Letteratura scientifica selezionata sul tema "Developmental neurophysiology Genetic aspects"

Abstract With less than a million neurons, the western honeybee Apis mellifera is capable of complex olfactory behaviors and provides an ideal model for investigating the neurophysiology of the olfactory circuit and the basis of olfactory perception and learning. Here, we review the most fundamental aspects of honeybee’s olfaction: first, we discuss which odorants dominate its environment, and how bees use them to communicate and regulate colony homeostasis; then, we describe the neuroanatomy and the neurophysiology of the olfactory circuit; finally, we explore the cellular and molecular mechanisms leading to olfactory memory formation. The vastity of histological, neurophysiological, and behavioral data collected during the last century, together with new technological advancements, including genetic tools, confirm the honeybee as an attractive research model for understanding olfactory coding and learning.

Differences in sex development (DSD) in patients with 46,XX karyotype occur by foetal or postnatal exposure to an increased amount of androgens. These disorders are usually diagnosed at birth, in newborns with abnormal genitalia, or later, due to postnatal virilization, usually at puberty. Proper diagnosis and therapy are mostly based on the knowledge of normal development and molecular etiopathogenesis of the gonadal and adrenal structures. This review aims to describe the most relevant data that are correlated with the normal and abnormal development of adrenal and gonadal structures in direct correlation with their utility in clinical practice, mainly in patients with 46,XX karyotype. We described the prenatal development of structures together with the main molecules and pathways that are involved in sex development. The second part of the review described the physical, imaging, hormonal and genetic evaluation in a patient with a disorder of sex development, insisting more on patients with 46,XX karyotype. Further, 95% of the etiology in 46,XX patients with disorders of sex development is due to congenital adrenal hyperplasia, by enzyme deficiencies that are involved in the hormonal synthesis pathway. The other cases are explained by genetic abnormalities that are involved in the development of the genital system. The phenotypic variability is very important in 46,XX disorders of sex development and the knowledge of each sign, even the most discreet, which could reveal such disorders, mainly in the neonatal period, could influence the evolution, prognosis and life quality long term.

"May 2002." Addendum inside back cover. Bibliography: p. 139-157. Aims to isolate ephrin ligands from Drosophila melanogaster and analyse their involvement in Drosophila deveopment. Also investigates the potential of ephrin B-1 as a causative gene in the human condition Aicardi's syndrome.

Pervasive developmental disorders are a group of neurodevelopmental-neuropsychiatric disorders that are characterized by variable and severe pervasive impairments in several areas of child development, notably social interaction, communication and imagination. They all share clinical features but differ in the severity and age of onset of the impairments. Except for Rett Syndrome (RTT), the etiology of these disorders is unknown, but there is strong evidence that genetic factors contribute to their pathogenesis. While no major genes have been linked to theses disorders linkages, association and chromosomal studies suggest that many loci may be involved.
One aim of the present study was to search for genetics variants associated with autism and other related disorders. This study represents the first family-based association study looking at the entire X chromosome using a French-Canadian autistic population, a genetically homogenous group. We found association between autism and markers at two loci. Our results support the existence of a putative gene located on the X chromosome and moreover the founder effect, in the French-Canadian population, may provide greater power to fine map disease genes especially in complex traits.
The second aim of the present thesis was to confirm the involvement of the MECP2 gene in our RTT group of patients. While we confirm the presence of mutations in this gene in our cohort of RTT patients we also demonstrated that clinical stringency greatly influences the mutation detection rate for this disorder.

