The good folks at Stonemaier Games sent us a review copy of the newest expansion for Tapestry recently. We have the base game and the previous expansion, Plans and Ploys, in our game library. Arts & Architecture is designed by Jamey Stegmaier and Mike Young, with artwork by Andrew Bosley and landmark sculptures by Rom Brown. The expansion adds more of the familiar components: five new civilizations, six new capital city mats, 5 new landmark cards with landmarks, twenty new tapestry cards, and eleven new tech cards. Arts & Architecture also adds completely new features to the game, including an arts track with accompanying landmarks, twenty masterpiece cards, twenty inspiration tiles, and an upgraded science die to include iconography referencing the arts track.

The new arts development track is quite useful and thematically blends well with the overall concept of the game.

It gives you the opportunity to place more of your income buildings, score victory points for tech cards and exploration tiles, acquire masterpiece cards which provide benefits during income turns, and place inspiration tiles on your income mat over existing income tracks to improve the rewards gained during income turns. In the first few games I played (2 player), I concentrated heavily on the arts track, progressing to the end of it easily before game end, all the while also making steady progress on two of the base development tracks.

In the most recent game (4 player), I didn’t use the arts track much at all, which was a huge mistake, landing me in third place while the frontrunners leaned on the arts track significantly. I’ve previously noted in my review of Tapestry (https://www.thatswhatjennisaid.com/2020/07/board-game-review-tapestry.html) and Tapestry Plans and Ploys (https://www.thatswhatjennisaid.com/2020/12/board-game-review-tapestry-plans-and.html) that to win the game, you must diversify and progress on at least two tracks simultaneously, but to be careful trying to do much more than that or you’ll spread yourself too thin. With this expansion, I’ll amend that to note you’re unlikely to win the game unless you focus on the arts track as well as two of the base development tracks, as the arts track is really an enhancer for all the other tracks. It will be interesting to see how development track focus will need to be adapted when Stonemaier releases additional expansions for the game (anticipating a religion track at minimum; every civilization has its religious scholars).

The additions to the tapestry deck include a new ability type - continuous. These abilities begin when played and continue for the duration of the game instead of just the current era. There are also new tapestry cards that allow you to place landmarks on them for scoring as an alternative to placing the landmarks on the capital city (or on the map as some civ powers allow you to do). I did not have a chance to play any of the continuous tapestry cards during my recent games (although they look useful), and I passed over playing any of the landmark tapestry cards I acquired as they did not seem as beneficial as the other tapestry cards I had in my hand.  I don’t think I’m a big fan of any of the cards that let you place landmarks on the for points (including the new tech cards with this feature); I prefer to prioritize my city map for landmark placement first. Maybe I’m just doing it wrong, but I haven’t made use of my landmark cards at all, even in the games where I won by a large margin. They seem to be an entirely optional aspect of the game and not necessary for a win.

One more change with the Arts & Architecture expansion is another refinement of the civilization adjustments first introduced in the Plans and Ploys expansion. This fine tuning of civilization powers comes as a result of extensive real-world player testing and aims to rebalance the game for greater fairness. I think it might need further refinements because my husband Chris played the Architects civilization in our last game and the adjustment afforded him 30 VPs at the start of the game as some sort of handicap to balance out perceived weakness, but his city mat was so perfectly attuned to his civilization (the mesa) that he won in a landslide (80 points above the second place player).

Overall, I think that the Arts & Architecture expansion is a great addition to the Tapestry portfolio. It adds more variety, layers in additional ways to strategize and score, and provides some new opportunities for player interaction on the map, without causing any additional complexity. While it’s not a must have for the base game, it’s certainly a nice-to-have addition that I’m happy to recommend.

Beyond the details of the new expansion, I did want to take this opportunity to mention that with repeated plays of the base game as well as across the expansions, I’ve noticed that 4 player games are much more competitive than two player games (at least in our household). There isn’t a single time Chris and I have played the game by ourselves that I haven’t walloped him by 100+ points, yet when we play at 4 players, he has won twice or been neck in neck with the winner, whereas my scores are significantly lower. That’s got to be tied to the dynamics of how this game plays at higher player counts because it doesn’t make any sense that all on my own I could go from being a genius at 2 player to just average at 4 player.

