BlackHole is a modern macOS virtual audio driver that allows applications to pass audio to other applications with zero additional latency. Perfect for Streamers, Podcasters, and Online Instructors.

YouTuber Jake Paul and boxing heavyweight legend Mike Tyson are finally set to battle in their much-anticipated match at AT&T Stadium in Dallas on Friday night.

The post ‘I’m a Natural-Born Killer’: Mike Tyson Highlights the Difference Between Him and YouTuber Jake Paul appeared first on Breitbart.

As public support for marijuana decriminalization grows, new research is shedding light on the drug’s impact on sleep and memory.

MJ gets naughty in the office.

There are “between 4 and 6 RTCs being reported daily,” and the police are urging people to “slow down, always drive sober, do not drive when stressed or tired, put your phone down and please wear your seatbelt and fasten your helmet.” Acting Superintendent Robert Cardwell said, “By design, it was hoped that increased traffic […]

Years ago, on a snowy winter excursion to Bavaria, I took a tour of King Ludwig (Mad King Ludwig) II's  castles. I really feel for the poor chap Ludwig II. He was very excited to be king and wanted to be a *real* king of the old order with power and dominion. Alas, he was born much to late in Germany’s evolution for such things and was reduced constitutionally to being a mere figurehead (such as Queen Elizabeth II is in England today). So he consoled himself by building castles throughout the countryside where he would escape and  fully immerse himself in his pretend kingdom where all subjects worshipped him and did as they were told.  Linderhof was one of the first castles he built and it was pretty modest so the taxpayers didn’t really bat an eye. This was the first stop on our tour.

The same could not be said for his next building project: Castle Neuschwanstein. This grand and glorious castle (just up the hill from his parents’ country castle) was the castle to end all castles. He fancied he’d build himself a castle in medieval style (probably because that was a time when subjects dutifully respected their king or perhaps because it appealed to his alpha-male decorating sense) and he spent his way through a good portion of the national treasury before the impoverished taxpayers had enough and called shenanigans. The castle was never finished, King Ludwig II came to a premature end and within a year the political leadership had turned the castle into a tourist attraction. It was *this* castle, by the way, that Walt Disney held in his mind’s eye when designing the Disney Princess Castles. With the snow falling softly around it, it was truly an amazing site to behold. So beautiful!

With the happy memories of the castle tour, I was drawn to Castles of Mad King Ludwig  when it was released by Bezier Games a few years later.

Another Bezier release – Suburbia – is in my top 10 list, so the positive track record with the publisher was another indicator that I’d probably enjoy Castles. After a bit of research, I found the general consensus in the board game community is that Castles  plays so similar to Suburbia that it feels like a reskin of the game with a castle theme. Players purchase tiles from a market to build a great infrastructure, with various points awarded based on which tiles are used and how they are arranged. After this discovery, I actually didn’t follow through with the purchase, as I’ve never been one who is keen to get every iteration of a game. For example, I rarely keep both the card game and board game version of a given game in my collection – I force myself to pick one and let go of the other. Since Surburbia was so close to my heart, I let go of any ideas to purchase Castles.

A year after Bezier released Castles, Stonemaier Games released Between Two Cities. In BTC, players draft tiles and then use them to build cities collaboratively with other players.  We build one city with the player to our left and a separate city with the player to our right; each of our partners also contributes tiles to our respective cities in common. At the end of the game, all cities are scored and the lower scoring city of the two we helped build is assigned to us as our final score. The player with the highest score at the table wins. It’s a pretty unique approach to scoring and forces you to give both of your cities equal attention throughout the game. I don’t own a copy of this game either, mostly because I only began collecting Stonemaier games after I fell in love with Scythe in 2016, and have focused heavily on acquiring new releases (vs picking up their earlier games). 

