Fibroblast growth factor (Fgf) signaling plays multiple inductive roles during development of vertebrates (Itoh 2007). Some Fgfs, such as Fgf8, are locally secreted and signal over a long range to provide positional information in the target tissue (Scholpp and Brand 2004). Fgf ligands signal in a receptor-dependent manner via tyrosine kinase receptors, four of which have been so far identified. Fgf8 signaling was shown to depend both on receptor activation as well as endocytosis. The specificity of Fgf ligands and receptors as well as the function of receptors in the control of the Fgf signaling range have been, however, largely unclear. In this study, we show that the putative Fgf8 receptor Fgfr1 is duplicated in zebrafish and that it acts redundantly in the formation of the posterior mesoderm. Also, in overexpression studies we confirm the notion that receptor endocytosis influences Fgf8 signaling range. Through TILLING mutant recovery and morpholino knockdown studies we also show that Fgfr2 is required for growth and skeletal development in zebrafish, whereas Fgfr4 is required for pectoral fin specification and growth.

Recent research demonstrated that besides a role in sex determination and male fertility, the Y chromosome is involved in additional functions including prostate cancer, sex-specific effects on the brain and behaviour, graft-versus-host disease, nociception, aggression and autoimmune diseases. The results presented in this thesis include an analysis of sex-biased genes encoded on the X and Y chromosomes of rodents. Expression data from six different somatic tissues was analyzed and we found that the X chromosome is enriched in female biased genes and depleted of male biased ones. The second study described copy number variation (CNV) patterns in a world-wide collection of human Y chromosome samples. Contrary to expectations, duplications and not deletions were the most frequent variations. We also discovered novel CNV patterns of which some were significantly overrepresented in specific haplogroups. A substantial part of the thesis focuses on analysis of spatial expression of two Y-encoded brain-specific genes, namely PCDH11Y and NLGN4Y. The perhaps most surprising discovery was the observation that X and Y transcripts of both gene pairs are mostly expressed in different cells in human spinal cord and medulla oblongata. Also, we detected spatial expression differences for the PCDH11X gene in spinal cord. The main focus of the spatial investigations was to uncover genetically coded sexual differences in expression during early development of human central nervous system (CNS). Also, investigations of the expression profiles for 13 X and Y homolog gene pairs in human CNS, adult brain, testes and still-born chimpanzee brain samples were included. Contrary to previous studies, we found only three X-encoded genes from the 13 X/Y homologous gene pairs studied that exhibit female-bias. We also describe six novel non-coding RNAs encoded in the human MSY, some of which are polyadenylated and with conserved expression in chimpanzee brain. The description of dimorphic cellular expression patterns of X- and Y-linked genes should boost the interest in the human specific gene PCDH11Y, and draw attention to other Y-encoded genes expressed in the brain during development. This may help to elucidate the role of the Y chromosome in sex differences during early CNS development in humans. / <p>chinese, finnish, norwegian, schizophrenia, bipolar, bipolar disorder, msy, male specific region Y, PAR1, PAR2, pseudoautosomal, male-biased, female-biased, male biased, female biased, ashkenazi population, structure, variants, YHRD, Elena Jazin, Björn Reinius, Per Ahlberg, brain, hjärna, CNS, central nervous system, IR2, inverted repeat 2, isodicentric, genetics, genetik, padlock, rolling circle, amplification, PCR, sY1191, sY1291, STS, DDX3Y, DAZ, AZFa, AZFb, AZFc, AZF, Repping, haplogroup J, rearrangements, DE-M145, I-M170, E-M96, Q-M242, R-M207, O-M175, G-M201, D-M174, C-M130, NO-M214, N-M231, poland</p>

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Title from first page of PDF document. Includes bibliographical references (p. 20-23).