--------------------------------------------------------------------------------

Publisher: Stonemaier Games
Players: 1-5 (We played with 2 and 4)
Actual Playing Time (vs the guideline on the box): About 3 hours per game
Game type: tile placement, hand management, dice rolling, area control
Retail Price: $45 direct from the publisher https://store.stonemaiergames.com/products/tapestry-arts-architecture

Rating:

Jenni’s rating scale:
OUI: I would play this game again; this game is ok. I probably would not buy this game myself but I would play it with those who own it and if someone gave it to me I would keep it.
OUI OUI: I would play this game again; this game is good. I would buy this game.
OUI OUI OUI: I LOVE THIS GAME. I MUST HAVE THIS GAME.
NON: I would not play this game again. I would return this game or give it away if it was given to me.

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Los Angeles, often hailed as the entertainment capital of the world, is not only a hub for the film and music industries but also a fascinating canvas of urban design. The city's architectural landscape reflects a rich tapestry woven with threads of history, culture, and innovation. As one navigates the vast expanse of Los Angeles, it becomes apparent that the city's design is a dynamic fusion of tradition and modernity.[...]

Lando Norris cuts Max Verstappen’s lead to 47 points and labels his rival “dangerous” as the championship battle reaches boiling point at the Mexico City Grand Prix.

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McLaren's Lando Norris says title rival Max Verstappen "knows he did wrong" in their battle in last weekend's Mexico City Grand Prix.

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BBC Sport analyses the Formula 1 title battle including the factors that may help Lando Norris overhaul Max Verstappen.

Max Verstappen climbs up from 17th on the grid to win the Sao Paulo Grand Prix, one of his greatest victories taking him to the brink of a fourth world title.

Lando Norris’ already slim world title hopes were crushed at the Sao Paulo Grand Prix by a performance for the ages from Max Verstappen.

Dozens of videos involving a senior civil servant in Equatorial Guinea have flooded social media, shocking people in the country.

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Introducing Instapaper 4.0 for iPad and iPhone

The lede here is that my pal, Marco, has just released the stellar new 4.0 version of his Instapaper suite.

This is fantastic news, and–as if you needed one more of Marco’s beta testers to say so–I do sincerely hope you’ll mark the occasion (and support his hard work) by purchasing the Instapaper iOS app(s). I promise you’ll be treating yourself to a massive update to an already excellent product.

Now, it’s fortunate and appropriate that you’ll be hearing this advice at length from a lot of people this week. Because, if it’s not already obvious, Marco’s little app (and its associated services) enjoys a rabid fanbase of sundry paragraph cultists who are as eager as I am to spread the word; and, yes, we do want you to join the Reading Nerd cult.

But, I also want to mark the occasion by adding a few thoughts on exactly what Instapaper has done, and continues to do, for me. (As you may already know, I’m a big Marco fan.)

Thing is, I want to tell you how Marco has made a magical machine for people who have decided to read.

Long-Time Fan

For years, Instapaper has been one of the best made, most used, and most beloved apps in my iOS ecosystem. It’s always lived on my iPhone’s home page, and, as you can surmise, that’s because I use Instapaper a lot. Like, a lot a lot. Specifically, I use Instapaper a lot because it helps me do four things extremely well. Four things that work together to make my life a little better.

In that typically annoying mixed order I can’t seem to stop doing, here goes.

2. Deciding WHEN to read

Second, and most obviously, I use Instapaper maybe five to ten times a day to catch up on my reading. Which is great. This is what Instapaper is actually for, right? You read stuff.

Long articles, smaller features, short books, big piles of documentation, and really just anything that I would like to read…later. More saliently, these are things that I have decided to read. This decision part’s important, but more on that in a couple minutes.

But, how does all this “stuff” I’ve decided to read get in to Instapaper?

1. Deciding WHAT to read

See, this is the really important first part. Because as much as I use Instapaper for all manner of reading, its use as an ephemeral destination for mostly ephemeral content wouldn’t be nearly so useful if I didn’t have so many ways to collect all that stuff. So, that flexibility in collecting material is where I end up using some form of Instapaper dozens of times each day.

Examples?

I have a bookmarklet for adding items to Instapaper in 4 browsers on 7 devices. I have (and use the hell out of) the “Send to Instapaper” services that are built in to everything from Google Reader to Reeder to Flipboard to Instacast to Tweetbot to Zite to you name it. I can automate in or out of Instapaper with If This Then That, I can email items directly to Instapaper–hell, I can even just copy a URL from iOS Safari, and paste it directly into the motherscratching Instapaper app.

Suffice it to say, there are many ways to get “stuff” into Instapaper. E.g.:

But, that banner dump only tells part of the story.

Yes, a big part of this is about ubiquity and ease-of-use. But, the practical result is that all those little entrees to Instapaper are available to me everywhere I might need them, and they each represent a single little click that silently adds an item of “stuff” to my Instapaper pile.

Each button is one more simple opportunity for me to decide to read.