In 2018, Stonemaier (in collaboration with Bezier) released Between Two Castles of Mad King Ludwig. This game is designed by Ben Rosset and Matthew O’Malley and it takes the best of Between Two Cities and Castles of Mad King Ludwig and marries it all together. Now we find ourselves at the game table, working to build two castles at once, simultaneously but separately collaborating with our left and right neighbors. At the beginning of each round, each player draws nine tiles, comprised of various indoor and outdoor room types. Each turn, we select 2 tiles to keep (one destined for the castle we are building with the player to our left and the other for the castle we are building with the player to our right).  We pass the rest of the tiles to our neighbor (to the left in round 1 and to the right in round 2). Once everyone has selected their tiles and passed the leftovers, we begin collaborative discussions with each of our neighbors regarding the tiles we selected and where they should be placed within our castles. There are a few straightforward rules governing placement (for example, downstairs rooms can only be placed below the ground level) but generally the selection and placement decisions should be guided by maximizing victory point scoring. Also of note, when the third or fifth regular room tile of the same type is placed, a placement bonus is earned and redeemed immediately. These bonuses provide either additional tiles (including specialty room types) or bonus cards that award conditional victory points at the end of the game. After tile placement, the turns repeat in the same fashion three more times, except that on the last run, there is only 1 tile left after selecting two for placement and that tile is discarded out of the game. Round two begins, and follows the same process as the first round, with the only change being the direction the unselected tiles are passed around the table.

In anticipation of the upcoming Between Two Castles of Mad King Ludwig  expansion release (Secrets and Soirees), I received a review copy of the base game from Stonemaier.

Opening the eye-catching box (with artwork by Agnieszka Dqbrowiecka, Laura Bevon, and Bartlomiej Kordowski), we inventoried the components (cardboard tiles, wooden tokens, plastic coated cards, and score sheets) and set up our first game. The rulebook was easy to follow (as it always is with Stonemaier) and the handy player aids included proved valuable as we worked our way through the game. There were five of us playing that first time, including two teenagers, and I was surprised to see just how varied each team’s castle was from the others.

I worked really hard to give my all to both castles I was constructing, knowing that I would only score for the one that brought in the lower victory point total. I had to to correct my efforts a few times as it started to feel like one castle was building to a much higher score than the other. With both my neighbor on my left and right, I focused on bonus cards and tiles to increase point totals, whereas the competing castle builds leaned more heavily on amassing points directly through the regular room tiles. My strategy worked, and both of the castles I helped build were higher scoring than everyone else’s, giving me the victory even when taking the lower score of the two. In later games, my husband Chris and I played against each other, using the special 2 player rules in which a dummy player (“Ludwig” of course) is controlled by one of the players during the first round and by the other player during the second round. I focused on the same things in these two player games that I had previously at higher player counts. Meanwhile Chris focused almost exclusively on standard room tiles to accumulate points. Every time we played, the castle that Chris and I built together was by far the highest scoring one in the game (scoring highly on regular room tiles thanks to Chris and on bonus tiles and cards thanks to me), and my castle with Ludwig was runner up, giving me the victory again. 

I really really love this game. Much more than I thought I might, given its straightforward and simplistic mechanisms (I usually prefer complex strategy games).  Pick two tiles and arrange, rinse repeat. Sounds like it should get boring fast, but it never does.  I think the real draw of Between Two Castles of Mad King Ludwig,  that keeps engagement and enthusiasm high even among experienced gamers, is the puzzle of having to work both castles at once. Dividing your time between two equally important projects simultaneously that will be scored against each other is a personal challenge, regardless of your skill level, because you’re competing against yourself. That’s genius, and I can’t think of another game I own that implements this kind of scoring. The only drawback to this scoring mechanism is that players who are significantly weaker in strategy or skill than the rest of the group will drag down the scores of their partners, giving a clear advantage to the remaining players who weren’t yoked to the underperformer. Tactfully, since the game scores average in the direction of the weaker player on each team, this is a game to play with a group of your intellectual peers, unless you want to stew in resentment over how irrelevant all of your hard work turned out to be when it came to scoring.

In addition to the puzzle aspect of the game, the quick gameplay (less than an hour), family friendliness, and low level of analysis paralysis all help to make it an excellent go-to game, even on weeknights. 

I’m glad I gave Between Two Castles of Mad King Ludwig  a chance on our game table, and our friends who played with us have already asked when they can come over to play again. I’m quite excited to see what the upcoming Secrets and Soirees expansion adds to the game.

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

Publisher: Stonemaier Games
Players: 2-7
Actual Playing Time (vs the guideline on the box): About 45 minutes per game
Game type: card drafting, tile placement, set collection

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.