(Truncated abstract) The aims of this thesis are: (i) To estimate the prevalence of psychiatric illness among persons with intellectual disability and, conversely, the prevalence of intellectual disability among persons with a psychiatric illness; (ii) To describe the disability and service utilisation profile of persons with conjoint disorder; (iii) To examine, in particular, intellectual disability co-occurring with schizophrenia; and (iv) To explore the role of hereditary and environmental (specifically obstetric) risk factors in the aetiology of (i) intellectual disability and (ii) intellectual disability co-occurring with psychiatric illness. This thesis has a special interest in the relationship between intellectual disability and schizophrenia. Where data and sample sizes permit, it explores that relationship at some depth and has included sections on the putative nature of the link between intellectual disability and schizophrenia in the introductory and discussion chapters. To realise its objectives, the thesis comprises a core study focusing on aims (i) – (iii) and a supplementary study whose focus is aim (iv). It also draws on work from an ancillary study completed prior to the period of candidacy...This thesis found that, overall, 31.7% of persons with an intellectual disability had a psychiatric illness; 1.8% of persons with a psychiatric illness had an intellectual disability. The rate of schizophrenia, but not bipolar disorder or unipolar major depression, was greatly increased among cases of conjoint disorder: depending on birth cohort, 3.7-5.2% of individuals with intellectual disability had co-occurring schizophrenia. Down syndrome was much less prevalent among conjoint disorder cases despite being the most predominant cause of intellectual disability while pervasive developmental disorder was over-represented. Persons with conjoint disorder had a more severe clinical profile including higher mortality rates than those with a single disability. The supplementary study confirmed the findings in the core body of work with respect to the extent of conjoint disorder, its severity, and its relationship with pervasive development disorder and Down syndrome. Moreover, the supplementary study and the ancillary influenza study indicated a role for neurodevelopmental insults including obstetric complications in the adverse neuropsychiatric outcomes, with timing of the insult a potentially critical element in defining the specific outcome. The supplementary study also added new information on familiality in intellectual disability. It found that, in addition to parental intellectual disability status and exposure to labour and delivery complications at birth, parental psychiatric status was an independent predictor of intellectual disability in offspring as well as a predictor of conjoint disorder. In conclusion, the facility to collect and integrate records held by separate State administrative health jurisdictions, and to analyse them within the one database has had a marked impact on the capacity for this thesis to estimate the prevalence of conjoint disorder among intellectually disabled and psychiatric populations, and to understand more about its clinical manifestations and aetiological underpinnings.

Au cours de ce travail de thèse, nous avons abordé l’étude des gènes BTBD6 et Dmrt5 au cours du développement embryonnaire en utilisant les avantages complémentaires de plusieurs organismes modèles.

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Doctorat en Sciences
info:eu-repo/semantics/nonPublished

"May 2002."
Addendum inside back cover.
Bibliography: p. 139-157.
174 p. : ill. (some col.), col. plates ; 30 cm.
Aims to isolate ephrin ligands from Drosophila melanogaster and analyse their involvement in Drosophila deveopment. Also investigates the potential of ephrin B-1 as a causative gene in the human condition Aicardi's syndrome.
Thesis (Ph.D.)--University of Adelaide, Dept. of Molecular Biosciences, 2003

Computational genomics is at the intersection of computational applied physics, math, statistics, computer science and biology. With the advances in sequencing technology, large amounts of comprehensive genomic data are generated every year. However, the nature of genomic data is messy, complex and unstructured; it becomes extremely challenging to explore, analyze and understand the data based on traditional methods. The needs to develop new quantitative methods to analyze large-scale genomics datasets are urgent. By collecting, processing and organizing clean genomics datasets and using these datasets to extract insights and relevant information, we are able to develop novel methods and strategies to address specific genetics questions using the tools of applied mathematics, statistics, and human genetics. This thesis describes genetic and bioinformatics studies focused on utilizing and developing state-of-the-art computational methods and strategies in order to identify and interpret de novo mutations that are likely causing developmental disorders. We performed whole exome sequencing as well as whole genome sequencing on congenital diaphragmatic hernia parents-child trios and identified a new candidate risk gene MYRF. Additionally, we found male and female patients carry a different burden of likely-gene- disrupting mutations, and isolated and complex patients carry different gene expression levels in early development of diaphragm tissues for likely-gene-disrupting mutations. To increase the power to detect risk genes and risk variants, we developed a deep neural network classifier called MVP to accurately predict the pathogenicity of missense variants. MVP implemented an advanced structure of ResNet model and based on two independent data sets, MVP achieved clearly better results in prioritizing pathogenic variants than other methods. Additionally, we studied the genetic connection between developmental disorders and cancer. We found that in developmental disorder patients predicted deleterious de novo mutations are more enriched in cancer driver genes than non cancer driver genes. A Hidden Markov Model was implemented to discover cancer somatic missense mutation hotspots and we demonstrated many cancer driver genes shared a similar mode of action in developmental disorders and caner. By improving ability to interpret missense mutations and leveraging cancer genomics data, we can improve risk gene inference in developmental disorders.

