A Novel Pinkish-White Flower Color Variant Is Caused by a New Allele of Flower Color Gene W1 in Wild Soybean (Glycine soja)

The enzyme flavonoid 3',5'-hydroxylase (F3'5'H) plays an important role in producing anthocyanin pigments in soybean. Loss of function of the W1 locus encoding F3'5'H always produces white flowers. However, few color variations have been reported in wild soybean. In the present study, we isolated a new color variant of wild soybean accession (IT261811) with pinkish-white flowers. We found that the flower's pinkish-white color is caused by w1-s3, a single recessive allele of W1. The SNP detected in the mutant caused amino acid substitution (A(304)S) in a highly conserved SRS4 domain of F3'5'H proteins. On the basis of the results of the protein variation effect analyzer (PROVEAN) tool, we suggest that this mutation may lead to hypofunctional F3'5'H activity rather than non-functional activity, which thereby results in its pinkish-white color

Low-Power Complementary Inverter Based on Graphene/Carbon-Nanotube and Graphene/MoS₂ Barristors

The recent report of a p-type graphene(Gr)/carbon-nanotube(CNT) barristor facilitates the application of graphene barristors in the fabrication of complementary logic devices. Here, a complementary inverter is presented that combines a p-type Gr/CNT barristor with a n-type Gr/MoS2 barristor, and its characteristics are reported. A sub-nW (~0.2 nW) low-power inverter is demonstrated with a moderate gain of 2.5 at an equivalent oxide thickness (EOT) of ~15 nm. Compared to inverters based on field-effect transistors, the sub-nW power consumption was achieved at a much larger EOT, which was attributed to the excellent switching characteristics of Gr barristors

Defective DNA base excision repair in brain from individuals with Alzheimer's disease and amnestic mild cognitive impairment

Oxidative stress is thought to play a role in the pathogenesis of Alzheimer's disease (AD) and increased oxidative DNA damage has been observed in brain tissue from AD patients. Base excision repair (BER) is the primary DNA repair pathway for small base modifications such as alkylation, deamination and oxidation. In this study, we have investigated alterations in the BER capacity in brains of AD patients. We employed a set of functional assays to measure BER activities in brain tissue from short post-mortem interval autopsies of 10 sporadic AD patients and 10 age-matched controls. BER activities were also measured in brain samples from 9 amnestic mild cognitive impairment (MCI) subjects. We found significant BER deficiencies in brains of AD patients due to limited DNA base damage processing by DNA glycosylases and reduced DNA synthesis capacity by DNA polymerase β. The BER impairment was not restricted to damaged brain regions and was also detected in the brains of amnestic MCI patients, where it correlated with the abundance of neurofibrillary tangles. These findings suggest that BER dysfunction is a general feature of AD brains which could occur at the earliest stages of the disease. The results support the hypothesis that defective BER may play an important role in the progression of AD

Down-regulation of ARC contributes to vulnerability of hippocampal neurons to ischemia/hypoxia

AbstractARC is a caspase recruitment domain-containing molecule that plays an important role in the regulation of apoptosis. We examined ARC expression during neuronal cell death following ischemic injury in vivo and in vitro. After exposure to transient global ischemic conditions, the expression of ARC was substantially reduced in the CA1 region of hippocampus in a time-dependent manner with concomitant increase of TUNEL-positive cells. Quantitative analysis using Western blotting exhibited that most of ARC protein disappeared in the cultured hippocampal neurons exposed to hypoxia for 12 h and showing 60% cell viability. Forced expression of ARC in the primary cultures of hippocampal neurons or B103 neuronal cells significantly reduced hypoxia-induced cell death. Further, the C-terminal P/E rich region of ARC was effective to attenuate hypoxic insults. These results suggest that down-regulation of ARC expression in hippocampal neurons may contribute to neuronal death induced by ischemia/hypoxia

Increased O-GlcNAcylation of Drp1 by amyloid-beta promotes mitochondrial fission and dysfunction in neuronal cells.

