Miracle-dz/UniFAR-FTUs huggingface dataset:
Utilisation des séquences de génome complet pour l'identification de mutations délétères responsables d'anomalies génétiques récessives chez le bovin.

L’effectif genetique reduit des races bovines entraine une augmentation de consanguinite de l’ordre de 1% par generation et une forte derive genetique. Cette evolution favorise l’emergence reguliere d’anomalies genetiques recessives dans les populations, qu’elles soient de races laitieres ou allaitantes. En France, l’Observatoire National des Anomalies Bovines (ONAB) a ete cree dans le but de detecter et controler ces anomalies emergentes. Cependant, la detection par les observatoires sous-entend d’une part une diffusion large de l’allele defavorable dans la population et d’autre part que l’anomalie presente un phenotype avec un tableau clinique specifique permettant une declaration du phenotype a l’ONAB. L’impact des anomalies genetiques est donc encore largement sous-estime. Toutefois, le developpement des technologies de genotypage et de sequencage de genomes, associes a l’ensemble des informations disponibles permet une detection efficace des mutations causales. Ainsi, l’objectif de cette these a ete d’utiliser l’ensemble des donnees disponibles (phenotypes, genotypes, sequences, annotations fonctionnelles…) pour identifier et valider des mutations deleteres segregant dans races bovines laitieres et allaitantes francaises. Nous avons explore differentes strategies classiques - cartographies par homozygotie, haplotypes en deficit en homozygotes - qui gagnent en efficacite grâce aux donnees de sequence de genome complet (WGS). Nous avons egalement mis en place des approches alternatives de genetique inverse, basees sur l’exploitation des donnees WGS francaise et du consortium 1000 bull genomes.Les travaux realise ont permis d’identifier les mutations causales associees a deux syndromes recessifs rapportes a l’ONAB : l’epidermolyse bulleuse jonctionnelle en race Charolaise (ITGB4, g.chr19: g.56488278_56493087del) et d’epilepsie idiopathique (MTCL1, g.chr24:41661691 G>A) recemment emergee dans la race Parthenaise. Nous avons egalement demontre la forte association entre l’haplotype MH1 et un polymorphisme affectant le gene PFAS (Chr19:g.28511199C>T ; p.R1205C). Par les strategies de genetique inverse, nous avons egalement identifie une mutation probablement responsable de mortalite embryonnaire en race Normande affectant le gene CAD (Chr11:g72399397, p.Y452C) ainsi qu’une mutation affectant le gene RP1 (Chr14:g.23995411_23995412insA, p. R791KfsX13) responsable d’une degenerescence progressive de la retine et qui segrege a forte frequence en race Normande mais aussi dans d’autres races bovines europeennes. Ces etudes encore en cours, fournissent egalement un inventaire des variants genetiques potentiellement deleteres dont la caracterisation de l’effet sur le phenotype pourra etre exploree. Enfin, l’identification de ces anomalies et des mutations deleteres responsables ont abouti a la mise a disposition de tests de diagnostic efficaces pour permettre une contre-selection raisonnee de ces variants deleteres dans les populations bovines.
Effect of 2-Methoxyestradiol on Dephosphorylation of Neuronal Nitric Oxide Synthase in Osteosarcoma 143B Cells. An in vitro study

Objective: 2-methoxyestradiol, an endogenous metabolite of anticancer agent, has been evaluated in ongoing advanced phases of clinical trials as an anticancer agent. The aim of the study was to determine the impact of 2- methoxyestradiol on phosphorylation status of neuronal nitric oxide synthase at position of serine 847. We determined also influence of the compound on the gene and protein expressions, phosphorylation status of PP2A phosphatase. Methods: In the current study we used western blotting, real time PCR, and ELISA assays. Results: We demonstrated that 2-methoxyestradiol decreases the level of neuronal nitric oxide synthase phosphorylated at position of serine 847 referred to as inactive pool of enzyme. The expression of PP2CA gene was down-regulated by 2-methoxyestradiol at concentration of 1 μM. 10 μM did not statistically significant impact on phosphatase gene expression. Moreover, 1 μM 2-methoxyestradiol up-regulated protein level of PP2A while 10 μM did not exert any effect. Conclusions: 2-methoxyestradiol decreased an inactive pool of neuronal nitric oxide synthase. Additionally, in a concentration-dependent manner it impacts on the gene and protein expressions, as well as phosphorylation status of PP2A-α phosphatase. Increasing activity of neuronal nitric oxide synthase by reversible phosphorylation may constitute an important tool resulting in osteosarcoma cell death.
Expression of WIPI2B counteracts age-related decline in autophagosome biogenesis in neurons

