Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic intervention in Alzheimer's disease

Alzheimer's disease (AD) results from a series of dysfunctions which spread throughout the cortex in a precise spatiotemporal manner, and which subsequently give rise to a characteristic pattern of cognitive and non-cognitive symptoms. Whilst some of these symptoms can be controlled with specific drug regimes, there are still no treatments available to prevent the disease. Similarly, there are no drugs available which will reverse or even halt the progression of the pathological changes which occur in the AD brain. It is hypothesised that β-amyloid deposited within the brain as "plaques' causes slowly evolving physical damage to neurons, which then triggers a stereotypical neuronal response to trauma. This involves specific cytoskeletal alterations which give rise to the characteristic neuropathology of AD, and which can be experimentally modeled in both in vivo and in vitro models of neuronal injury. That the pathogenesis of AD crucially involves the cytoskeleton, and that targeting these changes may be an effective method of delaying or even preventing neurodegeneration in AD, was explored in this thesis. A number of broad hypotheses were posed. Firstly, that there are significant cytoskeletal alterations in the AD brain which may be ameliorated by the use of cytoskeletal stabilising agents, and which may subsequently limit the evolution of the neuropathological changes characteristic of AD. Secondly, that metallothioneins may play a role in AD, and perhaps be able to prevent the aberrant neuronal sprouting associated with AD. These hypotheses were addressed in a number of aims. The major conclusions from these investigations were that morphologically distinct plaque types differentially affect the architecture of the brain in the early and late stages of AD, to result in significant cytoskeletal alterations. Similar observations were made following experimental cortical injury, where it was demonstrated that the administration of cytoskeletal stabilising drugs can both prevent and delay the onset of neuropathological changes. Finally, metallothioneins were shown to be upregulated in both the early stages of AD and following cortical injury, suggesting that they may have a role in the pathogenesis of AD. This thesis has, therefore, demonstrated that it is possible to intervene in the sequence of events which ultimately leads to neurodegeneration in AD. Agents which target cytoskeletal alterations may represent alternatives to current therapeutic strategies.
Residue coevolution: modeling and interpretation

vi Chapter I: Background 1 Chapter II: Context Dependence and Co-evolution among Amino Acid Residues in Proteins 11 Chapter III: Coevolutionary Patterns in Cytochrome C Oxidase Depend on Domain Structure and Function 28 Chapter IV: Context Dependent Coevolution in Protein Complex Cytochrome C Oxidase Detected Using Bayes Factor Analysis 58 Chapter V: Structural and Functional Implications from Evolutionary Analysis of Photolyase/Cryptochrome Proteins 93 Appendix: Permission 126 Vita 128
Ant seed predation, pesticide applications and farmers' income from tropical multi‐cropping gardens

Tropical small‐holder farmers rely on sustainable food production. Crop seed predation by ants can cause substantial yield loss and result in high pesticide use. We conducted field experiments and questionnaire‐based surveys aiming to assess the effect of sown‐seed predation on four crop species (Cucumis sativus, Daucus carota, Capsicum frutescens and Solanum melongena) in 15 vegetable gardens and the resulting impact on the net income of Indonesian farmers. Furthermore, we tested a commonly applied insecticide and herbicide for seed, seedling and plant protection aiming to understand their effect on ant seed predation. We found that the mean percentage of seeds removed per garden was 42.0%, 49.4%, 48.0% and 50.6% for C. sativus, D. carota, C. frutescens and S. melongena, respectively, halving the farmers' income after considering initial and operational costs. Insecticide and herbicide treatments did not affect seed predation success or overall ant abundance, although they had positive and negative effects on ant species‐specific abundance. High overall ant abundance caused high seed predation rate in all gardens as a result of a functional redundancy of ant species, which compensated for pesticide‐related species loss. Environmentally‐friendly and more sustainable practices such as overseeding or seedling production in nurseries could substitute for these inefficient approaches of chemical pest control, although this requires further research.
Genetic etiology of hereditary colorectal cancer: new mechanisms and advanced mutation detection techniques