Between Two Castles of Mad King Ludwig is one of our board game library essentials. There’s a great puzzle aspect to the game, it plays in under an hour, it’s family friendly, and it keeps analysis paralysis to a minimum. It also plays up to seven players, filling that niche when so many other games are capped at 4 or 5. For all of these reasons, when the Secrets and Soirees expansion debuted, we knew we had to have it.

The expansion offers additional room types for your castle, extra bonus cards, two new solo modes, higher player count (up to 8), and a new variant of head to head castle building where each player builds their own exclusive castle.

My personal favorite bit of the expansion is the puppy room!!! Adorable little corgis, just like we have at home.

We have played the expansion dozens of times. The first few months we had the game, we stuck to standard play, with everyone building two castles, and just focused on the fun of the new room types. These are activity rooms, secret rooms, and ballrooms. The activity rooms are thematically just that – clever little rooms themed around activities that give you points for each other room adjacent or penalize you if the listed prohibited room type is within the radius. The secret rooms are quite innovative. Each one has a little arrow printed on the tile pointing up, down, left, or right and takes on the same identity as the room indicated by the arrow, giving players a lot of flexibility based on placement in the castle. The ballrooms score points for specific room types in your neighbors’ castles. I really enjoyed these plays with the expanded room types and have not ever wanted to go back to playing with just the base game tiles again.

More recently, we’ve explored the new variants provided by the expansion. The Mad King’s Demand variant has players each build a single castle instead of managing two castle builds at once. It solves the problem of weaker players bringing a section of the entire table down in scoring and it plays so much more quickly than the regular game, so it can be a good choice for player counts larger than two. While it’s also easier and smoother in a two player game to play this way versus playing with the 3rd NPC player normally required in a two player game, I’m much less fond of using this variant with two players. I like the extra tiles to choose from when a third castle is in the mix; it helps make it a bit more challenging and feels more interactive.

The Automa solo mode is very easy to learn and it’s the most enjoyable solo game I’ve ever played because it feels like you’re actually playing against other players.  I played on level 3 – normal difficulty – and won 58 to 55/55. I actually found myself wishing for longer rounds. The other solo mode (which is dubbed the Introvert variant and noted by the rulebook as technically not an Automa mode) feels less like a game against peers and more like a game of solitaire puzzling. It’s faster than the Automa solo mode and has the quirky hack of allowing you to force the NPC opponent to take a specific tile you don’t mind it having when there’s only one that meets the selection filter used to draft a tile for them. This is because, in this mode, the NPC follows an algorithm to pick between a tile you’ve marked as favored and desired for yourself and all the other tiles in demand under its selection filter that round. If there’s only one tile that meets the filter and you mark another tile you actually want, there’s a 50/50 chance you’ll lose your coveted tile to the NPC. However, if you mark the tile that meets the filter as if you wanted it for yourself, it’s forced to select it. Then you can choose whatever tile you actually prefer for yourself instead. The introverted solo mode is pretty great if you like that sort of thing, but I prefer the feeling of playing against others, so I’ll stick with the Automa solo mode, or competitive play against real life opponents.

With a retail price of just $15 on the Stonemaier website, and having so much quality content in the box, the Secrets and Soirees expansion is a must-have.

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

Publisher: Stonemaier Games
Players: 1-8
Actual Playing Time (vs the guideline on the box): About 45 minutes per game
Game type: card drafting, tile placement, set collection

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.

Paid listings and Pay per Click ads are not the same as buying links. For example, iAquire got hit by Google early this year. The company was selling links for profit of course and even lost their court case due to link selling. The company allowed for clients to pay for relevant links after companies […]

The roll, pitch and yaw of an object relative to another is complex to compute. We use 3D complex number to compute them which makes the computation easier and more intuitive. Roll, pitch and yaw are angles of orientation of an object in space and the conversion of these angles among different reference frames is...

The Better Breaks funding programme is focused on improving the range and availability of short break opportunities for disabled children and young people, particularly those with multiple support needs, including short break opportunities that families can enjoy together, or which allow parents and siblings to have time away from their caring responsibilities. This is the summary report.

