Why is the New York Times

Can we go back to proving that drugs work in preventing, postponing, and ameliorating familial Alzheimer's disease (ad)? Ad is so devastating that there is a great public interest in the drug discovery process as evinced by the sheer number of articles in the serious popular press. The presently available, yet poorly performing, drugs have been approved despite their multiple peripheral side effects. The research on disease-modifying agents for the treatment of ad is largely focused on reducing amyloid plaques. However, it is now clear that companies and researchers alike are losing hope in finding an efficacious therapy rapidly that works in ad patients who are already cognitively impaired, and that people who staked their scientific and professional career on finding a cure for ad based on the amyloid hypothesis are shaken by the series of failed clinical trials within a short period of time. It is emerging that we may start to treat ad far too late to be able to make any significant slowing of the disease or postponing the onset of the symptoms of the disease. The history of drug development for other diseases should encourage us to focus on patients in whom we can identify the genetic markers associated with familial ad. Then when we have an efficacious and very safe drug, we will be able to establish its efficacy on, most importantly, cognition, but also at the level of plaques. This will provide the pharmacological evidence needed to show that it is worth fighting amyloidosis because it saves memory. We have a successful and lucrative history of preventive medicine on a large scale, all we need now is the foresight and will to switch strategy and no longer look for a magic bullet to fix ad, but to discover drugs that will delay and prevent the onset of ad, drugs that may be safely taken by symptom-free patients who are vulnerable and susceptible to ad. The initial population that might be preventatively treated against ad would indeed be those with genetic predisposition. While prevention trials are long and expensive as emphasized by the industry, the market for a safe and effective drug would be extended to the large number of patients susceptible to sporadic ad. Since the highest risk factor for sporadic ad is age, this would be an extraordinarily large market

Budapest, Bratislava and Vienna conference facilities, comparative analysis

The aim of this study is to give an overview of conference facilities in three capital cities in the Central European area, along the Danube, analyse and compare their possibilities and venues. The utilized data within the study was collected from different sources, like websites of the Hungarian, Slovakian and Austrian Convention Bureaus, books dealing with convention and event management and statistics, ICCA publications. Budapest is highly ranked between cities transacting conferences for years. There are 146 different conference facilities with a total capacity for 114.000 participants. The 7 conference centres and all four- and five-star hotels suit all requirements of the different professional organizations. Budapest hosted many megaconferences; out of these the ASTA yearly session and the vein-surgery conference can be excelled. From the conference capacity of Budapest only one conference facility is missing which could host more than 5.000 participants. After analysing the conference capacities of the three Danube-band capitals – Budapest, Vienna, Bratislava, – it can be seen what kind of similarities and differences are characterizing the cities. At the end of this study the writer makes recommendations for the place of the mega-conference centre, the development of a modern and up-to-date conference database, as well as for the cooperation of the three capitals in connection with managing mega-conferences

UDMURT+LANGUAGE+IN+VIRTUAL+SPACE

This paper focuses on the presence of the Udmurt language in the virtual space, especially on the popular Russian social network site called Vkontakte. Unlike other endangered languages, the Udmurt language has a lot of materials online, and is one of the most active minority languages on SNS (Social Network Sites) in Russia [1]. There are factors that might add to the popularity of the Udmurt language, for example there is a famous music group, called «The Grannies of Burenovo», who participated in the finals of the Eurovision Song Contest 2012, and their success improved the Udmurt language’s prestige [2]. Bilingual studies show there is correlation between the choice of language and the topic of the message [3]. The Udmurt language is usually considered to be mostly a family language, like many of the minority languages of Russia. The tendency of strong russification leaves no or very few other domains for minority language use: the language of instruction in schools, the language of bureaucracy, the language of legislation, even the language of everyday life is usually Russian [4]. The study shows no correlation between the topic and the choice of language, even the source of the information is irrelevant from this perspective. The research also shows that judging by the number of posts on Vkontakte and the activeness of the community, the Udmurt language is not endangered, at least not digitally. However, it is unclear how Udmurt users are using the language outside their online communities