The human DNA mismatch repair (MMR) system functions to repair mispaired bases in DNA that result from DNA replication errors and thereby prevents the accumulation of mutations due to such replication errors. Hereditary nonpolyposis colorectal cancer (HNPCC), the most common form of inherited colon cancer, is associated with loss of MMR function. HNPCC is an autosomal dominant predisposition to early-onset colorectal cancer, often associated with an increased risk of extracolonic malignancies. Tumors are characterized by a high frequency of replication errors in short tandem repeats, known as microsatellite instability (MSI). The increased risk of developing cancer in HNPCC patients is nearly always due to an inherited mutation in a MMR gene, in most cases MSH2 or MLH1. Inactivation of the remaining copy of the gene by somatic genetic alteration results in a mutator phenotype. The most prevalent types of inherited genetic alterations in HNPCC are point mutations, deletions, insertions and genomic deletions. This thesis reports two novel types of germline genetic alterations of MMR genes in HNPCC patients. The first one involves methylation of the promoter region of the MLH1 gene. In one out of 14 HNPCC cases with high microsatellite instability (MSI-H) and mutation-negative for MMR genes, DNA hypermethylation of one allele was detected in DNA isolated from blood. In the MSI-H tumor from this case, the unmethylated MLH1 allele was eliminated by loss of heterozygosity and the methylated allele was retained. This biallelic inactivation resulted in loss of expression of MLH1 in the tumor as confirmed by immunohistochemistry. This suggests a novel mechanism of tumorigenesis that nonetheless fits the two-hit tumor suppressor gene inactivation hypothesis (Knudson hypothesis). The second novel genetic alteration involves single nucleotide polymorphisms (SNPs) in the regulatory areas of the MSH6 gene. Two SNPs were identified in the consensus sequence of two Sp1 transcription factor binding sites of the MSH6 promoter, resulting in altered promoter activity. Functional analysis showed that the MSH6 promoter contains seven functional putative Sp1 transcription factor binding sites, each bind Sp1 and Sp3 and all contribute to promoter activity. Analysis of the two mutant sites showed that the changes eliminated the Sp1 binding sites and were no longer bound by Sp1 and Sp3 transcription factors, resulting in reduced MSH6 expression at both the mRNA and protein level. In addition, the promoter with the two mutant sites was more sensitive to silencing by DNA methylation in vitro. This suggests that the polymorphic allele could be a preferential target of de novo methylation, resulting in transcriptional silencing of the gene.
The Prevalence of Nelson Bay Virus in Humans and Bats and its Significance within the Framework of Conservation Medicine

JENNIFER B. OLIVER The Prevalence of Nelson Bay Virus in Humans and Bats and Its Significance within the Framework of Conservation Medicine (Under the direction of KAREN GIESEKER, FACULTY MEMBER) Public health professionals strive to understand how viruses are distributed in the environment, the factors that facilitate viral transmission, and the diversity of viral agents capable of infecting humans to characterize disease burdens and design effective disease intervention strategies. The public health discipline of conservation medicine supports this endeavor by encouraging researchers to identify previously unknown etiologic agents in wildlife and analyze the ecologic of basis of disease. Within this framework, this research reports the first examination of the prevalence in Southeast Asia of the orthoreovirus Nelson Bay virus in humans and in the Pteropus bat reservoir of the virus. Contact with Pteropus species bats places humans at risk for Nipah virus transmission, an important emerging infectious disease. This research furthermore explores the environmental determinants of Nelson Bay and Nipah viral prevalence in Pteropus bats and reports the characterization of two novel orthoreoviruses isolated from bat tissues collected in Bangladesh. INDEX WORDS: Nelson Bay virus, Orthoreovirus, Nipah virus, Emerging infectious disease, Conservation medicine, Megachiropterans, Bats, Bangladesh THE PREVALENCE OF NELSON BAY VIRUS IN HUMANS AND BATS AND ITS SIGNIFICANCE WITHIN THE FRAMEWORK OF CONSERVATION MEDICINE
11. Taxonomic status and distribution of common toads in Iran

We report several new localities of common toads from northern Iran. Based on the study of external morphology and a fragment of the mitochondrial 16S rRNA gene, the Iranian common toads were identified as Bufo eichwaldi. Maximum entropy modelling was used to estimate the effects of altitude, precipitation and temperature on the distribution of B. eichwaldi. The distribution of the species is linked to a forest zone on the slopes of the Talysh and Elburz mountains.
Investigasi Asal Usul Ayam Indonesia Menggunakan Sekuens Hypervariable-1 D-loop DNA Mitokondria

