I just hope that the readers love the stories and connect with the characters. So we'll see what happens next!

~~

For more interviews with children's book creators, see the Inkygirl interview archives.

Brian McLachlan is a cartoonist who's worked for Nickelodeon, The Nib and the New Yorker. He writes the monthly comic Spruce Street Squad for Owl Magazine. His book, Draw Out The Story: 10 Secrets to Creating Your Own Comics is an ILA-nonfiction award winner. Each Tuesday he hosts a group of artists in a PG-13 game of Dungeons & Dragons where they live draw what happens in game on Twitch, called Magical Marker ( MM ). You can find Brian at his website, on Twitter, and Instagram.

Synopsis of COMPLETE THE QUEST: THE POISONOUS LIBRARY (Imprint/Macmillan):

Save your kingdom in this interactive role-playing adventure, which reads like a graphic novel but also plays like a game! It’s perfect for fans of all ages who are interested in the exciting world of fantasy gaming.

Q. How did you come up with the idea for Complete The Quest?

Complete the Quest in a brand new mix of role playing game (RPG) and comic. It started as an experiment to see what would happen if I took a Dungeons & Dragons or Chose Your Own Adventure multi-path story and made it into a comic. How would the gameplay change by putting it into a visual space? For me, it was a literal game changer, turning the CYOA anxiety of multiple choices, into a laid-out, laid-back invitation to check all paths for your favourite way forward. It also encourages people to come up with their own, better solution if they want. While I always give the reader a clear path forward, I invite them to forge their own. It's a great introduction to co-operative storytelling.

Q. What was your writing/illustration process?

I draw a scene much faster than I can write about it. A picture's worth a thousand words and all that. So I draw my scripts in rough, laying out out the word balloons, figuring out how much space I need, how the page turns feel, etc. This was especially important for this comic gamebook which also filled with maps for the reader to navigate. We needed to see if the pathing was clear. Creating the tutorial was the most time intensive part, trying to make the most elegant, clear way to ease the reader into how the game part functions. I think we nailed it. I hear from parents who don't play RPGs that they were worried about the reading a gamebook, but they quickly "got it".

Q. What advice do you have for young writers and illustrators?

Advice is hard to give because everyone's different. Some people need to hear "finish what you start" and some need to hear "stop working on that thing, it's good enough". So my advice is to train your inner advice-giver and follow it. What is it about the way you work that you've been putting off improving, but could do right now? Because you know what type of story or art you're making, and if you're trying to make an apple, the best advice in making a banana isn't going to help. And the best advice in making an apple right-handed isn't going to help you if you're left-handed. Not all advice is for you, it's a skill to figure out what part is for you to take right now, later, or never.

----

Also see my other Inkygirl interviews with book creators and advice for young writers and illustrators from book creators.

Netflix's film is based on a 1955 novel about a man who goes in search of the father he’d never met — only to discover that his father is dead, and the village he inhabited is haunted by ghosts.

Most classroom walls display rules about arriving on time or raising hands to speak. Tim Smyth’s has a sign reminding students: “You’re Not Allowed to Ask Which is Better, Marvel or DC.” Even as he sidesteps fervent debates about which comic book publisher is superior, Smyth leans into comics and graphic novels in his 10th and 11th grade social studies classes at Wissahickon High School in Ambler, Pa. He believes they can offer students an engaging entry point into history and world cultures.

Nonphotochemical quenching (NPQ) is a mechanism of regulating light harvesting that protects the photosynthetic apparatus from photodamage by dissipating excess absorbed excitation energy as heat. In higher plants, the major light-harvesting antenna complex (LHCII) of photosystem (PS) II is directly involved in NPQ. The aggregation of LHCII is proposed to be involved in quenching. However, the lack of success in isolating native LHCII aggregates has limited the direct interrogation of this process. The isolation of LHCII in its native state from thylakoid membranes has been problematic because of the use of detergent, which tends to dissociate loosely bound proteins, and the abundance of pigment–protein complexes (e.g. PSI and PSII) embedded in the photosynthetic membrane, which hinders the preparation of aggregated LHCII. Here, we used a novel purification method employing detergent and amphipols to entrap LHCII in its natural states. To enrich the photosynthetic membrane with the major LHCII, we used Arabidopsis thaliana plants lacking the PSII minor antenna complexes (NoM), treated with lincomycin to inhibit the synthesis of PSI and PSII core proteins. Using sucrose density gradients, we succeeded in isolating the trimeric and aggregated forms of LHCII antenna. Violaxanthin- and zeaxanthin-enriched complexes were investigated in dark-adapted, NPQ, and dark recovery states. Zeaxanthin-enriched antenna complexes showed the greatest amount of aggregated LHCII. Notably, the amount of aggregated LHCII decreased upon relaxation of NPQ. Employing this novel preparative method, we obtained a direct evidence for the role of in vivo LHCII aggregation in NPQ.

