Spread of vimentin-immunoreactive cells within the plaque-like lesion in the spinal anterior horn of a patient with post-poliomyelitis syndrome.

A Japanese man in the present study experienced acute weakness in his right leg as a two year old. The strength in his leg gradually recovered and developed, and he could play golf and climb mountains up to around the age of 50. From approximately 55 years of age, he became unable to stand up from a stooped position. Muscle weakness and atrophy spread to his right arm, and an electromyography revealed a neurogenic pattern in his lower and upper extremities. The patient was diagnosed as having post-poliomyelitis syndrome (PPS). Numbness in both the legs and pain in the buttocks occurred after 60 years of age. Computed tomography and magnetic resonance imaging at that time revealed spondylosis and protrusion of an osteophye in lower thoracic vertebrae compressing the second lumbar segment of the spinal cord. He died of malignant lymphoma and acute interstitial pneumonia at 80 years of age. Pathological examination revealed transverse myelopathy at the second lumbar segment of the spinal cord and total necrosis. The anterior horn and the intermediate zone of the third and fourth lumbar segments of the spinal cord on the right side were atrophic and diffusely gliotic. An oval-shaped plaque-like lesion was observed in the right anterior horn at the third and fourth lumbar segments of the spinal cord. Neurons and synaptophysin immunoreactivity had completely disappeared in the plaque-like lesion. A striking spread of vimentin-immunoreactive cells was found corresponding to the lesion, while glial fibrillary acidic protein-immunoreactive astrocytes existed evenly in the anterior horn and intermediate zone on both sides of the third and fourth lumber segments of the spinal cord. Virological examination using the autopsied materials was negative for poliovirus. Neither transactivation response DNA-binding protein of 43 kDa-immunoreactive inclusion nor Bunina body was seen in the spinal cord. The present paper demonstrates new findings of a noteworthy response of the vimentin-immunoreactive cells within the peculiar "plaque-like lesion" in the PPS.

Draft genome assembly and annotation of Glycyrrhiza uralensis, a medicinal legume.

Chinese liquorice/licorice (Glycyrrhiza uralensis) is a leguminous plant species whose roots and rhizomes have been widely used as a herbal medicine and natural sweetener. Whole-genome sequencing is essential for gene discovery studies and molecular breeding in liquorice. Here, we report a draft assembly of the approximately 379-Mb whole-genome sequence of strain 308-19 of G. uralensis; this assembly contains 34 445 predicted protein-coding genes. Comparative analyses suggested well-conserved genomic components and collinearity of gene loci (synteny) between the genome of liquorice and those of other legumes such as Medicago and chickpea. We observed that three genes involved in isoflavonoid biosynthesis, namely, 2-hydroxyisoflavanone synthase (CYP93C), 2,7,4'-trihydroxyisoflavanone 4'-O-methyltransferase/isoflavone 4'-O-methyltransferase (HI4OMT) and isoflavone-7-O-methyltransferase (7-IOMT) formed a cluster on the scaffold of the liquorice genome and showed conserved microsynteny with Medicago and chickpea. Based on the liquorice genome annotation, we predicted genes in the P450 and UDP-dependent glycosyltransferase (UGT) superfamilies, some of which are involved in triterpenoid saponin biosynthesis, and characterised their gene expression with the reference genome sequence. The genome sequencing and its annotations provide an essential resource for liquorice improvement through molecular breeding and the discovery of useful genes for engineering bioactive components through synthetic biology approaches.

Design of an optimal promoter involved in the heat-induced transcriptional pathway in Arabidopsis, soybean, rice and maize.

