Do amyloids remember their origin? New insights into the prion species barrier

Excellent work demonstrates that, in the test tube, prion protein itself is responsible for its species specificity, although questions remain about whether this occurs in the same way in the organism.     

Dinosaur protofeathers: pushing back the origin of feathers into the Middle Triassic?

Reports of primordial feathers (protofeathers) in dinosaurs have received widespread interest. Recently, it was proposed that a novel protofeather in the theropod dinosaur Beipiaosaurus completes the transitional series in the evolution of the feather and provides the first evidence of filamentous feathers as display in nonavian theropods. A more far-reaching evolutionary ramification is the claim that these structures push the origin of monofilamentous integumentary structures into the Middle Triassic or earlier. I discuss problems with the analyses within the broader context of studies concerning the hypothesis of protofeathers, and show that affinity between the integumentary structures in Beipiaosaurus and feathers is improbable. The scientific methodology is questioned by its failure to make phenomena perceivable by objective means, by questionable rationalizations in critical issues, and by lack of consideration of exceptions to the postulated thesis. The notion that primordial feathers occurred in a clade more inclusive than the Coelurosauria and that it is supported by the presence of integumental structures in Psittacosaurus is analyzed and rejected.     

Is loss of function of the prion protein the cause of prion disorders?

Transmissible spongiform encephalopathies are fatal neurodegenerative diseases that involve misfolding of the prion protein. Recent studies have provided evidence that normal prion protein might have a physiological function in neuroprotective signaling, suggesting that loss of prion protein activity might contribute to the pathogenesis of prion disease. However, studies using knockout animals do not support the loss-of-function hypothesis and argue that prion neurodegeneration might be associated with a gain of a toxic activity by the misfolded prion protein. Thus, the mechanism of neurodegeneration in spongiform encephalopathies remains enigmatic.     

Conversion of d-Glucose into d-Oxybiotin†

2,5-Anhydro-3-azido-3-deoxy-D-xylose dimethyl acetal (XI), the key intermediate for the stereospecific synthesis of d-oxybiotin, was prepared by methanolysis of 3-azido-3-deoxy-1,2-O-isopropylidene-5-O-p-tolylsulfonyl-α-d-xylofuranose (VIIIa) or of 3-azido-3-deoxy-l,2-O-cyclohexylidene-5-0-p-tolylsulfonyl-α-d-xylofuranose (VIIIb).     

Immunology: the origin of sweetbreads in lampreys?

The thymus is required for the differentiation of T lymphocytes. A new study in lampreys indicates that the pharyngeal epithelium of the gill basket supports the development of T-like cells, suggesting the existence of a primitive thymus in these oldest of vertebrates.     

Interactions between prion protein isoforms: the kiss of death?

Direct interactions between the normal and aberrant forms of prion protein appear to be crucial in the transmission and pathogenesis of transmissible spongiform encephalopathies (TSEs) or prion diseases. Recent studies of such interactions in vitro have provided mechanistic insight into how TSE-associated prion protein might promote its own propagation in a manner that is specific enough to account, at least in part, for TSE strains and species barriers.     

G-quadruplexes within prion mRNA: the missing link in prion disease?

Cellular ribonucleic acid (RNA) plays a crucial role in the initial conversion of cellular prion protein PrP^C to infectious PrP^Sc or scrapie. The nature of this RNA remains elusive. Previously, RNA aptamers against PrP^C have been isolated and found to form G-quadruplexes (G4s). PrP^C binding to G4 RNAs destabilizes its structure and is thought to trigger its conversion to PrP^Sc. Here it is shown that PrP messenger RNA (mRNA) itself contains several G4 motifs, located in the octarepeat region. Investigation of the RNA structure in one of these repeats by circular dichroism, nuclear magnetic resonance and ultraviolet melting studies shows evidence of G4 formation. In vitro translation of full-length PrP mRNA, naturally harboring five consecutive G4 motifs, was specifically affected by G4-binding ligands, lending support to G4 formation in PrP mRNA. A possible role of PrP binding to its own mRNA and the role of anti-prion drugs, many of which are G4-binding ligands, in prion disease are discussed.     

The origin of the Hominidae: Africa or Asia?

The authors review the evidence for the evolution of the apes and their geographical expansion out of Africa during the Miocene. The ecological background is discussed at each period.From this it is concluded that Dryopithecines in either Africa or Eurasia could have given rise to early Hominidae and that the ecological conditions in both continents were suitable for the appearance of Hominid adaptations.The evidence for early Hominids is at present more impressive in Eurasia than in Africa, though the African find from Fort Ternan, Kenya, is the earliest. On present evidence, neither continent can be precluded as the place of origin of the Hominidae and it appears to be a possibility that Hominidae evolved in both continents with intermittent gene exchange.     

