Chondroitinase and Growth Factors Enhance Activation and Oligodendrocyte Differentiation of Endogenous Neural Precursor Cells after Spinal Cord Injury

The adult spinal cord harbours a population of multipotent neural precursor cells (NPCs) with the ability to replace oligodendrocytes. However, despite this capacity, proliferation and endogenous remyelination is severely limited after spinal cord injury (SCI). In the post-traumatic microenvironment following SCI, endogenous spinal NPCs mainly differentiate into astrocytes which could contribute to astrogliosis that exacerbate the outcomes of SCI. These findings emphasize a key role for the post-SCI niche in modulating the behaviour of spinal NPCs after SCI. We recently reported that chondroitin sulphate proteoglycans (CSPGs) in the glial scar restrict the outcomes of NPC transplantation in SCI by reducing the survival, migration and integration of engrafted NPCs within the injured spinal cord. These inhibitory effects were attenuated by administration of chondroitinase (ChABC) prior to NPC transplantation. Here, in a rat model of compressive SCI, we show that perturbing CSPGs by ChABC in combination with sustained infusion of growth factors (EGF, bFGF and PDGF-AA) optimize the activation and oligodendroglial differentiation of spinal NPCs after injury. Four days following SCI, we intrathecally delivered ChABC and/or GFs for seven days. We performed BrdU incorporation to label proliferating cells during the treatment period after SCI. This strategy increased the proliferation of spinal NPCs, reduced the generation of new astrocytes and promoted their differentiation along an oligodendroglial lineage, a prerequisite for remyelination. Furthermore, ChABC and GF treatments enhanced the response of non-neural cells by increasing the generation of new vascular endothelial cells and decreasing the number of proliferating macrophages/microglia after SCI. In conclusions, our data strongly suggest that optimization of the behaviour of endogenous spinal NPCs after SCI is critical not only to promote endogenous oligodendrocyte replacement, but also to reverse the otherwise detrimental effects of their activation into astrocytes which could negatively influence the repair process after SCI

Characterization of the major fragance gene from an aromatic japonica rice and analysis of its diversity in Asian cultivated rice

In Asian cultivated rice (Oryza sativa L.), aroma is one of the most valuable traits in grain quality and 2-ACP is the main volatile compound contributing to the characteristic popcorn-like odour of aromatic rices. Although the major locus for grain fragrance (frg gene) has been described recently in Basmati rice, this gene has not been characterised in true japonica varieties and molecular information available on the genetic diversity and evolutionary origin of this gene among the different varieties is still limited. Here we report on characterisation of the frg gene in the Azucena variety, one of the few aromatic japonica cultivars. We used a RIL population from a cross between Azucena and IR64, a non-aromatic indica, the reference genomic sequence of Nipponbare (japonica) and 93–11 (indica) as well as an Azucena BAC library, to identify the major fragance gene in Azucena. We thus identified a betaine aldehyde dehydrogenase gene, badh2, as the candidate locus responsible for aroma, which presented exactly the same mutation as that identified in Basmati and Jasmine-like rices. Comparative genomic analyses showed very high sequence conservation between Azucena and Nipponbare BADH2, and a MITE was identified in the promotor region of the BADH2 allele in 93–11. The badh2 mutation and MITE were surveyed in a representative rice collection, including traditional aromatic and non-aromatic rice varieties, and strongly suggested a monophylogenetic origin of this badh2 mutation in Asian cultivated rices. Altogether these new data are discussed here in the light of current hypotheses on the origin of rice genetic diversity

Evolution and Association Analysis of Ghd7 in Rice

Plant height, heading date, and yield are the main targets for rice genetic improvement. Ghd7 is a pleiotropic gene that controls the aforementioned traits simultaneously. In this study, a rice germplasm collection of 104 accessions (Oryza sativa) and 3 wild rice varieties (O.rufipogon) was used to analyze the evolution and association of Ghd7 with plant height, heading date, and yield. Among the 104 accessions, 76 single nucleotide polymorphisms (SNPs) and six insertions and deletions were found within a 3932-bp DNA fragment of Ghd7. A higher pairwise π and θ in the promoter indicated a highly diversified promoter of Ghd7. Sixteen haplotypes and 8 types of Ghd7 protein were detected. SNP changes between haplotypes indicated that Ghd7 evolved from two distinct ancestral gene pools, and independent domestication processes were detected in indica and japonica varietals respectively. In addition to the previously reported premature stop mutation in the first exon of Ghd7, which caused phenotypic changes of multiple traits, we found another functional C/T mutation (SNP S_555) by structure-based association analysis. SNP S_555 is located in the promoter and was related to plant height probably by altering gene expression. Moreover, another seven SNP mutations in complete linkage were found to be associated with the number of spikelets per panicle, regardless of the photoperiod. These associations provide the potential for flexibility of Ghd7 application in rice breeding programs

