Miracle-dz/UniFAR-FTUs huggingface dataset:
Hedgehog Signaling in Anterior Development of the Mammalian Embryo

Sonic hedgehog (Shh) is a critical secreted signaling molecule that regulates many aspects of organogenesis. In the absence of Shh, many organs, including the foregut, larynx, palate, cerebellum and heart do not form properly. However, the cellular details of the roles of Shh, including the relevant domains of Shh expression and reception, have not been elucidated for many of these processes. The single embryonic foregut tube must divide into the trachea and esophagus, which does not occur in the Shh-null mutant. In Chapter 5, I use Cre-Lox technology to determine that the ventral foregut endoderm is the relevant source of Shh for this process and the mesoderm must directly receive that Shh signal. Surprisingly, this signaling event appears to occur two days before the foregut begins to divide, indicating an early essential role for Shh in foregut division. Shh is also expressed at later stages in the maturing trachea and esophagus. In Chapter 6, I demonstrate that these domains serve to establish differentiated mesoderm. In the trachea, Shh from the endoderm signals directly to the mesoderm to form the tracheal cartilage rings. In the esophagus, the roles of Shh are more complex. Shh regulates the size of the esophagus and controls patterning of the concentric rings of esophageal mesoderm, however this process seems to be indirect, requiring autocrine Shh signaling within the esophageal endoderm. The laryngeal apparatus is entirely absent in the Shh-null mouse. I n Chapter 3, I dissect the domains of Shh expression and reception required for laryngeal development and demonstrate that loss of endodermal Shh expression causes laryngotracheoesophageal clefts and malformed laryngeal cartilages. As much of laryngeal morphogenesis poorly understood, I also utilize dual mesodermal and neural crest fate maps to determine the embryonic origins of various laryngeal tissues. Finally, as Shh signaling often occurs in concert with Bone Morphogenic Protein (BMP) signaling, I investigate the roles of BMP signaling in laryngeal development. Much of Shh signaling occurs at the primary cilium, to which Smoothened, a critical pathway member, must translocate upon Shh signal transduction. This process requires a Smo-Kif3a-βarretin complex in mammalian cell culture. However, the roles of βarrestins in mouse development, and their relationship to Shh signaling have not been investigated in vivo. To do so, in Chapter 4, I analyze the phenotypes of the βarr1/βarr2 double knockout embryos and demonstrate that they have palatal, cerebellar, cardiovascular and renal defects consistent with a specific impairment of mitogenic Shh signaling. Altogether, my work dissects the cellular details of Shh signaling during multiple organ systems in the mouse embryo. I further analyze the consequences of absent or misregulated Shh signaling across multiple developmental contexts and determine that Shh plays critical and diverse roles in organogenesis.
Histological and Histochemical Studies on the Extensor Muscle of the Pectoral Fin of Rainbow Trout (Oncorhynchus mykiss)

In this study, taking the extensor muscle out of the pectoral fin of trout, lipid and mitochondria contents of muscle fibres were examined. Succinic dehydrogenase and Sudan black B stain methods were applied on the sections removed by freezing microtomy. Haematoxylen and eosin staining were also applied on the sections obtained from paraffin blocks. It was observed histologically that nuclei of muscle fibre were located just under the sarcolemma. Three types of fibres red, intermediate and white were identified by the applied histochemical methods. It was observed that this muscle was rich in red and intermediate fibres. As a result, it was found that the diameter of red, intermediate and white fibres were 66.6 m m, 93.3 m m, and 133.3 m m, respectively.
CD70 as a novel target of CAR-T-cell therapy for gliomas.