An important mechanism of resistance to β-lactam antibiotics is via their β-lactamase–catalyzed hydrolysis. Recent work has shown that, in addition to the established hydrolysis products, the reaction of the class D nucleophilic serine β-lactamases (SBLs) with carbapenems also produces β-lactones. We report studies on the factors determining β-lactone formation by class D SBLs. We show that variations in hydrophobic residues at the active site of class D SBLs (i.e. Trp105, Val120, and Leu158, using OXA-48 numbering) impact on the relative levels of β-lactones and hydrolysis products formed. Some variants, i.e. the OXA-48 V120L and OXA-23 V128L variants, catalyze increased β-lactone formation compared with the WT enzymes. The results of kinetic and product studies reveal that variations of residues other than those directly involved in catalysis, including those arising from clinically observed mutations, can alter the reaction outcome of class D SBL catalysis. NMR studies show that some class D SBL variants catalyze formation of β-lactones from all clinically relevant carbapenems regardless of the presence or absence of a 1β-methyl substituent. Analysis of reported crystal structures for carbapenem-derived acyl-enzyme complexes reveals preferred conformations for hydrolysis and β-lactone formation. The observation of increased β-lactone formation by class D SBL variants, including the clinically observed carbapenemase OXA-48 V120L, supports the proposal that class D SBL-catalyzed rearrangement of β-lactams to β-lactones is important as a resistance mechanism.

Yue Chen
May 1, 2007; 6:812-819
Research

Mitsunori Fukuda
Jun 1, 2008; 7:1031-1042
Research

Lawrence E. Ostrowski
Jun 1, 2002; 1:451-465
Research

Reactive oxygen species (ROS) are an unavoidable host environmental cue for intracellular pathogens such as Mycobacterium tuberculosis and Mycobacterium bovis; however, the signaling pathway in mycobacteria for sensing and responding to environmental stress remains largely unclear. Here, we characterize a novel CmtR-Zur-ESX3-Zn2+ regulatory pathway in M. bovis that aids mycobacterial survival under oxidative stress. We demonstrate that CmtR functions as a novel redox sensor and that its expression can be significantly induced under H2O2 stress. CmtR can physically interact with the negative regulator Zur and de-represses the expression of the esx-3 operon, which leads to Zn2+ accumulation and promotion of reactive oxygen species detoxication in mycobacterial cells. Zn2+ can also act as an effector molecule of the CmtR regulator, using which the latter can de-repress its own expression for further inducing bacterial antioxidant adaptation. Consistently, CmtR can induce the expression of EsxH, a component of esx-3 operon involved in Zn2+ transportation that has been reported earlier, and inhibit phagosome maturation in macrophages. Lastly, CmtR significantly contributes to bacterial survival in macrophages and in the lungs of infected mice. Our findings reveal the existence of an antioxidant regulatory pathway in mycobacteria and provide novel information on stress-triggered gene regulation and its association with host–pathogen interaction.

Rhodopsin is a canonical class A photosensitive G protein–coupled receptor (GPCR), yet relatively few pharmaceutical agents targeting this visual receptor have been identified, in part due to the unique characteristics of its light-sensitive, covalently bound retinal ligands. Rhodopsin becomes activated when light isomerizes 11-cis-retinal into an agonist, all-trans-retinal (ATR), which enables the receptor to activate its G protein. We have previously demonstrated that, despite being covalently bound, ATR can display properties of equilibrium binding, yet how this is accomplished is unknown. Here, we describe a new approach for both identifying compounds that can activate and attenuate rhodopsin and testing the hypothesis that opsin binds retinal in equilibrium. Our method uses opsin-based fluorescent sensors, which directly report the formation of active receptor conformations by detecting the binding of G protein or arrestin fragments that have been fused onto the receptor's C terminus. We show that these biosensors can be used to monitor equilibrium binding of the agonist, ATR, as well as the noncovalent binding of β-ionone, an antagonist for G protein activation. Finally, we use these novel biosensors to observe ATR release from an activated, unlabeled receptor and its subsequent transfer to the sensor in real time. Taken together, these data support the retinal equilibrium binding hypothesis. The approach we describe should prove directly translatable to other GPCRs, providing a new tool for ligand discovery and mutant characterization.

