Miracle-dz/UniFAR-FTUs huggingface dataset:
CMT2B Rab7V162M Mutations Induce Neuropathy in a Dosage-Dependent Manner

Author(s): Liu, Huayu | Advisor(s): Wu, Chengbiao; Ackerman, Susan | Abstract: Charcot-Marie-Tooth type 2B (CMT2B) is a debilitating hereditary peripheral sensory neuropathy. Patients with this autosomal dominant disease lose pain sensation and experience muscle weakness and atrophy in distal limbs. Clinical manifestations of CMT2B include axonal dysfunction and degeneration of peripheral sensory neurons. However, the cellular and molecular pathogenic mechanisms remain undefined. CMT2B is caused by missense point mutations (L129F, K157N, N161T/I, V162M) in Rab7, a regulator of late endocytic transport. Strong evidence suggests that CMT2B mutations enhance the cellular levels of activated Rab7 GTPase, thereby increasing lysosomal activity and autophagy. As a consequence, trafficking and signaling of neurotrophic factors such as nerve growth factor and epidermal growth factor in the long axons of peripheral sensory neurons are particularly vulnerable to premature degradation. A “gain of toxicity” model has, thus, been proposed based on these observations. In order to test the hypothesis that CMT2B mutations cause neural degeneration in a gene dosage-dependent, gain of toxicity manner, this study compares cutaneous autonomic innervation in footpad biopsies of wild-type, heterozygous and homozygous CMT2B mouse models. The results show significant neuronal degeneration associated with both disease genotypes compared to the wild-type control. In addition, disease phenotypes present in a gene dosage-dependent manner, with sensory deficits severely worsened in the homozygous model compared to the heterozygote. These results are consistent with data from previous behavioral tests showing a similar dosage-dependent effect of CMT2B mutant genes. Together, these findings affirm the gain of toxicity model of the disease and suggest that therapeutic development should aim to inhibit Rab7 hyperactivity in affected patients.
Effect of inorganic and organic zinc supplementation on serum testosterone level in Murrah buffalo (Bubalus bubalis) bulls.

The present study was conducted to elucidate the effect of zinc supplementation from inorganic (zinc sulphate) and organic (zinc propionate) sources on blood serum testosterone level vis-a-vis serum zinc concentration of Murrah buffalo bulls. Twelve buffalo bulls (2 years of age and 302.0±1.55 kg average body weight) were divided into 3 equal groups on the basis of their body weight. All the animals were fed on wheat straw and concentrate mixture to meet their nutrient requirement as per NRC (1989). Animals in group 1 were treated as control (no zinc supplementation), whereas animals in group 2 and 3 were experimental and supplemented with 70 ppm and 35 ppm zinc through zinc sulphate and zinc propionate, respectively. This feeding practice lasted for 6 months. Before the start of experiment, all the bulls were trained to donate semen by artificial vagina method using nymphomaniac buffalo as a dummy. Blood from all the buffalo bulls was collected at 0 day and subsequently at the end of experimental feeding to estimate the level of zinc and testosterone in the serum. Statistical analysis of the data revealed that serum testosterone concentration (ng/ml) and zinc concentration (ppm) were statistically similar in 3 groups of buffalo bulls at the start of experiment. However, values of testosterone and zinc concentration were significantly higher in zinc supplemented group as compared to control (non-zinc supplemented group) after 180 days of experimental feeding. Among the zinc supplemented groups serum zinc level and serum testosterone level were significantly more in zinc propionate supplemented group as compared to zinc sulphate supplemented group. It may be concluded that supplementation of zinc in the diet improved blood testosterone level in buffalo bulls and in this regard zinc propionate at half the dose of zinc sulphate supplementation in the diet of buffalo bulls was more effective in doing so.
Population dynamics and production of Streblospio benedicti (Polychaeta) in a non-polluted estuary on the Basque coast (Gulf of Biscay)