As a dynamic organelle, mitochondria continuously fuse and divide with adjacent mitochondria. Imbalance in mitochondria dynamics leads to their dysfunction, which implicated in neurodegenerative diseases. However, how mitochondria alteration and glucose defect contribute to pathogenesis of Alzheimer's disease (AD) is still largely unknown. Dynamin-related protein 1 (Drp1) is an essential regulator for mitochondria fission. Among various posttranslational modifications, O-GlcNAcylation plays a role as a sensor for nutrient and oxidative stress. In this study, we identified that Drp1 is regulated by O-GlcNAcylation in AD models. Treatment of Aβ as well as PugNAc resulted in mitochondrial fragmentation in neuronal cells. Moreover, we found that AD mice brain exhibits an upregulated Drp1 O-GlcNAcylation. However, depletion of OGT inhibited Drp1 O-GlcNAcylation in Aβ-treated cells. In addition, overexpression of O-GlcNAc defective Drp1 mutant (T585A and T586A) decreased Drp1 O-GlcNAcylation and Aβ-induced mitochondria fragmentation. Taken together, these finding suggest that Aβ regulates mitochondrial fission by increasing O-GlcNAcylation of Drp1

Long-term follow-up of Fanconi anemia: clinical manifestation and treatment outcome

PurposeThe aim of this study was to characterize Korean patients with Fanconi anemia (FA), which is a rare but very challenging genetic disease.MethodsThe medical records of 12 FA patients diagnosed at Chonnam National University Hospital from 1991 to 2012 were retrospectively reviewed.ResultsThe median age at diagnosis was 6.2 years. All patients showed evidence of marrow failure and one or more physical stigmata. Chromosome breakage tests were positive in 9 out of 11 available patients. The median follow-up duration was 69.5 months. The Kaplan-Meier (KM) survival of all patients was 83.3% at 10 years and 34.7% at 20 years, respectively. Seven patients underwent 9 stem cell transplantations (SCTs). Among them, 5 were alive by the end of the study. Ten-year KM survival after SCT was 71.4% with a median follow-up of 3.4 years. All 5 patients treated with supportive treatment alone died of infection or progression at the median age of 13.5 years, except for one with short follow-up duration. Acute leukemia developed in 2 patients at 15.4 and 18.1 years of age. Among 6 patients who are still alive, 3 had short stature and 1 developed insulin-dependent diabetes mellitus.ConclusionWe provide information on the long-term outcomes of FA patients in Korea. A nation-wide FA registry that includes information of the genotypes of Korean patients is required to further characterize ethnic differences and provide the best standard of care for FA patients

Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand on the Reduction of Joint Inflammation in Experimental Rheumatoid Arthritis

ABSTRACT This study focused on the potential therapeutic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on collagen-induced arthritis (CIA) and on the elucidation of the mechanisms involved. DBA/1J mice with established CIA were treated with various amount of recombinant soluble human TRAIL. The effects of TRAIL on the development and severity of CIA in this DBA/1J mouse model were assessed clinically and histologically, and a detailed investigation was conducted on proinflammatory cytokine and anticollagen-specific antibody levels. Cellular immunity was evaluated by investigating the proliferative responses and cytokine release profiles of splenocytes after TRAIL treatment. TRAIL treatment significantly reduced the severity and incidence of CIA, joint swelling, erythema, and edema. Histologic evaluations revealed that inflammatory cell infiltration, cartilage destruction, and bone erosion were significantly reduced in joints of TRAIL-treated mice with dose-dependent manner. TRAIL treatment also strongly decreased and/or normalized the productions of proinflammatory cytokines and of anti-collagen-specific antibodies in the sera of CIA mice. Furthermore, in vitro studies with primary splenocytes showed the cytotoxic effect of TRAIL on activated lymphocytes, with reduction of inflammatory cytokine release. These findings show that TRAIL administration is an effective anti-inflammatory treatment that prevents the development and progression of CIA in DBA/1J mice, and they suggest that TRAIL might be considered a potential treatment for human RA