Fish gonad development: Search for differentially expressed genes in zebrafish

Ph.DDOCTOR OF PHILOSOPH

Transcriptomic analysis reveal novel genes with sexually dimorphic expression in the zebrafish gonad and brain

Our knowledge on zebrafish reproduction is very limited. We generated a gonad-derived cDNA microarray from zebrafish and used it to analyze large-scale gene expression profiles in adult gonads and other organs. We have identified 116638 gonad-derived zebrafish expressed sequence tags (ESTs), 21% of which were isolated in our lab. Following in silico normalization, we constructed a gonad-derived microarray comprising 6370 unique, full-length cDNAs from differentiating and adult gonads. Labeled targets from adult gonad, brain, kidney and ‘rest-of-body’ from both sexes were hybridized onto the microarray. Our analyses revealed 1366, 881 and 656 differentially expressed transcripts (34.7% novel) that showed highest expression in ovary, testis and both gonads respectively. Hierarchical clustering showed correlation of the two gonadal transcriptomes and their similarities to those of the brains. In addition, we have identified 276 genes showing sexually dimorphic expression both between the brains and between the gonads. By in situ hybridization, we showed that the gonadal transcripts with the strongest array signal intensities were germline-expressed. We found that five members of the GTP-binding septin gene family, from which only one member (septin 4) has previously been implicated in reproduction in mice, were all strongly expressed in the gonads. We have generated a gonad-derived zebrafish cDNA microarray and demonstrated its usefulness in identifying genes with sexually dimorphic co-expression in both the gonads and the brains. We have also provided the first evidence of large-scale differential gene expression between female and male brains of a teleost. Our microarray would be useful for studying gonad development, differentiation and function not only in zebrafish but also in related teleosts via cross-species hybridizations. Since several genes have been shown to play similar roles in gonadogenesis in zebrafish and other vertebrates, our array may even provide information on genetic disorders affecting gonadal phenotypes and fertility in mammals.Fellowships from Temasek Life Science Laboratory Internal research grants from Temasek Life Science LaboratoryWeb of Scienc

Polygenic Sex Determination System in Zebrafish

Contains fulltext : 94011.pdf (publisher's version ) (Open Access

Gonad differentiation in zebrafish is regulated by the canonical Wnt signalling pathway

Zebrafish males undergo a ‘‘juvenile ovary-to-testis’’ gonadal transformation process. Several genes, including nuclear receptor subfamily 5, group A (nr5a) and anti-Mu¨ llerian hormone (amh), and pathways such as Tp53-mediated germ-cell apoptosis have been implicated in zebrafish testis formation. However, our knowledge of the regulation of this complex process is incomplete, and much remains to be investigated about the molecular pathways and network of genes that control it. Using a microarray-based analysis of transforming zebrafish male gonads, we demonstrated that their transcriptomes undergo transition from an ovary-like pattern to an ovotestis to a testislike profile. Microarray results also validated the previous histological and immunohistochemical observation that there is high variation in the duration and extent of commitment to the juvenile ovary phase among individuals. Interestingly, global gene expression profiling of diverging zebrafish juvenile ovaries and transforming ovotestes revealed that some members of the canonical Wnt/beta-catenin signaling pathway were differentially expressed between these two phases. To investigate whether Wnt/beta-catenin signaling plays a role in zebrafish gonad differentiation, we used the Tg (hsp70l:dkk1b-GFP)w32 line to inhibit Wnt/beta-catenin signaling during gonad differentiation. Activation of dkk1b-GFP expression by heat shock resulted in an increased proportion of males and corresponding decrease in gonadal aromatase gene (cyp19a1a) expression. The Wnt target gene, lymphocyte enhancer binding factor 1 (lef1), was also down-regulated in the process. Together, these results provide the first functional evidence that, similarly to mammals, Wnt/beta-catenin signaling is a ‘‘pro-female’’ pathway that regulates gonad differentiation in zebrafish.Web of Scienc