3. Deciding WHERE to read

Now, the third part of this magic is less immediately obvious, not least because the reading experience of the Instapaper iOS apps is, for my own purposes, perfect. But, there’s more.

Because, all that support for getting stuff into Instapaper is mirrored by an endless number of ways to get stuff back out. To, in fact, read. That thing I decided to read is now everywhere.

However I ended up deciding to read something, seconds after that *click*, the real magic starts happening, and–through whatever inscrutable black art and transmogrification is happening inside the fearsome celestial engine Marco has made–that decision to read is expressed in the most elegant of results and in a startlingly broad variety of convenient places.

It’s readable on a website; it’s readable on an iPhone, and 2 iPads; it’s readable on a Kindle 3; it’s readable on the crazy number of apps and services that display Instapaper items. And, it’s even preserved for posterity in my private Pinboard archive.

So, for practical purposes, this stuff that I’ve decided to read can now go whooshing through a network of customized tubes, and gently land practically anywhere that well-formed bits may reside.

4. Just…Deciding to Read

I know most of you know these things. I know you’re familiar with the many “Features and Benefits” of Instapaper. And, I even know that most of you reading this are probably already using Instapaper–perhaps even to read this very article.

So, the point here is not simply that Instapaper is flexible, idiot-proof, and sanity-savingly redundant. Although it is all those things and many more.

The point is that my life always gets better when I decide to read things–and then actually read those things I decided to read. This is not a trivial point.

We’re all busy, and we’re all bombarded with 10,000 potential calls on our attention every day. Some days, we handle that better than others. Some days, we don’t handle it all.

All I know, is that, throughout my life, deciding to read has made that life better.

It made my life better at 7 with Henry Huggins. It made my life better at 16 with Slaughterhouse-Five. It made my life better at 20 with Absalom, Absalom!. And, it made my life way better at 25 with A Confederacy of Dunces (cf.).

And, now, for the past few years–following over a decade during which I read way more href tags than actual prose paragraphs–my life has gotten better, in part, due to Instapaper. I’ve finally gotten my hands around this “too much stuff” issue, at least insofar as it relates to words of theoretical interest. Now, I know where it goes. It goes into Instapaper.

Because, now? Yeah. Twenty-some years after a college career sucking down over 1,000 pages a week, I am finally returning to reading a lot more. Because, I am deciding to read a lot more. Instapaper means there’s no excuse for not reading a lot more. Period.

How about you?

What Are YOU Deciding?

When you’re in line at the ATM or the professional sporting event, what do you do?

If you’re like a lot of people, you hit your mobile device like a pigeon on a goddamned pellet. Then, you decide what happens.

You can decide to throw birds at pigs. You can decide to check in on which strangers are pretending to like you today. You may even decide to see what you would look like if you were really fat.

Thing is, you could also decide to read. Just for a couple minutes. Maybe more. Maybe less. Who knows. It’s your decision.

A Nudge Towards “Better”

But, if you have followed the circuitous skeins of yarn comprising this little sweater you’ve been reading, it comes down to this:

If you’ve decided that you want to read, Marco’s app will really help you. He’s removed any phony barriers you’ve built about “not having time” or “not having it with you” or “not knowing where to put it.” There are no excuses, apart from the superficial animated ones you’ve constructed out of cartoon birds.

As for me? In the last week alone, I decided to read a lot of things in Instapaper. A small sampling:

I decided to read about an American family’s educational experiment in Russia.

I decided to read about what Heidegger means by Being-in-the-World.

I decided to read about why toasters are so bad.

I decided to read about responsive web design.

I decided to read about why Charlie Kaufman wrote Being John Malkovich.

I decided to read about how Open Data could make San Francisco Public Transportation better.

I decided to read about how John Siracusa remembers Steve Jobs.

I decided, and then I read. I read, and I read.

So, thanks, Marco. You’ve made my life better by making it easier to decide to read. Then, you made it way easier to do the actual reading.

And, to you–the kind readers-of-prose-paragraphs who were inexplicably patient enough to decide to read this long article–please consider supporting Marco’s work.

Please get an account at Instapaper and, if you have an iOS dingus, please do buy the Instapaper app.

In addition to having exquisite taste in app icons and a lovely speaking voice, Marco’s just a very good human. And, good humans more than deserve our support.

Buy Instapaper 4.0 by Marco Arment.