Autophagy defects are implicated in multiple late-onset neurodegenerative diseases including Amyotrophic Lateral Sclerosis (ALS) and Alzheimer’s, Huntington’s, and Parkinson’s diseases. Since aging is the most common shared risk factor in neurodegeneration, we assessed rates of autophagy in mammalian neurons during aging. We identified a significant decrease in the rate of constitutive autophagosome biogenesis during aging and observed pronounced morphological defects in autophagosomes in neurons from aged mice. While early stages of autophagosome formation were unaffected, we detected the frequent production of stalled LC3B-negative isolation membranes in neurons from aged mice. These stalled structures recruited the majority of the autophagy machinery, but failed to develop into LC3B-positive autophagosomes. Importantly, ectopically expressing WIPI2B effectively restored autophagosome biogenesis in aged neurons. This rescue is dependent on the phosphorylation state of WIPI2B at the isolation membrane, suggesting a novel therapeutic target in age-associated neurodegeneration.
Comparative efficacy of MIRU-VNTR and IS 6110-RFLP for differentiation of Mycobacterium tuberculosis isolates

The aim of this study was To characterize Mycobacterium tuberculosis isolates by MIRU-VNTR typing and IS 6110 – RFLP and to compare the efficiency of MIRU-VNTR typing and IS 6110 – RFLP in discriminating Mycobacterium tuberculosis isolates. In Mycobacterium genome a large number of insertional and repetitive elements have been identified. In the genome of Mycobacterium tuberculosis insertation sequence IS 6110 is present. In Mycobacterium tuberculosis, 41 mini satellites like structure have been identified. They are specific class of variable number of tandem repeats at different loci varies between strain. MIRU-VNTR, is a widely accepted technique for strain typing of Mycobacterium tuberculosis. Analysis of fingerprinting of M.tuberculosis strains showed the presence of both low (5%) and multiple (95%) IS6110 copy number strains. After genotyping the same isolates by MIRU-VNTR typing it is showed that MIRU-VNTR typing is more sensitive than IS 6110-RFLP. As MIRU-VNTR typing is less time taking, less DNA are required and Bands obtained are clear so easy to interpretate.
Isolation and characterization of plant TAF9, an orthologous gene for TATA-binding protein-associated factor 9, from wintersweet (Chimonanthus praecox)

TAF9 is one of the TATA-binding protein-associated factors (TAFs) that constitute the TFIID complex. We isolated a plant TAF9 ortholog from the Chimonanthus praecox (L.) Link cDNA library and named it CpTAF9. The CpTAF9 protein contained the conserved TAF9 and H2A superfamily domain, which is highly conserved among the TAF9s of other organisms. It also showed a specific tissue expression pattern that the transcript level of CpTAF9 was higher in mature leaves than in other tissues. In addition, CpTAF9 expression in wintersweet leaves could be induced by treatment with salt or high temperatures, or by exogenous abscisic acid application. Overexpression of CpTAF9 in Arabidopsis thaliana (L.) Heynh. under the cauliflower mosaic virus 35S promoter improved salt and high-temperature stress tolerance to some extent. These results demonstrated that CpTAF9 may have a role in gene regulation associated with salt and heat stress responses in wintersweet, providing a foundation for further elucidating the molecular mechanisms that underlined TAF-mediated control of the stress response processes in plant.
Phenolic Compounds and Hepatoprotective Activity of Centaurea aegyptiaca L. on Carbon Tetrachloride-induced Hepatotoxicity in Rats

