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Citral is a mixture of neral and geranial, which are of great interest to the fragrance industry due to its lemon-scented aroma. A newly characterized nerol dehydrogenase of Persicaria minor (PmNeDH) from our recent findings has shown a capacity to convert citral from nerol. Differential gene expression analysis revealed that the expression level of PmNeDH was highly upregulated during early treatment of several stress-related phytohormones i.e. methyl jasmonate (MeJA), salicylic acid (SA) and abscisic acid (ABA). SA and ABA were shown to have a prolonged effect on PmNeDH expression level until second day of treatment. The findings were in agreement with the cis-regulatory elements predicted from the gene promoter. The phylogenetic relationship of PmNeDH with its homologs from the medium-chain dehydrogenases/reductases (MDR) superfamily was also mentioned. In this study, we proposed a possible biological function of PmNeDH gene in P. minor, which might play significant roles in plant defence mechanism.

Singapore is a rapidly ageing society, underpinned by national policies to promote successful and active ageing. Whilst older worker participation in the workforce is encouraged, policymakers are challenged to ensure that work competency is not compromised with any normal age- and/or health-related changes. This paper will briefly outline how policymakers responded to the needs of two subgroups of older workers aged 70 years and above (taxi drivers; crane operators) who desire to continue working in the last two decades. Whilst a mandatory retirement age policy exists for older taxi drivers in Singapore, there is none for older crane operators. Despite this, stricter relicensing protocols were introduced for both types of workers, with active collaboration involving additional occupational therapy services for functional work competency assessments to complement the routine medical fitness screening. Comparisons will be made of these two relicensing frameworks, including the mention of any relevant studies to align with the call of evidence-based practices. In mid-2020, the relicensing policy for older taxi drivers was revised based on findings of a retrospective national database study. Currently, a 4-year national database study on older crane operators aged 70 years and above is being undertaken with preliminary findings to be reported.

Mesial temporal lobe epilepsy, a well-characterized epilepsy syndrome, is most commonly accompanied by the pathological feature of hippocampal sclerosis. Patients with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) typically present in childhood to early adolescence. We describe a cohort of patients who presented with their first epileptic seizure in late adulthood with atypical features. We characterized five patients with late-onset MTLE-HS by describing their demographics, electroclinical features, imaging, autoantibody status, and response to antiseizure medication (ASM) therapy. All five patients had their first seizure after the age of 50 with no history of initial precipitating incidents. None of our patients had positive serum or CSF autoantibodies and they have all remained seizure-free for a minimum of two years on ASMs alone. Two patients had motor vehicle crashes associated with seizures whilst three patients experienced seizures in sleep. A milder form of MTLE, previously described as benign TLE, does exist in routine clinical practice. These patients respond well to ASM therapy, but potentially harmful consequences such as motor vehicle crashes can occur in the untreated.

The dataset presented in this article describes microarray experiment of Auxin-binding protein 57, Abp57-overexpressing transgenic rice. The gene expression profiles were generated using Affymetrix GeneChip® Rice (Cn) Gene 1.0 ST Arrays. Total RNA from seedlings tissue of transgenic rice and wildtype, which serve as control were used as starting materials for microarray experiment. Detailed experimental methods and data analysis were described here. The raw and normalized microarray data were deposited into Gene Expression Omnibus (GEO) under accession number GSE99055.

Agarwood is a resinous part of the non-timber Aquilaria tree, which is a highly valuable product for medicine and fragrance purposes. To protect the endangered Aquilaria species, mass plantation of Aquilaria trees has become a sustainable way in Asian countries to obtain the highly valuable agarwood. As only physiologically triggered Aquilaria tree can produce agarwood, effective induction methods are long sought in the agarwood industry. In this paper, we attempt to provide an overview for the past efforts toward the understanding of agarwood formation, the evolvement of induction methods and their further development prospects by integrating it with high-throughput omics approaches.