This report is about double documentation in health care. In today's healthcare, there is a problem with the staff entering the same information in several different systems. It creates more work and takes precious time for an already strained business. The healthcare professionals are feeling more stressed with the increasing workload. Double documentation is today a work problem for healthcare professionals. The purpose of the report is to make a current report on how and why duplicate documentation occurs in the health care sector in the region of Gävleborg. A descriptive case study was conducted focusing on how healthcare professionals insert patient data into multiple information systems. The case study has been conducted in cooperation with Tieto, a software company in Luleå. The study resulted in several different findings. A major reason why double documentation exist depends on the lack integration between the information systems used in today´s healthcare. It is also caused by the fragmented state Swedish healthcare is currently in. Double documentation occurs mostly in cases when healthcare personnel need register patient information in. Healthcare personnel is liable to register the same information in the information system handling medical records as well as the information system used hospital department. / Nej

Essential genes are those whose presence is imperative for an organism's survival, whereas the functions of non-essential genes may be useful but not critical. Abnormal functionality of essential genes may lead to defects or death at an early stage of life. Knowledge of essential genes is therefore key to understanding development, maintenance of major cellular processes and tissue-specific functions that are crucial for life. Existing experimental techniques for identifying essential genes are accurate, but most of them are time consuming and expensive. Predicting essential genes using computational methods, therefore, would be of great value as they circumvent experimental constraints. Our research is based on the hypothesis that mammalian essential (lethal) and non-essential (viable) genes are distinguishable by various properties. We examined a wide range of features of Mus musculus genes, including sequence, protein-protein interactions, gene expression and function, and found 75 features that were statistically discriminative between lethal and viable genes. These features were used as inputs to create a novel machine learning classifier, allowing the prediction of a mouse gene as lethal or viable with the cross-validation and blind test accuracies of ∼91% and ∼93%, respectively. The prediction results are promising, indicating that our classifier is an effective mammalian essential gene prediction method. We further developed the mouse gene essentiality study by analysing the association between essentiality and gene duplication. Mouse genes were labelled as singletons or duplicates, and their expression patterns over 13 developmental stages were examined. We found that lethal genes originating from duplicates are considerably lower in proportion than singletons. At all developmental stages a significantly higher proportion of singletons and lethal genes are expressed than duplicates and viable genes. Lethal genes were also found to be more ancient than viable genes. In addition, we observed that duplicate pairs with similar patterns of developmental co-expression are more likely to be viable; lethal gene duplicate pairs do not have such a trend. Overall, these results suggest that duplicate genes in mouse are less likely to be essential than singletons. Finally, we investigated the evolutionary age of mouse genes across development to see if the morphological hourglass pattern exists in the mouse. We found that in mouse embryos, genes expressed in early and late stages are evolutionarily younger than those expressed in mid-embryogenesis, thus yielding an hourglass pattern. However, the oldest genes are not expressed at the phylotypic stage stated in prior studies, but instead at an earlier time point - the egg cylinder stage. These results question the application of the hourglass model to mouse development.

Submitted by Izabel Franco (izabel-franco@ufscar.br) on 2016-09-12T20:08:21Z No. of bitstreams: 1 TeseSSD.pdf: 4196266 bytes, checksum: 852bdafbbad865e0ccb454503e54e11b (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-09-13T19:55:41Z (GMT) No. of bitstreams: 1 TeseSSD.pdf: 4196266 bytes, checksum: 852bdafbbad865e0ccb454503e54e11b (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-09-13T19:55:50Z (GMT) No. of bitstreams: 1 TeseSSD.pdf: 4196266 bytes, checksum: 852bdafbbad865e0ccb454503e54e11b (MD5) / Made available in DSpace on 2016-09-13T19:55:59Z (GMT). No. of bitstreams: 1 TeseSSD.pdf: 4196266 bytes, checksum: 852bdafbbad865e0ccb454503e54e11b (MD5) Previous issue date: 2015-06-12 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Roadkill and isolation of populations due to the barrier effect can be considered the main direct impacts of roads on wildlife. Mammals by behavioral, size and charisma features are one of the groups of vertebrates that require mitigation for mortality, as they are also among the most seriously injured on roads. An important approach to effectively mitigate roadkill on highways is to locate the points where roadkill are concentrated. The objective of this study was to evaluate the variation in mortality of mammals due to the duplication of the BR 101 highway south. In addition to the K Ripley aggregation analysis, were generated habitat suitability models (MAH) to identify favorable locations roadkill species, using the model functional groups for prediction of highway stretches with more chances to roadkill. It was recorded 21 taxa of mammals get hit, being the most abundant gender Didelphis (n = 721), followed by Cerdocyon thous (n = 108). The abundance of carcasses decreases between before and after the duplication (F 18.04 p = <0.001). Hotspots were not overlapped between the periods analyzed, indicating that some explanatory factor has changed over the work. Observing the variables that contributed most to the models for each functional group, we noted that there were differences in the most influential variables for each functional group in different periods. Of the nine generated models, we note that six variables contributed more than 20% in different models. There were differences between the