A Window on the Genetics of Human Speech: The FOXP2 Gene

The development of human speech seems to be a species-specific and genetically determined capacity and is considered an extremely important step in the rise of modern humans, human culture and civilisation. The multidisciplinary efforts of psychiatrists, linguists and human geneticists led to the identification of genetic elements in cohorts of patients, performing speech and language disorders. A form of special language impairment (SLI) has been identified in the KE family in Britain, as a dominant, autosomal trait, affecting the family members in three generations. Molecular genetic studies revealed a mutation in the FOXP2 gene as possible basis of SLI in these patients. The unique, human variant of FOXP2 is shared with Neandertals, indicating a common, ancestral population 3-400,000 years ago. Imprecise imitation of the tutor’s song occurs in young canaries with lowered FoxP2 expression

Drosophila type IV collagen mutation associates with immune system activation and intestinal dysfunction

This thesis introduces and explores a new type of representation for low and medium level vision operations called channel representation. The channel representation is a more general way to represent information than e.g. as numerical values, since it allows incorporation of uncertainty, and simultaneous representation of several hypotheses. More importantly it also allows the representation of “no information” when no statement can be given. A channel representation of a scalar value is a vector of channel values, which are generated by passing the original scalar value through a set of kernel functions. The resultant representation is sparse and monopolar. The word sparse signifies that information is not necessarily present in all channels. On the contrary, most channel values will be zero. The word monopolar signifies that all channel values have the same sign, e.g. they are either positive or zero. A zero channel value denotes “no information”, and for non-zero values, the magnitude signifies the relevance. In the thesis, a framework for channel encoding and local decoding of scalar values is presented. Averaging in the channel representation is identified as a regularised sampling of a probability density function. A subsequent decoding is thus a mode estimation technique.' The mode estimation property of channel averaging is exploited in the channel smoothing technique for image noise removal. We introduce an improvement to channel smoothing, called alpha synthesis, which deals with the problem of jagged edges present in the original method. Channel smoothing with alpha synthesis is compared to mean-shift filtering, bilateral filtering, median filtering, and normalized averaging with favourable results. A fast and robust blob-feature extraction method for vector fields is developed. The method is also extended to cluster constant slopes instead of constant regions. The method is intended for view-based object recognition and wide baseline matching. It is demonstrated on a wide baseline matching problem. A sparse scale-space representation of lines and edges is implemented and described. The representation keeps line and edge statements separate, and ensures that they are localised by inhibition from coarser scales. The result is however still locally continuous, in contrast to non-max-suppression approaches, which introduce a binary threshold. The channel representation is well suited to learning, which is demonstrated by applying it in an associative network. An analysis of representational properties of associative networks using the channel representation is made. Finally, a reactive system design using the channel representation is proposed. The system is similar in idea to recursive Bayesian techniques using particle filters, but the present formulation allows learning using the associative networks

4-Hydroxy-2-nonenal alkylated and peroxynitrite nitrated proteins localize to the fused mitochondria in malpighian epithelial cells of type IV collagen Drosophila mutants

Background. Human type IV collagenopathy is associated with mutations within the COL4A1 and to a less extent the COL4A2 genes. The proteins encoded by these genes form heterotrimers and are the highest molar ratio components of the ubiquitous basement membrane. The clinical manifestations of the COL4A1/A2 mutations are systemic affecting many tissues and organs among these kidneys. In order to uncover the cellular and biochemical alterations associated with aberrant type IV collagen, we have explored the phenotype of the Malpighian tubules, the secretory organ and insect kidney model, in col4a1 collagen gene mutants of the fruit fly Drosophila melanogaster. In Malpighian epithelial cells of col4a1 mutants, robust mitochondrial fusion indicated mutation-induced stress. Immunohistochemistry detected proteins nitrated by peroxynitrite that localized to the enlarged mitochondria and increased level of membrane peroxidation, assessed by the amount of proteins alkylated by 4-hydroxy-2-nonenal that similarly localized to the fused mitochondria. Nuclei within the Malpighian epithelium showed TUNEL-positivity suggesting cell degradation. The results demonstrated that col4a1 mutations affect the epithelia and, consequently, secretory function of the Malpighian tubules and provide mechanistic insight into col4a1 mutation-associated functional impairments not yet reported in human patients and in mouse models with mutant COL4A1

Altered stress fibers and integrin expression in the Malpighian epithelium of Drosophila type IV collagen mutants

Basement membranes (BMs) are highly specialized extracellular matrices (ECMs) that provide support and polarization cues for epithelial cells. Proper adhesion to the BM is pivotal in epithelial cell function and survival. Type IV collagens are the predominant components of all types of BMs, that form an irregular, polygonal lattice and serve as a scaffold for numerous other BM components and BM-associated cells. Mutations in the ubiquitous human BM components COL4A1 and COL4A2 cause a multisystem disorder involving nephropathy. Affected patients develop renal dysfunction and chronic kidney failure with or without hematuria. Mouse Col4a1 and Col4a2 mutants recapitulate the human symptoms. In vertebrates, excretion is accomplished by the kidneys and by the Malpighian tubules in insects, including the fruit fly Drosophila. Our present results with dominant, temperature-sensitive mutation of the Drosophila col4a1 gene demonstrate altered integrin expression and amplified effects of mechanical stress on the Malpighian epithelial cytoskeleton. Keywords: col4a1 mutation, Integrin misexpression, Stress fiber