Chicken taxonomy and pedigree investigation are important parts to understand the domesticationprocess occurred on chicken in Indonesia. The Indonesian native chickens have very different clade with thechickens from other Asian countries and others. This study was conducted to construct phylogeny junglefowls (red and green jungle fowls) and Indonesian native chickens, in order to know their relationship.Among the available DNA marker, the region D-loop on DNA mitochondria is the most effective markerused in the investigation. Mitochondrial DNA D-loop (hypervariable-1 segment) was PCR amplified andsubsequently sequenced for a total 33 individuals of green jungle fowls (Gallus varius), 9 individuals of redjungle fowls (Gallus g. gallus) from Indonesia, and 30 individuals of Indonesian native chickens (Lombok,Cemani, Kedu, Kedu Putih, Nunukan, Kate, Pelung, Gaok, Merawang, dan Sentul). Seventy two (72)sequences were used for analysis. Seven (7) published reference D-loop sequences of genus Gallus fromGenBank were also included in the analysis: Gallus varius (GenBank accession number D64163 danD82912), Gallus gallus (GenBank accession number AB098668), G. gallus spadiceus (GenBank accessionnumber AB007721), Gallus gallus bankiva (GenBank accession number AB007718), Gallus lafayetti(GenBank accession number D66893), and Gallus sonneratii (GenBank accession number D66892). Phylogenyanalysis indicates that Indonesia jungle fowls can be grouped into two clades (clades of red jungle fowls/Indonesia native chicken and green jungle fowls). Monophyletic phylogeny trees of jungle fowls from Indonesiawere shown in this study for pedigree investigation of domesticated chickens.
Classificação taxonômica, diferenças fisiológicas e aspectos nutricionais de marrecos e patos no Brasil

O objetivo deste artigo foi contribuir para o esclarecimento da classificacao taxonomica internacional e nacional, diferencas fisiologicas e aspectos nutricionais de marrecos e patos. A revisao da literatura foi realizada a partir da investigacao de artigos e material tecnico-cientifico relacionados ao tema. Os estudos avaliados evidenciaram papel de destaque das aves da ordem dos Anseriformes, onde na familia Anatidae destacam-se os marrecos e os patos. Os marrecos (Anas platyrhynchos) descendem dos patos selvagens mallard, sendo originarios da Asia e contando com uma vasta variedade de linhagens distribuidas pelo mundo. Os patos sao divididos em duas subespecies: o Cairina moschata moschata, forma selvagem dos patos, sendo um anseriforme originario de regioes neotropicais e comum em grande parte do territorio brasileiro; e o Cairina moschata domesticus, considerado a forma domestica dos patos, sendo originario de regioes do Mexico, da America Central e da America do Sul. No Brasil, a partir de processos de melhoramento genetico, houve a classificacao de quatro linhagens: paysandu (ou paissandu), gigante alemao, moscovy e crioulo. O mulard duck e um hibrido esteril resultante do cruzamento do pato macho com o marreco femea. Quantos as diferencas anatomicas e fisiologicas em relacao aos galinaceos, verificou-se principalmente adaptacoes na cavidade oral, ausencia de ingluvio, modificacoes estruturais na cavidade estomacal e adaptacoes fisiologicas relacionadas ao comportamento alimentar destas aves. Outrora, e importante salientar a dificuldade existente para obtencao de trabalhos de pesquisa que disponibilizem informacoes para uma eficiente producao de marrecos e patos no Brasil.
Metabolic changes in Arabidopsis thaliana plants overexpressing chalcone synthase