讀寫障礙是最普遍的一種學習障礙（80%)，影響全球大約一成的學童。讀寫障礙患者於閱讀及書寫能力方面出現困難，而這並非因為患者本身的智力、學習動機或學習機會引致。對於引至讀寫障礙的理仍未清楚，但在西方人士的遺傳研究方面已發現多個與讀寫障礙相聯的基因位點及基因。本研究針對其中4個基因位點（DYX1 ’ DYX2 ’ DYX3 ’ DKX8)及其覆蓋的11基因測試了 131讀寫障礙的中國人家庭與讀寫障礙的關聯性。是項研究從國際人類基因組單體型圖(HapMap)中選擇標籤單核苷酸多型性(Tag-SNPs)及選擇以往報告與讀寫障礙有關的單核苷酸多型性進行測試。並在DYXZa基因（rs3743205 ’ padjusted =0.0072' OR = 0.08 ( 95% CI: 0.01 - 0.64 ))私MRPL19 (風險單体型rs2422229-rs7570229,風險單体型T-G, Padjusted=0.0020, OR = 2.345 (95% CI: 1.402 - 3.923))發現與讀寫障礙有正關聯性。單核苷酸多態性亦與閱讀的幾個特徵相關：DYX1C1 ( rs3743205 )與快速命名（Digit Rapid Naming ) ’語音記憶（Non-word repetition)，字型結構的左右逆轉（Left-Right Reversal )相關；KIAA0319 ( rs2760157 rs807507 )與語音意識（Onset Detection )相關；MRPL19 ( rs2422229-rs7570229 ) 與字型結構的部首位置(Radical Position)相關；SFPQand ZMYM4 ( rs3738697 - rs12093076 )與詞彙決策（Lexical Decision )相關。本研究是首個對於讀寫障礙的中國人族群進行的的基因研究（Lim et al. 2011) ’結果有助提供我們了解讀寫障礙在使用不同語言的族群的情況。
在過往歐洲的研究樣本中’位於KAA0319基因5'-上游的基因變異重複地被找出與讀寫障礙有關的閱讀特徵有關。過往研究亦指出位於KIAA0319的假定調控區上的單核苷酸多態性(SNP)顯示與KIAA0315的基因表達有關。唯本項研究於這區域並無發現陽性結果。為了找出這區域中與讀寫障礙有關聯但未被本研究策略選擇使用基因組單體型圖的標籤-單核苷酸多態性(Hapmap Tag-SNPs)的基因變異，本研究對KAM0319基因的5'-上游進行了基因组重测序。其中發現的3個短序變異（-121的rs6456625，-128到- 1 5 4 的r s 7 1 8 1 5 1 4 3 及- 1 5 7 的6 > A )出現了不同的榮光素酶報告基因活動，當中單体型A-DEL-A的活動訊號最高，而G-INS-G則最低。然而，它們的等位基因和單体型基因出現率於讀寫障礙樣本與對照組沒有顯著不同。
至今有關對KIAA0319基因抑制的行為研究仍然不足。本研究亦對位於果繩的CG7565基因，即KIAA0319的同源基因’進行特性分析。CG7565在果繩的發展階段出現了不同的表達水平及基因剪接形式。本研究使用了UAS-RNAi糸統和飛行模擬器對CG7565基因抑制的果繩的行為變化作出了分析，結果顯示於泛神經基因抑制晰/+; e/aV-Gal4/+; 3707/+及晰/+; e/av-Gal4/+; 8396/+的果蠅視覺模式記憶出現了缺陷。當CG7565在果繩大腦中央複合區的神經元F5(扇形體)和R2/R4m(摘球体)被基因抑制時，果繩視覺模式記憶亦出現了缺陷。是次有關M/PL119的遺傳關聯研究跟以往MRPL19中5'-上游與讀寫障礙的關聯報導的一致’顯示這可能是真正的致病序列變異的位置。在M/PL119上的假定調控區進行基因突變分析顯示，在其中一個讀寫障礙的樣本中發現一個新的序列變化(-647 T>G)，而在對照組則沒有發現此變化。計算機預測模型分析估計這個序列變化會取消了熱休克轉錄因子1的結合位點。攜帶了 G等位基因的調控區會增加榮光素酶的活動。這種變異的作用必須得到進一步的證實。我們亦觀察到在其中兩個讀寫障礙樣本中出現了非孟德爾遺傳，在一個個体身上帶有3或4種單倍型的基因。基因拷貝數目變異或基因轉換可能是一個引至這種現象的因素。