Antisense oligonucleotides (ASOs) hold promise for gene-specific knockdown in diseases that involve RNA or protein gain-offunction effects. In the hereditary degenerative disease myotonic dystrophy type 1 (DM1), transcripts from the [...]

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by a deficiency of survival motor neuron (SMN) due to mutations in the SMN1 gene. In this study, an adeno-associated virus (AAV) vector expressing human SMN (AAV8-hSMN) was injected at birth into the CNS of mice modeling SMA. Western blot analysis showed that these injections resulted in widespread expression of SMN throughout the spinal cord, and this translated into robust improvement in skeletal muscle physiology, including increased myofiber size and improved neuromuscular junction architecture. Treated mice also displayed substantial improvements on behavioral tests of muscle strength, coordination, and locomotion, indicating that the neuromuscular junction was functional. Treatment with AAV8-hSMN increased the median life span of mice with SMA-like disease to 50 days compared with 15 days for untreated controls. Moreover, injecting mice with SMA-like disease with a human SMN-expressing self-complementary AAV vector--a vector that leads to earlier onset of gene expression compared with standard AAV vectors--led to improved efficacy of gene therapy, including a substantial extension in median survival to 157 days. These data indicate that CNS-directed, AAV-mediated SMN augmentation is highly efficacious in addressing both neuronal and muscular pathologies in a severe mouse model of SMA., Introduction Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by mutations in the survival motor neuron 1 (SMN1) gene and loss of encoded SMN protein (1). The [...]

Classic galactosemia (CG) is a rare disorder of autosomal recessive inheritance. It is caused predominantly by point mutations as well as deletions in the gene encoding the enzyme galactose‐1‐phosphate uridyltransferase (GALT). The majority of the more than 350 mutations identified in the GALT gene cause a significant reduction in GALT enzyme activity resulting in the toxic buildup of galactose metabolites that in turn is associated with cellular stress and injury. Consequently, developing a therapeutic strategy that reverses both the oxidative and ER stress in CG cells may be helpful in combating this disease. Recombinant adeno‐associated virus (AAV)‐mediated gene therapy to restore GALT activity offers the potential to address the unmet medical needs of galactosemia patients. Here, utilizing fibroblasts derived from CG patients we demonstrated that AAV‐mediated augmentation of GALT protein and activity resulted in the prevention of ER and oxidative stress. We also demonstrate that these CG patient fibroblasts exhibit reduced CD109 and TGFβRII protein levels and that these effectors of cellular homeostasis could be restored following AAV‐mediated expression of GALT. Finally, we show initial in vivo proof‐of‐concept restoration of galactose metabolism in a GALT knockout mouse model following treatment with AAV‐GALT. [ABSTRACT FROM AUTHOR]

Niemann-Pick type A disease is a lysosomal storage disorder caused by a deficiency in acid sphingomyelinase (ASM) activity. Previously we showed that storage pathology in the ASM knockout (ASMKO) mouse brain can be corrected by adeno-associated virus serotype 2 (AAV2)-mediated gene transfer. The present experiment compared the relative therapeutic efficacy of different recombinant AAV serotype vectors (1, 2, 5, 7, and 8) using histological, biochemical, and behavioral endpoints. In addition, we evaluated the use of the deep cerebellar nuclei (DCN) as a site for injection to facilitate global distribution of the viral vector and enzyme. Seven-week-old ASM knockout mice were injected within the DCN with different AAV serotype vectors encoding human ASM (hASM) and then killed at either 14 or 20 weeks of age. Results showed that AAV1 was superior to serotypes 2, 5, 7, and 8 in its relative ability to express hASM, alleviate storage accumulation, and correct behavioral deficits. Expression of hASM was found not only within the DCN, but also throughout the cerebellum, brainstem, midbrain, and spinal cord. This finding demonstrates that targeting the DCN is an effective approach for achieving widespread enzyme distribution throughout the CNS. Our results support the continued development of AAV based vectors for gene therapy of the CNS manifestations in Niemann-Pick type A disease. axonal transport | deep cerebellar nuclei | gene therapy | lysosomal storage diseases | adeno-associated virus