Staphylococcus aureus adhesion to the host's skin and mucosae enables asymptomatic colonization and the establishment of infection. This process is facilitated by cell wall-anchored adhesins that bind to host ligands. Therapeutics targeting this process could provide significant clinical benefits; however, the development of anti-adhesives requires an in-depth knowledge of adhesion-associated factors and an assay amenable to high-throughput applications. Here, we describe the development of a sensitive and robust whole cell assay to enable the large-scale profiling of S. aureus adhesion to host ligands. To validate the assay, and to gain insight into cellular factors contributing to adhesion, we profiled a sequence-defined S. aureus transposon mutant library, identifying mutants with attenuated adhesion to human-derived fibronectin, keratin, and fibrinogen. Our screening approach was validated by the identification of known adhesion-related proteins, such as the housekeeping sortase responsible for covalently linking adhesins to the cell wall. In addition, we also identified genetic loci that could represent undescribed anti-adhesive targets. To compare and contrast the genetic requirements of adhesion to each host ligand, we generated a S. aureus Genetic Adhesion Network, which identified a core gene set involved in adhesion to all three host ligands, and unique genetic signatures. In summary, this assay will enable high-throughput chemical screens to identify anti-adhesives and our findings provide insight into the target space of such an approach.

Leukocidin ED (LukED) is a pore-forming toxin produced by Staphylococcus aureus, which lyses host cells and promotes virulence of the bacteria. LukED enables S. aureus to acquire iron by lysing erythrocytes, which depends on targeting the host receptor Duffy antigen receptor for chemokines (DARC). The toxin also targets DARC on the endothelium, contributing to the lethality observed during bloodstream infection in mice. LukED is comprised of two monomers: LukE and LukD. LukE binds to DARC and facilitates hemolysis, but the closely related Panton–Valentine leukocidin S (LukS-PV) does not bind to DARC and is not hemolytic. The interaction of LukE with DARC and the role this plays in hemolysis are incompletely characterized. To determine the domain(s) of LukE that are critical for DARC binding, we studied the hemolytic function of LukE–LukS-PV chimeras, in which areas of sequence divergence (divergence regions, or DRs) were swapped between the toxins. We found that two regions of LukE's rim domain contribute to hemolysis, namely residues 57–75 (DR1) and residues 182–196 (DR4). Interestingly, LukE DR1 is sufficient to render LukS-PV capable of DARC binding and hemolysis. Further, LukE, by binding DARC through DR1, promotes the recruitment of LukD to erythrocytes, likely by facilitating LukED oligomer formation. Finally, we show that LukE targets murine Darc through DR1 in vivo to cause host lethality. These findings expand our biochemical understanding of the LukE–DARC interaction and the role that this toxin-receptor pair plays in S. aureus pathophysiology.

RNase J enzymes are metallohydrolases that are involved in RNA maturation and RNA recycling, govern gene expression in bacteria, and catalyze both exonuclease and endonuclease activity. The catalytic activity of RNase J is regulated by multiple mechanisms which include oligomerization, conformational changes to aid substrate recognition, and the metal cofactor at the active site. However, little is known of how RNase J paralogs differ in expression and activity. Here we describe structural and biochemical features of two Staphylococcus epidermidis RNase J paralogs, RNase J1 and RNase J2. RNase J1 is a homodimer with exonuclease activity aided by two metal cofactors at the active site. RNase J2, on the other hand, has endonuclease activity and one metal ion at the active site and is predominantly a monomer. We note that the expression levels of these enzymes vary across Staphylococcal strains. Together, these observations suggest that multiple interacting RNase J paralogs could provide a strategy for functional improvisation utilizing differences in intracellular concentration, quaternary structure, and distinct active site architecture despite overall structural similarity.

Nadine Prust
Dec 17, 2020; 0:RA120.002232v1-mcp.RA120.002232
Research

Recent efforts in gut microbiome studies have highlighted the importance of explicitly describing the ecological processes beyond correlative analysis. However, we are still at the early stage of understanding the organizational principles of the gut ecosystem, partially because of the limited information provided by currently used analytical tools in ecological modeling practices. Proteomics and metaproteomics can provide a number of insights for ecological studies, including biomass, matter and energy flow, and functional diversity. In this Mini Review, we discuss proteomics and metaproteomics-based experimental strategies that can contribute to studying the ecology, in particular at the mucosal-luminal interface (MLI) where the direct host-microbiome interaction happens. These strategies include isolation protocols for different MLI components, enrichment methods to obtain designated array of proteins, probing for specific pathways, and isotopic labeling for tracking nutrient flow. Integration of these technologies can generate spatiotemporal and site-specific biological information that supports mathematical modeling of the ecosystem at the MLI.