Population dynamics and production of a population of Streblospio benedicti from the Gernika estuary (Basque coast, Gulf of Biscay) were studied monthly for one year, from May 1991 to May 1992. S. Benedicti was present in the muddy sand community of Gernika throughout the period of study except in March, when it all but disappeared. Continuous recruitment was observed throughout the year, even though it was stronger in autumn. Abundance fluctuations were principally due to the incorporation of recruits and so the highest density in Gernika was recorded in autumn, and the lowest in spring, with an annual mean of 6346 ± 4582 ind m -2 . The same pattern of seasonal variation was shown in biomass: the annual mean biomass of S.benedicti in Gernika was estimated at 0.80 ± 0.54 g dry weight m-2. Secondary production was 3.57 g dry weight m-2 year, giving a P/B ratio of 4.46. S. benedicti in Gernika behaved similarly to those described for Mediterranean Streblospio populations as regards practically continuous recruitment, but the number of individuals and the annual average density were considerably lower on the Basque coast.
naive and memory phenotype CD4 T cells Effects of donor T cell trafficking and priming site on GVHD induction by

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Propriétés anti-angiogéniques et anti-migratoires de peptides transmembranaires ciblant le complexe neuropiline-1/plexine-A1 dans le glioblastome

Ce travail poursuit l’exploration du potentiel therapeutique de peptides antagonistes des domaines transmembranaires (TM) de recepteurs impliques dans la croissance tumorale. J’ai montre l’effet anti-angiogenique de MTP-NRP1, un peptide ciblant le recepteur Neuropline-1 et confirme sa capacite d’inhibition de proliferation, migration et de croissance d’une lignee de glioblastome (GBM) humain. J’ai ensuite demontre que le recepteur Plexine-A1 est correle a l’agressivite des gliomes et semble etre un marqueur pronostique negatif de la survie des patients atteints de GBM. J’ai demontre le role du segment TM de PlexA1 dans ses interactions. Le peptide MTP-PlexA1, inhibe la signalisation et la formation du complexe NRP1-PlexA1, reduit la proliferation et la migration des cellules de GBM, impacte la croissance tumorale in vivo y compris de cellules souches tumorales. J’ai decrit le role pro-angiogenique de PlexA1 par des tests d’angiogenese et de CAM ou MTP-PlexA1 bloque cette fonction.
Isolation and identification of Brucella abortus from aborted cattle and buffaloes and evaluation of their antibiogram

Samples (61) comprising 37 foetal stomach contents, 9 vaginal mucus and 15 foetal membranes from the cases of aborted cattle and buffaloes were processed for the isolation and identification ofBrucella abortus. Seventeen (27.86%) isolates of B. abortus were isolated, 11 belonged to biotype 1, 3 belonged to biotype 3, and 3 belonged to biotype 2. Rose Bengal plate test (RBPT) conducted on sera of 51 animals detected 10 positive cases whereas with serum agglutination test (SAT) 11 positive cases were detected. Thus isolation was more sensitive as compared to RBPT and SAT. Maximum number of B. abortus (25.92%) isolations in cattle and in buffaloes (41.17%) were obtained from animals in the age group of4-6 years. Maximum number ofB. abortus isolations in cattle (30%) and in buffaloes (50%1) were obtained from animals that aborted in 6-8 months of gestation. Brucellosis was maximum in indigenous cattle (50%) and in Murrah buffaloes (62.5%). Antibiotic sensitivity of B. abortus revealed that it was 94.11% sensitive to ampicillin, enrofloxacin and cotrimoxazole, 88.23% to gentamicin, streptomycin and chloramphenicol, 82.35% to neomycin, 76.47% to norfloxacin, 70.58% to amoxycillin, 17.64% to tetracycline and cephalexin and resistant to penicillin.
Andrology : male reproductive health and dysfunction

Scope and Goals * Biology of Reproduction,- Physiologym * Sperm Maturation and Fertilization * Classification of Andrological Disorders * Diagnosis of Male Infertility and Hypogonadism * Diseases of the Hypothalamus and Pituitary Gland * Disorders at the Testicular Level * Diseases of the Seminal Ducts * Disorders of Sperm Deposition * Disorders of the Androgen Target Organs * Testicular Dysfunction in Systemic Diseases * Occupational and Environmental Influences on Male Fertility * Gynecology Relevant to Andrology * Testosterone Therapy * Empirical Therapies for Idiopathic Male Infertility * Assisted Fertilization * Cryopreservation of Sperm * The Psychology of Fertility Disorders in Males * Male Contribution to Contraception * Senescence * Ethical Aspects of Reproductive Medicine.
Novel approaches for large-scale phylogeneticsand applications in the context of theamphibian tree of life

