Crawling the Web

Everyday, Scientist Live turns its eyes to the Web around it and highlights news and research across the Internet. Today's spin through cyberspace brings us news regarding neuronal vulnerability and neuroprotective Wallerian Degeneration Slow mutations, evolution and the primate brain, and how climate change and pathogen affects pathogenicity.



NEUROLOGY

Altered neuronal vulnerability underlies many diseases of the human nervous system, resulting in degeneration and loss of neurons. The neuroprotective Wallerian Degeneration Slow (WldS) mutation delays degeneration in axonal and synaptic compartments of neurons following a wide range of traumatic and disease-inducing stimuli, providing a powerful experimental tool with which to investigate modulation of neuronal vulnerability. Although the mechanisms through which WldS confers neuroprotection remain unclear a diverse range of downstream modifications, incorporating several genes/pathways, have been implicated. These include: elevated NAD levels associated with nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1; a part of the chimeric WldS gene); altered mRNA expression levels of genes such as pituitary tumor transforming gene 1 (Pttg1); changes in the location/activity of the ubiquitin-proteasome machinery via binding to valosin-containing protein (VCP/p97); and modified synaptic expression of proteins such as ubiquitin-activating Enzyme E1 (Ube1).

WldS expression in mouse cerebellum and HEK293 cells induced robust increases in a broad spectrum of cell cycle-related genes. Both NAD- and Pttg1-dependent pathways were responsible for mediating different subsets of these alterations, also incorporating changes in VCP/p97 localisation and Ube1 expression. Cell proliferation rates were not modified by WldS, suggesting that later mitotic phases of the cell cycle remained unaltered. We also demonstrate that WldS concurrently altered endogenous cell stress pathways.

We report a novel cellular phenotype in cells with altered neuronal vulnerability. We show that previous reports of diverse changes occurring downstream from WldS expression converge upon modifications in cell cycle status. These data suggest a strong correlation between modified cell cycle pathways and altered vulnerability of axonal and synaptic compartments in post-mitotic, terminally differentiated neurons.

- "Modified cell cycle status in a mouse model of altered neuronal vulnerability (Wallerian Degeneration Slow; WldS)" Wishart, Thomas M; Pemberton,Helen M; James, Sally R; McCabe, Chris J; and Gillingwater, Thomas H. Genome Biology 2008, 9:R101doi:10.1186/gb-2008-9-6-r101


EVOLUTIONPrimate

The left hemisphere of the human brain is dominant in the production of speech and signed language. Whether similar lateralization of function for communicative signal production is present in other primates remains a topic of considerable debate. In the current study, we examined whether oro-facial movements associated with the production of learned attention-getting sounds are differentially lateralized compared to facial expressions associated with the production of species-typical emotional vocalizations in chimpanzees.

Still images captured from digital video were used to quantify oro-facial asymmetries in the production of two attention-getting sounds and two species-typical vocalizations in a sample of captive chimpanzees. Comparisons of mouth asymmetries during production of these sounds revealed significant rightward biased asymmetries for the attention-getting sounds and significant leftward biased asymmetries for the species-typical sounds.

These results suggest that the motor control of oro-facial movements associated with the production of learned sounds is lateralized to the left hemisphere in chimpanzees. Furthermore, the findings suggest that the antecedents for lateralization of human speech may have been present in the common ancestor of chimpanzees and humans ~5 mya and are not unique to the human lineage.

IMAGE CAPTION: Bisection of the face through midpoint of line connecting inner eye corners and additional lines drawn between midline and outer eye and mouth corners.

- "Left Hemisphere Specialization for Oro-Facial Movements of Learned Vocal Signals by Captive Chimpanzees." Reynolds Losin EA, Russell JL, Freeman H, Meguerditchian A, Hopkins WD (2008) PLoS ONE 3(6): e2529. doi:10.1371/journal.pone.0002529


CLIMATE CHANGE/PATHOGENS


Extreme climatic conditions may alter historic host-pathogen relationships and synchronize the temporal and spatial convergence of multiple infectious agents, triggering epidemics with far greater mortality than those due to single pathogens. Here we present the first data to clearly illustrate how climate extremes can promote a complex interplay between epidemic and endemic pathogens that are normally tolerated in isolation, but with co-infection, result in catastrophic mortality.

A 1994 canine distemper virus (CDV) epidemic in Serengeti lions (Panthera leo) coincided with the death of a third of the population, and a second high-mortality CDV epidemic struck the nearby Ngorongoro Crater lion population in 2001. The extent of adult mortalities was unusual for CDV and prompted an investigation into contributing factors. Serological analyses indicated that at least five “silent” CDV epidemics swept through the same two lion populations between 1976 and 2006 without clinical signs or measurable mortality, indicating that CDV was not necessarily fatal. Clinical and pathology findings suggested that hemoparsitism was a major contributing factor during fatal epidemics. Using quantitative real-time PCR, we measured the magnitude of hemoparasite infections in these populations over 22 years and demonstrated significantly higher levels of Babesia during the 1994 and 2001 epidemics. Babesia levels correlated with mortalities and extent of CDV exposure within prides. The common event preceding the two high mortality CDV outbreaks was extreme drought conditions with wide-spread herbivore die-offs, most notably of Cape buffalo (Syncerus caffer).

As a consequence of high tick numbers after the resumption of rains and heavy tick infestations of starving buffalo, the lions were infected by unusually high numbers of Babesia, infections that were magnified by the immunosuppressive effects of coincident CDV, leading to unprecedented mortality. Such mass mortality events may become increasingly common if climate extremes disrupt historic stable relationships between co-existing pathogens and their susceptible hosts.


- "Climate Extremes Promote Fatal Co-Infections during Canine Distemper Epidemics in African Lions." Munson L, Terio KA, Kock R, Mlengeya T, Roelke ME, et al. (2008) PLoS ONE 3(6): e2545. doi:10.1371/journal.pone.0002545



 

 

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