Objectives: This study aimed to isolate phenolic compounds from the 70% aqueous methanol extract of the aerial parts (leaves, flowers and stems) of Centaurea aegyptiaca , evaluate in-vivo hepatoprotective activity and determine total phenolic and total flavonoid contents. Methods: 70% aqueous methanol extract of the aerial parts subjected to different chromatographic separation techniques. The identities of the isolated compounds were established on the basis of their spectral data and comparing with previously reported data. The crude extract was evaluated for in-vivo hepatoprotective activity on CCl4-induced hepatotoxicity in rats. Total phenolic and total flavonoid contents of the aqueous methanol extract were determined using Folin-Ciocalteu and aluminum chloride colorimetric methods, respectively. Results: The aqueous methanol extract of the aerial parts of Centaurea aegyptiacaafforded seven compounds. A phenolic acid ester; protochatechuic acid methyl ester (1) along with six known flavonoids; apigenin-6-C-β-D-glucopyranoside (isovitexin) (2), apigenin-8-C-β-D-glucopyranoside (vitexin) (3), quercetin-3-O-b-D-glucopyranoside (isoquercetin) (4), apigenin (5), 3-O-methylquercetin (6) and quercetin (7). Administration of the extract at doses of 100 and 200 mg/kg b.wt showed a hepatoprotective activity similar to that of the standard drug; silymarin at a dose of 25 mg/kg b.wt. Comparative histopathological study of liver exhibited moderate changes in liver histoarchitecture when compared to the CCl4 group. The methanolic extract showed high concentration of phenolic and flavonoid contents. Conclusion: The aqueous methanol extract of the aerial parts of C. aegyptiaca afforded seven phenolic compounds for the first time from this species, with promising in-vivo hepatoprotective activity.
Biophysical studies of asymmetric homodimerisation of the microRNA biogenesis cofactors PACT and TRBP

Processing of precursor microRNAs by Dicer is a key step in microRNA biogenesis. This process is assisted by the homologous proteins PACT and TRBP, which bind to the helicase domain of Dicer. The mechanism by which they assist microRNA biogenesis is poorly understood, but could include facilitating substrate positioning, assisting Argonaute loading, or discriminating between different classes of pre-miRNA. PACT also regulates innate immune pathways that respond to viral double-stranded RNA, including via the kinase PKR. Mutations in PACT lead to early onset dystonia in humans, while depletion of PACT in mice results in both growth and fertility defects: both have been linked to inappropriate or altered activation of PKR. Homodimerisation of PACT via its C-terminal domain (PACT-D3) is thought to be necessary for it to induce PKR activation. Homodimerisation of wild-type and mutant constructs of PACT-D3 was assayed using biophysical techniques. SEC-MALLS and analytical ultracentrifugation data demonstrate that PACT-D3 homodimerises via a different mechanism to a previously reported dsRBD homodimer, dsRBD-5 of Staufen1. Instead, NMR analyses show that PACT-D3 forms an asymmetric homodimer similar to that observed in the Drosophila melanogaster homologue Loquacious. Dimerisation could be abolished by the L273R mutation, while phospho-mimic mutations did not appear to significantly affect dimerisation. TRBP domain 3 also forms asymmetric dimers, but with weaker affinity due to sequence differences in its C- terminal -helix. Asymmetry is caused by a register shift between intermolecular parallel beta-strands, but the functional significance of asymmetric homodimerisation remains unclear. The data presented in this thesis supports a model in which the homodimerisation interface of PACT-D3 overlaps with the surface that binds to Dicer, and suggests that PACT homodimerisation and the formation of a Dicer-PACT complex are incompatible.
IDENTIFIKASI PENANDA GENETIK DAERAH D-LOOP PADA SAPI ACEH

