Biomarkers of the Dementia

Recent advances in biomarker studies on dementia are summarized here. CSF Aβ40, Aβ42, total tau, and phosphorylated tau are the most sensitive biomarkers for diagnosis of Alzheimer's disease (AD) and prediction of onset of AD from mild cognitive impairment (MCI). Based on this progress, new diagnostic criteria for AD, MCI, and preclinical AD were proposed by National Institute of Aging (NIA) and Alzheimer's Association in August 2010. In these new criteria, progress in biomarker identification and amyloid imaging studies in the past 10 years have added critical information. Huge contributions of basic and clinical studies have established clinical evidence supporting these markers. Based on this progress, essential therapy for cure of AD is urgently expected

AtUBL5 regulates growth and development through pre-mRNA splicing in Arabidopsis thaliana

Ubiquitin-like proteins play important roles in the regulation of many biological processes. UBL5 (Ubiquitin-like protein 5)/Hub1 (Homologous to ubiquitin 1), a member of the ubiquitin family, acts as a ubiquitin-like modifier on a specific target, the spliceosomal protein Snu66, in yeast and human cells. The 22nd aspartic acid (Asp22) is involved in the attachment of Hub1 to the Hub1 interaction domain (HIND) of Snu66 in yeast to modulate spliceosomal activity. Hub1 differs from other modifiers which interact covalently with their targets. It modulates pre-mRNA splicing by binding to Snu66 non-covalently in both yeast and human cells. However, the molecular mechanisms of Hub1-mediated pre-mRNA splicing in plant systems remains unclear. To better understand the function of Hub1 in plants, we examined the role of this ubiquitin-like modifier in Arabidopsis thaliana, which has two Hub1 homologues. Arabidopsis UBL5/Hub1(UBL5) is highly conserved at the amino acid level, compared to eukaryotic homologues in both plants and animals. In this study, phenotypic analysis of A. thaliana with reduced UBL5 gene expression, generated by RNA interference of AtUBL5a and AtUBL5b were performed. Interestingly, knock down plants of AtUBL5 showed abnormalities in root elongation, plant development, and auxin response. AtUBL5b is highly expressed in the vascular tissue of the leaf, stem, and root tissue. Yeast two-hybrid analysis revealed that AtUBL5a and AtUBL5b interact with the putative splicing factor AtPRP38 through its C-terminal domain (AtPRP38C). Knock down of AtUBL5b resulted in a pattern of insufficient pre-mRNA splicing in several introns of AtCDC2, and in introns of IAA1, IAA4, and IAA5. Defects of pre-mRNA splicing in an AtPRP38 mutant resulted in an insufficient pre-mRNA splicing pattern in the intron of IAA1. Based on these results, we showed that AtUBL5b positively regulates plant root elongation and development through pre-mRNA splicing with AtPRP38C in A. thaliana

Designing Novel Breeding Strategies for Producing High-Oil Crops Based on a Molecular Understanding of Triacylglycerol Metabolism

Seeds are storage organ in plants and main resource of plant oils to human civilization and the demand of plant oils are increasing yearly and expansion of the production capacity is an urgent issue worldwide. Thus, it is necessary to improve oil yields per unit area and generation of crops with high-oil content is needed. Arabidopsis thaliana plays a vital role in advancement of genetics and molecular biology in plant sciences. The forward and reverse genetic approaches with Arabidopsis have provided an overview of triacylglycerol metabolism. The elucidation of the overview contributes to understanding of spatiotemporal regulation of a metabolic flow of triacylglycerol metabolism in plant cell. This understanding sheds light on bottlenecks in triacylglycerol biosynthesis and provides novel clues for increasing seed triacylglycerol content. Recent advance in metabolic engineering approaches demonstrate several evidences that triacylglycerol metabolism is coordinated with other metabolisms. Most notably, triacylglycerol biosynthesis competes with biosynthesis of starch or seed storage proteins. These studies indicate that alterations of the metabolic pathways to avoid the competitions could be a novel concept for increasing seed oil content

Intrapulmonary venous anastomosis after PV obstraction

Pulmonary venous (PV) obstruction is associated with a poor prognosis, as well as a high risk of recurrence, following surgical treatment. It can also interfere with the successful completion of Fontan circulation in patients with complex congenital heart disease. A case of a patient who had right isomerism (also known as asplenia syndrome), total anomalous pulmonary venous connection (TAPVC), and a single right ventricle is presented. Although bilateral total occlusion of the inferior PVs was identified postoperatively, the formation of the anastomosis and collateral vessels into the superior and middle PVs enabled successful completion of Fontan circulation. Anastomoses and collateral flow of the PVs were found largely in the interlobar pleura and not in the lung parenchyma