Developmental dyslexia is a learning disability characterized by difficulties in acquisition of reading and writing skills not due to intelligence, motivation or schooling. Being the most common form of learning disability (80%), it affects 10% of schoolchildren worldwide. Research delineating genetic factors in developmental dyslexia identified loci and candidate genes in Caucasian populations, although disease mechanisms are still unknown. Four loci covering eleven genes (DYX1, DYX2, DYX3, DYXS) were tested for association in 131 Chinese families with dyslexic children in our study. Tagged-SNPs selected from International HapMap Consortium and reported SNPs were used as markers for this study. Positive associations with dyslexia were found in two genes, DYX1C1 (rs3743205, padjusted=0.0072, OR =0.08 (95% CI: 0.01 - 0.64)) and MRPL19(rs2422229-rs7570229, risk haplotype T-G,Padjusted=0.0020, OR = 2.345 (95% CI: 1.402 一 3.923)), in our study. SNPs associated with several reading-related traits were also identified: DYX1C1(rs3743205) associated with Rapid Naming (Digit Rapid Naming), Phonological Memory (Non-word repetition),Orthographic skill (Left-Right Reversal); KIAA0319 (rs2760157-rs807507) with honological awareness (Onset Detection); MRPL19 (rs2422229-rs7570229) with Orthographic knowledge (Radical Position); SFPQ and ZMYM4 (rs3738697 - rs12093076) with Orthographic knowledge (Lexical Decision). This is the first genetic study in Chinese dyslexia (Lim et al.2011), and results provide knowledge into dyslexia in populations using different languages.
Variants located 5' upstream of KIAA0319 were consistently reported for association with DD reading-related traits in European samples. A SNP in the putative promoter of KIAA0319 showed functional significance in KIAA0319 expression. However, no positive result of this region is found in this study. Resequencing of the 5' upstream of KIAA0319 was done to reveal potentially associated variants not selected using current strategies in genetic association (Hapmap Tagged-SNPs). A short sequence fragment of 3 variants (-121 rs6456625, -128 to -154 rs71815143 and -157 G>A) show differential luciferase activities, haplotype A-del-A have highest signal, G-Ins-G the lowest. However, allele and haplotype frequencies in dyslexia samples were not significantly different from controls.