The Short Breaks Fund helping to make breaks better and brighter for unpaid carers and cared-for people in Scotland. Launched in 2010 for one year, the fund has now been running for five years and has proved to be a lifeline for many carers. During the past five years the Scottish Government, through Shared Cared Scotland has distributed 12,547,409 to 697 projects to deliver innovative, tailor made breaks to groups and individuals.

In a world overflowing with information, the ability to discern reliable sources has never been more critical. Many individuals resonate with a moment of uncertainty—perhaps it was a social media post that seemed too outrageous, or an article that didn’t quite align with the facts they knew. This is a common experience in today’s digital ... Read more

The post How to Distinguish Between Reliable and Unreliable Sources in the Digital Age appeared first on Star Two.

The move comes after US officials were quoted saying they would not accept Hamas's presence in Qatar.

It was business as usual at the Lebombo border post between SA and Mozambique on Saturday morning, with vehicles moving freely between both countries after a shutdown earlier this week.

I’m worried about AI. I’m not worried about it taking my job. I believe AI is a genuine productivity tool. By which I mean it can make developers produce more. The question is whether those developers are producing something good or not. The difference between an experienced developer and a junior is that an experienced […]

Former Kaizer Chiefs legend Brian Baloyi says that holding the Kaizer Chiefs No 1 jersey requires a hardened mentality, but he is upbeat over Amakhosi's chances this season.

Gijs den Besten
Sep 1, 2013; 54:2325-2340
Reviews

RK Tangirala
Nov 1, 1995; 36:2320-2328
Articles

CARM1 is a protein arginine methyltransferase (PRMT) that acts as a coactivator in a number of transcriptional programs. CARM1 orchestrates this coactivator activity in part by depositing the H3R17me2a histone mark in the vicinity of gene promoters that it regulates. However, the gross levels of H3R17me2a in CARM1 KO mice did not significantly decrease, indicating that other PRMT(s) may compensate for this loss. We thus performed a screen of type I PRMTs, which revealed that PRMT6 can also deposit the H3R17me2a mark in vitro. CARM1 knockout mice are perinatally lethal and display a reduced fetal size, whereas PRMT6 null mice are viable, which permits the generation of double knockouts. Embryos that are null for both CARM1 and PRMT6 are noticeably smaller than CARM1 null embryos, providing in vivo evidence of redundancy. Mouse embryonic fibroblasts (MEFs) from the double knockout embryos display an absence of the H3R17me2a mark during mitosis and increased signs of DNA damage. Moreover, using the combination of CARM1 and PRMT6 inhibitors suppresses the cell proliferation of WT MEFs, suggesting a synergistic effect between CARM1 and PRMT6 inhibitions. These studies provide direct evidence that PRMT6 also deposits the H3R17me2a mark and acts redundantly with CARM1.

Expert

Bangladesh: The Trade-Off Between Economic Prosperity and Human Rights 11 March 2020 — 1:00PM TO 2:00PM Anonymous (not verified) 28 February 2020 Chatham House | 10 St James's Square | London | SW1Y 4LE

Bangladesh’s recent gains in economic and social indices, set against its record of corruption and poor civil rights, has at times been termed the ‘Bangladesh Paradox’. Yet this label is overly simplistic; the current situation proves that these trends can coexist.

The Awami League government, in power since 2009, has increased political stability, delivered unprecedented economic and social advances, and adopted a counter-terrorism strategy to stamp out extremist groups. At the same time, it is criticized for curbing civil rights and failing to hold credible elections. However, as the two previous regimes have demonstrated, the rights situation is unlikely to improve even if the Awami League were replaced.

How did worsening rights become a feature of the state irrespective of its political dispensation? An unresolved contest between political and non-political state actors may hold the key to that puzzle. The perils of the current dispensation have recently manifested in weakening economic indicators, which jeopardize the very stability and social progress for which the country has garnered much praise.

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.

2 July 2020

Africa Aware: Relations between Ethiopia and Sudan Audio bhorton.drupal 9 April 2022

This episode of Africa Aware examines the relationship between Ethiopia and Sudan.

Ahmed Soliman provides an overview of the Africa Programme’s work on cross-border conflict as part of the XCEPT project.