Выявление понятий и их взаимосвязей в рамках технологии контент-мониторинга

Приведены подходы к решению проблемы выявления фактографической информации из неструктурированных текстовых потоков. Описаны технологические решения, позволяющие извлекать из полнотекстовых документов такие понятия как фирмы, фамилии, географические названия и т.п., а также выявлять силу их взаимосвязей на основе применения двух алгоритмов. Первый из этих алгоритмов основывается на учете совместного вхождения понятий в одни и те же документы, а второй на учете общего для рассматриваемых понятий контекста.Наведено підходи до вирішення проблеми виявлення фактографічної інформації з неструктурованих текстових потоків. Описано технологічні рішення, що дозволяють добути з повнотекстових документів такі поняття як фірми, прізвища, географічні назви тощо, а також виявляти силу їхніх взаємозв’язків на базі застосування двох алгоритмів. Перший з цих алгоритмів базується на врахуванні спільного входження понять до одних і тих самих документів, а другий — на врахуванні загального для понять, що розглядаються, контексту.Approaches to the solution of a problem of revealing factual information from unstructured text flows are given. The technological solutions, allowing to take from text-through documents such concepts as a firm, a surname, place names, etc., and also to reveal force of their interrelations on the basis of application of two algorithms are described. The first of these algorithms is based on the account of joint concepts occurrence in the same documents, and the second one on the account of the context common for considered concepts

Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar

We study the process $e^+e^-\to J/\psi\pi^{+}\pi^{-}$ with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BaBar detector at center-of-mass energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454 $\mathrm{fb^{-1}}$. We investigate the $J/\psi \pi^{+}\pi^{-}$ mass distribution in the region from 3.5 to 5.5 $\mathrm{GeV/c^{2}}$. Below 3.7 $\mathrm{GeV/c^{2}}$ the $\psi(2S)$ signal dominates, and above 4 $\mathrm{GeV/c^{2}}$ there is a significant peak due to the Y(4260). A fit to the data in the range 3.74 -- 5.50 $\mathrm{GeV/c^{2}}$ yields a mass value $4244 \pm 5$ (stat) $\pm 4$ (syst)$\mathrm{MeV/c^{2}}$ and a width value $114 ^{+16}_{-15}$ (stat)$\pm 7$(syst)$\mathrm{MeV}$ for this state. We do not confirm the report from the Belle collaboration of a broad structure at 4.01 $\mathrm{GeV/c^{2}}$. In addition, we investigate the $\pi^{+}\pi^{-}$ system which results from Y(4260) decay

NG2 and phosphacan are present in the astroglial scar after human traumatic spinal cord injury

BACKGROUND: A major class of axon growth-repulsive molecules associated with CNS scar tissue is the family of chondroitin sulphate proteoglycans (CSPGs). Experimental spinal cord injury (SCI) has demonstrated rapid re-expression of CSPGs at and around the lesion site. The pharmacological digestion of CSPGs in such lesion models results in substantially enhanced axonal regeneration and a significant functional recovery. The potential therapeutic relevance of interfering with CSPG expression or function following experimental injuries seems clear, however, the spatio-temporal pattern of expression of individual members of the CSPG family following human spinal cord injury is only poorly defined. In the present correlative investigation, the expression pattern of CSPG family members NG2, neurocan, versican and phosphacan was studied in the human spinal cord. METHODS: An immunohistochemical investigation in post mortem samples of control and lesioned human spinal cords was performed. All patients with traumatic SCI had been clinically diagnosed as having "complete" injuries and presented lesions of the maceration type. RESULTS: In sections from control spinal cord, NG2 immunoreactivity was restricted to stellate-shaped cells corresponding to oligodendrocyte precursor cells. The distribution patterns of phosphacan, neurocan and versican in control human spinal cord parenchyma were similar, with a fine reticular pattern being observed in white matter (but also located in gray matter for phosphacan). Neurocan staining was also associated with blood vessel walls. Furthermore, phosphacan, neurocan and versican were present in the myelin sheaths of ventral and dorsal nerve roots axons. After human SCI, NG2 and phosphacan were both detected in the evolving astroglial scar. Neurocan and versican were detected exclusively in the lesion epicentre, being associated with infiltrating Schwann cells in the myelin sheaths of invading peripheral nerve fibres from lesioned dorsal roots. CONCLUSION: NG2 and phosphacan were both present in the evolving astroglial scar and, therefore, might play an important role in the blockade of successful CNS regeneration. Neurocan and versican, however, were located at the lesion epicentre, associated with Schwann cell myelin on regenerating peripheral nerve fibres, a distribution that was unlikely to contribute to failed CNS axon regeneration. The present data points to the importance of such correlative investigations for demonstrating the clinical relevance of experimental data

The USDA Barley Core Collection:Genetic Diversity, Population Structure, and Potential for Genome-Wide Association Studies