Interactions between heat shock (HS) factors (HSFs) and heat shock response elements (HSEs) are important during the heat shock response (HSR) of flora and fauna. Moreover, plant HSFs that are involved in heat stress are also involved in abiotic stresses such as dehydration and cold as well as development, cell differentiation and proliferation. Because the specific combination of HSFs and HSEs involved in plants under heat stress remains unclear, the mechanism of their interaction has not yet been utilized in molecular breeding of plants for climate change. For the study reported herein, we compared the sequences of HS-inducible genes and their promoters in Arabidopsis, soybean, rice and maize and then designed an optimal HS-inducible promoter. Our analyses suggest that, for the four species, the abscisic acid-independent, HSE/HSF-dependent transcriptional pathway plays a major role in HS-inducible gene expression. We found that an 18-bp sequence that includes the HSE has an important role in the HSR, and that those sequences could be classified as representative of monocotyledons or dicotyledons. With the HS-inducible promoter designed based on our bioinformatic predictions, we were able to develop an optimal HS-specific inducible promoter for seedlings or single cells in roots. These findings demonstrate the utility of our HS-specific inducible promoter, which we expect will contribute to molecular breeding efforts and cell-targeted gene expression in specific plant tissues.

Cassava (Manihot esculenta) transcriptome analysis in response to infection by the fungus Colletotrichum gloeosporioides using an oligonucleotide-DNA microarray.

Cassava anthracnose disease (CAD), caused by the fungus Colletotrichum gloeosporioides f. sp. Manihotis, is a serious disease of cassava (Manihot esculenta) worldwide. In this study, we established a cassava oligonucleotide-DNA microarray representing 59,079 probes corresponding to approximately 30,000 genes based on original expressed sequence tags and RNA-seq information from cassava, and applied it to investigate the molecular mechanisms of resistance to fungal infection using two cassava cultivars, Huay Bong 60 (HB60, resistant to CAD) and Hanatee (HN, sensitive to CAD). Based on quantitative real-time reverse transcription PCR and expression profiling by the microarray, we showed that the expressions of various plant defense-related genes, such as pathogenesis-related (PR) genes, cell wall-related genes, detoxification enzyme, genes related to the response to bacterium, mitogen-activated protein kinase (MAPK), genes related to salicylic acid, jasmonic acid and ethylene pathways were higher in HB60 compared with HN. Our results indicated that the induction of PR genes in HB60 by fungal infection and the higher expressions of defense response-related genes in HB60 compared with HN are likely responsible for the fungal resistance in HB60. We also showed that the use of our cassava oligo microarray could improve our understanding of cassava molecular mechanisms related to environmental responses and development, and advance the molecular breeding of useful cassava plants.

Determination of growth stages and metabolic profiles in Brachypodium distachyon for comparison of developmental context with Triticeae crops.

Brachypodium distachyon is an emerging model plant for studying biological phenomena in temperate grasses. Study of the growth scale is essential to analyse spatio-temporal changes in molecular factors throughout the life cycle. For sensitive and robust staging based on morphology in B. distachyon, we demonstrated the utility of the BBCH (Biologische Bundesanstalt, Bundessortenamt and CHemical industry) scale, which is comparable to the Zadoks scale conventionally used for Triticeae crops. We compared the chronological progression of B. distachyon accessions Bd21 and Bd3-1, in addition to the progression of Chinese Spring wheat. The comparison of growth stages illustrates the morphological similarities and differences in the timing of life cycle events. Furthermore, we compared metabolite accumulation patterns across different growth stages and across different stress conditions using a widely targeted metabolome analysis. Metabolic profiling determined commonalities and specificities in chemical properties that were dependent on organisms, growth stages and/or stress conditions. Most metabolites accumulated equivalently in B. distachyon and wheat. This qualitative similarity indicated the superiority of B. distachyon as a model for Triticeae crops. The growth scale of B. distachyon should provide a conceptual framework for comparative analysis and for knowledge integration between this model grass and crops in the Pooideae subfamily.

Glycyrrhiza uralensis transcriptome landscape and study of phytochemicals.