First, we speak to Kholood Khair on the steady deterioration in relations between Sudan and Ethiopia. Then Abel Abate Demissie discusses how recent political developments in Ethiopia and Sudan have impacted relations between the two countries.

This podcast was produced with support from the Cross-Border Conflict Evidence, Policy and Trends (XCEPT) project, funded by UK Aid from the UK government. The views expressed do not necessarily reflect the UK government’s official policies.

It is also part of a series of outputs on Ethiopia’s political transition.

Visual Abstract

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

Juntuo Zhou
Nov 30, 2020; 0:RA120.002384v1-mcp.RA120.002384
Research

Post-transcriptional modifications of pre-mRNAs expand the diversity of proteomes in higher eukaryotes. In the brain, these modifications diversify the functional output of many critical neuronal signal molecules. In this study, we identified a brain-specific A-to-I RNA editing that changed glutamine to arginine (Q/R) at exon 20 and an alternative splicing of exon 4 in Tmem63b, which encodes a ubiquitously expressed osmosensitive cation channel. The channel isoforms lacking exon 4 occurred in ∼80% of Tmem63b mRNAs in the brain but were not detected in other tissues, suggesting a brain-specific splicing. We found that the Q/R editing was catalyzed by Adar2 (Adarb1) and required an editing site complementary sequence located in the proximal 5' end of intron 20. Moreover, the Q/R editing was almost exclusively identified in the splicing isoform lacking exon 4, indicating a coupling between the editing and the splicing. Elimination of the Q/R editing in brain-specific Adar2 knockout mice did not affect the splicing efficiency of exon 4. Furthermore, transfection with the splicing isoform containing exon 4 suppressed the Q/R editing in primary cultured cerebellar granule neurons. Thus, our study revealed a coupling between an RNA editing and a distant alternative splicing in the Tmem63b pre-mRNA, in which the splicing plays a dominant role. Finally, physiological analysis showed that the splicing and the editing coordinately regulate Ca2+ permeability and osmosensitivity of channel proteins, which may contribute to their functions in the brain.

Ryunosuke Ohkawa
Dec 1, 2020; 61:1577-1588
Research Articles

Lipoproteins play a key role in transport of cholesterol to and from tissues. Recent studies have also demonstrated that red blood cells (RBCs), which carry large quantities of free cholesterol in their membrane, play an important role in reverse cholesterol transport. However, the exact role of RBCs in systemic cholesterol metabolism is poorly understood. RBCs were incubated with autologous plasma or isolated lipoproteins resulting in a significant net amount of cholesterol moved from RBCs to HDL, while cholesterol from LDL moved in the opposite direction. Furthermore, the bi-directional cholesterol transport between RBCs and plasma lipoproteins was saturable and temperature-, energy-, and time-dependent, consistent with an active process. We did not find LDLR, ABCG1, or scavenger receptor class B type 1 in RBCs but found a substantial amount of ABCA1 mRNA and protein. However, specific cholesterol efflux from RBCs to isolated apoA-I was negligible, and ABCA1 silencing with siRNA or inhibition with vanadate and Probucol did not inhibit the efflux to apoA-I, HDL, or plasma. Cholesterol efflux from and cholesterol uptake by RBCs from Abca1^+/+ and Abca1^–/– mice were similar, arguing against the role of ABCA1 in cholesterol flux between RBCs and lipoproteins. Bioinformatics analysis identified ABCA7, ABCG5, lipoprotein lipase, and mitochondrial translocator protein as possible candidates that may mediate the cholesterol flux. Together, these results suggest that RBCs actively participate in cholesterol transport in the blood, but the role of cholesterol transporters in RBCs remains uncertain.