The aims of this study were to describe the genetic variation of D-loop of mtDNA which is useful database for conducting conservation programe. The whole blood samples were collected (8 samples for Dloop analysis) from four locations which were Aceh Besar, Pidie, North Aceh regencies and Banda Aceh city. Out group whole blood samples were collected from two samples from Bali cattles (Bali Island), Madura cattle (Madura Island), and Pesisir cattle (West Sumatera) respectively and one sample from PO cattle (West Java). Amplification of D-loop sequences of mtDNA with BIDLF and BIDLR primary had PCR product 980 bp length and sequences length which could be analyzed 479 bp. The Data were analyzed using Squint 1.02 and MEGA4.0 programme. The result of D-loop mtDNA analysis as showed that there were 27 sites of variance in Aceh cattle. This marker can be used to differentiate and subdivide of Indonesia local cattle, and indicated that Aceh cattle had the same cluster as Pesisir cattle where PO cattle comes into their group, has closer genetic distance to Bos indicus, while Bali and Madura cattle had the same cluster.
Rotenone treatment has a short-term effect on New Zealand stream macroinvertebrate communities

ABSTRACT Invasive fish eradication is a key management strategy in aquatic ecosystems, and is often accomplished using piscicides such as rotenone. However, the effects of piscicides on aquatic invertebrate communities are poorly understood, particularly over long time scales. We monitored invertebrate communities in two treatment and two reference streams prior to and for one year following the use of rotenone to eradicate trout in Zealandia wildlife sanctuary, Wellington. Immediately following treatment, invertebrate density and taxonomic richness declined significantly, and community composition diverged markedly relative to reference streams, with pollution sensitive taxa declining greater than more tolerant taxa. Treatment streams recovered to pre-treatment conditions within 4–12 months of rotenone application, indicating minor long-term impacts on invertebrate communities. Speed of recovery of individual taxa appeared to be associated with life history variables, e.g. generation times and dispersal ability. Untreated upstream reaches and nearby water bodies likely facilitated successful invertebrate community recovery. Our results demonstrate that rapid recovery of New Zealand stream invertebrate communities is possible within one year of rotenone application.
Frequency Distribution of Avian group-D Rotavirus in Southern and Northern Parts of India

Enteric infections foist massive losses in commercial and backyard poultry sector. Rotavirus, the leading cause of enteric infections, is of great concern among researchers and industry, as the epidemiological reports confirm that new rotavirus groups are evolving in poultry and might inflict the growing poultry sector in the coming years. The diversity and epidemiology in avian group A rotaviruses throughout the world have been studied by several researchers, but epidemiological studies are barely accessible for other groups of rotaviruses like D, F and G. A timely identification of rotavirus is, therefore, critical for control of disease and to minimize losses to the poultry sector. Therefore, the frequency distribution of avian RVD infection in northern and southern states of India was ascertained by using RNA-PAGE and a RT-PCR assay. RVD was detected in 6.04% (13/215) of the intestinal contents examined during January 2012 to January 2013. The results confirm the existence of RVD in chicken of temperate northern India. Sequence based inquiry confirmed higher homology with existing type D avian rotavirus isolates from rest of the world. Thus, an understanding of the viruses that cause gastrointestinal tract disease in poultry, along with an understanding of their epidemiology is necessary for the development of be–fitting control measures.
Phenotypic and genetic differentiation of invasive gobies in the upper Danube River

This thesis contributes to the basic understanding of invasion success of non-native gobies in the upper Danube River. Genetic and phenotypic differentiation was more pronounced in Neogobius melanostomus than in Ponticola kessleri. In addition, N. melanostomus showed rapid genomic adaptation and phenotypic plasticity. A further invasive goby was recorded for the first time in Germany, i.e. Babka gymnotrachelus and the first case of hybridization between two invasive species was documented on a global scale.
Differential Plasticity in Response to Simulated Climate Warming in a High-Elevation Amphibian Assemblage