148Background: Gliomas are the most common primary malignant brain tumor and are uniformly lethal. Cancer immunotherapy has the potential to target gliomas; however, its antitumor effects are restricted by limitations in clinically useful tumor specific targets. Chimeric antigen receptor modified T-cell (CAR-T) therapy is a highly promising option for cancer treatment, due to its combination of precision antibody recognition and T-cell tumor-specific killing. CD70 is an antigen expressed by limited subsets of normal lymphocytes and dendritic cells but is aberrantly overexpressed by glioma cells, which makes it an outstanding glioma-antigen target. Methods: The gene and protein expression of CD70 were evaluated to identify its potential as a glioma target. Human and mouse versions of CD70-specific CAR-T cells were generated, and human primary GBM lines as well as murine lines (GL-261, KR-158B) were used as human and mouse tumor targets, respectively. The antitumor effect of the human and mouse CD70-sepecif.
Currents and turbulence as top-down regulator in intertidal seagrass communities

In the intertidal Sylt-Romo Bay (German Bight, North Sea), Zostera noltii- beds grow under different hydrodynamic exposure. The impact of currents on seagrasses and associated fauna was assessed comparing high and low waters. Abundance of species decreased with increasing water dynamics. Especially the abundance of the dominant grazer Hydrobia ulvae was negatively correlated with water flow. Grazing limits the growth of epiphytes, which form a dense cover on seagrass leaves, where grazers were absent. Further experiments showed that growth of epiphytes on seagrasses is triggered by occurrence of grazers. Hydrodynamics induce a top-down mechanism on grazers by flushing and induce a cascading by promoting growth of epiphytes and inhibiting seagrass growth.
Novel experimental therapies for atherosclerosis : a genomics based approach

Atherosclerosis is a progressive disease of the large arteries characterized by lipid deposition, inflammation, cell death and fibrosis and it is the major cause of death in the Western world. In this thesis new and experimental therapies against atherosclerosis are designed and tested. New targets for these therapies were identified by using a mouse model for atherosclerosis, the LDL receptor deficient mouse. We used micro-arrays to compare gene expression from mice with atherosclerosis to control mice and the following targets, all related to leukocyte migration and activation, were identified; CCR5, CXCR3, CD99, IL-16, OX-40 and CD127. Vaccines against CD99, IL-16 and CD127 were designed and tested. Specific antagonists of CCR5 and CXCR3 were used to block these molecules and a specific antibody against OX40 ligand was tested in LDL receptor deficient mice. The effects of these treatment strategies are described in the chapters of this thesis. In conclusion, modulation of leukocyte activation and migration provides an attractive possibility for future drug design in the field of atherosclerosis.
Functional roles of nitric oxide signalling during zebrafish nervous system development

ii Functional roles of nitric oxide signalling during zebrafish nervous system development Sophie Bradley Abstract Nitric oxide (NO) is a highly diffusible signalling molecule that serves a wide range of physiological functions. During development, biosynthetic enzymes for NO are often expressed in nascent neurons, although little is known of how this molecule regulates in vivo nervous system development. This thesis aims to address this problem by examining the functional roles of NO signalling in the zebrafish embryo, focusing specifically on nitrergic regulation of spinal locomotor network assembly. The first aim of this study is to characterise the spatiotemporal distribution of NO synthase 1 (NOS1), the enzyme responsible for NO biosynthesis in the zebrafish nervous system. NOS1 transcript and protein was observed in discrete regions of the brain as well as a distinct class of spinal interneuron from early stages of embryonic development. The second aim was to examine functional roles of NO signalling during in vivo spinal cord development. Using molecular antisense and pharmacological approaches, NO levels were disrupted during early life and the consequences to spinal circuit maturation assessed. NO was found to specifically regulate the growth of spinal motoneurons that innervate axial trunk muscles. Abrogation of NO signalling dramatically increased the number of motor axon branches formed within the muscle across the first three days of life whilst exogenous elevation of NO levels had the opposite effect. The third aim was to determine downstream signalling pathways underpinning NOs effects. Pharmacological studies revealed that NO regulates motoneuron branching through the cyclic guanosine monophosphate pathway and subsequent analysis revealed that this pathway can modify neuromuscular synapse density, with high NO levels suppressing synaptogenesis and retarding locomotor maturation and low NO levels having the converse effect. In summary, the work presented in this thesis identifies a novel and important role for NO signalling, demonstrating that it functions to sculpt neuromuscular synapse assembly and modify locomotor maturation.
From laboratory to field: uses and limitations of pesticide behaviour models for the soil-plant system

