Primate Genus Miopithecus: Evidence for the Existence of Species and Subspecies of Dwarf Guenons Based on Cellular and Endogenous Viral Sequences

Sequence data from the mitochondrial 12S rRNA gene were combined with endogenous retrovirus sequences to study the position of the genus Miopithecus in the primate tree. The mitochondrial sequences indicated that Miopithecus is a true genus distinct from Cercopithecus, although talapoin monkeys are commonly referred to as dwarf guenons. The existence of two species of dwarf guenons, suggested by differences in coat color, pigmentation, and geographic location, was supported by substantial mitochondrial 12S rRNA gene divergence. In line with the informal proposal of J. Kingdon (1997, “The Kingdon Field Guide to African Mammals,” Academic Press, London), we use the names Miopithecus talapoin for the southern, darker species and Miopithecus ougouensis for the northern, lighter-colored monkeys. Different 12S rRNA gene haplotypes found in M. ougouensis individuals suggest the possible existence of additional subspecies. Simian endogenous retrovirus (SERV) strain 23.1 proviruses were introduced in the primate germ-line after the Cercopithecinae split from the Colobinae, estimated at around 9–14 million years ago. SERV sequences were used for timing of divergence events in Cercopithecinae and confirmed the close relationship between the genera Cercopithecus and Miopithecus, which was only weakly supported by the more variable mtDNA sequences in a distance analysis, demonstrating the utility of these pseudogenes in phylogenetic grouping.     

Binding of an analog of the simian virus 40 T antigen to wild-type and mutant viral replication origins

DNAase footprint analyses of purified AD2 + D2 (D2) T protein binding to simian virus 40 origin region fragments revealed a series of four specific interactions with contiguous sequences constituting a 120 base-pair block, in keeping with previous DNAase protection results reported by others. Protection was observed to extend from a 30 base-pair strong affinity site located on the early side of the replication origin (site 1) to two adjacent lower affinity sites, including the origin of replication (site 2) and a 11 to 13 base-pair site between site 1 and the beginning of the T/t coding sequence (site 1′). A fourth site (site 3) was noted abutting the late border of site 2. Binding to site 1 was associated with enhanced D2T binding to sites 2 and 1′. Thus, binding to these sites is co-operative and/or the sequences which constitute site 1 affect the conformation of the sites 1′ and 2 sequences such that they now serve as sites of more efficient D2T binding. In addition, while deletion of all of site 2 and its substitution by late viral sequences ablated processive T binding to sequences abutting site 1 on its late side, various site 2 deletions comprising up to approximately 40% of that sequence did not affect binding to that site to a major degree. Therefore, binding to the replication origin is a sequence-specific event, but there may be multiple strong protein contact sites within that sequence.     

Chromlook: an interactive program for error detection and mapping in reference linkage data.

Preliminary genetic linkage maps of every human chromosome have been generated over the past few years, and efforts to extend and refine these maps are under way. However, fine-resolution mapping is tedious and difficult because the inevitable errors in the data confound estimates of both the placement of loci and the distances between them. Fortunately, in most cases these errors result in observed recombinants where no true recombinant has occurred. The simple strategy presented here identifies these recombinants by relying on the assumption that recombinants between two adjacent markers are relatively rare events. This strategy has been implemented in the computer program CHROMLOOK, and examples of its use are given. Identification of recombinants allows for the directed regenotyping of suspicious data, the quick mapping of new polymorphisms using recombination minimization, and the development of a meiotic breakpoint map.     

Sisyphus desperately seeking publisher

As a punishment for his trickery, King Sisyphus was made to endlessly roll a huge boulder up a steep hill. The maddening nature of the punishment was reserved for King Sisyphus due to his hubristic belief that his cleverness surpassed that of Zeus himself. Today’s scientists also pay a heavy price for their hubris and narcissism. They try to trick the editors of a few ‘top’ journals by peppering their papers with glitter and ‘bling-bling’, making overblown promises, and giving minimal credit to their predecessors. The editors wield their Olympian authority by making today’s scientists endlessly push their weighty boulders up steep hills. By bowing to this implacable ritual, we scientists confer undue power to a handful of popular but irresponsible journals.     

Revisiting misfolding propensity of serum amyloid A1: Special focus on the signal peptide region

AA amyloidosis is the result of overproduction and aberrant processing of acute-phase serum amyloid A1 (SAA1) by hepatocytes. Proteolytic cleavage of SAA1 is believed to play a central role in AA amyloid formation. The SAA1 protein undergoes a cleavage of 18 residues consisting of the signal peptide at the N-terminal region. To better understand the mechanism behind systemic amyloidosis in the SAA1 protein, we studied the misfolding propensity of the signal peptide region. We first examined the signal peptide amino acid SAA derived from different animal species. A library of 16 peptides was designed to evaluate the propensity of aggregation. The amyloidogenic potential of each SAA1 signal peptide homolog was assessed using in silico Tango program, thioflavin T (ThT) fluorescence, transmission electron microscopy (TEM), and seeding with misfolded human SAA1 signal peptide. After 7 days of incubation, most of the SAA1 signal peptide fragments had the propensity to form fibrils at a concentration of 100 μM in 50 mM Tris buffer at 37 °C by TEM. All peptides were able to generate fibrils at a higher concentration, i.e 500 μM in 25 mM Tris buffer with 50% HFIP, by ThT. All SAA1 signal synthetic peptides designed from the different animal species had the propensity to misfold and form fibrils, particularly in species with low occurrence of systemic amyloidosis. The human SAA1 signal peptide region was capable to seed the SAA1 1–25 and 32–47 peptide regions. Characterizing fibrillar conformations are relevant for seeding intact and/or fragmented SAA, which may contribute, to the mechanism of protein misfolding. This research signifies the importance of the signal peptide region and its possible contribution to the misfolding of aggregation-prone proteins.