Muscle damage indicated by maximal voluntary contraction strength changes from immediately to 1 day after eccentric exercise of the knee extensors

The present study examined if the magnitude of changes in indirect muscle damage markers could be predicted by maximal voluntary isometric contraction (MVIC) torque changes from immediately to 1 day after eccentric exercise. Twenty-eight young men performed 100 maximal isokinetic (60°/s) eccentric contractions of the knee extensors. MVIC torque, potentiated doublet torque, voluntary activation (VA) during MVIC, shear modulus of rectus femoris (RF), vastus medialis and lateralis, and muscle soreness of these muscles were measured before, immediately after, and 1–3 days post-exercise. Based on the recovery rate of the MVIC torque from immediately to 1-day post-exercise, the participants were placed to a recovery group that showed an increase in the MVIC torque (11.3–79.9%, n = 15) or a no-recovery group that showed no recovery (−71.9 to 0%, n = 13). No significant difference in MVIC torque decrease immediately post-exercise was found between the recovery (−33 ± 12%) and no-recovery (−32 ± 9%) groups. At 1–3 days, changes in MVIC torque (−40 to −26% vs. −22 to −12%), potentiated doublet torque (−37 to −22% vs. −20 to −9%), and proximal RF shear modulus (29–34% vs. 8–15%) were greater (p \u3c 0.05) for the no-recovery than recovery group. No significant group differences were found for muscle soreness. The recovery rate of MVIC torque was correlated (p \u3c 0.05) with the change in MVIC torque from baseline to 2 (r = 0.624) or 3 days post-exercise (r = 0.526), or peak change in potentiated doublet torque at 1–3 days post-exercise from baseline (r = 0.691), but not correlated with the changes in other dependent variables. These results suggest that the recovery rate of MVIC torque predicts changes in neuromuscular function but not muscle soreness and stiffness following eccentric exercise of the knee extensors

A novel plant nuclear gene encoding chloroplast ribosomal protein S9 has a transit peptide related to that of rice chloroplast ribosomal protein L12

AbstractWe have cloned a novel nuclear gene for a ribosomal protein of rice and Arabidopsis that is like the bacterial ribosomal protein S9. To determine the subcellular localization of the gene product, we fused the N-terminal region and green fluorescent protein and expressed it transiently in rice seedlings. Localized fluorescence was detectable only in chloroplasts, indicating that this nuclear gene encodes chloroplast ribosomal protein S9. The N-terminal region of rice ribosomal protein S9 was found to have a high sequence similarity to the transit peptide region of the rice chloroplast ribosomal protein L12, suggesting that these transit peptides have a common lineage

Sucrose starvation induces microautophagy in plant root cells

Abstract Autophagy is an essential system for degrading and recycling cellular components for survival during starvation conditions. Under sucrose starvation, application of a papain protease inhibitor E-64d to the Arabidopsis root and tobacco BY-2 cells induced the accumulation of vesicles, labeled with a fluorescent membrane marker FM4-64. The E-64d-induced vesicle accumulation was reduced in the mutant defective in autophagy-related genes ATG2, ATG5, and ATG7, suggesting autophagy is involved in the formation of these vesicles. To clarify the formation of these vesicles in detail, we monitored time-dependent changes of tonoplast, and vesicle accumulation in sucrose-starved cells. We found that these vesicles were derived from the tonoplast and produced by microautophagic process. The tonoplast proteins were excluded from the vesicles, suggesting that the vesicles are generated from specific membrane domains. Concanamycin A treatment in GFP-ATG8a transgenic plants showed that not all FM4-64-labeled vesicles, which were derived from the tonoplast, contained the ATG8a-containing structure. These results suggest that ATG8a may not always be necessary for microautophagy.This study was supported by the National Science Centre, Poland [UMO-2016/21/P/NZ9/01089 to SG-Y (the project has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 665778) and UMO-2016/23/B/NZ1/01847 to KeY]; the Foundation for Polish Science (TEAM/2017-4/41 to KeY); KAKENHI from the Japan Society for the Promotion of Science, Japan (JP15J40032 to SG-Y, JP17K07457 to SM, and JP15H05776 to IH-N); and KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology, Japan (JP26111523 to SG-Y); as well as the institutional support provided from the National Institute for Basic Biology (NIBB), Kyoto University, and Małopolska Centre of Biotechnology, Jagiellonian University. Next-generation sequencing was supported by NIBB Collaborative Research Programs 11-711