periods before, during and after the duplication of the variables that contributed most or contribution value in functional groups. These differences may reflect the change in the distribution of roadkill among highway doubling periods. Both approaches demonstrated that there have been changes in the magnitude and distribution of roadkill in the period prior to the period after duplication. So a highway with two paviments differ from a highway with four paviments about how the mammals react in terms of movement and relationship to landscape. / A morte por atropelamentos e o isolamento de populações devido ao efeito de barreira podem ser considerados os principais impactos diretos das rodovias sobre a fauna silvestre. Os mamíferos pelas características comportamentais, tamanho e carisma são um dos grupos de vertebrados que necessitam mitigações para a mortalidade, visto que também estão entre os que mais morrem em rodovias. Uma abordagem importante para mitigar efetivamente os atropelamentos em rodovias é localizar os pontos onde os atropelamentos estão concentrados. O objetivo deste trabalho foi avaliar a variação da mortalidade de mamíferos em função da duplicação da rodovia BR 101 sul. Além da análise de agregação de K de Ripley, foram gerados modelos de adequabilidade de habitat (MAH) para identificar locais favoráveis a atropelamentos de espécies, usando no modelo grupos funcionais para a predição de trechos da rodovia com mais chances de atropelamento. Registrou-se 21 taxóns de mamíferos atropelados, sendo o mais abundante o gênero Didelphis (n=721), seguido de Cerdocyon thous (n=108). A abundância de carcaças diminui entre o antes e o depois da duplicação (F=18,04; p<0,001). Os hotspots não foram sobrepostos entre os períodos analisados, indicando que algum fator explicativo mudou ao longo da obra. Observando as variáveis que mais contribuíram com os modelos para cada grupo funcional, notamos que houve diferença nas variáveis mais influentes para cada grupo funcional nos diferentes períodos. Dos nove modelos gerados, notamos que seis variáveis contribuíram em mais de 20% em diferentes modelos. Houve diferença entre os períodos de antes, durante e depois da duplicação das variáveis que mais contribuíram ou do valor de contribuição nos grupos funcionais. Estas diferenças podem ser reflexo da mudança na distribuição dos atropelamentos entre os períodos da duplicação da rodovia. As duas abordagens demonstraram que houveram mudanças na magnitude e distribuição dos atropelamentos no período antes em relação ao período após a duplicação. Portanto uma rodovia com dois pavimentos funciona diferente de uma rodovia de quatro pavimentos em relação a como a mastofauna reage em termos de movimentação e relação com paisagem.

Este trabalho tem como objetivo observar as estratégias de relativização utilizadas por estudantes brasileiros adultos de espanhol como língua estrangeira e uma eventual influência da língua 1 (L1) nas preferências constatadas nessa produção. Para tanto, fizemos, primeiramente, um estudo comparado entre as estratégias de relativização presentes no português brasileiro (PB) e no espanhol (E). Nesse estudo, observamos a presença e a ausência, junto às relativas do tipo padrão simples (sem preposição) e às relativas do tipo padrão piedpiping (com preposição), das chamadas relativas cortadoras, (TARALLO, 1993), típicas do português brasileiro (PB), e das relativas com pronomes cópia, estruturas conhecidas como de despronominalización de relativos (LOPE BLANCH, 1983) ou como de (re)duplicación de relativos (BRUCART, 1999). As duas últimas estratégias de relativização, ainda que apareçam em ambas as línguas, de acordo com diversos estudos, ocorrem com diferente frequência e aceitação na língua culta dos dois idiomas, e, portanto, têm especial importância em nossa pesquisa. Para observar as consequências que a influência dessas construções relativas poderia ocasionar na produção não nativa de estudantes brasileiros aprendizes de espanhol como língua estrangeira (ELE), analisamos uma amostra de aceitabilidade, outra de produção oral e outra de produção escrita, e verificamos que a influência da L1 ocorre em algumas circunstâncias e que essa influência se deve ao fato de que as relativas cortadoras e as despronominalizadas ou (re)duplicadas fazem parte de um conjunto de características que corroboram a existência de uma inversa assimetria entre o português do Brasil e o espanhol no que se refere à presença e/ou à ausência das formas pronominais átonas ou tônicas para a expressão dos argumentos do verbo, tal como constatou González (1994). / It is aim in this paper to observe the strategies of relativization used by Brazilian adults who study Spanish as a foreign language and a possible influence of the first language in the preferences shown in their production. For this, firstly, we did a compared study between the strategies of relativization in Brazilian Portuguese (PB) and in Spanish (E). In this study, we observe the presence and the absence, in the simple standard relative (without preposition) and the piedpiping standard relative (with preposition), relative clauses known as cortadoras relative or pp-chopping, (TARALLO, 1993), typical of Brazilian Portuguese (PB) relatives, and the relative with redundance inside relative clauses or with resumptive pronouns, structures known as despronominalizadoras (LOPE BLANCH, 1983) or as (re)duplication of relative (BRUCART, 1999). According to several studies, although the two last strategies of relativization are present in both languages, they appear with different frequency and approval in the standard language, and, therefore, have a particular importance in our investigation. To observe the consequences that the influence of these relative structures could have in the non native production of Brazilian students of ELE (Spanish as foreign language), we have analyzed a sample of acceptability, a sample of oral production and a sample of written production, and verify that the influence of the first language happens under some circumstances and that it happens because of the cortadoras relative and the despronominalizadas or (re)duplicate are part of a group of characteristics that reinforce the existence of a reverse asymmetry between Brazilian Portuguese and Spanish regarding the presence and/or the absence of the atonic or tonic pronominales forms for the expression of the verb arguments, as it was found by González (1994).