AIDS as a zoonosis? Confusion over the origin of the virus and the origin of the epidemics

Based on findings demonstrating the simian ancestry of HIV, AIDS has been reported to be a zoonosis. However, this theory has never been proved and must seriously be questioned. Several arguments show that HIV-AIDS is not a zoonosis. (i) If AIDS were a zoonosis, there must be evidence of AIDS being directly acquired from an animal species, as is rabies, a disease that is directly acquired from animals. (ii) Despite long-term and frequent human exposure to SIV-infected monkeys in Africa, only 11 cross-species transmission events are known, and only four of these have resulted in significant human-to-human transmission, generating HIV-1 groups M and O and HIV-2 groups A and B. The closest relatives of SIVcpz (HIV-1 group N) and of SIVsm (HIV-2 groups C-H) are extremely rare, with only six HIV-1 group N-infected patients and only single individuals known to be infected by HIV-2 groups C-H. SIV, while capable of cross-species transmission, is thus poorly adapted for disease and epidemic spread. If AIDS were a zoonosis that is capable of significant human-to-human spread, there would be a plethora of founder subtypes and groups. (iii) Human exposure to SIV is thousands of years old, but AIDS emerged only in the 20th century. If AIDS were a zoonosis that spread into the human population, it would have spread to the West during slave trade. (iv) Experimental transmission of SIVs to different species of monkeys is often well controlled by the new host, showing that the virus and not the disease is transmitted. Therefore, we conclude that cross-species transmission of SIV does not in itself constitute the basis for a zoonosis. Transmission per se is not the major requirement for the generation of the AIDS epidemic. All HIVs do derive from simian species, but AIDS does not qualify as a zoonosis and this explanation cannot in itself account for the origin of AIDS epidemic. It is important to distinguish AIDS from true zoonoses (e.g. rabies) because research is needed to understand the processes by which animal viruses cause sustained human-to-human transmission, epidemics and even pandemics. Much is known about emerging viruses, but almost nothing is known about emerging viral diseases.     

Where is the origin of the Japanese gamecocks?

The tradition of cockfighting is widespread throughout the world. There is no doubt that the gamecock has evolved together with the human culture of cockfighting for a long time. In Japan, there is a group of gamecocks called "Shamo" that are used specifically for cockfighting. However, the process of the geographic distribution of cockfighting and the influx route of gamecocks into Japan are totally unclear. The molecular evolutionary study of gamecocks is obviously useful to gain profound insight into the understanding of not only the evolutionary origin of "Shamo" but also the distribution process of cockfighting as a culture. In this study, we collected blood samples of gamecocks from 11 different prefectures in Japan. Then, a phylogenetic tree was constructed using a total of 42 mtDNAs (D-loop, 1100 bp) sequenced. It showed that Japanese Shamo was clearly separated into two different groups: One group contains the samples from the island of Okinawa and the other group is composed of the samples mainly from Kyushu and Honshu of Japan. It suggests that Japanese Shamo must have been brought to Japan from two different origins. Our examination of historical records showed that the results of the phylogenetic analysis is consistent with the view that Japanese Shamo was originated from Southeast Asia and the mainland China independently, but was geographically a bit mixed afterwards.     

Chemical Conversion of Some Ribonucleosides into the Corresponding β-D-Arabinofuranosyl Derivatives1

Abstract

Five 3′,5′-di-O-acylribonucleosides were converted into the corresponding β-D-arabinofuranosyl derivatives through DMSO-oxidation followed by NaBH₄-reduction and deacylation with NaOMe-MeOH.     

On the origin of cancer: can we ignore coherence?

A growing number of inconsistencies have accumulated within the genetically deterministic paradigm of the origin of cancer. Among them the most important are the nonspecific nature of cancer mutations and the non-cell-autonomous factors of cancer initiation and progression. Epigenetic aspects of cancer and cancer systems biology represent novel approaches to cancer aetiology and converge in the notion that cancer is characterized by a nonspecific progressive destabilization of multiple molecular pathways. The coherent behaviour of certain cellular subsystems has been theoretically predicted for a long time to have a general role in coordinating biological processes. However, it has only recently gained major scientific interest when it was measured on photosynthetic complexes at physiological temperatures and confirmed to have a direct effect over the dynamics of the energy transfer. Several theoretical and experimental considerations suggest that cancer might be associated with the absence or impairment of the proper coherent dynamics in certain biological structures, most notably in the microtubules. We review those models and suggest that impaired coherence might largely contribute to the progressive destabilization of the molecular and gene regulatory networks, thus connecting different non-genetic aspects of cancer.     

Conversion of β-carotene into astaxanthin: Two separate enzymes or a bifunctional hydroxylase-ketolase protein?

Astaxanthin is a xanthophyll of great interest in animal nutrition and human health. The market prospect in the nutraceutics industries for this health-protective molecule is very promising. Astaxanthin is synthesized by several bacteria, algae and plants from β-carotene by the sequential action of two enzymes: a β-carotene, 3,3'-hydroxylase that introduces an hydroxyl group at the 3 (and 3') positions of each of the two β-ionone rings of β-carotene, and a β-carotene ketolase that introduces keto groups at carbons 4 and 4' of the β-ionone rings. Astaxanthin is also produced by the yeast-like basidiomycete Xanthophyllomyces dendrorhous. A gene crtS involved in the conversion of β-carotene to astaxanthin has been cloned simultaneously by two research groups. Complementation studies of X. dendrorhous mutants and expression analysis in Mucor circinelloides reveals that the CrtS enzyme is a β-carotene hydroxylase of the P-450 monooxygenase family that converts β-carotene to the hydroxylated derivatives β-cryptoxanthin and zeaxanthin, but it does not form astaxanthin or the ketolated intermediates in this fungus. A bifunctional β-carotene hydroxylase-ketolase activity has been proposed for the CrtS protein. The evidence for and against this hypothesis is analyzed in detail in this review.