Reliable, specific polyclonal and monoclonal antibodies are important tools in research and medicine. However, the discovery of antibodies against their targets in their native forms is difficult. Here, we present a novel method for discovery of antibodies against membrane proteins in their native configuration in mammalian cells. The method involves the co-expression of an antibody library in a population of mammalian cells that express the target polypeptide within a natural membrane environment on the cell surface. Cells that secrete a single-chain fragment variable (scFv) that binds to the target membrane protein thereby become self-labeled, enabling enrichment and isolation by magnetic sorting and FRET-based flow sorting. Library sizes of up to 109 variants can be screened, thus allowing campaigns of naïve scFv libraries to be selected against membrane protein antigens in a Chinese hamster ovary cell system. We validate this method by screening a synthetic naïve human scFv library against Chinese hamster ovary cells expressing the oncogenic target epithelial cell adhesion molecule and identify a panel of three novel binders to this membrane protein, one with a dissociation constant (KD) as low as 0.8 nm. We further demonstrate that the identified antibodies have utility for killing epithelial cell adhesion molecule–positive cells when used as a targeting domain on chimeric antigen receptor T cells. Thus, we provide a new tool for identifying novel antibodies that act against membrane proteins, which could catalyze the discovery of new candidates for antibody-based therapies.

Tricia Rowlison
Dec 1, 2020; 19:2090-2103
Research

Xiao-Ting Wen
Dec 17, 2020; 0:RA120.002119v1-mcp.RA120.002119
Research

Yi Liu
Dec 1, 2020; 19:1968-1985
Research

Sylwia Struk
Dec 28, 2020; 0:RA119.001766v1-mcp.RA119.001766
Research

Mingkun Yang
Nov 24, 2020; 0:RA120.002144v1-mcp.RA120.002144
Research

Type I and III interferons induce expression of the “myxovirus resistance proteins” MxA in human cells and its ortholog Mx1 in murine cells. Human MxA forms cytoplasmic structures, whereas murine Mx1 forms nuclear bodies. Whereas both HuMxA and MuMx1 are antiviral toward influenza A virus (FLUAV) (an orthomyxovirus), only HuMxA is considered antiviral toward vesicular stomatitis virus (VSV) (a rhabdovirus). We previously reported that the cytoplasmic human GFP-MxA structures were phase-separated membraneless organelles (“biomolecular condensates”). In the present study, we investigated whether nuclear murine Mx1 structures might also represent phase-separated biomolecular condensates. The transient expression of murine GFP-Mx1 in human Huh7 hepatoma, human Mich-2H6 melanoma, and murine NIH 3T3 cells led to the appearance of Mx1 nuclear bodies. These GFP-MuMx1 nuclear bodies were rapidly disassembled by exposing cells to 1,6-hexanediol (5%, w/v), or to hypotonic buffer (40–50 mosm), consistent with properties of membraneless phase-separated condensates. Fluorescence recovery after photobleaching (FRAP) assays revealed that the GFP-MuMx1 nuclear bodies upon photobleaching showed a slow partial recovery (mobile fraction: ∼18%) suggestive of a gel-like consistency. Surprisingly, expression of GFP-MuMx1 in Huh7 cells also led to the appearance of GFP-MuMx1 in 20–30% of transfected cells in a novel cytoplasmic giantin-based intermediate filament meshwork and in cytoplasmic bodies. Remarkably, Huh7 cells with cytoplasmic murine GFP-MuMx1 filaments, but not those with only nuclear bodies, showed antiviral activity toward VSV. Thus, GFP-MuMx1 nuclear bodies comprised phase-separated condensates. Unexpectedly, GFP-MuMx1 in Huh7 cells also associated with cytoplasmic giantin-based intermediate filaments, and such cells showed antiviral activity toward VSV.