Modelling is an economic way of assessing pesticide behaviour under field conditions; it is cheaper and faster than field experiments. Modelling attempts to generalize knowledge of pesticide field behaviour through identification of the most important pesticide/soil properties that can be measured in the laboratory. The technology to simulate volatilization of volatile pesticides that are incorporated or injected into the soil is well developed. However, modelling of volatilization rates from plant and soil surfaces before the first significant rainfall event after application is barely possible with current knowledge. The technology to simulate pesticide persistence in the plough layer is well developed; the PERSIST model has been tested at least 178 times, usually resulting in a slightly faster decline in the field than was simulated. In general, available pesticide leaching models are reliable enough to assess the leaching of the bulk of the dose (leaching levels above 1%). The EU drinking water limit of 0.1 μg L1 implies leaching of less than 0.1% of a dose of 1 kg ha1. At such a low leaching level, the validation status of the models is still low, mainly because preferential flow processes in both structured and unstructured soils and the factors controlling the transformation rate in subsoil are not well enough understood.
Orchid bees (Hymenoptera: Apidae) of the Brazilian Atlantic Forest

A detailed synopsis of all the orchid-bee species known to occur in the Atlantic Forest Domain, eastern Brazil, is provided, including synonymy, complete type data, diagnoses, relevant data on biology and geographic distribution (with detailed localities of known occurrence of each species), colorful illustrations of onomatophores (“name-bearing type specimens”), and a list with the main references dealing with each species. Fifty-four species are recognized to occur in the Atlantic Forest Domain. Identification keys are presented for each genus and their species occurring in the Atlantic Forest. Euglossa carinilabris Dressler, 1982, Euglossa cyanaspis Moure, 1968, Eulaema (Eulaema) niveofasciata (Friese, 1899) and Exaerete lepeletieri Oliveira & Nemesio, 2003, considered junior synonyms of other species by different authors, are reinstated as valid species. A full discussion on the status of the four orchid-bee species described by Linnaeus is presented, as well as colorful illustrations of the four onomatophores. The two existing onomatophores of orchid bee species described by Fabricius are also illustrated and his Apis cingulata has been shown to be the species recently described as Eulaema (Apeulaema) pseudocingulata Oliveira, 2006, which, thus, becomes a junior synonym (syn. n.). Euglossa aratingae sp. n. , Euglossa carolina sp. n. , Euglossa nanomelanotricha sp. n. , Euglossa roderici sp. n. , Euglossa roubiki sp. n. , Eulaema (Eulaema) atleticana sp. n. , and Eulaema (Apeulaema) marcii sp. n. are described as new species. Neotypes are designated for Eufriesea violacea (Blanchard, 1840) and Exaerete frontalis (Guerin-Meneville, 1844). Some corrections concerning the repository institutions of some onomatophores of orchid bees were also made: Eufriesea auriceps (Friese, 1899) holotype has been listed as belonging to the US National Museum (Washington) or to the American Museum of Natural History (New York) but, in fact, it belongs to the Zoologisches Museum der Humboldt Universitat (Berlin); the lectotype of Eufriesea aeneiventris (Mocsary, 1896) has been listed as belonging to the Istituto e Museo di Zoologia, Universita di Torino (Turin), but it actually belongs to the Hungarian Museum of Natural History (Budapest). Publication dates of both Exaerete frontalis Guerin-Meneville and Exaerete smaragdina Guerin-Meneville have been listed as 1845 but, in fact, the actual date is 1844. Based on the known geographic distribution and abundance of each species in orchid-bee inventories, IUCN criteria were applied and three species are recommended to be included in future lists of threatened species in one of the IUCN categories of risk: Eufriesea brasilianorum (Friese, 1899) and Euglossa cognata Moure, 1970 are suggested to be listed as “vulnerable”, and Euglossa cyanocholora Moure, 1996 is suggested to be listed as “endangered”. A fully annotated check list of all known orchid bee species is also presented as an Appendix.
PRODUKSI IgA & IgG MUKOSAL DAN SISTEMIK SETELAH IMUNISASI PER ORAL DENGAN PROTEIN AdhO36 SALMONELLA TYPHI PADA MENCIT BALB/C

