Raman Probes for in Situ Molecular Analyses of Peripheral Nerve Myelination

The myelinating activity of living Schwann cells in coculture with neuronal cells was examined in situ in a Raman microprobe spectroscope. The Raman label-free approach revealed vibrational fingerprints directly related to the activity of Schwann cells' metabolites and identified molecular species peculiar to myelinating cells. The identified chemical species included antioxidants, such as hypotaurine and glutathione, and compartmentalized water, in addition to sphingolipids, phospholipids, and nucleoside triphosphates also present in neuronal and nonmyelinating Schwann cells. Raman maps at specific frequencies could be collected, which clearly visualized the myelinating action of Schwann cells and located the demyelinated ones. An important finding was the spectroscopic visualization of confined water in the myelin structure, which exhibited a quite pronounced Raman signal at ∼3470 cm-1. This peculiar signal, whose spatial location precisely corresponded to a low-frequency fingerprint of hypotaurine, was absent in unmyelinating cells and in bulk water. Raman enhancement was attributed to frustration in the hydrogen-bond network as induced by interactions with lipids in the myelin sheaths. According to a generally accepted morphological model of myelin, an explanation was offered of the peculiar Raman scattering of water confined in intraperiod lines, according to an ordered hydrogen bonding structure. The possibility of concurrently mapping antioxidant molecules and compartmentalized water structure with high spectral accuracy and microscopic spatial resolution enables probing myelinating activity and might play a key-role in future studies of neuronal pathologies. Compatible with life, Raman microprobe spectroscopy with the newly discovered probes could be suitable for developing advanced strategies in the reconstruction of injured nerves and nerve terminals at neuromuscular junctions

Activation of heat-shock response by an adenovirus is essential for virus replication

Successful viral infection requires viruses to redirect host biochemistry to replicate the viral genome, and produce and assemble progeny virions. Cellular heat-shock responses, which are characterized as elevation and relocalization of heat-shock proteins, occur during replication of many viruses1,2,3,4,5,6,7. Such responses might be host reactions to the synthesis of foreign protein, or might be irrelevant consequences of the viral need to activate transcription. Alternatively, as heat-shock proteins can facilitate protein folding8,9, activating a heat-shock response might be a specific virus function ensuring proper synthesis of viral proteins and virions. It is not possible to determine whether heat-shock response is essential for virus replication, because the implicated viral genes (such as Ad5 E1A, ref. 10) also control other essential replication steps. Here we report that expression of Gam1, a protein encoded by the avian virus CELO (ref. 11), elevates and relocalizes hsp70 and hsp40. Gam1-negative CELO is replication-defective; however, Gam1 function can be partially replaced by either heat shock or forced hsp40 expression. Thus, an essential function of Gam1 during virus replication is to activate host heat-shock responses with hsp40 as a primary target

Trace element contents in toenails are related to regular physical activity in older adults

The aim was to assess the trace element contents in toenails of older adults and its association with regular physical activity. Cross-sectional multicentre study in Spain, collecting data from a random sample of 380 participants (54% female) aged 55-80 years (men) and 60-80 years (women) with no previously documented cardiovascular disease. Physical activity performed was measured using the Minnesota Leisure-time Physical Activity Questionnaire. The 25 most inactive and 25 most active individuals for each sex were selected for this study (final sample n = 100). Anthropometric measurements were performed and toenail samples collected for calcium (Ca), chromium (Cr), iron (Fe), cobalt (Co), nickel (Ni), zinc (Zn), selenium (Se) and mercury (Hg) analysis. Significant differences between sexes were reported in Ca concentrations, women having lower concentrations than men. No differences were reported in trace element contents between active and inactive men. Active women showed higher Ca, Cr, Fe, Co, and Zn and lower Hg contents than their inactive peers (all p<0.05). Inactive women showed lower Ca and Co levels (735.0 mg/kg and 4.5 μg/kg, respectively) than inactive men (1170.0 mg/kg and 7.9 μg/kg, respectively). Active women had lower Ca and higher levels of Cr (936.0 mg/kg and 1230.0 μg/kg, respectively) than active men (1070.0 mg/kg and 522.0 μg/kg, respectively). The present data added new information on the element contents in toenails of healthy Spanish older adults. The concentration of trace elements was similar in both sexes except for Ca which were lower in women. The trace element contents in women's toenails, but not in men, were markedly influenced by physical activity, with higher levels of Ca and Fe and lower Hg among active females