Aging Is a Risk Factor for Utricular Dysfunction in Idiopathic Benign Paroxysmal Positional Vertigo

Benign paroxysmal positional vertigo (BPPV) is the most common cause of balance disorders in the elderly. Dislodgement of the otoconia in BPPV might have an association with damage to the otolith organs. The aim of this study was to investigate whether aging is a risk factor for otolith organ dysfunction in idiopathic BPPV. We retrospectively reviewed the medical records of 112 consecutive idiopathic BPPV patients who underwent cervical VEMP testing to air-conducted sound (ACS cVEMP), ocular VEMP testing to bone-conducted vibration (BCV oVEMP), and caloric testing. We performed binomial logistic regression analyses to see whether age, the side affected by BPPV or the canal affected by BPPV have an association with the presence of peripheral vestibular dysfunction in idiopathic BPPV patients. The elderly group (aged ≥65 years) had a significantly positive association with abnormalities in BCV oVEMPs (p = 0.0109), while the side affected by BPPV (p = 0.598) and the canal affected by BPPV (p = 0.576) did not. The odds ratio of the abnormal BCV oVEMPs for the elderly group compared with the non-elderly group (aged < 65 years) was 2.676 (95% confidence interval, 1.254–5.079). The elderly group had no significant association with the abnormalities in ACS cVEMPs (p = 0.0955) or caloric testing (p = 0.488). Dysfunction of the utricle, where the dislodgement of the otoconia mainly occurs, is affected by aging in idiopathic BPPV

Regulation of BMAL1 Protein Stability and Circadian Function by GSK3β-Mediated Phosphorylation

Circadian rhythms govern a large array of physiological and metabolic functions. To achieve plasticity in circadian regulation, proteins constituting the molecular clock machinery undergo various post-translational modifications (PTMs), which influence their activity and intracellular localization. The core clock protein BMAL1 undergoes several PTMs. Here we report that the Akt-GSK3beta signaling pathway regulates BMAL1 protein stability and activity.GSK3beta phosphorylates BMAL1 specifically on Ser 17 and Thr 21 and primes it for ubiquitylation. In the absence of GSK3beta-mediated phosphorylation, BMAL1 becomes stabilized and BMAL1 dependent circadian gene expression is dampened. Dopamine D2 receptor mediated signaling, known to control the Akt-GSK3beta pathway, influences BMAL1 stability and in vivo circadian gene expression in striatal neurons.These findings uncover a previously unknown mechanism of circadian clock control. The GSK3beta kinase phosphorylates BMAL1, an event that controls the stability of the protein and the amplitude of circadian oscillation. BMAL1 phosphorylation appears to be an important regulatory step in maintaining the robustness of the circadian clock

The 2nd DBCLS BioHackathon: interoperable bioinformatics Web services for integrated applications

<p>Abstract</p> <p>Background</p> <p>The interaction between biological researchers and the bioinformatics tools they use is still hampered by incomplete interoperability between such tools. To ensure interoperability initiatives are effectively deployed, end-user applications need to be aware of, and support, best practices and standards. Here, we report on an initiative in which software developers and genome biologists came together to explore and raise awareness of these issues: BioHackathon 2009.</p> <p>Results</p> <p>Developers in attendance came from diverse backgrounds, with experts in Web services, workflow tools, text mining and visualization. Genome biologists provided expertise and exemplar data from the domains of sequence and pathway analysis and glyco-informatics. One goal of the meeting was to evaluate the ability to address real world use cases in these domains using the tools that the developers represented. This resulted in i) a workflow to annotate 100,000 sequences from an invertebrate species; ii) an integrated system for analysis of the transcription factor binding sites (TFBSs) enriched based on differential gene expression data obtained from a microarray experiment; iii) a workflow to enumerate putative physical protein interactions among enzymes in a metabolic pathway using protein structure data; iv) a workflow to analyze glyco-gene-related diseases by searching for human homologs of glyco-genes in other species, such as fruit flies, and retrieving their phenotype-annotated SNPs.</p> <p>Conclusions</p> <p>Beyond deriving prototype solutions for each use-case, a second major purpose of the BioHackathon was to highlight areas of insufficiency. We discuss the issues raised by our exploration of the problem/solution space, concluding that there are still problems with the way Web services are modeled and annotated, including: i) the absence of several useful data or analysis functions in the Web service "space"; ii) the lack of documentation of methods; iii) lack of compliance with the SOAP/WSDL specification among and between various programming-language libraries; and iv) incompatibility between various bioinformatics data formats. Although it was still difficult to solve real world problems posed to the developers by the biological researchers in attendance because of these problems, we note the promise of addressing these issues within a semantic framework.</p