Direct behavioral study of KIAA0319-knockdown is still inadequate. A homolog of KIAA0319, CG7565 in Drosophila, was characterized. Differential gene expression and splicing forms were observed during Drosophila development stages. Using UAS-RNAi system and flight simulator to study behavioral change in CG7565-knockdown Drosophila showed pan-neural knockdown lines w/+; elav-Gal4/+; 3707/+ and w/+; elav-Gal4/+; 8396/+ are defective in visual pattern memory. The study of neuronal specific knockdown showed this memory was impaired when CG7565 was selectively knocked down in F5 neuron (fan-shaped body) and R2/R4m (ellipsoid body) of the central complex in Drosophila brain.
Our genetic association study of MRPL19 agrees with reports of the association of 5' upstream of MRPL19 with DD, showing that true causative sequence variants may lie here. Mutational analyses of the putative promoter of MRPL19 revealed a novel sequence change T>G at -647 in a dyslexic sample not found in controls. In-silico analysis indicates a binding site of heat shock factor-1 that is predicted to be abolished by this variant. Luciferase activity increased in the promoter carrying the G allele. The role of this variant must be confirmed. Non-Mendelian Inheritance was observed in 2 individual dyslexic samples with 3 and 4 types of haplotypes. Copy number variation or gene conversion may be a factor.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Detailed summary in vernacular field only.
Lim, King Poo.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2012.
Includes bibliographical references (leaves 201-225).
Abstracts also in Chinese.
Dedication --- p.I
Abstract --- p.II
摘要 --- p.IV
Acknowledgements --- p.V
Table of contents --- p.VI
List of Figures --- p..XI
List of Tables --- p.XIV
List of Abbreviations --- p.XVII
Chapter 1. --- Chapter 1 --- p.1
Genetic Association of dyslexia-candidate genes in Chinese children with dyslexia --- p.1
Chapter 1.1. --- Introduction --- p.2
Chapter 1.2. --- Prevalence --- p.4
Chapter 1.3. --- Definition --- p.7
Chapter 1.4. --- Theories of developmental dyslexia --- p.9
Chapter 1.4.1. --- Phonological deficit theory --- p.9
Chapter 1.4.2. --- Double deficit hypothesis --- p.10
Chapter 1.4.3. --- Cerebellar deficit theory --- p.11
Chapter 1.4.4. --- Magnocellular deficit theory --- p.12
Chapter 1.4.5. --- Deficits in Chinese people with dyslexia --- p.12
Chapter 1.5. --- Neurobiological aspects of Dyslexia --- p.15
Chapter 1.5.1. --- Postmortem studies --- p.15
Chapter 1.5.2. --- Structural Neuroimaging studies of dyslexia --- p.16
Chapter 1.5.3. --- Functional Neuroimaging studies --- p.17
Chapter 1.5.4. --- fMRI results in Chinese --- p.18
Chapter 1.6. --- Genetics of Dyslexia --- p.19
Chapter 1.6.1. --- Familial studies --- p.19
Chapter 1.6.2. --- Twin studies --- p.21
Chapter 1.6.3. --- Mode of Inheritance --- p.24
Chapter 1.6.4. --- Genetic mapping of disease gene --- p.26
Linkage analysis --- p.26
Association study --- p.29
Molecular genetic findings in dyslexia --- p.33
Chapter 1.6.5. --- Statement of Research Rationale --- p.47
Chapter 1.6.6. --- Objectives --- p.48
Chapter 1. --- Chapter 2 --- p.49
Genetic association of dyslexia-candidate genes in Chinese children with dyslexia --- p.49
Chapter 2.1. --- Introduction --- p.50
Chapter 2.2. --- Materials and methods --- p.51
Chapter 2.2.1. --- Subjects --- p.51
Chapter 2.2.2. --- DNA extraction and genotyping --- p.54
Chapter 2.2.3. --- SNP marker selection --- p.55