Abstract Climate change is expected to increase amphibian extinction rates; however, little is known about the physiological responses of amphibian populations to climate change projections for their region. For the Cascade Mountain Range of the U.S. Pacific Northwest, high-resolution climate models predict temperature increases during summer months. We evaluated phenotypic plasticity in larval growth and development in response to this projected increase in temperature in three co-occurring Anuran species: Cascades Frogs (Rana cascadae), Western Toads (Anaxyrus boreas), and Pacific Chorus Frogs (Pseudacris regilla). We exposed each species to two temperature regimes: the control treatment simulated the historical summer temperatures for the decade of 2001–11; the warmed treatment mirrored this seasonal trend but simulated a 4°C average increase in temperature. To quantify the magnitude of plasticity and any consequences to body size, we measured growth characteristics throughout larval development and metamorphosis. We found significant acceleration in larval developmental rates and increased larval body mass under the warmed temperature treatment for all three species. When compared across Gosner developmental stages, however, the perceived weight gain in the warmed treatment was largely because of the advancement in development triggered by warming. As a consequence of rapid development, we observed differential shifts in body size features. We further identified an optimal temperature range (22–25°C) within which all three species showed maximum weight gain and development rates and above which performance plateaued. We provide empirical evidence for species-specific thermal tolerances and the potential for individualistic responses to climate change among co-occurring amphibian species.
Loss of the Histone Demethylase Phf8 Is Compatible With Development but Confers Resilience to Anxiety and Depression

Phf8 is a histone demethylase associated with human developmental disorders and cancer. Early studies of Phf8 in humans indicated that inactivating mutations in the gene were linked to syndromic intellectual disability with cleft lip and palate (Siderius syndrome). However, Phf8’s functional role in regulating mammalian development and behavior has not been demonstrated. In this thesis I present my findings on a knockout mouse model of Phf8, which I have generated and characterized to interrogate Phf8’s function in these processes in an in vivo mammalian system. Unexpectedly, I did not detect any gross physiological defects nor intellectual disability, but instead report here that mice null for Phf8 are resilient to anxiety and depression. I further characterized the molecular nature of Phf8’s role regulating mammalian behavior by performing RNA-seq on regions in the brain key to mediating anxiety disorders and depression. Here I find evidence that Phf8 directly regulates multiple serotonin receptors in the prefrontal cortex, which have a long standing link to anxiety disorders and depression, suggesting a likely mechanism for resiliency. In addition to its proposed function in behavior and development, multiple studies have implicated Phf8 cancer. It has been suggested that Phf8 can behave as an oncogene, notably in
Effect of Extraction Conditions on Pectin Yield Extracted from Sweet Potato Peels Residues Using Hydrochloric Acid

Pectins are complex polysaccharides obtained from higher plants which are structurally composed mainly of α-1, 4-linked-D-galacturonic acid (Gal A). Pectin has a good property of gelling, thickening and emulsification thus it is used widely in food and beverage industry. The applications of pectin in food industry are developing thus the demand of pectin is also increasing. Sweet potato residue is a potential local source of pectin. The peels of sweet potato are usually discarded prior to the consumption of the fruit. In Malaysia, starch industries and small local business are generating a lot of residual waste from sweet potato. Converting the waste into a value-Added product such as pectin would bring great advantage in term of environmental concern and profit. Effects of extraction conditions such as extraction temperature (60 - 100 °C), extraction time (60 - 180 min) and solution pH (1 - 3) on the extraction yield of pectin (%) from sweet potato residues were investigated in this study. The extracting solvent used was hydrochloric acid. The highest yield was 2.59 % which was obtained at extraction temperature 90 °C, extraction time 60 min and solution pH 1.5. All three extraction conditions showed significant effect on the yield of pectin (%).
Studies on the entry and persistence of canine distemper virus in the central nervous system

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Sampling effects on the effectiveness of ecological indicators in detecting fishery-induced community changes

Effective ecological indicators (EI) should reflect changes to ecosystem status in a timely manner to guide fisheries management; however, the robustness of EIs in the face of sampling uncertainty is not well understood and sampling errors may result in delayed or even unhelpful actions for management. In this study, we use a size-spectrum model to evaluate the effectiveness of EIs in detecting fishery-induced ecosystem changes given various levels of sampling uncertainty. We demonstrate that there is a time-lag that exists between changes in fishing pressure and EI response. The selectivity of survey gears can strongly determine the level of EI responses within certain size ranges. EIs may lose statistical power once sampling errors exceed a certain level, implying that several decades of monitoring data may be needed to be sure of detecting even a large change. Multivariate methods can strengthen the statistical powers of EIs, but only when the level of sampling noises is low. This study suggests the need for considering the impact of sampling uncertainty on the use of EIs in fisheries management.