The study has shown that it is possible to introduce the heterologous CHS gene in Arabidopsis thaliana and common multicopies of transgenes containing plants were obtained. Analysis of the change in metabolome of CHS transgenic plants, high expression transgenic lines can be identified by markers such as flavonoids and phenylpropanoids. It is also clear that UV-A/blue light stress does not further increase the levels of these marker compounds in CHS transgenic Arabidopsis plants, whereas in wild type plants such a treatment results in increased levels of these compounds, in fact similar to that in the transgenic plants. There are certain physiological limitations in the accumulation of certain products. This thesis starts with a review of the function of CHS in plants and especially in plant resistance (Chapter 2). Chapter 3 deals with the work on Agrobacterium-mediated transformation of heterologous chalcone synthase in Arabidopsis thaliana Col. 0. The effect of overexpression of CHS on the transcriptional level is discribed in this chapter. The activity of the CHS enzyme in the transgenic plants is reported in Chapter 4. In Chapter 5 metabolic profiling of Arabidopsis thaliana using nuclear magnetic resonance spectroscopy (NMR) is described. In this chapter the primary and secondary metabolites of Arabidopsis thaliana Col. 0 which can be detected by NMR are reported. Chapter 6 reports the metabolic profiling of CHS transgenic Arabidopsis. Metabolomic changes upon UV-A/blue light treatment of Arabidopsis thaliana were investigated (Chapter 7). Chapter 8 deals with the study of the effect of the non-pesticide chemical, Benzo(1,2,3)thiadiazole-7-carbothioic acid S-methyl ester (BTH) on the Arabidopsis metabolome. Finally, the general summary and discussion of thesis are given in Chapter 9.
The effect of post-metamorphic dispersal on the population genetic structure of Fowler''s toad

Plastic laminates are prepared using decor layers containing 10-25% of particulate polyacrylonitrile resin, the polyacrylonitrile resin being incorporated in the decor during its manufacture on a paper machine. The laminates meet NEMA specifications even though less resin is used and fewer process steps are required.
The role of forest maturation in causing the decline of Black Grouse Tetrao tetrix

Black Grouse Tetrao tetrix in Britain have declined through the 20th century, and most birds are now in Scotland. Many causes for this decline have been suggested, notably agricultural intensification, increased grazing levels and moorland afforestation. We examine habitat correlates of Black Grouse distribution and population change from a 700-km2 area in the core of the Scottish range, where the numbers of lekking male Black Grouse declined by an estimated 70% to 270 between 1990 and 2002. Habitat data were derived from satellite imagery, in combination with map and field-collected data. Lek occurrence, lek size and changes in lek size were all correlated with forest structure, either positively with the amount of pre-thicket forest cover, or negatively with closed canopy cover. Additional effects of the cover of grass moor and dry heath suggest that Black Grouse are most likely to occur where moorland comprises Heather Calluna vulgaris and grass mosaics. Analysis of the change in Black Grouse abundance within 1.5 km of discrete forest blocks suggests that forest maturation, which has been the dominant habitat change during the course of the study, alone accounts for 58–78% of the decline. Given the close association of Black Grouse and the occurrence of woodland (and particularly conifer plantation) throughout much of their British range, these findings can be used to inform the design of management schemes for the recovery of Black Grouse.
Germ cell development and migration

Sexually reproducing organisms arise from gametes (sperm and egg), which develop from primordial germ cells (PGCs), a small population of cells that set aside from other cell lineages early in embryonic life in most animal species. A common theme for many species is that the germ cells are specified in regions distinct from the site where the gonad will form. Therefore, PGCs have to migrate from their site of specification towards the region where the gonad develops. Unlike in other organism however, in avian embryos the PGCs use the vascular system as a vehicle to transport them to the region of the gonad where they exit the blood vessels and reach their target. In this thesis, the function of SDF-1 in germ cell migration in the chick and the mouse embryo was studied. sdf-1 mRNA is expressed in locations where PGCs are found and towards which they migrate at the time they leave the blood vessels. Ectopically expressed chicken SDF-1 led to accumulation of PGCs at those positions. In the mouse embryo, SDF-1 is expressed in locations where PGCs are found when these cells transmigrate the hindgut epithelium and migrate towards the genital ridge, but not during earlier stages. This expression based analysis as well as analysis of PGC behaviour in the mouse embryo suggests that similar to our findings in chick, SDF-1 functions during the second phase of PGC migration, but not at earlier phases. While SDF-1 is essential and sufficient for directional migration of PGCs in zebrafish and plays conserved roles in the mouse and chick embryo for germ line migration, PGC motility is independent of SDF-1 signaling. I demonstrate that PGCs requires the function of dead end to be motile. dead end mRNA becomes restricted to the germline during the first hours of development and Dead end protein is localized to the perinuclear granules. Germ cells in Dead end depleted zebrafish embryos are not motile and die by the end of the first day of development resembling cells undergoing apoptosis. Finally, I show that the expression of dead end in the germ plasm or in germ cells is conserved among different vertebrate species.
Is growth hormone expression correlated with variation in growth rate along a latitudinal gradient in Rana temporaria