ムショウ シンリョウジョ ノ カンリエイヨウシ ハイチ ニ タイスル セイカツ シュウカンビョウ カンジャ カラ ノ ニーズ ニ ツイテ

【目的】これまで我々は、無床診療所医師を対象とした調査を行い、管理栄養士による栄養指導が普及していない理由として、「患者からのニーズがない」という意見が多くあることを明らかにした。一方、無床診療所の管理栄養士配置に対する患者からのニーズを調査した成績はない。そこで今回、無床診療所の管理栄養士配置に対する生活習慣病患者からのニーズを明らかにすることを目的とした。【方法】東大阪地域の市民祭りや老人クラブの活動拠点に集まった方のうち、糖尿病や高血圧症などの生活習慣病を患い、病院もしくは診療所に通院されていた245 名を対象として、聞き取り式のアンケート調査を行った。【結果】管理栄養士の名称や業務を認知していた者は75.1％（184/245 名）であった。このうち「管理栄養士を無床診療所に配置する必要がある」と回答した者は70.7％（130/184 名）であり、その理由として「食生活について身近に相談できる人がいると嬉しい」「食の専門家である管理栄養士の意見を聞きたい」という意見が多くみられた。一方、「管理栄養士を配置する必要がない」と回答した者は16.3％（30/184 名）であり、その理由として「他の医療従事者による栄養指導で十分」「自分自身で食事管理できる」という意見が多くみられた。また、「どちらでもない」と回答した者は13.0％（24/184 名）であり、その理由として「管理栄養士を置く必要性が分からない」という意見が多くみられた。【結論】今回調査した地域における無床診療所の管理栄養士配置に対する生活習慣病患者からのニーズは、約7 割と高いものであった。今後は無床診療所医師に対する普及活動や、管理栄養士の役割を理解できていない患者に対する啓発活動が必要である。In this study, we aimed to clarify the needs of patients suffering from lifestyle related diseases, to determine the perceived role and importance of a registered dietitian placement in a non bed clinic. A previous survey of non bed clinic physicians suggested that nutritional guidance provided by registered dietitians was not valued in the clinical setting; many physicians felt that “there is no need for the patient” to receive dietary advice from registered dietitians. However, no research has examined patients’ perspectives regarding the placement of a registered dietitian in a non bed clinic.Methods: We conducted a questionnaire with 245 participants suffering from lifestyle related diseases such as diabetes and hypertension. They were recruited from those who gathered in the activity base of a civic festival, and from a seniors club in the Higashi Osaka region. All of the participants had visited the hospital or clinic at one time.Results: Of the 245 participants, 184 (75.1%) had been advised by a registered dietitian. The opinion that “a registered dietitian needs to be placed in a non bed clinic” was expressed by 70.7% (130 of 184) of those surveyed. Many wanted “to hear the opinion of a registered dietitian who is an expert on food” and gave reasons such as, “I’m happy to have people who can consult closely with me about my diet.” By con- trast, 30 of the 184 participants (16.3%) responded that “there is no need to place a registered dietitian” in a non bed clinic. They believed that “the nutritional guidance offered by other health care workers was enough” or that “their own opinion” provided adequate dietary management. Finally, 24 (13.0%) participants answered “Neither,” giving “I do not know whether there is a need to place a registered dietitian” as their reason.Conclusions: It needs from lifestyle related diseases a patient to a registered dietitian placement of the non bed clinic in conclusion was this time the study area were those about 70% and higher. Based on our findings, we suggest that in future dissemination activities, including those provided by non bed clinic doctors, there is a need for awareness raising for patients who do not understand the role of registered dietitians in a non bed clinic setting

BioHackathon series in 2011 and 2012: penetration of ontology and linked data in life science domains

The application of semantic technologies to the integration of biological data and the interoperability of bioinformatics analysis and visualization tools has been the common theme of a series of annual BioHackathons hosted in Japan for the past five years. Here we provide a review of the activities and outcomes from the BioHackathons held in 2011 in Kyoto and 2012 in Toyama. In order to efficiently implement semantic technologies in the life sciences, participants formed various sub-groups and worked on the following topics: Resource Description Framework (RDF) models for specific domains, text mining of the literature, ontology development, essential metadata for biological databases, platforms to enable efficient Semantic Web technology development and interoperability, and the development of applications for Semantic Web data. In this review, we briefly introduce the themes covered by these sub-groups. The observations made, conclusions drawn, and software development projects that emerged from these activities are discussed