New sources of genetic diversity must be incorporated into plant breeding programs if they are to continue increasing grain yield and quality, and tolerance to abiotic and biotic stresses. Germplasm collections provide a source of genetic and phenotypic diversity, but characterization of these resources is required to increase their utility for breeding programs. We used a barley SNP iSelect platform with 7,842 SNPs to genotype 2,417 barley accessions sampled from the USDA National Small Grains Collection of 33,176 accessions. Most of the accessions in this core collection are categorized as landraces or cultivars/breeding lines and were obtained from more than 100 countries. Both STRUCTURE and principal component analysis identified five major subpopulations within the core collection, mainly differentiated by geographical origin and spike row number (an inflorescence architecture trait). Different patterns of linkage disequilibrium (LD) were found across the barley genome and many regions of high LD contained traits involved in domestication and breeding selection. The genotype data were used to define 'mini-core' sets of accessions capturing the majority of the allelic diversity present in the core collection. These 'mini-core' sets can be used for evaluating traits that are difficult or expensive to score. Genome-wide association studies (GWAS) of 'hull cover', 'spike row number', and 'heading date' demonstrate the utility of the core collection for locating genetic factors determining important phenotypes. The GWAS results were referenced to a new barley consensus map containing 5,665 SNPs. Our results demonstrate that GWAS and high-density SNP genotyping are effective tools for plant breeders interested in accessing genetic diversity in large germplasm collections

Diversity and selective sweep in the OsAMT1;1 genomic region of rice

<p>Abstract</p> <p>Background</p> <p>Ammonium is one of the major forms in which nitrogen is available for plant growth. <it>OsAMT1;1 </it>is a high-affinity ammonium transporter in rice (<it>Oryza sativa </it>L.), responsible for ammonium uptake at low nitrogen concentration. The expression pattern of the gene has been reported. However, variations in its nucleotides and the evolutionary pathway of its descent from wild progenitors are yet to be elucidated. In this study, nucleotide diversity of the gene <it>OsAMT1;1 </it>and the diversity pattern of seven gene fragments spanning a genomic region approximately 150 kb long surrounding the gene were surveyed by sequencing a panel of 216 rice accessions including both cultivated rice and wild relatives.</p> <p>Results</p> <p>Nucleotide polymorphism (Pi) of <it>OsAMT1;1 </it>was as low as 0.00004 in cultivated rice (<it>Oryza sativa</it>), only 2.3% of that in the common wild rice (<it>O. rufipogon</it>). A single dominant haplotype was fixed at the locus in <it>O. sativa</it>. The test values for neutrality were significantly negative in the entire region stretching 5' upstream and 3' downstream of the gene in all accessions. The value of linkage disequilibrium remained high across a 100 kb genomic region around <it>OsAMT1;1 </it>in <it>O. sativa</it>, but fell rapidly in <it>O. rufipogon </it>on either side of the promoter of <it>OsAMT1;1</it>, demonstrating a strong natural selection within or nearby the ammonium transporter.</p> <p>Conclusions</p> <p>The severe reduction in nucleotide variation at <it>OsAMT1;1 </it>in rice was caused by a selective sweep around <it>OsAMT1;1</it>, which may reflect the nitrogen uptake system under strong selection by the paddy soil during the domestication of rice. Purifying selection also occurred before the wild rice diverged into its two subspecies, namely <it>indica </it>and <it>japonica</it>. These findings would provide useful insights into the processes of evolution and domestication of nitrogen uptake genes in rice.</p

The endogenous proteoglycan-degrading enzyme ADAMTS-4 promotes functional recovery after spinal cord injury

<p>Abstract</p> <p>Background</p> <p>Chondroitin sulfate proteoglycans are major inhibitory molecules for neural plasticity under both physiological and pathological conditions. The chondroitin sulfate degrading enzyme chondroitinase ABC promotes functional recovery after spinal cord injury, and restores experience-dependent plasticity, such as ocular dominance plasticity and fear erasure plasticity, in adult rodents. These data suggest that the sugar chain in a proteoglycan moiety is essential for the inhibitory activity of proteoglycans. However, the significance of the core protein has not been studied extensively. Furthermore, considering that chondroitinase ABC is derived from bacteria, a mammalian endogenous enzyme which can inactivate the proteoglycans' activity is desirable for clinical use.</p> <p>Methods</p> <p>The degradation activity of ADAMTS-4 was estimated for the core proteins of chondroitin sulfate proteoglycans, that is, brevican, neurocan and phosphacan. To evaluate the biological significance of ADMATS-4 activity, an <it>in vitro </it>neurite growth assay and an <it>in vivo </it>neuronal injury model, spinal cord contusion injury, were employed.</p> <p>Results</p> <p>ADAMTS-4 digested proteoglycans, and reversed their inhibition of neurite outgrowth. Local administration of ADAMTS-4 significantly promoted motor function recovery after spinal cord injury. Supporting these findings, the ADAMTS-4-treated spinal cord exhibited enhanced axonal regeneration/sprouting after spinal cord injury.</p> <p>Conclusions</p> <p>Our data suggest that the core protein in a proteoglycan moiety is also important for the inhibition of neural plasticity, and provides a potentially safer tool for the treatment of neuronal injuries.</p