ABSTRACT An experiment has been conducted to determine the production of mucosal and systemic IgA and IgG after oral immunization with AdhO36 protein Salmonella typhi using CTB as adjuvant. The results of ELISA Test, shows that AdhO36 protein Salmonella typhi were highly significantly (p = 0.001) able to induce the production of S-IgA (secretory IgA), as compared to control and CTB treatment. The analysis of variance results show that the effect of AdhO36 protein to the IgA content in serum is high significantly different to IgA content in mucus (p=0.001). This finding is relevant to the previous experiments that the oral administration of AdhO36 protein can inhibit the in vivo adhessive process of Salmonella typhi at enterocytes of Balb/c mice. Therefore, it can be concluded that AdhO36 protein Salmonella typhi is a potential mucosal immunogen which can induce mucosal immune response as the results of the formation of protective S-IgA, which in turn, can inhibit the adhesive process as the initial stage of infection process at enterocytes of Balb/c mice. Apart from S-IgA,
Ramularia collo-cygni. Un nouveau champignon pathogène de l'orge

tions climatiques s’y prêtent, et notamment lors d’alternance d’épisodes très ensoleillés et couverts, ces nécroses peuvent s’étendre très rapidement sur toute la surface foliaire, en provoquant la sénescence précoce de la feuille et la perte de ses fonctions photosynthétiques et métaboliques. Ce développement drastique des nécroses foliaires entraîne des chutes de rendement, sur le plan quantitatif et qualitatif, pouvant dépasser 20%. Pendant longtemps, les grillures foliaires des céréales ont été imputées à des troubles d’ordre physiologique. A la fin du 19e siècle, Cavara (Cavara 1892) décrit un nouveau champignon présent dans les nécroses foliaires de cultures d’orge du nord de l’Italie, qu’il nomme Ophiocladium hordei. Dès 1986, la présence de ce champignon est mentionnée en Suisse, puis dans tous les pays du nord des Alpes. Entre temps, Ophiocladium hordei a changé de nom pour s’appeler désormais Ramularia collo-cygni. Les grillures de l’orge sont principalement causées par Ramularia collo-cygni qui produit une molécule phytotoxique, la rubelline D (Miethbauer et al. 2003). Mais elles peuvent aussi être dues à des stress physiologiques liés aux conditions climatiques. Il reste toutefois difficile d’attribuer la formation des nécroses à des stress biotiques ou abiotiques en l’absence de sporulation du champignon. Depuis 2002, les grillures ont un statut officiel de maladie, assorti d’un seuil d’intervention à l’apparition des premières nécroses visibles sur les trois dernières feuilles. Le chlorothalonil a été le premier fongicide homologué en Suisse en 2003 contre les grillures. Ce contexte a motivé Agroscope à entamer des recherches afin de mieux comprendre la biologie, l’épidémiologie et la transmission de cette maladie, ou encore son implication avec des nécroses d’origine physiologique.
Innovación en los actores productivos de la región de Maquinaria Agrícola Argentina en la etapa del nuevo desarrollismo

Las políticas regionales y sectoriales de estímulo a la innovación empresarial parecen haber sido elementos protagónicos del modelo del nuevo desarrollismo planteado en la Argentina con posterioridad a la crisis de 2001. La producción de maquinaria agrícola nacional estuvo entre las principales receptoras de estas políticas, pero la dinámica de comportamiento innovativo de los actores económicos de la región fue débil, con poco apoyo institucional local virtuoso y escaso potencial de desarrollo regional. Mostramos esas debilidades con un estudio de caso (2003-2015). El trabajo se propone debatir con las posturas que ubican la innovación como motor de la dinámica de la maquinaria agrícola argentina, rediscutir nuevas perspectivas sobre innovación y políticas de fomento, y repensar la manera de estimular la competitividad en las regiones argentinas.
Novel Antiviral Strategies Targeting the Human Immunodeficiency Virus Type 1 (HIV-1) Viral Protein R and Its Cellular Partner, the Glucocorticoid Receptor