Jiayan Guo
Dec 1, 2020; 61:1764-1775
Research Articles

Frank C. Nichols
Dec 1, 2020; 61:1645-1657
Research Articles

N-acylethanolamines (NAEs) are endogenous lipid-signaling molecules derived from fatty acids that regulate numerous biological functions, including in the brain. Interestingly, NAEs are elevated in the absence of fatty acid amide hydrolase (FAAH) and following CO₂-induced ischemia/hypercapnia, suggesting a neuroprotective response. Tetracosahexaenoic acid (THA) is a product and precursor to DHA; however, the NAE product, tetracosahexaenoylethanolamide (THEA), has never been reported. Presently, THEA was chemically synthesized as an authentic standard to confirm THEA presence in biological tissues. Whole brains were collected and analyzed for unesterified THA, total THA, and THEA in wild-type and FAAH-KO mice that were euthanized by either head-focused microwave fixation, CO₂ + microwave, or CO₂ only. PPAR activity by transient transfection assay and ex vivo neuronal output in medium spiny neurons (MSNs) of the nucleus accumbens by patch clamp electrophysiology were determined following THEA exposure. THEA in the wild-type mice was nearly doubled (P < 0.05) following ischemia/hypercapnia (CO₂ euthanization) and up to 12 times higher (P < 0.001) in the FAAH-KO compared with wild-type. THEA did not increase (P > 0.05) transcriptional activity of PPARs relative to control, but 100 nM of THEA increased (P < 0.001) neuronal output in MSNs of the nucleus accumbens. Here were identify a novel NAE, THEA, in the brain that is elevated upon ischemia/hypercapnia and by KO of the FAAH enzyme. While THEA did not activate PPAR, it augmented the excitability of MSNs in the nucleus accumbens. Overall, our results suggest that THEA is a novel NAE that is produced in the brain upon ischemia/hypercapnia and regulates neuronal excitation.

Of the known regulators of atherosclerosis, miRNAs have been demonstrated to play critical roles in lipoprotein homeostasis and plaque formation. Here, we generated a novel animal model of atherosclerosis by knocking in LDLR^W483X in C57BL/6 mice, as the W483X mutation in LDLR is considered the most common newly identified pathogenic mutation in Chinese familial hypercholesterolemia (FH) individuals. Using the new in vivo mouse model combined with a well-established atherosclerotic in vitro human cell model, we identified a novel atherosclerosis-related miRNA, miR-23a-3p, by microarray analysis of mouse aortic tissue specimens and human aortic endothelial cells (HAECs). miR-23a-3p was consistently downregulated in both models, which was confirmed by qPCR. Bioinformatics analysis and further validation experiments revealed that the TNFα-induced protein 3 (TNFAIP3) gene was the key target of miR-23a-3p. The miR-23a-3p-related functional pathways were then analyzed in HAECs. Collectively, the present results suggest that miR-23a-3p regulates inflammatory and apoptotic pathways in atherogenesis by targeting TNFAIP3 through the NF-B and p38/MAPK signaling pathways.

Porphyromonas gingivalis is a Gram-negative anaerobic periodontal microorganism strongly associated with tissue-destructive processes in human periodontitis. Following oral infection with P. gingivalis, the periodontal bone loss in mice is reported to require the engagement of Toll-like receptor 2 (TLR2). Serine-glycine lipodipeptide or glycine aminolipid classes of P. gingivalis engage human and mouse TLR2, but a novel lipid class reported here is considerably more potent in engaging TLR2 and the heterodimer receptor TLR2/TLR6. The novel lipid class, termed Lipid 1256, consists of a diacylated phosphoglycerol moiety linked to a serine-glycine lipodipeptide previously termed Lipid 654. Lipid 1256 is approximately 50-fold more potent in engaging TLR2 than the previously reported serine-glycine lipid classes. Lipid 1256 also stimulates cytokine secretory responses from peripheral blood monocytes and is recovered in selected oral and intestinal Bacteroidetes organisms. Therefore, these findings suggest that Lipid 1256 may be a microbial TLR2 ligand relevant to chronic periodontitis in humans.

Using a simple, environment friendly proteome extraction (TOP), we were able to optimize the analysis of clinical samples. Using our TOP method we analyzed a clinical cohort of microsatellite stable (MSS) and unstable (MSI-H) colorectal carcinoma (CRC). We identified a tumor cell specific, STAT1-centered, immune signature expressed by the MSI-H tumor cells. We then showed that long, but not short, exposure to Interferon- induces a similar signature in vitro. We identified 10 different temporal protein expression patterns, classifying the Interferon- protein temporal regulation in CRC. Our data sheds light on the changes that tumor cells undergo under long-term immunological pressure in vivo, the importance of STAT proteins in specific biological scenarios. The data generated could help find novel clinical biomarkers and therapeutic approaches.