In ectotherms, decreasing season length and lower temperature towards higher latitudes often favour higher growth and developmental rates. However, the underlying physiological mechanisms and particularly the hormonal correlates of clinal variation remain unexplored. The growth hormone (GH) plays a crucial role in growth of all vertebrates and high expression of GH is associated with rapid growth in many species. We tested the hypothesis that GH expression is correlated with a latitudinal gradient in growth in Scandinavian Rana temporaria tadpoles. Using quantitative polymerase chain reaction, we measured GH and growth hormone receptor (GHR) expression at two time points from laboratory-raised tadpoles originating from eight populations collected along the latitudinal gradient. To explore latitudinal differences in stress-induced changes in GH expression, we also compared GH expression in tadpoles raised with and without predators. In accordance with previous studies we found a clear latitudinal gradient in growth. There were no latitudinal effects, or predator-induced effects on GH or GHR expression. However, there was some indication for among-population variation in GH expression. The lack of a latitudinal pattern in GH and GHR expression may be due to that the growth promoting effects of GH is dependent on other factors including insulin-like growth factor-I (IGF), IGF-binding proteins or prolactin. Further studies on these factors may provide insight on the proximal mechanisms of differences in growth in R. temporaria tadpoles.
How do rhizosphere bacteria interact with their environment at the microhabitat scale

The rhizosphere supports greater bacterial densities than root-free soil. Rhizosphere bacteria (RB) can affect plant health and nutrition however, attempts to manipulate introduced and/or indigenous communities to benefit plants are unreliable. Current evidence indicates that habitat factors strongly influence bacterial communities. In the rhizosphere many processes give rise to a high degree of habitat heterogeneity therefore, to understand how RB interact with their environment their ecology should be studied at the micro-spatial-scale. The objectives of this research were to develop a method for sampling RB at the microhabitat-scale, and to investigate techniques that can link these samples with key factors, such as substrate availability and pH. A novel method enabling non-destructive, micro-scale sampling of bacteria was developed. Its efficiency for removing bacteria from the root surface was similar to that of existing methods but offered greater accuracy in estimating RB densities. The novel method revealed that RB density was inversely proportional to distance from the apex of Brassica napus roots and that the composition of RB communities was highly variable at the micro-scale. Imaging of 14C-labelled root exudates revealed that RB density was not reflective of exudate availability but attempts to link RB with available C were unsuccessful. A key outcome of this work was the development of a strategy to combine micro sampling with microelectrode measurements. Microelectrodes revealed that pH at the root surface was highly variable at the micro-scale which, combined with similar observations for RB density/diversity, highlights the appropriateness of this scale for linking RB communities with their environment. This thesis considers the link between RB community structure, habitat and function and provides a detailed description of micro-sample analyses as well as a set of methods that will enable for the first time, the interactions between any surface-associated bacteria and their environment to be investigated at a microhabitat-scale.
Protective Effect of Kimchi against Aβ25-35-induced Impairment of Cognition and Memory

Kimchi is a Korean traditional fermented food with various health functionalities. However, the protective effects of kimchi against Alzheimer"s disease (AD) have not been studied yet. In this study, the protective activities of kimchi extract against oxidative stress and AD were investigated in an amyloid beta (Aβ)-induced AD model using ICR mice. Kimchi extract exerted strong scavenging activities against 1,1-diphenyl-2-picrylhydrazyl and hydroxyl radical. In addition, T-maze, object cognition, and water maze tests were carried out using the AD model. The Aβ 25-35 -injected groups showed impairment of cognition and memory. However, the abilities of novel object recognition and new route awareness were improved by administration of kimchi extract (100 and 200 mg/kg/day) for 2 weeks. Furthermore, the results on water maze test indicated that kimchi extract exerted protective activity against cognitive impairment induced by Aβ 25-35 . The present study suggested that kimchi protected against Aβ-induced impairment of memory and cognition as well as attenuated oxidative stress.