Staphylococcus aureus is a major cause of infections worldwide and infection results in a variety of diseases. As of no surprise, protein phosphorylation is an important game player in signaling cascades and has been shown to be involved in S. aureus virulence. Albeit long neglected, eukaryotic-type serine/threonine kinases in S. aureus have been implicated in this complex signaling cascades. Due to the sub-stoichiometric nature of protein phosphorylation and a lack of suitable analysis tools, the knowledge of these cascades is however, to date, still limited.

Here, were apply an optimized protocol for efficient phosphopeptide enrichment via Fe3+-IMAC followed by LC-MS/MS to get a better understanding of the impact of protein phosphorylation on the complex signaling networks involved in pathogenicity. By profiling a serine/threonine kinase and phosphatase mutant from a methicillin-resistant S. aureus mutant library, we generated the most comprehensive phosphoproteome dataset of S. aureus to date, aiding a better understanding of signaling in bacteria. With the identification of 3800 class I p-sites we were able to increase the number of identifications by more than 21 times compared to recent literature. In addition, we were able to identify 74 downstream targets of the only reported eukaryotic-type Ser/Thr kinase of the S. aureus strain USA300, Stk1. This work allowed an extensive analysis of the bacterial phosphoproteome and indicates that Ser/Thr kinase signaling is far more abundant than previously anticipated in S. aureus.

President-elect Donald Trump announced his choice Tuesday for CIA Director, tapping his former intelligence chief John Ratcliffe, who he called a "warrior of truth."

President-elect Donald Trump on Monday announced plans to nominate South Dakota Gov. Kristi Noem to head the Department of Homeland Security of his incoming administration.

An internationally known gifted-education center is scouting—and helping to develop—gifted students in after-school programs and pullout classes in one of Maryland’s most challenged school districts.

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Low-intensity transcranial focused ultrasound stimulation (TUS) is a novel technique for noninvasive brain stimulation (NIBS). TUS delivered in a theta (5 Hz) burst pattern (tbTUS) induces plasticity in the human primary motor cortex (M1) for 30–60 min, showing promise for therapeutic development. Metaplasticity refers to activity-dependent changes in neural functions governing synaptic plasticity; depotentiation is the reversal of long-term potentiation (LTP) by a subsequent protocol with no effect alone. Metaplasticity can enhance plasticity induction and clinical efficacy of NIBS protocols. In our study, we compared four NIBS protocol combinations to investigate metaplasticity on tbTUS in humans of either sex. We delivered four interventions: (1) sham continuous theta burst stimulation with 150 pulses (cTBS150) followed by real tbTUS (tbTUS only), (2) real cTBS150 followed by sham tbTUS (cTBS only), (3) real cTBS150 followed by real tbTUS (metaplasticity), and (4) real tbTUS followed by real cTBS150 (depotentiation). We measured motor-evoked potential amplitude, short-interval intracortical inhibition, long-interval intracortical inhibition, intracortical facilitation (ICF), and short-interval intracortical facilitation before and up to 90 min after plasticity intervention. Plasticity effects lasted at least 60 min longer when tbTUS was primed with cTBS150 compared with tbTUS alone. Plasticity was abolished when cTBS150 was delivered after tbTUS. cTBS150 alone had no significant effect. No changes in M1 intracortical circuits were observed. Plasticity induction by tbTUS can be modified in manners consistent with homeostatic metaplasticity and depotentiation. This substantiates evidence that tbTUS induces LTP-like processes and suggests that metaplasticity can be harnessed in the therapeutic development of TUS.

The work of Diné artist DY Begay, now on view at the National Museum of the American Indian, blends tradition and modernity

Cancun, Mexico. On [...]

Coffee - it's a staple of American life, and inside the vaults of the National Museum of American History, they know the secret to its wide spread success: packaging

Unexplored iron-rich magma could help power current and future technologies

Containing a small engine within the wheel itself, the RevoPower Wheel opens the door to a new healthy and affordable means of transportation for global markets

SA's tax ombud has had "informal discussions" with its counterpart in Australia over combating refund scams as it investigates the hijacking of eFiling profiles.

President-elect Donald Trump announced that John Ratcliffe, his former director of national intelligence, is his pick to lead the CIA.

Fox News host Pete Hegseth is Donald Trump's pick to be defense secretary, the president-elect announced.

Donald Trump has announced that Elon Musk and Vivek Ramaswamy, a former presidential candidate and ally of Trump, will lead a new Department of Government Efficiency.

Read the in depth Review of Philips TAPB603 3.1 Soundbar Audio Video. Know detailed info about Philips TAPB603 3.1 Soundbar configuration, design and performance quality along with pros & cons, Digit rating, verdict based on user opinions/feedback.