Medicinal and industrial properties of phytochemicals (e.g. glycyrrhizin) from the root of Glycyrrhiza uralensis (licorice plant) made it an attractive, multimillion-dollar trade item. Bioengineering is one of the solutions to overcome such high market demand and to protect plants from extinction. Unfortunately, limited genomic information on medicinal plants restricts their research and thus biosynthetic mechanisms of many important phytochemicals are still poorly understood. In this work we utilized the de novo (no reference genome sequence available) assembly of Illumina RNA-Seq data to study the transcriptome of the licorice plant. Our analysis is based on sequencing results of libraries constructed from samples belonging to different tissues (root and leaf) and collected in different seasons and from two distinct strains (low and high glycyrrhizin producers). We provide functional annotations and the expression profile of 43,882 assembled unigenes, which are suitable for various further studies. Here, we searched for G. uralensis-specific enzymes involved in isoflavonoid biosynthesis as well as elucidated putative cytochrome P450 enzymes and putative vacuolar saponin transporters involved in glycyrrhizin production in the licorice root. To disseminate the data and the analysis results, we constructed a publicly available G. uralensis database. This work will contribute to a better understanding of the biosynthetic pathways of secondary metabolites in licorice plants, and possibly in other medicinal plants, and will provide an important resource to further advance transcriptomic studies in legumes.

Coupling deep transcriptome analysis with untargeted metabolic profiling in Ophiorrhiza pumila to further the understanding of the biosynthesis of the anti-cancer alkaloid camptothecin and anthraquinones.

The Rubiaceae species, Ophiorrhiza pumila, accumulates camptothecin, an anti-cancer alkaloid with a potent DNA topoisomerase I inhibitory activity, as well as anthraquinones that are derived from the combination of the isochorismate and hemiterpenoid pathways. The biosynthesis of these secondary products is active in O. pumila hairy roots yet very low in cell suspension culture. Deep transcriptome analysis was conducted in O. pumila hairy roots and cell suspension cultures using the Illumina platform, yielding a total of 2 Gb of sequence for each sample. We generated a hybrid transcriptome assembly of O. pumila using the Illumina-derived short read sequences and conventional Sanger-derived expressed sequence tag clones derived from a full-length cDNA library constructed using RNA from hairy roots. Among 35,608 non-redundant unigenes, 3,649 were preferentially expressed in hairy roots compared with cell suspension culture. Candidate genes involved in the biosynthetic pathway for the monoterpenoid indole alkaloid camptothecin were identified; specifically, genes involved in post-strictosamide biosynthetic events and genes involved in the biosynthesis of anthraquinones and chlorogenic acid. Untargeted metabolomic analysis by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) indicated that most of the proposed intermediates in the camptothecin biosynthetic pathway accumulated in hairy roots in a preferential manner compared with cell suspension culture. In addition, a number of anthraquinones and chlorogenic acid preferentially accumulated in hairy roots compared with cell suspension culture. These results suggest that deep transcriptome and metabolome data sets can facilitate the identification of genes and intermediates involved in the biosynthesis of secondary products including camptothecin in O. pumila.

Global landscape of a co-expressed gene network in barley and its application to gene discovery in Triticeae crops.

Accumulated transcriptome data can be used to investigate regulatory networks of genes involved in various biological systems. Co-expression analysis data sets generated from comprehensively collected transcriptome data sets now represent efficient resources that are capable of facilitating the discovery of genes with closely correlated expression patterns. In order to construct a co-expression network for barley, we analyzed 45 publicly available experimental series, which are composed of 1,347 sets of GeneChip data for barley. On the basis of a gene-to-gene weighted correlation coefficient, we constructed a global barley co-expression network and classified it into clusters of subnetwork modules. The resulting clusters are candidates for functional regulatory modules in the barley transcriptome. To annotate each of the modules, we performed comparative annotation using genes in Arabidopsis and Brachypodium distachyon. On the basis of a comparative analysis between barley and two model species, we investigated functional properties from the representative distributions of the gene ontology (GO) terms. Modules putatively involved in drought stress response and cellulose biogenesis have been identified. These modules are discussed to demonstrate the effectiveness of the co-expression analysis. Furthermore, we applied the data set of co-expressed genes coupled with comparative analysis in attempts to discover potentially Triticeae-specific network modules. These results demonstrate that analysis of the co-expression network of the barley transcriptome together with comparative analysis should promote the process of gene discovery in barley. Furthermore, the insights obtained should be transferable to investigations of Triticeae plants. The associated data set generated in this analysis is publicly accessible at http://coexpression.psc.riken.jp/barley/.