Preconditioning in cultured cardiomyocytes elevates the expression of several protective genes including Glut-4 and heat shock protein (HSP)70. Hypoxiainducible factor-1 (HIF-1) is known to mediate the transcriptional activation of hypoxia-responsive genes. In this study, we examined the effect of adenovirus-mediated expression of constitutively stable hybrid forms of HIF-let on cardiomyocyte viability and gene expression. Cultured neonatal rat cardiomyocytes were subjected to simulated ischemia-reperfusion with or without preinfection with recombinant adenoviral vectors [Ad2/H1F-1[alpha]/herpes simplex virus protein VP 16 and Ad2/HIF-1[alpha]/nuclear factor-[kappa]B (NF-[kappa]B)]. Cellular viability and mRNA levels of several cardioprotective genes were measured. We demonstrated that infection with Ad2/HIF-1[alpha]VP16 and Ad2/ HIF-1[alpha]/NF-[kappa]B mimicked the upregulation of the mRNA levels of vascular endothelial growth factor (VEGF), Glut-1, Glut-4, HSP70, and inducible NO synthase (iNOS) and the protection of cultured neonatal rat cardiomyocytes by late-phase preconditioning against simulated ischemia-reperfusion. The same dose of a control viral vector expressing no transgene had no effect. Preconditioning also elevated HIF-1[alpha] protein levels. These results suggest that adenovirus-mediated expression of HIF-1[alpha]/VP16 or HIF-1[alpha]/NF-[kappa]B, a constitutively stable hybrid transcriptional factor, protected cultured neonatal cardiomyocytes against simulated ischemia-reperfusion injury by inducing multiple protective genes. ischemic preconditioning: myocardial protection

Expression of angiopoietins in renal epithelial and clear cell carcinoma cells: regulation by hypoxia and participation in angiogenesis. Am J Physiol Renal Physiol 287: F649-F657, 2004. First published June 15, 2004; 10.1152/ajprenal.00028.2004.--The hereditary von Hippel-Lindau (VHL) syndrome predisposes sufferers to highly vascularized tumors such as renal clear cell carcinoma (RCC) and central nervous system hemangioblastoma. In RCC4 and RCC786-0 VH[L.sup.-] ceils with VHL mutations, the protein of hypoxia-inducible factor-1[alpha] (HIF-1[alpha] is constitutively stabilized and the mRNA levels of HIF target genes, including vascular endothelial growth factor (VEGF), are elevated. However, the expression of angiopoietins in these cells and their involvement in angiogenesis are not well known. In this study, we compared the mRNA levels of angiopoietins in human kidney proximal tubule epithelial (RPTE) and RCC4 and RCC786-0 VH[L.sup.-] cells. In RPTE cells, angiopoietin-4 (Ang-4) expression was selectively induced by hypoxia or by expression of a hybrid form of HIF-1[alpha]. Under normoxic conditions, the mRNA levels of Ang-4 were higher in RCC4 and RCC786-0 VH[L.sup.+] than RPTE cells. Angiopoietin-1 expression was detectable in RCC4 and RCC786-0 VH[L.sup.-] cells but not RPTE cells. In RCC786-0 VH[L.sup.+] cells, which were stably transfected with a wild-type copy of VHL, the mRNA levels of VEGF and Ang-4 were suppressed and the hypoxic response was restored. We also demonstrated that stimulation of endothelial tube formation by conditioned medium harvested from RCC4 cells was inhibited by a soluble Tie-2 receptor. These results suggest that the angiopoietin/Tie-2 system may participate in the angiogenic response to hypoxia in renal tissues and in tumor angiogenesis in renal carcinoma. hypoxia-inducible factor-[alpha] ; von Hippel-Lindau; vascular endothelial growth factor; Tie-2 receptor