During this thesis, I addressed some problems associated with large-scale phylogenetic analyses by tackling issues related to missing data and careful handling and addition of novel data in large-scale reconstructions, presenting an application of this approach in the context of amphibian phylogenetics. I developed a method (called “Concatabominations”) building on the original Safe Taxonomic Reduction method (Wilkinson 1995) as an alternative approach to the issue of identifying rogue taxa. The safe removal of rogue taxa due to missing data can potentially reduce the terraces in tree space search and improve resolution in the final consensus tree. In a pragmatic point of view, the new method can help in targeting taxa that require further sampling during a research design. Novel sequence data for the rediscovered Ericabatrachus baleensis allowed to explore its placement in the Amphibian tree of life. I tested the inclusion of novel data using a backbone alignment from a previous work (de novo analysis) and a backbone phylogenetic tree (constrained analysis), after careful curation of gene partitions to include in an analysis. I found that the use of a constrained phylogenetic inference using a previous accepted tree seems to be a practical solution to the rapid phylogenetic placement of a taxon in cases of well-supported relationships. However, a de novo analysis might ensure an optimal alignment and avoid risks introduced when adding new data. Finally, I investigated the evolutionary relationships of the three lineages of the extant amphibians (Anura, Caudata and Gymnophiona) using an independent source of evidence: miRNAs, recently used to help resolve difficult phylogenetic problems. The analyses yielded a high number of shared miRNAs using the Xenopus tropicalis genome, contrasting with a lower number of miRNAs discovered using the Axolotl transcriptome. This suggests that not using genomic data is not ideal to validate miRNAs. Nevertheless, in spite of the limitations, I was able to find two potential novel miRNAs: one supporting the monophyly of Lissamphibia, and another supporting the Batrachia hypothesis. Overall, I hope the work developed in this thesis contributes with new insights into large-scale phylogenetics and in particular to amphibian phylogenetics.
Phylogeography of Podocarpus matudae (Podocarpaceae): pre‐Quaternary relicts in northern Mesoamerican cloud forests

Aim Cloud forests of northern Mesoamerica represent the northern and southern limit of the contact zone between species otherwise characteristic of North or South America. Several phylogeographic studies featuring temperate conifer species have improved our understanding of species responses to environmental changes. In contrast, conifer species that presumably colonized northern Mesoamerica from South America are far less studied. A phylogeographic study of Podocarpus matudae (Podocarpaceae) was conducted to identify any major evolutionary divergences or disjunctions across its range and to determine if its current distribution is associated with pre‐Quaternary climatic and/or long‐distance dispersal events.
Characterization of novel microsatellite markers from the Yesso scallop Mizuhopecten yessoensis

AbstractTwelve polymorphic and informative microsatellite markers were isolated and characterizedfor the Yesso scallop, Mizuhopecten yessoensis . We characterized these loci by genotyping48 individuals; the number of alleles ranged from two to eight, and the values of observedheterozygosity and expected heterozygosity varied from 0 to 0.8333 and from 0.2546 to0.8231, respectively. No significant linkage disequilibrium between pairs of loci was foundand three loci showed significant heterozygote deficiency from the Hardy–Weinberg equi-librium. These markers are potential for studies of the population structure, individual orhybrid identification of the species. Keywords : microsatellites, Mizuhopecten yessoensis , polymorphic marker, Yesso scallop Received 25 June 2006; revision accepted 25 July 2006 The Yesso scallop, Mizuhopecten yessoensis (Jay, 1956), isa cold-water scallop species and distributes in northernJapan, Sakhalin, Kuril Islands and northern Korea (Sakurai& Seto 2000; Sato & Nagashima 2001). Having great fameof luxuriant, delicious and large adductor muscle, theYesso scallop is highly required in the Northern American,European and Asian markets; e.g. more than 400 000 tonsper year are produced in Japan (Sato & Nagashima 2001). The Yesso scallop became one of the main bivalves culturedafter being introduced to China in the 1980s. Many breed-ing programs have been carried out to increase the yieldsince 1998. A fundamental question raised is whether thepopulation genetic structures have varied with the wideexpansion of culturing operations of the Yesso scallop. AsDNA markers, microsatellites can be used for the analysisof population structure (Sato & Nagashima 2001; An
Vertical disease transmission in the Cakile-Alternaria host-pathogen interaction