LegumeTFDB: an integrative database of Glycine max, Lotus japonicus and Medicago truncatula transcription factors.

UNLABELLED: We have established a database named LegumeTFDB to provide access to transcription factor (TF) repertoires of three major legume species: soybean (Glycine max), Lotus japonicus and Medicago truncatula. LegumeTFDB integrates unique information for each TF gene and family, including sequence features, gene promoters, domain alignments, gene ontology (GO) assignment and sequence comparison data derived from comparative analysis with TFs found within legumes, in Arabidopsis, rice and poplar as well as with proteins in NCBI nr and UniProt. We also analyzed the promoter regions for all of the TFs to identify all types of cis-motifs provided by the PLACE database. Additionally, we supply hyperlinks to make available expression data of 2411 soybean TF genes. LegumeTFDB provides an important user-friendly public resource for comparative genomics and understanding of transcriptional regulation in agriculturally important legumes. AVAILABILITY: http://legumetfdb.psc.riken.jp/. SUPPLEMENTARY INFORMATION: Supplementary data available at Bioinformatics online.

Primary AL amyloid polyneuropathy successfully treated with high-dose melphalan followed by autologous stem cell transplantation.

We report 2 patients with polyneuropathy associated with amyloid derived from light chains (AL) who were treated successfully with high-dose melphalan followed by autologous peripheral blood stem cell transplantation (HDM/SCT). Neuropathic symptoms improved in conjunction with normalization of serum-free light chains. In addition to amyloid deposits in tissues, an amyloidogenic light chain itself produced by abnormal plasma cells might be harmful to peripheral nerve function, and thus HDM/SCT seems to be a promising therapy for primary AL amyloid polyneuropathy.

An attack of acute neuro-Behçet's disease during the course of chronic progressive neuro-Behçet's disease: report of two cases.

A 29-year-old man and a 36-year-old man developed attacks of acute neuro-Behçet's disease (NB) (right Horner's syndrome and right hemiplegia and dysarthria, respectively) during the course of chronic progressive NB (acute on chronic). Although both patients recovered from acute NB after treatment with infliximab or corticosteroids, they continued to show manifestations of chronic progressive NB. It is suggested that acute NB and chronic progressive NB are different in their pathogenesis.

TriMEDB: a database to integrate transcribed markers and facilitate genetic studies of the tribe Triticeae.

BACKGROUND: The recent rapid accumulation of sequence resources of various crop species ensures an improvement in the genetics approach, including quantitative trait loci (QTL) analysis as well as the holistic population analysis and association mapping of natural variations. Because the tribe Triticeae includes important cereals such as wheat and barley, integration of information on the genetic markers in these crops should effectively accelerate map-based genetic studies on Triticeae species and lead to the discovery of key loci involved in plant productivity, which can contribute to sustainable food production. Therefore, informatics applications and a semantic knowledgebase of genome-wide markers are required for the integration of information on and further development of genetic markers in wheat and barley in order to advance conventional marker-assisted genetic analyses and population genomics of Triticeae species. DESCRIPTION: The Triticeae mapped expressed sequence tag (EST) database (TriMEDB) provides information, along with various annotations, regarding mapped cDNA markers that are related to barley and their homologues in wheat. The current version of TriMEDB provides map-location data for barley and wheat ESTs that were retrieved from 3 published barley linkage maps (the barley single nucleotide polymorphism database of the Scottish Crop Research Institute, the barley transcript map of Leibniz Institute of Plant Genetics and Crop Plant Research, and HarvEST barley ver. 1.63) and 1 diploid wheat map. These data were imported to CMap to allow the visualization of the map positions of the ESTs and interrelationships of these ESTs with public gene models and representative cDNA sequences. The retrieved cDNA sequences corresponding to each EST marker were assigned to the rice genome to predict an exon-intron structure. Furthermore, to generate a unique set of EST markers in Triticeae plants among the public domain, 3472 markers were assembled to form 2737 unique marker groups as contigs. These contigs were applied for pairwise comparison among linkage maps obtained from different EST map resources. CONCLUSION: TriMEDB provides information regarding transcribed genetic markers and functions as a semantic knowledgebase offering an informatics facility for the acceleration of QTL analysis and for population genetics studies of Triticeae.

