I read this book the same weekend that the Packers took on the Rams, and the experience of the latter event, obviously, colored my judgment. Although I abhor anything that smacks of being a handbook (like, \"How to Earn a Merit Badge in Neurosurgery\") because too many volumes in biomedical science already evince a boyscout-like approach, I must confess that parts of this volume are fast, scholarly, and significant, with certain reservations. I like parts of this well-illustrated book because Dr. Sj6strand, without so stating, develops certain subjects on technique in relation to the acquisition of judgment and sophistication. And this is important! So, given that the author (like all of us) is somewhat deficient in some areas, and biased in others, the book is still valuable if the uninitiated reader swallows it in a general fashion, realizing full well that what will be required from the reader is a modulation to fit his vision, propreception, adaptation and response, and the kind of problem he is undertaking. A major deficiency of this book is revealed by comparison of its use of physics and of chemistry to provide understanding and background for the application of high resolution electron microscopy to problems in biology. Since the volume is keyed to high resolution electron microscopy, which is a sophisticated form of structural analysis, but really morphology in a modern guise, the physical and mechanical background of The instrument and its ancillary tools are simply and well presented. The potential use of chemical or cytochemical information as it relates to biological fine structure , however, is quite deficient. I wonder when even sophisticated morphol-ogists will consider fixation a reaction and not a technique; only then will the fundamentals become self-evident and predictable and this sine qua flon will become less mystical. Staining reactions (the most inadequate chapter) ought to be something more than a technique to selectively enhance contrast of morphological elements; it ought to give the structural addresses of some of the chemical residents of cell components. Is it pertinent that auto-radiography gets singled out for more complete coverage than other significant aspects of cytochemistry by a high resolution microscopist, when it has a built-in minimal error of 1,000 A in standard practice? I don't mean to blind-side (in strict football terminology) Dr. Sj6strand's efforts for what is \"routinely used in our laboratory\"; what is done is usually well done. It's just that …

Methods in Enzymology.

https://scholarlypublications.universiteitleiden.nl/access/item%3A3138188/view

A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis.

Thousands of mutations are identified yearly. Although many directly affect protein expression, an increasing proportion of mutations is now believed to influence mRNA splicing. They mostly affect existing splice sites, but synonymous, non-synonymous or nonsense mutations can also create or disrupt splice sites or auxiliary cis-splicing sequences. To facilitate the analysis of the different mutations, we designed Human Splicing Finder (HSF), a tool to predict the effects of mutations on splicing signals or to identify splicing motifs in any human sequence. It contains all available matrices for auxiliary sequence prediction as well as new ones for binding sites of the 9G8 and Tra2-beta Serine-Arginine proteins and the hnRNP A1 ribonucleoprotein. We also developed new Position Weight Matrices to assess the strength of 5' and 3' splice sites and branch points. We evaluated HSF efficiency using a set of 83 intronic and 35 exonic mutations known to result in splicing defects. We showed that the mutation effect was correctly predicted in almost all cases. HSF could thus represent a valuable resource for research, diagnostic and therapeutic (e.g. therapeutic exon skipping) purposes as well as for global studies, such as the GEN2PHEN European Project or the Human Variome Project.

https://www.hal.inserm.fr/inserm-00396239/document

Human Splicing Finder: an online bioinformatics tool to predict splicing signals

Why genes in pieces

The noncoding RNA revolution-trashing old rules to forge new ones.

An mRNA fraction coding for hexon polypeptide, the major virion structural protein, was purified by gel electrophoresis from extracts of adenovirus 2-infected cells late in the lytic cycle. The mRNA sequences in this fraction were mapped between 51.7 and 61.3 units on the genome by visualizing RNA-DNA hybrids in the electron microscope. When hybrids of hexon mRNA and single-stranded restriction endonuclease cleavage fragments of viral DNA were visualized in the electron microscope,branched forms were observed in which 160 nucleotides of RNA from the 5' terminus were not hydrogen bonded to the single-stranded DNA. DNA sequences complementary to the RNA sequences in each 5' tail were found by electron microscopy to be located at 17, 20, and 27 units on the same strand as that coding for the body of the hexon mRNA. Thus, four segments of viral RNA may be joined together during the synthesis of mature hexon mRNA. A model is presented for adenovirus late mRNA synthesis that involves multiple splicing during maturation of a larger precursor nuclear RNA.

https://www.pnas.org/content/pnas/74/8/3171.full.pdf

Spliced segments at the 5' terminus of adenovirus 2 late mRNA

https://www.cell.com/cell/pdf/S0092-8674(85)80065-9.pdf

Accurate cleavage and polyadenylation of exogenous RNA substrate.

Site-specific polyadenylation in a cell-free reaction

The infectivity of adenovirus 5 DNA-protein complex.

The postnatal development of myelin in the optic nerve and tract of normal and dark reared cats has been studied quantitatively with light and electron microscopy. In the newborn cat few myelinated fibers (3% of the population) are seen in the optic tract. Until the end of the second postnatal week, the total number of myelinated axons in the tract remains low (23%). At this time, however, there is an explosive increase in the rate of myelination and by the end of the fourth postnatal week 80% of the optic tract axons have acquired a myelin sheath. Thereafter, the number of myelinated axons increases gradually, reaching adult levels (100%) at 12 weeks. During the initial period of myelination, the average axon diameter is 0.6 mu for unmyelinated fibers and a.2 mu for myelinated fibers. Both of these means remain substantially unchanged until myelination is completed, suggesting that initial myelination of an axon is not a continuous process but rather proceeds in a step-wise manner. Dark rearing appears to have no effect on the initiation of myelination.

Claire L. Moore

Papers

Spliced segments at the 5' terminus of adenovirus 2 late mRNA

Accurate cleavage and polyadenylation of exogenous RNA substrate.

Site-specific polyadenylation in a cell-free reaction

The infectivity of adenovirus 5 DNA-protein complex.

Development of myelination in optic tract of the cat.