Most highly active anti-retroviral treatment (HAART) regimens eventually fail to provide complete and long-term suppression of virus replication due to the inability to fully clear virus from cellular reservoirs. The HIV-1 viral protein R, Vpr, increases virus replication in T cells and is necessary for the optimal infection of primary monocytes/macrophages and other non-dividing cells. In this essay, it is demonstrated that Vpr interacts with the cellular Glucocorticoid Receptor (GR) and transactivates the HIV-1 LTR through GRE and that this event can be blocked by the GR antagonist, mifepristone. Based on these observations, it is shown that targeting Vpr-mediated virus transcription with the glucocorticoid antagonist, mifepristone, can demonstrate a potent anti-retroviral therapy. Results demonstrated that Vpr-induced transactivation of both autologous and heterologous promoters was inhibited by mifepristone in a dose-dependent manner by >90% at a 1 µM concentration. Infectivity assays using T-tropic, dual-tropic, and macrophage-tropic viruses demonstrated antiviral effects on a dose-dependent regimen of mifepristone. The effects of mifepristone were also tested in HIV-1 latent cells that could be activated with extracellular viral protein and results exhibited a greater than 90% inhibition of re-activation in the presence of this antagonist. Cytotoxic effects of mifepristone demonstrated a CT50 from 10 to 100 µM in normal human primary cells, HeLa, HEK293, and CV-1 cells. Statement of Public Health Relevance: By utilizing the interaction between Vpr and the glucocortoicoid receptor, glucocorticoid antagonists such as mifepristone hold promise for anti-retroviral therapy by both preventing viral transactivation in currently-infected cell populations as well as preventing the reactivation of latent virus.
SEXUAL BEHAVIOR OF RAMS AS INFLUENCED BY THE DEGREE OF RESTRAINING ESTROUS EWES AND BY THE ADDITIONAL PRESENCE OF ANESTROUS EWES

The purpose of this study was to determine whether the sexual performance of rams in serving capacity tests was influenced by the degree of restraining estrous ewes (in stanchions, tethered or unrestrained) and the additional presence of nonreceptive (anestrous) ewes. Twelve rams, previously identified as low-level sexual performers, were exposed individually for 15-min periods to four estrous ewes presented in each of six conditions: in stanchions, tethered and unrestrained, with and without four unrestrained anestrous ewes present. The degree of restraining estrous ewes influenced ram behavior. Rams investigated unrestrained and tethered estrous ewes more times than ewes in stanchions (P < .01 and P < .05, respectively). The frequency and duration of ram courtship behaviors also were greater when the ewes were unrestrained or tethered than when they were in stanchions (all P < .01). Rams tended to mount unrestrained ewes more times than ewes in stanchions (P < .10); however, serving capacity (number of completed matings per unit of time) was not influenced by the degree of restraining estrous ewes. The presence of anestrous ewes reduced the frequency and time spent investigating and the number of ejaculations with estrous ewes (all P < .01) and increased the latency to first ejaculation (P < .01). When estrous ewes were given more freedom to move about, rams investigated and courted estrous ewes more and anestrous ewes less (all interactions were significant). In conducting sexual performance tests with rams, only ewes observed to be in standing estrus should be present in the testing pen.
Post embrionary development and life-span of adult Gasterophilus nasalis (Linnaeus, 1758) (Diptera: Oestridae) in laboratory conditions.

The genus Gasterophilus (Leach, 1817) attack equids of different ages. The objective of this investigation was to analyze: larval weight, pupation period, emergence and adult longevity, from 3rd instar larvae of G. nasalis obtained from naturally infected horses from July 1994 to July 1996. The animals remained confined to the stables thereby facilitating larvae collection. From the 409 3rd instar larvae collected, 294 (71,88%) emerged of which 52,72% were males and 47,28% were females with a sexual ratio of 0,47. It was observed that larval weight varied from 80 to 340 mg, with a mean of 239 mg. Correlation analysis demonstrated that the weight of the larvae was not an indicator of the sex of the adults, females weighed 240 ± 40 mg and males 250 ± 50 mg, indicating that the body mass of the males did not influence the overall specimen weight. The pupal period of G. nasalis varied from 16 to 46 days, with a peck at the 27th day. The longevity of the 200 collected adults varied from one to nine days, indicating a higher frequency from the second to the fifth day (76,67%). The mortality index was higher on the fifth day.