A infertilidade é um problema de saúde pública com um significativo impacto social, econômico e psicológico. Em todo o mundo, a incidência da infertilidade entre a população geral é estimada em 10-15%. Cerca de 50% da infertilidade dos casais são de origem masculina. Em mais da metade dos homens inférteis, a causa da infertilidade é desconhecida (idiopática). Etiologicamente, a infertilidade masculina apresenta causas genéticas e não genéticas. Dentre as causas genéticas mais conhecidas temos mutação do receptor de andrógenos, mutação do gene regulador da condutibilidade transmembrana da fibrose cística (CFTR), anomalias cromossômicas clássicas, anomalias meióticas, microdeleções do cromossomo Y, etc. As anomalias cromossômicas são encontradas com muito mais frequência em homens inférteis, com uma incidência de 4-16% em relação à incidência de 0,4% na população fértil. Estudos mostram que as CNVs também podem estar relacionadas com a infertilidade masculina, especificamente com a falha na espermatogênese. CNVs encontradas tanto no cromossomo Y quanto nos cromossomos autossômicos também foram associadas a possíveis falhas na espermatogênese. Um outro fator que também pode estar envolvido com a infertilidade masculina é a expressão desregulada dos miRNAs. O presente trabalho teve como objetivo promover a análise em larga escala da distribuição de CNVs e do perfil transcricional dos miRNAs em amostras de biopsias testiculares de paciente com azoospermia. Para o estudo das CNVs nós utilizamos a metodologia do CytoScan HDTM da Affymetrix. O perfil transcricional de miRNAs nos indivíduos estudados foi avaliado por meio da tecnologia de microarranjos também da plataforma Affymetrix. Para estas analises montamos dois grupos de estudo (Parada de Maturação (MA) de Células Germinativas e Síndrome de Células Sertoli Only (SCOS)) e um grupo controle (azoospermia obstrutiva e espermatogênese normal). Através das análises das CNVs nós encontramos 94 CNVs nos cromossomos autossômicos e sexuais, 35 (37%) CNVs foram classificadas como benignas, 24 (23%) como potencialmente benignas, sete CNVs (7,4%) como patogênicas e sete foram classificadas como potencialmente patogênica. Todas as CNVs classificadas como patogênica estão presentes no cromossomo Y, cinco CNVs são do tipo duplicação e duas do tipo deleção. A CNV do tipo duplicação foi encontrada no paciente MA e a CNV do tipo deleção foi encontrada no paciente SCOS. As CNVs se sobrepõem e quando analisadas em conjunto (formando uma única CNV de cada condição) elas apresentam um tamanho parecido. Estas CNVs apresentam genes envolvidos na espermatogênese. As CNVs classificadas como potencialmente patogênicas estavam presentes nos cromossomos autossômicos e cromossomo X. Nestas CNVs estavam presentes genes que foram associados com a falha na espermatogênese. A análise da expressão dos miRNAs revelou um perfil transicional muito mais alterado nos pacientes com SCOS. As duas condições apresentaram miRNAs exclusivos, mas também compartilharam: 30 miRNAs. Nós identificamos duas famílias de miRNAs (miR449 e miR34) diferencialmente expressos nas duas condições e que apresentam expressão preferencial no testículo. Nossos resultados mostram que alterações no número de copias (CNVs) no cromossomo Y levam a infertilidade masculina e CNVs nos cromossomos autossômicos e X podem levar a infertilidade masculina. As alterações do tipo deleção podem levar a uma falha na espermatogênese maior que as alterações do tipo duplicação. A expressão diferencial dos miRNAs em tecido testicular de pacientes com diferenças histopatológicas (SCOS e MA) apresentam um padrão de expressão de miRNAs diferentes devido ao tipo de células germinativas que eles apresentam no tecido epitelial do testículo. / Infertility is a public health problem with significant social, economic and psychological impact. Worldwide, the incidence of infertility in the general population is estimated at 10- 15%. Approximately 50% of infertility of couples is of male origin. In more than half of infertile men, the cause of infertility is unknown (idiopathic). Etiologically, male infertility has genetic and non-genetic causes. Among the best known genetic causes we found the mutation of the androgen receptor, the cystic