Chapter 2.2.4. --- Statistical analyses --- p.57
Chapter 2.3. --- Results --- p.59
Chapter 2.3.1. --- DYX1C1 --- p.59
Single marker analysis --- p.59
Haplotype analyses --- p.62
Chapter 2.3.2. --- KIAA0319 --- p.67
Association of KIAA0319 with Chinese dyslexic children --- p.67
Association of KIAA0319 with reading related traits --- p.67
Chapter 2.3.3. --- DCDC2 --- p.74
Association of DCDC2 with Chinese dyslexic children --- p.74
Chapter 2.3.4. --- MRPL19 and C2orf3 --- p.78
Haplotypes located within 5' upstream of MRPL19 are significantly associated with DD --- p.78
Association of the 5' upstream variants with reading related traits --- p.79
Chapter 2.3.5. --- KIAA0319L and its surrounding genes --- p.85
Association of KIAA03190L and its surrounding genes with Chinese dyslexic children --- p.85
Chapter 2.3.6. --- Gene-Gene interaction analyses --- p.88
Chapter 2.3.7. --- Parent-of-origin analysis --- p.92
Chapter 2.4. --- Discussion --- p.94
Chapter 2.4.1. --- DYX1C1 variant associated with DD and reading skills --- p.94
Chapter 2.4.2. --- KIAA0319 associated with phonological awareness in Chinese --- p.99
Chapter 2.4.3. --- DCDC2 is not associated with DD in Chinese children --- p.108
Chapter 2.4.4. --- Association of MRPL19 and C2ORF3 in a Chinese sample --- p.111
Chapter 2.4.5. --- Association of KIAA03190L and its surrounding genes with Chinese children with dyslexia --- p.115
Chapter 2.4.6. --- Gene-Gene interaction --- p.118
Chapter 2.4.7. --- Parent-of-origin --- p.119
Chapter 2.5. --- Summary --- p.122
Chapter 3. --- Chapter 3 --- p.126
Resequencing analyses and characterization of 5' upstream of KIAA0319 --- p.126
Chapter 3.1. --- Introduction --- p.127
Chapter 3.2. --- Materials and Methods --- p.129
Chapter 3.2.1. --- DNA samples --- p.129
Chapter 3.2.2. --- DNA re-sequencing --- p.129
Chapter 3.2.3. --- KIAA0319 Promoter constructs --- p.131
Chapter 3.2.4. --- Luciferase Reporter Assays --- p.133
Chapter 3.2.5. --- In-silico sequence analyses --- p.133
Chapter 3.3. --- Results --- p.134
Chapter 3.4. --- Discussion --- p.143
Chapter 4. --- Chapter 4 --- p.148
Characterization of CG7565, a homolog of KIAA0319, in a Drosophila model --- p.148
Chapter 4.1. --- Introduction --- p.149
Chapter 4.2. --- Methods and Materials --- p.152
Chapter 4.2.1. --- Drosophila stock --- p.152
Chapter 4.2.2. --- Sequence analyses --- p.153
Chapter 4.2.3. --- RNA extraction and quantitative reverse-transcription PCR (RT-PCR) --- p.153
Chapter 4.2.4. --- Behavioral Assays --- p.156
Visual pattern memory assays --- p.156
Optomotor Response Assays --- p.158
Visual Discrimination Analyses --- p.159
Chapter 4.3. --- Results --- p.160
Chapter 4.4. --- Discussion --- p.174
Chapter 5. --- Chapter 5 --- p.181
Mutational analyses of 5' region of MRPL19 in children with dyslexia --- p.181
Chapter 5.1. --- Introduction --- p.182
Chapter 5.2. --- Materials and Methods --- p.183
Chapter 5.2.1. --- DNA samples --- p.183
Chapter 5.2.2. --- High resolution melting analyses (HRM) --- p.183
Chapter 5.2.3. --- MRPL19 promoter constructs --- p.185
Chapter 5.2.4. --- In-silico sequence analyses --- p.186

As exogenously administered RA suppressed the expression of the RA synthesizing enzymes, further investigation on whether this would lead to deficiency in endogenous RA concentrations was conducted. Results showed that exogenously administered RA significantly reduced the endogenous RA level in the head region with C57 embryos showing a greater reduction than ICR embryos.