Transcriptional alterations during proliferation and lignification in Phyllostachys nigra cells.

Highly-lignified culms of bamboo show distinctive anatomical and mechanical properties compared with the culms of other grass species. A cell culture system for Phyllostachys nigra has enabled investigating the alterations in cellular states associated with secondary cell wall formation during its proliferation and lignification in woody bamboos. To reveal transcriptional changes related to lignification in bamboo, we analyzed transcriptome in P. nigra cells treated with the synthetic auxin 2,4-dichlorophenoxyacetic acid (2,4-D) and the synthetic cytokinin benzylaminopurine (BA) by RNA-seq analysis. We found that some genes putatively involved in cell wall biogenesis and cell division were up-regulated in response to the 2,4-D treatment, and the induction of lignification by the BA treatment was correlated with up-regulation of genes involved in the shikimate pathway. We also found that genes encoding MYB transcription factors (TFs) show correlated expression patterns with those encoding cinnamyl alcohol dehydrogenase (CAD), suggesting that MYB TFs presumably regulate secondary cell wall formation in the bamboo cells. These findings suggest that cytokinin signaling may regulate lignification in P. nigra cells through coordinated transcriptional regulation and metabolic alterations. Our results have also produced a useful resource for better understanding of secondary cell wall formation in bamboo plants.

Sepsis Caused by Newly Identified Capnocytophaga canis Following Cat Bites: C. canis Is the Third Candidate along with C. canimorsus and C. cynodegmi Causing Zoonotic Infection.

Sepsis caused by a Capnocytophaga canis infection has only been rarely reported. A 67-year-old female with a past medical history of splenectomy was admitted to our hospital with fever and general malaise. She had been bitten by a cat. She showed disseminated intravascular coagulation and multi-organ failure because of severe sepsis. On blood culture, characteristic gram-negative fusiform rods were detected; therefore, a Capnocytophaga species infection was suspected. A nucleotide sequence analysis revealed the species to be C. canis, which was newly identified in 2016. C. canis may have low virulence in humans; however, C. canis with oxidase activity may cause severe zoonotic infection.

Seronegative Sjögren syndrome with asymptomatic autoimmune sclerosing pancreatitis.

We report two elderly patients with seronegative Sjögren syndrome who showed benign swelling of the pancreas on computed tomography. Immunostaining of the biopsied lip tissue or serum examination confirmed an increase in production of IgG4, leading to a diagnosis of autoimmune sclerosing pancreatitis (ASP) as a cause of the asymptomatic swelling of the pancreas. Sicca symptoms and ASP spontaneously improved in one patient, and the other responded well to oral prednisolone. Seronegative Sjögren syndrome and ASP can concurrently occur as a clinical manifestation of the IgG4-related systemic disorder, particularly in elderly subjects, and, in such a case, corticosteroid may be a potent therapeutic option.

Diurnal Transcriptome and Gene Network Represented through Sparse Modeling in Brachypodium distachyon.

We report the comprehensive identification of periodic genes and their network inference, based on a gene co-expression analysis and an Auto-Regressive eXogenous (ARX) model with a group smoothly clipped absolute deviation (SCAD) method using a time-series transcriptome dataset in a model grass, Brachypodium distachyon. To reveal the diurnal changes in the transcriptome in B. distachyon, we performed RNA-seq analysis of its leaves sampled through a diurnal cycle of over 48 h at 4 h intervals using three biological replications, and identified 3,621 periodic genes through our wavelet analysis. The expression data are feasible to infer network sparsity based on ARX models. We found that genes involved in biological processes such as transcriptional regulation, protein degradation, and post-transcriptional modification and photosynthesis are significantly enriched in the periodic genes, suggesting that these processes might be regulated by circadian rhythm in B. distachyon. On the basis of the time-series expression patterns of the periodic genes, we constructed a chronological gene co-expression network and identified putative transcription factors encoding genes that might be involved in the time-specific regulatory transcriptional network. Moreover, we inferred a transcriptional network composed of the periodic genes in B. distachyon, aiming to identify genes associated with other genes through variable selection by grouping time points for each gene. Based on the ARX model with the group SCAD regularization using our time-series expression datasets of the periodic genes, we constructed gene networks and found that the networks represent typical scale-free structure. Our findings demonstrate that the diurnal changes in the transcriptome in B. distachyon leaves have a sparse network structure, demonstrating the spatiotemporal gene regulatory network over the cyclic phase transitions in B. distachyon diurnal growth.