Ensuring that the RTL designs correctly implement the C++ algorithmic intent in every circumstance is difficult to achieve with conventional verification. Learn more how Jasper C2RTL App helps to perform equivalence checking with 100x performance improvement(read more)

Austin is drawing people to jobs, music venues, comedy clubs, barbecue and more. But with this boom has come a big city blues: traffic jams. Rekor, which offers traffic management and public safety analytics, has a front-row seat to the increasing traffic from an influx of new residents migrating to Austin. Rekor works with the Read Article

Rubio, 53, has said in recent interviews that Ukraine needs to seek a negotiated settlement with Russia rather than focus on regaining all territory that Russia has taken in the last decade.

Zeldin, a Republican, voted for key environmental legislation just 14% of the time during his tenure in the House of Representatives.

The U-Tapao International Airport is the core infrastructure of the EEC and its expansion project is to be implemented via Public-Private Partnership modality. Land transport network connecting the U-Tapao International Airport in the Eastern Economic Corridor (EEC) to the rest of the Pattaya City and country cannot adapt to changing needs as a result of the expansion plan of the airport due to the limitations of the existing land transport network to cope with traffic increase.

Title: African Chimps Carry Drug-Resistant, Human-Linked Staph
Category: Health News
Created: 8/24/2012 4:05:00 PM
Last Editorial Review: 8/27/2012 12:00:00 AM

The neuronal nucleus houses a meticulously organized genome. Within this structure, genetic material is not simply compacted but arranged into a precise and functional 3D chromatin landscape essential for cellular regulation. This mini-review highlights the importance of this chromatin landscape in healthy neurodevelopment, as well as the diseases that occur with aberrant chromatin architecture. We discuss insights into the fundamental mechanistic relationship between histone modifications, DNA methylation, and genome organization. We then discuss findings that reveal how these epigenetic features change throughout normal neurodevelopment. Finally, we highlight single-gene neurodevelopmental disorders that illustrate the interdependence of epigenetic features, showing how disruptions in DNA methylation or genome architecture can ripple across the entire epigenome. As such, we emphasize the importance of measuring multiple chromatin architectural aspects, as the disruption of one mechanism can likely impact others in the intricate epigenetic network. This mini-review underscores the vast gaps in our understanding of chromatin structure in neurodevelopmental diseases and the substantial research needed to understand the interplay between chromatin features and neurodevelopment.

Bacterial regulatory RNAs (sRNAs) are important players to control gene expression. In Staphylococcus aureus, SprC is an antivirulent trans-acting sRNA known to base-pair with the major autolysin atl mRNA, preventing its translation. Using MS2-affinity purification coupled with RNA sequencing, we looked for its sRNA-RNA interactome and identified 14 novel mRNA targets. In vitro biochemical investigations revealed that SprC binds two of them, czrB and deoD, and uses a single accessible region to regulate its targets, including Atl translation. Unlike Atl regulation, the characterization of the SprC-czrB interaction pinpointed a destabilization of the czrAB cotranscript, leading to a decrease of the mRNA level that impaired CzrB zinc efflux pump expression. On a physiological standpoint, we showed that SprC expression is detrimental to combat against zinc toxicity. In addition, phagocyctosis assays revealed a significant, but moderate, increase of czrB mRNA levels in a sprC-deleted mutant, indicating a functional link between SprC and czrB upon internalization in macrophages, and suggesting a role in resistance to both oxidative and zinc bursts. Altogether, our data uncover a novel pathway in which SprC is implicated, highlighting the multiple strategies used by S. aureus to balance virulence using an RNA regulator.

Affibody molecules are small (6-kDa) affinity proteins generated by directed evolution for specific binding to various target molecules. The first step in this workflow involves the generation of an affibody library, which can then be used for biopanning using multiple display methods. This protocol describes selection from affibody libraries using display on Staphylococcus carnosus. Display of affibodies on staphylococci is very efficient and straightforward because of the single cell membrane and the use of a construct with a constitutive promoter. The workflow involves display of affibody libraries on the surface of S. carnosus cells, followed by screening and selection of binders using fluorescence-activated cell sorting (FACS). The transformation of DNA libraries into S. carnosus is less efficient and more complicated than for Escherichia coli. Because of this, staphylococcal display is suitable for affinity maturation or other protein-engineering efforts that are not dependent on very high diversity, and thus magnetic-activated cell sorting (MACS) is often not required before FACS. However, MACS is an option, and MACS procedures used for E. coli can easily be adapted for use in S. carnosus if needed.

