LSm protein Hfq hexamer torus (search wikipedia for their image below ). This is going to be an awesome hunt, especially in the hepatocyte nuclei in the 14CoS ko mice where the hepatocytes undergo a pan-apoptosis, synchronized across the entire liver. There will be (I predict) many cases where this group of proteins will cause clearly visible electron microscopic ultrastructure in that process. The ultrastructure of the nucleus is determined by the status of ribosomes production.
Life is such a mix of mundane and completely outrageous… ha ha….. felt compelled to clean a few gutters of oak catkins before predicted-storm for this afternoon…an important but “nothing” task, then treked into work, and happened to look at a structure in an old electron micrograph of CoS 14 mouse hepatocyte, micrograph looking like something between a coiled strand of DNA and a Cajal body adjacent to a nucleolus, and find of course this enormous field of protein research on small nuclear RNAs, which I had only hear of briefly and know nothing about…. Oh my god…. How big and unknowable is the known (pun intended) universe… and what unfathomable event-entity could have brought it all into being…. Makes me “fearful” ha ha ha… just like those old Hebrews — they knew of and felt an awesomeness of nature/biology/cosmos that we don’t think of today since we are insulated by tech and devices.
Really nice electron micrograph of liver nucleus and enormous nucleolus, lots of nuclear pores and perichromatin granules and condensed chromatin. 16029_65718_no_NTBC_14CoS/14CoS ko
Abstract from a paper by Deiter et al, follows: Whereas ch/ch wild-type mice and ch/14CoS heterozygotes are viable, 14CoS/14CoS mice homozygous for a 3800 kb deletion on chromosome 7 die during the first day postpartum. Death is caused by disruption of the fumarylacetoacetate hydrolase (Fah) gene; absence of FAH, final enzyme in the tyrosine catabolism pathway, leads to accumulation of reactive electrophilic intermediates. In this study, we kept 14CoS/14CoS mice alive for 60 d with oral 2-(2-nitro-4-trifluoromethyl-benzyol)-1,3-cyclohexanedione (NTBC), an inhibitor of p-hydroxyphenylpyruvate dioxygenase, second enzyme in the tyrosine catabolic pathway. The 70% of NTBC-treated 14CoS/14CoS mice that survived 60 d showed poor growth and developed corneal opacities, compared with ch/14CoS littermates; NTBC-rescued Fah(-/-) knockout mice did not show growth retardation or ocular toxicity. NTBC-rescued 14CoS/14CoS mice also exhibited a striking oxidative stress response in liver and kidney, as measured by lower GSH levels and mRNA induction of four genes: glutamate cysteine ligase catalytic (Gclc) and modifier (Gclm) subunits, NAD(P)H:quinone oxidoreductase (Nqo1), and heme oxygenase-1 (Hmox1). Withdrawal of NTBC for 24-48 h from rescued adult 14CoS/14CoS mice resulted in severe apoptosis of the liver, detected histologically and by cytochrome c release from the mitochondria, increased caspase 3-like activity, and further decreases in GSH content. In kidney, proximal tubular epithelial cells were abnormal. Human hereditary tyrosinemia type I (HT1), caused by mutations in the FAH gene, is an autosomal recessive disorder in which the patient usually dies of liver fibrosis and cirrhosis during early childhood; NTBC treatment is known to prolong HT1 children’s lives-although liver fibrosis, cirrhosis, hepatocarcinoma, and corneal opacities sometimes occur. The mouse data in the present study are consistent with the possibility that endogenous oxidative stress-induced apoptosis may be the underlying cause of liver pathology seen in NTBC-treated HT1 patients.
From the archives just four images associated with something for a graduate student that went nowhere in particular, but these four images are nice even vesicles that someone might enjoy looking at.
Electron micrograph: liver: Alb w/w Gclc i/i D120 NAC. So here is a perfect example of not having the right data written down while doing collaborative ultrastructure on a project for a colleague. So after so many years I have to assume that this is a control liver receiving NAC for 120 days after birth, for a conditional Gclc ko mouse.
Liver looks really nice, WNL in my opinion, nice RER, nice mitochondira, one part of a lipid droplet visible. I partially hid two pen marks on this micrograph (using the bandaid tool in photoshop) which you can still see, but this did not change any data. Contrast enhanced as well to even up the tone of the liver histology. liver, neg 17909, block 74119, anm#702, alb w/w Gclc i/i NAC 120 days post partum. 10000x orig mag. No profile of nucleus in this image.
Mitochondria from vinyl chloride exposed animals have been posted on this blog before. HERE and HERE. I have made the assumption (no proof what-so-ever) that this just seems a perfect match for ATPsynthase. Here is another example of such a mitochondrion, also showing the highly organized repeating pattern found in the intra-cristal-space of mitochondria from other liver electron micrographs from guinea pigs treated with vinyl chloride. Amazing similarity. THis waits for someone else to confirm, but in the meantime when I see the images, I will post. Someone out there will know. So here is a mitochondrion with such a cristi, and below that is someone elses micrograph (publication site linked) which shows the spiral repeating structure of ATPsynthase.