Influenza A virus (IAV) mutates rapidly, resulting in antigenic drift and poor year-to-year vaccine effectiveness. One challenge in designing effective vaccines is that genetic mutations frequently cause amino acid variations in IAV envelope protein hemagglutinin (HA) that create new N-glycosylation sequons; resulting N-glycans cause antigenic shielding, allowing viral escape from adaptive immune responses. Vaccine candidate strain selection currently involves correlating antigenicity with HA protein sequence among circulating strains, but quantitative comparison of site-specific glycosylation information may likely improve the ability to design vaccines with broader effectiveness against evolving strains. However, there is poor understanding of the influence of glycosylation on immunodominance, antigenicity, and immunogenicity of HA, and there are no well-tested methods for comparing glycosylation similarity among virus samples. Here, we present a method for statistically rigorous quantification of similarity between two related virus strains that considers the presence and abundance of glycopeptide glycoforms. We demonstrate the strength of our approach by determining that there was a quantifiable difference in glycosylation at the protein level between WT IAV HA from A/Switzerland/9715293/2013 (SWZ13) and a mutant strain of SWZ13, even though no N-glycosylation sequons were changed. We determined site-specifically that WT and mutant HA have varying similarity at the glycosylation sites of the head domain, reflecting competing pressures to evade host immune response while retaining viral fitness. To our knowledge, our results are the first to quantify changes in glycosylation state that occur in related proteins of considerable glycan heterogeneity. Our results provide a method for understanding how changes in glycosylation state are correlated with variations in protein sequence, which is necessary for improving IAV vaccine strain selection. Understanding glycosylation will be especially important as we find new expression vectors for vaccine production, as glycosylation state depends greatly on the host species.

Extracellular vesicles (EVs) secreted by the epididymal epithelium transfer to spermatozoa key proteins that are essential in promoting motility and subsequent fertilization success. Using the domestic cat model, the objectives were to (1) characterize and compare protein content of EVs between segments of the epididymis, and (2) compare EV protein compositions between normo- and teratospermic individuals (producing >60% of abnormal spermatozoa). Epididymal EVs from adult cats were isolated and assessed via liquid chromatography tandem MS. Both male types shared 3008 proteins in total, with 98 and 20 EV proteins unique to normospermic and teratospermic males, respectively. Expression levels of several proteins changed between epididymal segments in both male types. Several proteins in both groups were related to sperm motility (e.g. hexokinase 1, adenylate kinase isoenzyme) and zona pellucida or oolemma binding (e.g. disintegrin and metalloproteinase domain proteins, zona binding proteins 1 and 2). Interestingly, seven cauda-derived EV proteins trended downward in teratospermic compared with normospermic males, which may relate to poor sperm quality. Collective results revealed, for the first time, EV proteins related to sequential sperm maturation with differences observed between normospermic and teratospermic individuals.

No abstract

Mass spectrometry-based glycoproteomics has gone through some incredible developments over the last few years. Technological advances in glycopeptide enrichment, fragmentation methods, and data analysis workflows have enabled the transition of glycoproteomics from a niche application, mainly focused on the characterization of isolated glycoproteins, to a mature technology capable of profiling thousands of intact glycopeptides at once. In addition to numerous biological discoveries catalyzed by the technology, we are also observing an increase in studies focusing on global protein glycosylation and the relationship between multiple glycosylation sites on the same protein. It has become apparent that just describing protein glycosylation in terms of micro- and macro-heterogeneity, respectively the variation and occupancy of glycans at a given site, is not sufficient to describe the observed interactions between sites. In this perspective we propose a new term, meta-heterogeneity, to describe a higher level of glycan regulation: the variation in glycosylation across multiple sites of a given protein. We provide literature examples of extensive meta-heterogeneity on relevant proteins such as antibodies, erythropoietin, myeloperoxidase and a number of serum and plasma proteins. Furthermore, we postulate on the possible biological reasons and causes behind the intriguing meta-heterogeneity observed in glycoproteins.