When I was reviewing Final Fantasy VII Rebirth a few months ago, it looked set to be my Game of the Year. Metaphor: ReFantazio was still a distant concept and, I thought, communication of that concept was anything great. It turns out that I was really underestimating Atlus at the time. It's been eight years since Persona 5, and maybe I had begun to forget its magic, because as a JRPG from the creators of Persona 5, the magic is undoubtedly there in Metaphor: ReFantazio.

When I was younger, I used to watch the Columbo series, where you know the culprit's identity right away at the start. Metaphor: ReFantazio is a bit like that, because the introduction shows the King of Euchronia (Metaphor's fantasy world) being murdered in his sleep by an ambitious aristocrat named Louis, which throws the whole country into turmoil. From there, the protagonist and the comrades he meets all have different reasons for sharing the same goal: to prevent the wicked Louis from seizing the throne.

As simple as it seems, the narrative has its fair share of surprises. This has to do with the tremendous wealth of characters in the game. Due to a certain magic, the race for the throne is turned into an election, in which the protagonists gets to runs. Adding to the eight playable characters, you meet several competitors and followers who back you. All of them have personal stories and strange personalities that make Metaphor's adventure strikingly vivid.

The sub-stories are quite interesting for most part, for they convey a range of different emotions: sometime are heart-breaking, sometime heart-warming or just purely fun, and they'll keep you engaged for hours. They often leave you in suspense, since the structure of the game has you experiencing them little by little. And, just like in Persona, you can spend extensive time with your allies in a whole lot of mini sequences that play a great part in making the cast truly unforgettable.

But that doesn't mean you'll forget about the main story. Metaphor: ReFantazio offers some fascinating chapters. Take for instance the Opera house one, it's a breathtaking chapter very reminiscent of the great Final Fantasy VI, absolutely loaded with memorable sequences, grandiose fights, and striking reveals. And in the end, the whole game is like that. The thirst for more is real, as Atlus always drops a little something to make you eager to progress and feel engaged - a new character, intense combat, a shocking truth, stunning landscapes, etc. Even the most common NPCs sometimes tell a tale that blows your mind. Metaphor: ReFantazio has so much to offer in terms of characters, creativity, and storytelling that I couldn't help feeling overwhelmed at times.

The incongruity of an election in a kingdom ruled by Royals for ages is in reality an occasion for the story to develop elaborate thoughts about democracy and society. The protagonist always carries with him a strange book about an ideal world, where people have equal chances, decide their own fates, and live in harmony. It's a dream-like realm wholly different from Euchronia, which is a medieval regime plagued by injustice, greed, and poverty.

But there are whispers of a past, of a very advanced civilisation that ultimately failed, creating a scenario that raises the question of the relationship between democracy and freedom. There are also different tribes in the game, and it's worth noticing that the protagonist's party has one representative of each tribe, like a call for tolerance in a kingdom known for its inequality. The narrative therefore has powerful philosophic elements - something that only the greatest works in JRPG history possess.

Metaphor: ReFantazio boasts world design like you seldom see, starting with the giant flying rock that has symbolized it since reveal. Here again Atlus' creativity is absolutely inspired. The designers left their comfort zone and came up with an innovative take on characters, meaning that they ditched the classical human hero or heroine. You befriend an elf-like girl, a bat-like character or a maiden with a third eye, but no real typical human. The result is a party that literally breathes fantasy, a bit like Final Fantasy Tactics Advance did in its time. Humans exist, though, but on the opposite side of the divide.

These so-called Humans are twisted and awfully misshapen creatures roaming Euchronia as dangerous enemies. Atlus went beyond the boundaries of the bizarre with these designs and the result is amazing. I could also mention the funny Runner, a land vessel with legs that the party owns. Just travelling with it feels incredible. There are numerous examples like this, but in short the world is packed with wonders that I've never seen in a game before.

As for combat, Metaphor: ReFantazio is a good old turn-based JRPG, where strategy and careful planning matter. Characters wield the power of Archetypes, abstract figures that party members turn into when attacking. Archetypes are essentially jobs, hence my mention of Final Fantasy Tactics above. You can equip a character with an archetype, and they then acquire attack and passive skills specific to that archetype. For example, the Gunner can deal what is called "pierce" damage from behind, the Warrior heavy "slash" damage with its greatsword, and the Mage masters the natural elements.

There are also very complex Archetypes like the Masked Dancer, which can wear different masks to mimic other Archetypes, or the all-powerful Summoner, who masters absolutely ever type of damage once you acquire the corresponding stones (needless to say, these are incredibly difficult to come by). Unlike Persona 5, every character can equip any archetype, so you can choose the allies you like the most. Besides that, the currently-equipped Archetype can also inherit a couple of skills or spells from another, allowing for very elaborate lineups.