REF
One of their figures (not pictured here) shows about 16 dimers per 200 nm = 1 per 12.5 nm. When I measur
ed the ribosome at 27 nm in my image (to the left) of intra-cristi structures, then there were about 19 densities per 200 nm. So the numbers don’t add up too well. Particularly with one of their figures copied above where their measurement (white bar in the figures and insets above) is noted in their publication to be 50 nm. This is quite far off what I see in the intra-cristi space in the figure to the left. It also seems clear that they have a propensity to be found in these groups between the outer and inner mitochondrial membranes and less frequently on the inner cristi.
It has been three or more decades since I visited (revisited) the artificial blood research that was done in the Institute for Developmental Research (which is no longer an entity of that name, changed, many iterations ago. But this research was spearheaded by the Late Leland Clark Jr, major inventor in medicine in cincinnati. I took so many tissues, looked at so many images of artificial blood in various animals that when I consider it in retrospect, it is just off the charts. Few really time honored publications came from that scattered search for a good oxygen carrying substitute for real blood, but Clark was determined that in and among the myriad compounds that he would find something great. As an electron microscopist, all I saw was a reticuloendothelial system packed with little white fluorocarbon “footprints”, and a lot of activated macrophages. Here is an interesting image (i dont have the neg and animal numbers off hand) of monkey kidney and on the left you see the remnants of perfluorodecalin (outlined in purple).
Here is what wikipedia has to say about PFD, as we tagged on the acronym back in the 1970s.
Medical applications Of all the perfluorocarbons, perfluorodecalin has probably seen the most interest in medical applications. Most applications utilize its ability to dissolve large amounts of oxygen (100 mL of perfluorodecalin at 25 °C can dissolve 49 mL of oxygen at STP). Perfluorodecalin was an ingredient in Fluosol, an artificial blood product developed by Green Cross Corporation in the 1980s. It is also being studied for use in liquid breathing. Perfluorodecalin can be applied topically, to provide extra oxygen to a specific location, to accelerate wound healing. Organs and tissues can be stored for longer in oxygenated perfluorodecalin; the “two-layer method” uses perfluorodecalin and UW s
olution to preserve tissue for pancreas transplants.
nb… green cross developed it maybe, and sunventures, but clark was the main proponent for many years. Here is what PFD looks like
come on….. this administration is so out of touch, we need something besides terrorists as our leaders. Stooping to the level of North Korea makes them low lifers, just like those they disagree with. No brains on either side. Who voted for these people to run america, you should be ashamed. looking at what is posted (far left column with more red than blue), the approval of the american public is not in lock-step with the administrators’ (pres and vp) opinions.
This plot, obtained from the internet makes me wonder what truman (far right) did right…. seems someone should be paying attention to this.
Pseudo-colored alveolar type II cell granules, and unretouched, and composite image. I am just about finished with this study. I submitted the manuscript, I do hope if flies without too much revision. I am very aware that it is totally descriptive, but then descriptive science was the first science and it has great value. We all learn by what we observe, more so than what we propose (hypothesize) and test.
Here is a granule from my fav guinea pig #301 neg 9837, block 17084, which has several stacked parallel periods of the layered granule all in pretty nice array perpendicular to the layering. I extracted and then rotated the cropped portions, and increased contrast, and added half transparency to these four seemingly ideal areas. I merged them (with their transparencies matched as best I could) and flattened them as a fifth inset. This image is the inset in pink with 100 nm markers vertical and horizontal. The individual crops are shown below, colored just for fun.
We all know that freedom is not free. The cost in human effort, human life, human suffering, is extraordinarily great, and the trek has been extraordinarily long, actually since the first ‘self aware’ hominids. It all comes down to protecting diversity while in our own genetic makeup (and epigenetic reinforcement), knowing and loving self and like creatures, at the expense of all others, was necessary for survival of the species.
The beginning of the dilemma is that by allowing the presence of diversity we protect ourselves, by repressing, enslaving, gagging, and eliminating diversity, we allow the process of elimination of any group. The paradox goes even to the University where I work(ed). In 50 years I have watched the silent elimination of diversity in teaching styles, and attitudes, these mostly being trimmed from us by administrators who seem to be pushing the University into a Big Business mode and profit….a total corollary with who now holds the office of president of the US…. confine, reduce, suppress, revert, ignore, disbelieve, disable, criticize, ignore facts. So I saw this happen insidiously a long time ago, when the then director of toxicology came to my office and said… “you must use Word for word processing” on his left was a newly hired “secretary” of course now not called that. I just said, George, I prefer to use Word Perfect, it is a better program for me, and i can export my document to Word so you can read them. He became flushed and said that was not good enough. My retort was “you mean you are telling me, in this university, what kind of pencil i can use”…. So mandates went into existence anyway. While that was a tiny infraction on my freedom, many similar choices have disappeared. One that comes to mind and is a particularly offensive (to me) reduction in my freedom of expression is that I there is total control over webpages from UCIT. There should be self control in what one puts on a webpage, I am not interested in a negative or shameful site, but when I write a food blog or newsletter for cancer prevention for young girls and women, I don’t feel that it is appropriate for UCIT to tell me to make the page in red and black with a “swoosh” to comply with their branding. Inappropriate, and control that is just beyond sensible.
That they read my page, this is fine, that they comment, this is fine, that they control the colors, the words, the style of outreach, nope. From pencils to colors and topics. what next.