fibrosis transmembrane conductance regulator (CFTR), classic chromosomal abnormalities, meiotic abnormalities and microdeletions of the Y chromosome. Chromosomal abnormalities are found much more frequently in infertile men, with an incidence of 4-16% in the incidence of 0.4% in the fertile population. Studies show that CNVs can also be related to male infertility, specifically in the failure of spermatogenesis. CNVs found in both the Y and autosomes chromosomes were also associated with possible failures in spermatogenesis. Another factor that may also be involved in male infertility is the deregulated expression of miRNAs. This work aimed to promote the analysis of large-scale distribution of CNVs and the transcriptional profile of miRNAs in testicular biopsy samples from patients with azoospermia. For the study of CNV we used the CytoScan HDTM Affymetrix methodology and the transcriptional profile of miRNAs in the samples was assessed by means of microarray technology from Affymetrix platform. For these analyzes we set up two study groups (Stop Maturation (MA) of Germ Cells and Sertoli Cell Only Syndrome (SCOS)) and compared them to a control group (obstructive azoospermia, normal spermatogenesis). Through analysis of CNVs, we found 94 CNVs in sexual and autosomes chromosomes, 35 (37%) were classified as benign CNVs, 24 (23%) as a potentially benign seven CNVs (7.4%) as pathogenic and 7 were classified as potentially pathogenic. All CNVs classified as pathogenic are present on the Y chromosome, five CNVs are of duplication type and two are deletion type. The duplication type CNV was found in MA patients and deletion type CNV was found in SCOS patient. We identified that CNVs overlap and when analyzed jointed - as a single CNV of each condition - they have a similar size. These CNVs have genes involved in spermatogenesis. CNVs classified as potentially pathogenic were present in autosomes and in the X chromosome. In these CNVs were present genes that were associated with failure in spermatogenesis. The analysis of the expression of miRNAs revealed a transitional profile much more altered in patients with SCOS. The two conditions presented exclusive miRNAs, but shared 30 miRNAs differentially expressed when compared to the control group. We identify two families of miRNAs (miR449 and miR34) which exhibit preferential expression in testis as differentially expressed in both conditions. Our results show that changes in the number of copies (CNVs) on the Y chromosome lead to male infertility and CNVs in autosomes and X chromosomes may lead to male infertility. The deletion type changes can lead to a failure of spermatogenesis greater than the duplication type changes. The differential expression of miRNAs in patients with testicular tissue histopathologic differences (SCOS and MA) has a different pattern of miRNA expression due to the type of germ cells they present in epithelial tissue of the testis.

All orchid species studied so far have been shown to participate in orchideoid mycorrhizal symbiosis. Morover, this symbiosis is absolutely vital component of their life cycle. Exchange of nutrients occurs between symbionts where the fungi provides the orchid with energy and carbon supply at least in its early developmental stages. This study focuses on the possible role of trehalose in this transfer. In vitro experiments have showed in five species from three different subfamilies of Orchidaceae family that they can utilize trehalose comparably with sucrose and glucose. Thus, the ability of trehalose utilization seems to be conserved among orchids. Trehalase enzyme activity was localized histochemically in orchid mycorrhizas. The activity strongly colocalized with colonized tissue supporting a hypothesis that trehalose transfer occurs in this site and is mediated by trehalase. Using bioinformatic methods, trehalase gene duplications were identified in many taxons of Embryophyta including three orchid species. Interestingly, highest number of trehalase gene copies was identified in genome of orchid Dactylorhiza majalis. Trehalose utilization, high trehalase activity in mycorrhizas and trehalase gene duplications in some orchids together indicate that trehalose transfer in orchid myccorhizas...