Cakile maritima (Brassicaceae) is an introduced herb growing on temperate beaches in Australia. In these situations it is attacked by the fungal pathogen Alternaria brassicicola (Dematiaceae), which forms necrotic lesions on all above-ground parts. Cakile plants produce dimorphic fruits, with half of the seeds produced by C. maritima being adapted for dispersal by water. This raises the possibility that pathogen movement among host populations may occur as a consequence of wave action and ocean currents. A field survey showed that 30% of the seeds were infected with A. brassicicola, with the frequency of infection positively correlated with lesion density on the fruit surface. Glasshouse inoculation trials demonstrated that infection of seeds could occur either through the flowers or, more readily, when spores were deposited on fruits. Seedlings grown from field-collected seeds were found to emerge with infections, indicating seed infection may lead to disease in emergent plants. Overall, the findings of this study suggest that vertical transmission is likely to be by far the most important component of disease transmission among separate host populations in this host–pathogen system. However, once disease is established in a host population, both vertical and horizontal transmission will contribute to epidemic development. A second species of Alternaria (A. alternata) was detected in many isolates from disease lesions. Simple pure culture and mixed competition trials between this fungus and A. brassicicola on C. maritimashowed both to be capable of establishing infections, although A. brassicicola was much more successful both on its own and when both fungi were applied simultaneously.
A new species of Opsiphanes Doubleday, [1849] from western México (Nymphalidae: Morphinae: Brassolini)

A new species of Opsiphanes occurring in western Mexico is described, illustrated, and compared with congeners and other members of the tribe Brassolini. It is known from relatively mesic canyons at the interface between the Sonoran Desert and the Sierra Madre Occidental in Sonora and, possibly disjunctly, in Colima. Larval foodplants are identified, the mature larva and pupa are described and illustrated, and biogeographic attributes are discussed.
Differentiation of pancreatic and hepatic cell types

The endoderm gives rise to many different cell types including those that will form the liver and pancreas. How cells differentiate during embryonic development is an important focus for the field of regenerative medicine. Understanding the normal development of liver and pancreatic cell types may allow us to develop strategies for the production of hepatocytes and pancreatic beta-cells for therapeutic purposes. One potential method of producing cells for therapeutic purposes is via transdifferentiation, or, the conversion of one cell type to another. In this thesis we aimed to establish a protocol for the transdifferentiation of liver ductal cells (termed cholangiocytes) to either hepatocyte or pancreatic lineages. We also aimed to investigate the signalling pathways important for normal differentiation of embryonic liver and pancreas. In order to address the potential of a cholangiocyte cell line (biliary epithelial cells or BECs) to transdifferentiate to other cell types, BECs were infected with a combination of candidate transcription factors known as ‘master switch’ genes that have previously been demonstrated to induce transdifferentiation to hepatic or pancreatic lineages. We demonstrated that overexpression of the hepatic transcription factors C/EBPα, C/EBPβ and HNF4 resulted in the up-regulation of the hepatocyte genes Albumin and Gs and de novo expression of Afp. In complementary experiments we also demonstrated that overexpression of the pancreatic transcription factors Pdx1, Ngn3, NeuroD and Pax4 resulted in de novo expression of insulin II in BECs. While these results were encouraging further work is necessary to enhance the maturation status of the nascent cells. We also addressed the role of the Notch signalling pathway in the differentiation of embryonic hepatic and pancreatic cells using ex vivo organ culture models of liver and pancreas development. We treated pancreata with N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-S- phenylglycine t-Butyl Ester (DAPT) a gamma-secretase inhibitor. Treatment with DAPT inhibits the Notch signalling pathway. Following treatment with DAPT we observed reduced branching morphogenesis, loss of the acinar cell phenotype (amylase expression) and an enhancement in endocrine differentiation (insulin and glucagon expression). We propose that in the absence of Notch signalling the proendocrine gene Ngn3 is no longer repressed by the Notch target Hes1, allowing endocrine differentiation to take place. Finally we observed that β-cells in pancreata treated with DAPT are functionally more mature in terms of responsiveness to glucose stimulation. Overall these results have important implications for the development of potential therapies in the treatment of liver failure and diabetes.
National and urban public policy in tourism. Towards the emergence of a hyperneoliberal script

