Brain regeneration in anuran amphibians

Urodele amphibians are highly regenerative animals. After partial removal of the brain in urodeles, ependymal cells around the wound surface proliferate, differentiate into neurons and glias and finally regenerate the lost tissue. In contrast to urodeles, this type of brain regeneration is restricted only to the larval stages in anuran amphibians (frogs). In adult frogs, whereas ependymal cells proliferate in response to brain injury, they cannot migrate and close the wound surface, resulting in the failure of regeneration. Therefore frogs, in particular Xenopus, provide us with at least two modes to study brain regeneration. One is to study normal regeneration by using regenerative larvae. In this type of study, the requirement of reconnection between a regenerating brain and sensory neurons was demonstrated. Functional restoration of a regenerated telencephalon was also easily evaluated because Xenopus shows simple responses to the stimulus of a food odor. The other mode is to compare regenerative larvae and non-regenerative adults. By using this mode, it is suggested that there are regeneration-competent cells even in the non-regenerative adult brain, and that immobility of those cells might cause the failure of regeneration. Here we review studies that have led to these conclusions.     

Trivalent recognition unit of innate immunity system: crystal structure of trimeric human M-ficolin fibrinogen-like domain

Ficolins are a kind of pathogen-recognition molecule in the innate immune systems. To investigate the discrimination mechanism between self and non-self by ficolins, we determined the crystal structure of the human M-ficolin fibrinogen-like domain (FD1), which is the ligand-binding domain, at 1.9A resolution. Although the FD1 monomer shares a common fold with the fibrinogen gamma fragment and tachylectin-5A, the Asp-282-Cys-283 peptide bond, which is the predicted ligand-binding site on the C-terminal P domain, is a normal trans bond, unlike the cases of the other two proteins. The trimeric formation of FD1 results in the separation of the three P domains, and the spatial arrangement of the three predicted ligand-binding sites on the trimer is very similar to that of the trimeric collectin, indicating that such an arrangement is generally required for pathogen-recognition. The ligand binding study of FD1 in solution indicated that the recombinant protein binds to N-acetyl-d-glucosamine and the peptide Gly-Pro-Arg-Pro and suggested that the ligand-binding region exhibits a conformational equilibrium involving cis-trans isomerization of the Asp-282-Cys-283 peptide bond. The crystal structure and the ligand binding study of FD1 provide an insight of the self- and non-self discrimination mechanism by ficolins.     

Effective tempo of the step test for dynamic balance ability in the elderly

This study aimed to examine the reliability and sex- and age-related differences of step tests with stipulated tempos as well as to clarify useful test parameters and tempos. One hundred forty elderly people and fifty young adults conducted tapping and stepping tests, matching the tempo provided by a metronome. Both tests involve movements where the subject touches a sheet with both the right and left hands or right and left legs at a designated spot. Evaluation parameters were the time difference between the beep sound and the time at which the sheet was touched in both tests as well as two-leg support and one-leg support times in the step test. The trial-to-trial reliability of the parameters in both tests was high. The time differences of both 40 bpm tests in the elderly were larger in males than in females. In the step test, the time difference and two-leg support times of the elderly were larger, in the order of 40, 60, and 120 bpm, and the one-leg support time was less in 40 bpm than 60 bpm or 120 bpm. The one-leg support time of the young subjects was larger, in the order of 40, 60, and 120 bpm. A significant age-related difference was found in the 40 bpm and 60 bpm test, and the time difference and two-leg support time were larger in the elderly while the one-leg support time was larger in the young subjects. The time difference at 40 bpm in the elderly was larger in the step test than in the tap test. There was no significant difference between both tests in the young subjects. In conclusion, the step test with the slow tempo, because it requires a long one-leg support phase, is effective for evaluating dynamic balance in the elderly. The time difference and two-leg and one-leg support times are effective evaluation parameters of the step test.     

Reduced-intensity stem cell transplantation for hematological malignancies: current status and the future

Reduced-intensity stem cell transplantation (RIST) has opened a new era for hematopoietic stem cell transplantation (HSCT). It was developed based on the knowledge that graft-versus-tumor (GVT) effect is the main anti-tumor effect in allogeneic HSCT. Because RIST is associated with less morbidity and mortality, it can be applied to many patients who could not undergo conventional HSCT. Experiences in the last decade clarified many issues related to RIST. For example, graft-versus-host disease (GVHD) in RIST may differ in character compared to conventional HSCT. Also, it is now known that intensity of conditioning is important in disease control, and the optimal regimens may be different for each disease or for each disease status. There are still many unsolved questions, and large prospective randomized trials are necessary to resolve these.     