Bortezomib-dexamethasone versus high-dose melphalan for Japanese patients with systemic light-chain (AL) amyloidosis: a retrospective single-center study.

Bortezomib-dexamethasone (BD) and high-dose melphalan (HDM) are effective for systemic light-chain (AL) amyloidosis, but have not been compared in detail. We retrospectively investigated patients treated with BD or HDM at our center between September 2001 and June 2016. Among 234 patients, 20 were treated with BD and 30 received HDM. With the exception of age, transplant eligibility, and previous history of other chemotherapy, there were no significant differences in most background parameters between the two groups. Median age was higher (63.2 vs. 55.8, P = 0.001), number of transplant-eligible patients was lower (60.0 vs. 96.7%, P = 0.002), and number of previously treated patients was higher (35.0 vs. 0.0%, P < 0.001) in the BD group. The BD group showed trends toward lower treatment-related mortality (5.0 vs. 10.0%, P = 0.641), greater hematological response (partial response or better) (90.0 vs. 73.3%, P = 0.279), higher complete response (60 vs. 50%, P = 0.487), and similar survival with the HDM group (neither reached, P = 0.705). In conclusion, BD was as effective and safe as HDM. Notably, BD achieved this outcome among patients with poorer clinical backgrounds compared with HDM.

Severe cranial nerve involvement in a patient with monoclonal anti-MAG/SGPG IgM antibody and localized hard palate amyloidosis.

We report a patient with severe cranial polyneuropathy as well as sensory limb neuropathy. Biclonal serum IgM-kappa/IgM-lambda gammopathy was found and serum anti-myelin-associated glycoprotein (MAG)/sulfoglucuronyl paragloboside (SGPG) IgM antibody was also detected. Immunofluorescence analysis of a sural nerve biopsy specimen revealed binding of IgM and lambda-light chain on myelin sheaths. No amyloid deposition was detected in biopsied tissues except for the hard palate, suggesting that the amyloidosis was of the localized type and had no relation to the pathogenesis of cranial neuropathy. Our observations indicate that the anti-MAG/SGPG IgM antibody may be responsible for this patient's cranial polyneuropathy, which is a rare manifestation in anti-MAG/SGPG-associated neuropathy.

Analysis of single nucleotide polymorphisms based on RNA sequencing data of diverse bio-geographical accessions in barley.

Barley is one of the founder crops of Old world agriculture and has become the fourth most important cereal worldwide. Information on genome-scale DNA polymorphisms allows elucidating the evolutionary history behind domestication, as well as discovering and isolating useful genes for molecular breeding. Deep transcriptome sequencing enables the exploration of sequence variations in transcribed sequences; such analysis is particularly useful for species with large and complex genomes, such as barley. In this study, we performed RNA sequencing of 20 barley accessions, comprising representatives of several biogeographic regions and a wild ancestor. We identified 38,729 to 79,949 SNPs in the 19 domesticated accessions and 55,403 SNPs in the wild barley and revealed their genome-wide distribution using a reference genome. Genome-scale comparisons among accessions showed a clear differentiation between oriental and occidental barley populations. The results based on population structure analyses provide genome-scale properties of sub-populations grouped to oriental, occidental and marginal groups in barley. Our findings suggest that the oriental population of domesticated barley has genomic variations distinct from those in occidental groups, which might have contributed to barley's domestication.