Following the 2007-2009 Global Financial Crisis (GFC), some national governments have been pursuing a counter-reform of the public sector characterised by further policy centralisation and the 'hollowing out' of regional authorities. Public expenditure and sovereign public debt reductions have become the pretext for the implementation of hyperneoliberal development agendas aimed at the attraction of inward capitals and a further 'competitive' repositioning of major cities within a global market. Tourism and the visitor economy have been used as leverage for the attraction of capital and skilled people in the long-term development strategies of cities. This article illustrates how crises have led the way in the recent restructuring of the public sector and of destination management organisations (DMOs) in particular. Findings from national and urban development strategies recently implemented in New Zealand suggest a strong, market-driven agenda that follows a hyperneoliberal script.
Isotopic tracking of migrant wildlife

KEITH A. HOBSONIntroductionAnimal movement, including dispersal and migration, is a phenomenon that captures the imagination of scientist and layperson alike. In the Northern Hemisphere, we are perhaps most familiar with the annual movements of birds and much research has been devoted to understanding proximate and ultimate mechanisms that trigger these impressive patterns in nature (Ber-thold et al. 2003). However, tracking animal movements, including those of insects, ﬁ sh, and mammals, is also an endeavor important to both theoretical and conservation disciplines. Unfortunately, we have been severely restricted in our ability to follow vagile organisms using conventional techniques that rely on extrinsic markers. In addition, many organisms of interest are simply too small to hold satellite or radio transmitters for direct monitoring (re-viewed by Hobson 2003). All studies that rely on the initial capture and ul-timate recapture of an individual also are typically subject to sampling bias, especially for those species with widespread distributions, the so-called “nee-dle in a haystack” problem. In contrast, animal tracking methods that rely on intrinsic markers are dependent only on the “recovery” sampling sites. Hobson (2005a) referred to this advantage as “every capture is a recapture”. The measurement of naturally occurring stable isotopes in animal tissues represents one means of assaying intrinsic markers in animals in order to infer information on their origins. Few areas involving the application of stable isotope methods to ecological studies have seen such an explo-sive growth as the ﬁ eld of animal tracking, a consequence of the funda-mental limitations of conventional methods involving extrinsic markers (Hobson 2005b). Rubenstein & Hobson (2004) provided a review of the relative advantages of using intrinsic vs. extrinsic markers to track animal movements. Intrinsic biogeochemical markers include trace elements (Szep et al. 2003) as well as stable isotopes and each have advantages and disadvantages. As with trace elements, the use of stable isotopes is based on the fact that concentrations in animal tissues reﬂ ect those in their foodwebs and that spatial patterns, gradients, or changes in such markers exist in nature. Thus by making iso-topic measurements in animal tissues and knowing how stable isotopic pat-terns in foodwebs change spatially, it is often possible to infer their origins. By combining our knowledge of the behavior of stable isotopes in animal
Role of adenosine and adenine nucleotides in the biological system : metabolism, release, transport, receptors, transduction mechanisms and biological actions

Section I-A: Purinergic Receptors, P2 (ATP) Receptor and "P-Site" (5 papers). Section I-B: Adenosine Receptors (4 papers). Section II: Agonists and Antagonists of Adenosine Receptors (3 papers). Section III: Transport of Purines, Nucleosides and Nucleotides (3 papers). Section IV: Transduction Mechanisms (8 papers). Section V: Metabolism of Adenosine and Adenine Nucleotides (7 papers). Section VI: Functional Aspects of Adenosine and Adenine Nucleotides (17 papers). Section VII: Clinical Aspects (4 papers). Section VIII: Nervous System (15 papers). Author Index. Key Word Index.