Wednesday 22nd of September 2021

under stay-at-home orders and an outage...


















Lucky we have our own personal sanity to rely upon. For a while still anyhow... As I was roaming through some of the 9,567 cartoons on this site, I suddenly had this feeling that the world outside my door is insane. Totally. It’s full of people from politicians to gangsters who are trying to con you out of your last remnant of intelligence. They even enter your abode through your smartphone, emails and TV set, and the News on radio… You start becoming paranoid that even your innocuous CDs are transmitting to the greater world that you have been captured, by the cheer choice of music you listen to. I suppose we could stay in a silent lockdown (Stay-At-Home Orders) and go crazy. 


You wonder if you would be doing the planet a service by going under the floor boards through the trapdoor and die of desiccation and radon gas below. But the bastards are trying hard to make sure you stay alive and watch the News. If you get vaccinated, you have three chance in a million to die from blood clot, but if you don’t get vaccinated you have one chance in one hundred to catch Covid-19 and then one chance in four from dying from it… These are the official stats for oldies… The government has forked out more than a billion dollars on buying the vaccines from reputable Big Pharmas and is giving it to you for free! Fuck, this is the first time any government is giving something free! (apart from slop when kissing babies at election time)… But apparently, the delivery is a slow fucup… Rejoice. Under the floorboards, you have discovered the old stack of baked beans and a few bottle of Pinot Noir that you had forgotten about. You can surface again. Your local electricity supplier has an outage and all your electronic gizmos have gone silent. You boil the kettle by burning a couple of stick of wood… If you don’t go outside your front door, your chance of catching covid-19 drops to about one in 500,000 or one in 10,000 should you get home deliveries. Use a mask. Get them delivery people to drop things three feet from the door and wait ten minutes of fresh air before collecting your goodies. I have been using the same mask for the last five months. Unwashed. Does not make any difference except when I was going to shops before lockdown (Stay-At-Home Orders as it’s now called) I was playing the game of breathing. I did my my bit of raiding the shelves at the local supermarket BEFORE the general Stay-At-Home Orders, because I knew that once the local Stay-At-Home Orders had been declared on four Sydney areas, the whole city would soon shut down. The local restaurants will demand hand-outs from the government once more… The arts that had barely survived and were about to restart at some local venues took the biggest hit as usual. The young people would be in a tizz, become depressed once more and be disoriented. We oldies know the routines. Wars, lockdowns, revolutions, protests, cancelled visit to the Archibald's… But now after having saved the planet from our own emissions, we are forced to burn more gas to stay warm. By a strange flow-on effect, global warming is cold because of the humidity. Sydney in winter is coldish but sunny, usually. But 2021 has been cold and wet in the mornings — and above average during the day. The humidity is cutting. May as well stay under the doona and read about those antibodies that lack specific sugar modifications that can worsen acute viral diseases… We’re stuffed.


The aliens who taunt the US military would be laughing.






Antibody sugars are bittersweet


Antibodies constitute an integral arm of the adaptive immune system that, in its fight against viruses, can occasionally perform as a double-edged sword. Antibodies are Y-shaped molecules. Historically, research on humoral responses to viral infection have mostly focused on the V end of the Y: the antigen-binding regions, or Fab, which bind and neutralize viral infections. Conversely, the tail of the Y (also called the fragment crystallizable, or Fc, domain) possesses numerous functional properties—namely induction of antibody-dependent complement deposition, cellular phagocytosis and cellular cytotoxicity (1)—but is relatively understudied. On page 1102 of this issue, Bournazos et al. (2) and another recent study by Larsen et al. (3) demonstrate that modifying the Fc domain with chains of sugar molecules (glycosylation) can trigger cellular immune functions that can either protect against or worsen viral diseases, such as dengue and COVID-19.

Antibodies are produced by B cells, and the most abundant form in humans is immunoglobulin G (IgG). IgG is produced in the endoplasmic reticulum (ER) of B cells and then transported through the Golgi network for secretion. The ER is also where chains of sugar molecules—composed of N-acetylglucosamine, mannose, and glucose—are produced in a stepwise manner (see the figure). This sugar chain is then transferred to the Fc domain of IgG molecules and covalently attached to Asp297 (4). The sugar chain is then further modified with the addition of new sugar molecules, such as fucose, and trimmed as the antibodies pass through the Golgi network. The order of addition and trimming of sugar molecules on the glycan chain is highly organized and determined by Golgi-resident enzymes, leading to a total of 36 possible N-linked glycan structures (5).

The N-linked glycosylation of IgG enables proper protein folding and influences the interaction with Fcγ-receptors (FcγRs) on immune cells to shape the specificity of the cellular response. IgG interacts with a total of three types and six subtypes of FcγR. The specificity and strength of this interaction is governed by variability in the sugar chain on the Fc domain. This in turn influences the type and strength of the antiviral killing mechanism triggered by IgG (6). One such variability is the absence of fucose on the glycan. More than 90% of serum IgG is fucosylated and has low affinity to FcγRs. However, afucosylation increases the binding affinity of IgG to FcγRIIIa and activates macrophages and natural killer cells (7). Although beneficial for immune-mediated killing of cancer cells, such afucosylated IgGs appear to trigger excessive immune-mediated damage to patients with dengue and COVID-19....


Science 04 Jun 2021:
Vol. 372, Issue 6546, pp. 1041-1042