Winter Orographic Precipitation and ENSO in Sapporo, Japan

The effect of global climate change on the distribution of snow water is a great concern. Thus, it is important to clarify the characteristics of winter precipitation variability, including mountain precipitation, together with climate indices. In this study, regional snowfall characteristics were investigated with the daily gridded precipitation over Sapporo City (located on the Japan Sea side of Hokkaido in northern Japan), which was quantified by the APHRODITE method and by adding local precipitation observation data. We found places of showing large interannual variability that is different from that of daily precipitation variability. Applying an EOF analysis to the daily grid precipitation, we defined four local precipitation types. The occurrence of each precipitation type and associated atmospheric circulation was analyzed, and the results revealed that (except for the Super El Ni&ntilde;o winter of 1997/1998) more snow fell in the southwestern mountains and inland areas during El Ni&ntilde;o winters, and more snow fell in the northeastern plains and along the sea during La Ni&ntilde;a winters. Continued development and evaluation of the precise data that incorporate local precipitation network is needed

The Role of Non-Coding RNAs in the Neuroprotective Effects of Glutathione

The establishment of antioxidative defense systems might have been mandatory for most living beings with aerobic metabolisms, because oxygen consumption produces adverse byproducts known as reactive oxygen species (ROS). The brain is especially vulnerable to the effect of ROS, since the brain has large amounts of unsaturated fatty acids, which are a target of lipid oxidation, as well as comparably high-energy consumption compared to other organs that results in ROS release from mitochondria. Thus, dysregulation of the synthesis and/or metabolism of antioxidants—particularly glutathione (GSH), which is one of the most important antioxidants in the human body—caused oxidative stress states that resulted in critical diseases, including neurodegenerative diseases in the brain. GSH plays crucial roles not only as an antioxidant but also as an enzyme cofactor, cysteine storage form, the major redox buffer, and a neuromodulator in the central nervous system. The levels of GSH are precisely regulated by uptake systems for GSH precursors as well as GSH biosynthesis and metabolism. The rapid advance of RNA sequencing technologies has contributed to the discovery of numerous non-coding RNAs with a wide range of functions. Recent lines of evidence show that several types of non-coding RNAs, including microRNA, long non-coding RNA and circular RNA, are abundantly expressed in the brain, and their activation or inhibition could contribute to neuroprotection through the regulation of GSH synthesis and/or metabolism. Interestingly, these non-coding RNAs play key roles in gene regulation and growing evidence indicates that non-coding RNAs interact with each other and are co-regulated. In this review, we focus on how the non-coding RNAs modulate the level of GSH and modify the oxidative stress states in the brain

microRNA as a new agent for regulating neuronal glutathione synthesis and metabolism

microRNA (miRNA) is a small non-coding RNA molecule that plays a role in the post-transcriptional regulation of gene expression. Recent evidence shows that miRNAs are involved in various diseases, including neurodegenerative diseases (NDs) such as: Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, Amyotrophic lateral sclerosisand multiple system atrophy (MSA). The initiation and progression of NDs is generally considered to be induced by oxidative stress arising from an imbalance of oxidants and antioxidants. One of the most important antioxidants against oxidative stress is glutathione (GSH), which is a tripeptide composed of cysteine, glutamate and glycine. Among these precursor amino acids, cysteine is the determinant of neuronal GSH synthesis. Cysteine uptake in the neurons is mostly mediated by excitatory amino acid carrier 1 (EAAC1), a member of the sodium-dependent excitatory amino acid transporters. Interestingly, it has been reported that one miRNA, miR-96-5p, regulates the neuroprotective effect of GSH by directly regulating EAAC1 expression. Furthermore, the expressions of miR-96-5p and its target EAAC1 are specifically deregulated in the brains of patients with MSA, suggesting that deregulated miR-96-5p induces MSA via EAAC1 down-regulation. Since miR-96-5p regulation of EAAC1 expression and GSH level is indicated to be under circadian control, a greater understanding of rhythmic miRNA regulation could lead to the use of miRNA in chronotherapy for ND. In this review, we focus on the role of miRNA in the mechanism of GSH synthesis and metabolism; particularly with respect to a critical transport system of its rate-limiting substrate via EAAC1, as well as on the implications and chronotherapeutic potential of miRNA for NDs

Glutathione Depletion and MicroRNA Dysregulation in Multiple System Atrophy: A Review

Multiple system atrophy (MSA) is a rare neurodegenerative disease characterized by parkinsonism, cerebellar impairment, and autonomic failure. Although the causes of MSA onset and progression remain uncertain, its pathogenesis may involve oxidative stress via the generation of excess reactive oxygen species and/or destruction of the antioxidant system. One of the most powerful antioxidants is glutathione, which plays essential roles as an antioxidant enzyme cofactor, cysteine-storage molecule, major redox buffer, and neuromodulator, in addition to being a key antioxidant in the central nervous system. Glutathione levels are known to be reduced in neurodegenerative diseases. In addition, genes regulating redox states have been shown to be post-transcriptionally modified by microRNA (miRNA), one of the most important types of non-coding RNA. miRNAs have been reported to be dysregulated in several diseases, including MSA. In this review, we focused on the relation between glutathione deficiency, miRNA dysregulation and oxidative stress and their close relation with MSA pathology