In addition, detailed morphological and histological studies were conducted to determine if RA treatment caused early embryonic changes with strain difference. When compared with ICR embryos, C57 embryos exhibited more pronounced responses to RA, including developmental retardation, underdevelopment of the anterior neural plate and absence of or smaller optic pit/optic vesicle formation. However, RA treatment did not cause abnormal apoptosis in the early stages in both strains.
Since the teratogenic effect of RA is highly developmental stage-dependent, it is possible that there is a difference in the developmental stage between these 2 mouse strains at the time of RA injection. Indeed, it was found that the developmental stage of ICR embryos was approximately 6 hours ahead of C57 embryos. However, the role that this factor plays in the differential strain susceptibility to RA can be excluded since C57 fetuses were still 3 times more susceptible to developing anophthalmia/microphthalmia than ICR fetuses that were subject to RA treatment at equivalent developmental stages. Comparison of susceptibility to RA-induced anophthalmia/microphthalmia was also made among heterozygous fetuses obtained from reciprocal matings between C57 and ICR male and female mice, and those in homozygous ICR and C57 fetuses. Results showed that the C57 strain has conferred both genetic predisposition and maternal effects in increasing the embryo's susceptibility to RA-induced ocular defects.
Since the type of RA-induced ocular defects mimic those that developed in Raldh2 null mutant embryos, the effect of RA treatment on the expression of RA synthesizing enzymes, Raldh2 and Raldh3, and the RA-inducible gene Cyp26a1, as well as some early eye development genes were examined. Exogenously administered RA reduced the mRNA expression levels of Raldh2, Raldh3 and Cyp26a1 in the head region, with C57 embryos showing a greater reduction than ICR embryos.
Taken together, results of this thesis suggest that there is a strain difference in susceptibility to RA-induced ocular defects in which exogenously applied RA suppresses the expression of RA synthesizing enzymes and leads to endogenous RA deficiency. This finding may shed light on understanding why both excess and deficiency of RA can lead to similar types of ocular defects.
To determine if there are strain differences in the susceptibility to RA-induced ocular defects, two mouse strains were used. They are C57BL/6J (C57), mice that spontaneously develop ocular defects and ICR mice, which are not prone to developing ocular defects. Detailed time and dose response studies were conducted and eye defects were examined in near-term fetuses. C57 fetuses were found to be significantly more susceptible to RA-induced anophthalmia/microphthalmia than ICR fetuses.
Vitamin A (retinol) and its most active metabolite, all- trans retinoic acid (RA) is essential for vision in the adult and for eye development in the embryo. It is well documented that in humans, excess intake or deficiency of vitamin A or RA is associated with congenital ocular defects such as microphthalmia. However, the underlying mechanism remains unclear. The aim of this study is to examine the pathogenic mechanism of RA-induced developmental ocular defects.
Lau, Wing Sze Josephine.
Source: Dissertation Abstracts International, Volume: 71-01, Section: B, page: 0240.
Thesis (Ph.D.)--Chinese University of Hong Kong, 2009.
Includes bibliographical references (leaves 186-211).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstracts in English and Chinese.

Abstract There is considerable overlap in the categories of sleep-wake disorders of adults and children. The indications for various sleep diagnostic tests, the recording scenarios, scoring of various sleep-related events in children, and reference values, however, differ from those of adults. Many childhood sleep disorders are treatable, hence their early recognition and diagnosis is important. Certain aspects of the pediatric sleep history and examination are also unique due to developmental influences that change with age. This chapter provides an overview of these aspects. The optimum assessment requires integration of patient and parental concerns, questionnaire surveys, a sleep-focused examination and data from the various diagnostic modalities.