Combat isn't simplistic or easy; basic skills won't do much against bosses or even the relatively big enemies within dungeons. For these, the player must analyze how Archetypes can cooperate. Two Healers can, for example, cast a light spell on all opponents, while a single healer only targets one. Three magic-type archetypes lets the Mage unleash the mightiest fire spell available, which comes in handy at times. Such cooperation skills take more than one turn crystal (as turns are represented in game), but you can save turn crystals by exploiting the enemy's weakness, like you can in Shin Megami Tensei and its spin-offs.

The possibilities offered by Archetypes are fantastic and their complexity goes well beyond anything I've experienced from Atlus thus far. You have several types of Archetypes that work against a set weakness (three Archetype lineages have fire spells, for example). So you can choose the ones that fit your current goal or preferences. Boss fights are no joke and it's a renewed pleasure to overcome the various (tough) challenges after devising the right strategy. Metaphor: ReFantazio also lives up to Persona 5 in two particular aspects: main dungeons are never short of surprises, and the presentation of the battle menu is once again fantastic.

Like in Persona, Metaphor: ReFantazio is played in limited time. There's an in-game calendar with deadlines set to clear the main dungeons. So you can't have everyone master every archetype - you need to choose and use every day wisely. Unlike Persona 5, which gives you fixed Personas that you have to figure out how to use optimally, building characters and Archetypes in Metaphor: ReFantazio must be planned well ahead of time. This a fundamental difference between the two and the reason why this new IP elevates Atlus' core gameplay conceits, which were already very good. Exploration is important and quite entertaining too: you can tackle tricky secondary dungeons, discover special shops, or visit your followers. 

The latter provide perks, like increased slots for inherited skills, greater experience gain and, most importantly, the ability to unlock advanced Archetypes. The Healer can become the Cleric, for instance, with far superior healing capabilities, and you can become a General after being a Commander, gaining powerful ice skills in addition to the potent fire skills the latter had.

The whole game must be seen as a wide array of possibilities, with the player finding their own way to victory with their choices and favorite characters. As far as I'm concerned, this feels rewarding beyond anything I expected. Overflowing with content, the game is very long (around 70 hours), even with Atlus allowing you save time (any low-level enemy on the map can be beaten instantly without entering a turn-based battle, and you'll still gain experience and materials). 

The visuals are Metaphor's clear weakness. The game modeling isn't what you'd expect from a PS5 game in 2024, and I'd say it's fairly underwhelming for PS4 too. The backgrounds aren't very sharp and you see aliasing here and there. Secondary dungeons look very common; actually, they don't look like much of anything really. And there are several towers to explore across Euchronia, but the interior of each tower looks the exact same everytime. This kind of reuse of assets is fairly disappointing for a game of this magnitude. I shiver at the thought of what Metaphor: ReFantazio could have looked like with a Final Fantasy-sized budget. I expect it would have been my first perfect score, but it looks like I'll need to withhold that one once again.

One aspect that does score perfect marks is the original music score. Here again, I was pretty sure that Final Fantasy VII Rebirth would be my soundtrack of the year, but Metaphor's music blows it away completely. Atlus' sound team has crafted vibrant choruses befitting the heroic fantasy genre, but with such unorthodox compositions that it felt fresh to my ears. Other vocals and melodies are bewitching to the point they lift your spirit in battle or dungeons. And there's the strange theme of Virga island, with its weird vocals and hypnotic murmurs. It sounds like a tribal chant from afar, a bit like what Genshin Impact achieved with the Natlan soundtrack two months ago. The music is a splendid journey in itself.   

Metaphor: ReFantazio is the type of game you feel was made to achieve something greater than just sales. It's a completely new world, boasting an immense wealth of gameplay, characters, locations, and music, redefining heroic fantasy like no JRPG has done for decades. Atlus' latest title is also a fantastic challenge for turn-based combat and strategy lovers, with highly enjoyable and rewarding dungeons. Put another way, Metaphor: ReFantazio is the golden age of fantasy JRPGs, revived from the ashes in all its majesty, no less.

During the day, Thomas is a normal account manager. But at night he becomes Ryuzaki57, an extreme otaku gamer hungry for Japanese games (preferably with pretty girls in the main role). He spends a lot of time on F2P RPGs, but never misses the lastest interesting releases. Feel free to contact on twitter at @Ryuz4ki57

Full Article - https://www.vgchartz.com/article/463032/metaphor-refantazio-ps5/

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