The histopathological subtype of lung adenocarcinoma (LUAD) is closely associated with prognosis. Micropapillary or solid predominant LUAD tends to relapse after surgery at an early stage, whereas lepidic pattern shows a favorable outcome. However, the molecular mechanism underlying this phenomenon remains unknown. Here, we recruited 31 lepidic predominant LUADs (LR: low-risk subtype group) and 28 micropapillary or solid predominant LUADs (HR: high-risk subtype group). Tissues of these cases were obtained and label-free quantitative proteomic and bioinformatic analyses were performed. Additionally, prognostic impact of targeted proteins was validated using The Cancer Genome Atlas databases (n=492) and tissue microarrays composed of early-stage LUADs (n=228). A total of 192 differentially expressed proteins were identified between tumor tissues of LR and HR and three clusters were identified via hierarchical clustering excluding eight proteins. Cluster 1 (65 proteins) showed a sequential decrease in expression from normal tissues to tumor tissues of LR and then to HR and was predominantly enriched in pathways such as tyrosine metabolism and ECM-receptor interaction, and increased matched mRNA expression of 18 proteins from this cluster predicted favorable prognosis. Cluster 2 (70 proteins) demonstrated a sequential increase in expression from normal tissues to tumor tissues of LR and then to HR and was mainly enriched in pathways such as extracellular organization, DNA replication and cell cycle, and high matched mRNA expression of 25 proteins indicated poor prognosis. Cluster 3 (49 proteins) showed high expression only in LR, with high matched mRNA expression of 20 proteins in this cluster indicating favorable prognosis. Furthermore, high expression of ERO1A and FEN1 at protein level predicted poor prognosis in early-stage LUAD, supporting the mRNA results. In conclusion, we discovered key differentially expressed proteins and pathways between low-risk and high-risk subtypes of early-stage LUAD. Some of these proteins could serve as potential biomarkers in prognostic evaluation.

The Phillies have been the favorites in the Bryce Harper sweepstakes for months, and that speculation heated up over the weekend.

The tumor marker cancer antigen 15-3 (CA 15-3) is that most commonly used to monitor metastatic breast cancer during active therapy and surveillance for disease recurrence after treatment. The association of CA 15-3 and ¹⁸F-FDG PET/CT findings can be considered complementary, since any significant rise may indicate the presence of disease and imaging is able to map the tumor sites. Although current guidelines do not recommend the routine performance of CA 15-3 in asymptomatic patients being followed up after definitive breast cancer treatment, most oncologists perform serial assessment of the tumor markers as part of routine follow-up of patients. The aim of this study was to evaluate the correlation between CA 15-3 levels and ¹⁸F-FDG PET/CT scan findings in patients with recurrent breast cancer. Methods: This was a cross-sectional study with data collected retrospectively. Patients being evaluated for breast cancer recurrence with ¹⁸F-FDG PET/CT imaging and CA 15-3 level were included. Evaluation of the association between CA 15-3 levels and ¹⁸F-FDG PET/CT scan findings was then done. Results: In total, 154 cases were included in this study; 62 patients had recurrence (positive) on the ¹⁸F-FDG PET/CT scans, whereas 92 patients had normal (negative) findings on follow-up ¹⁸F-FDG PET/CT scans. There was an association between CA 15-3 levels and the presence or absence of recurrence on ¹⁸F-FDG PET/CT scans, with 84.4% (27/32) of patients who had elevated CA 15-3 levels having disease recurrence on ¹⁸F-FDG PET/CT and 84.4% (27/32) of patients who had elevated CA 15-3 levels having disease recurrence on ¹⁸F-FDG PET/CT as well as a correlation with the burden of metastases. Most patients with disease recurrence on ¹⁸F-FDG PET/CT, however, had normal CA 15-3 levels. Conclusion: Higher CA 15-3 levels correlate with breast cancer recurrence on ¹⁸F-FDG PET/CT as well as with burden of metastasis. Notably, CA 15-3 levels within the reference range do not exclude breast cancer disease recurrence since more than half of patients with recurrence had normal CA 15-3 levels. ¹⁸F-FDG PET/CT should therefore be considered in patients with suspected breast cancer recurrence but normal CA 15-3 levels.

Pennsylvania's rejection of a formal complaint from the state Catholic Conference over COVID aid and private school students highlights a messy dispute taking place in many states.

A statewide survey of educators in Tennessee provides critical insights into connections that exist between standards, curriculum, professional development, and ultimately student success.

Jesse J. Langille
Jul 3, 2019; 39:5244-5246
Journal Club

Randy L. Buckner
Aug 24, 2005; 25:7709-7717
Neurobiology of Disease

AP Georgopoulos
Nov 1, 1982; 2:1527-1537
Articles

Looking at the future of geopolitics, the author reveals the surprising results of his research. Read more at http://www.smithsonianmag.com/specialsections/40th-anniversary/George-Friedman-on-World-War-III.html