Impaired long-term memory and long-term potentiation in N-type Ca2+ channel-deficient mice

Voltage-dependent N-type Ca(2+) channels, along with the P/Q-type, have a crucial role in controlling the release of neurotransmitters or neuromodulators at presynaptic terminals. However, their role in hippocampus-dependent learning and memory has never been examined. Here, we investigated hippocampus-dependent learning and memory and synaptic plasticity at hippocampal CA3-CA1 synapses in mice deficient for the alpha(1B) subunit of N-type Ca(2+) channels. The mutant mice exhibited impaired learning and memory in the Morris water maze and the social transmission of food preference tasks. In particular, long-term memory was impaired in the mutant mice. Interestingly, among activity-dependent long-lasting synaptic changes, theta burst- or 200-Hz-stimulation-induced long-term potentiation (LTP) was decreased in the mutant, compared with the wild-type mice. This type of LTP is known to require brain-derived neurotrophic factor (BDNF). It was found that both BDNF-induced potentiation of field excitatory postsynaptic potentials and facilitation of the frequency of miniature excitatory postsynaptic currents (mEPSCs) were reduced in the mutant. Taken together, these results demonstrate that N-type Ca(2+) channels are required for hippocampus-dependent learning and memory, and certain forms of LTP.     

High Performance Proteomics: 7th HUPO Brain Proteome Project Workshop March 7-9, 2007 Wellcome Trust Conference Centre, Hinxton, UK

The Wellcome Trust Conference Centre at Hinxton, UK, was the meeting place of the 7th HUPO Brain Proteome Project Workshop entitled "High Performance Proteomics". It started on Wednesday, March 7, 2007 with a steering committee meeting followed by a two days series of talks dealing with the standardization and handling of tissues, body fluids as well as of proteomics data. The presentation and accompanying vivid discussions created a picture of actual strategies and standards in recent proteomics.     

Pear scab resistance QTLs via a European pear (Pyrus communis) linkage map

Pear scab caused by Venturia pyrina is an economically important disease throughout the world and can cause severe crop loss in susceptible cultivars. The varying range of susceptibility to pear scab in F1 populations has made it possible to identify quantitative trait loci (QTLs). Ninety-five seedlings derived from the cross ‘Abbè Fétel’ (AF) × ‘Max Red Bartlett’ (MRB) were evaluated for scab resistance in greenhouse tests, with 39% being classified as resistant, 33 as moderately susceptible and 28 as highly susceptible. Amplified fragment length polymorphisms (157) and simple sequence repeats (41) were used to construct two maps, one of 908.1 cM (AF) and the other of 879.8 cM (MRB). The analysis of the resistance data collected made it possible to identify two major QTLs on linkage groups 3 and 7 associated with resistance to V. pyrina. Both QTLs explained 88% of the phenotypic variance and the log of odds values were higher than 10, suggesting the involvement of two major genes in pear scab resistance. L. Pierantoni and L. Dondini have contributed equally to this work.     

p53 promotes the fidelity of DNA end-joining activity by, in part, enhancing the expression of heterogeneous nuclear ribonucleoprotein G

Many studies have suggested the involvement of wild-type (wt) p53 in the repair of DNA double-strand breaks (DSBs) via DNA end-joining (EJ) process. To investigate this possibility, we compared the capacity and fidelity of DNA EJ in RKO cells containing wt p53 and RKO cells containing no p53 (RKO cells with p53 knockdown). The p53 knockdown cells showed lower fidelity of DNA EJ compared to the control RKO cells. The DNA end-protection assay revealed the association of a protein complex including heterogeneous nuclear ribonucleoprotein G (hnRNP G) with the DNA ends in RKO cells containing wt p53, but not with the DNA ends in RKO cells with p53 knockdown. Depletion of endogenous hnRNP G notably diminished the fidelity of EJ in RKO cells expressing wt p53. Moreover, an ectopic expression of hnRNP G significantly enhanced the fidelity of DNA EJ and the protection of DNA ends in human cancer cells lacking hnRNP G protein or containing mutant hnRNP G. Finally, using recombinant hnRNP G proteins, we demonstrated the hnRNP G protein is able to bind to and protect DNA ends from degradation of nucleases. Our results suggest that wt p53 modulates DNA DSB repair by, in part, inducing hnRNP G, and the ability of hnRNP G to bind and protect DNA ends may contribute its ability to promote the fidelity of DNA EJ.