Miracle-dz/UniFAR-FTUs huggingface dataset:
The Inhibition of Chk1/Chk2 and Wee-1 Kinases as a Promising Therapy for the Treatment of Adult Acute Lymphoblastic Leukemia

Due to inadequate treatments, the survival rate of adult patients with acute lymphoblastic leukemia (ALL) is still very poor. Thus there is a need to improve the efficacy of conventional therapy. In this study we evaluated the effectiveness of checkpoint kinase inhibitors (Chk-i) in single agent and in combination with different compounds conventionally used for the treatment of B-/T-ALL. We showed that Chk1 and Chk2 kinases are highly expressed and hyper-activated in tumor samples in comparison to normal tissue. On these bases we speculate that the inhibition of these kinases could mine the genetic stability and enhance cell death in ALL cells. We firstly evaluate the efficacy in single agent of the Chk1/Chk2 (PF-0477736 and LY2606368) and of the Wee1 (MK-1775) inhibitors on different cell lines and on primary cells isolated from adult B-ALL patients. We demonstrated that the inhibition of Chk1/Chk2 kinases reduces of the cell viability, activates the apoptosis and modify the expression of different elements of the G2/M checkpoint. To assess the chemo-sensitizer activity of different checkpoint kinase inhibitors, several combination studies were performed. To this purpose, LY2606368 and MK-1775 were combined with different tyrosine kinase inhibitors (imatinb, dasatinib and bosutinib) and with the purine nucleoside analogue, clofarabine. The efficacy of the combinations was not only evaluated in term of reduction of the cell viability but also in term of induction of apoptosis and induction of DNA damages. The results found were then confirmed on primary cells of B-ALL patients. Finally different class of checkpoint kinase inhibitors were combined together in order to evaluate their interaction. In our opinion the preclinical data presented in this study are the basis for a future evaluation of this class of compound in clinical trials in the treatment of adult ALL patients.
Varietal Differences in Nitrogen Response of Soybeans Associated with their Nodulation

Experiments were conducted in order to determine whether varietal differences in nitrogen response of soybean plants were associated with their nodulation. For this study, four pairs of nodulating and nonnodulating soybean isolines (Tol-1 and Tol-0, A62-1 and A62-2, Norin No. 2 and Tozan No. 89, and T202 and T201, the former is nodulating and the latter is nonnodulating) in Experiment I and five nodulating soybeans (Koganedaizu, Norin No. 2, Orihime, Tachisuzunari and T202) in Experiment II were planted under sand culture conditions. Nutrient solution 500 ml containing sufficient quantities of essential elements except nitrogen were applied to each plastic pot filled with 4.5 kg sand twice every week during the growth period. The concentration of nitrogen in the solutions ranged from 12.5 to 400 ppm (Table 1). The following results were obtained. 1) At higher concentration of nitrogen, more vegetative growth and higher seed yield were obtained in nonnodulating soybeans except Tol-0. The maximum vegetative growth of Tol-0 was almost attained at 50 ppm nitrogen (Tables 3 and 4). 2) Each isogenic pair of nodulating and nonnodulating soybeans except a pair of Norin No. 2 and Tozan No. 89 showed no significant differences in vegetative growth and seed yield at 400 ppm nitrogen (Tables 2, 3 and 4). 3) More vegetative growth of nodulating soybeans except T202 and Tachisuzunari was observed at high concentration of nitrogen (200 and 400 ppm) than at low concentration of nitrogen (12.5 and 50 ppm) (Tables 3 and 5). Maximum seed yields of Tol-1 and A62-1 were obtained at 400 ppm nitrogen and that of Koganedaizu at 200 ppm nitrogen, while those of Norin No. 2, Tachisuzunari and Orihime at lower concentration of nitrogen than 200 ppm (Tables 4 and 6). The former varieties, which responded well to nitrogen application, had low seed yields at low concentration of nitrogen and did not surpass those of latter varieties even at high concentration of nitrogen. 4) Norin No. 2 and Tachisuzunari had more nodule number and dry weight at low concentration of nitrogen at early and late growth stages than the other varieties (Table 7). 5) The amount of accumulated nitrogen at the early pod filling stage increased with higher applied nitrogen concentration in all nodulating soybeans. At low concentration of nitrogen it was larger in varieties which did not respond well to nitrogen application than in varieties which responded well (Table 9).
Defining microglial phenotypic diversity and the impact of ageing

VII LIST OF FIGURES . XVII LIST OF TABLES . XXIII LIST OF ABBREVIATIONS. XXV Introduction . 1 Chapter 1: Background. 1 1.1 Glial cells of the CNS . 2 1.2 Astrocytes . 3 1.2. 1 Oligodendrocytes . 5 1.2. 2 Ependymal cells . 6 1.2. 3 Microglia . 7 1.3 Origin of microglia . 7 1.3. 1 Important growth factors for microglial development . 9 1.3. 2 Microglia in the healthy brain . 10 1.3. 3 Microglial-astrocytic communication . 11 1.3. 4 Microglial-neuronal communication. 12 1.3. 5 Microglial-synapse interaction . 14 1.3. 6 Microglial phagocytic receptors . 17 1.3. 7 Microglia activation . 20 1.3. 8 Heterogeneity of microglial cells . 26 1.4 Region-dependent properties of the CNS. 26 1.4. 1 Current evidence for microglial heterogeneity . 26 1.4. 2 Ageing . 27 1.5 The ageing CNS . 28 1.5. 1
Etude de la variabilité de Leuciscus soufia, poisson cyprinidé, par analyse du polymorphisme enzymatique et de caractères méristiques

Differentes populations de Leuciscus (Telestes) soufia ont ete etudiees par analyse de 30 loci enzymatiques presumes et de 7 caracteres meristiques. L'espece, appartenant a la famille des Cyprinides, est consideree comme autochtone dans le sud-est de la France, ou Spillmann en denombre 3 sous-especes. Les estimateurs de la diversite genetique ont fourni des valeurs similaires a celles observees chez des cyprinides nord-americains, etudies par Avise et Buth. Nous avons remarque aussi que le taux d'heterozygotie et le pourcentage de loci polymorphes etaient plus eleves dans la haute Durance que dans les autres echantillons. De plus, l'ensemble durancien semble constituer une population, peu ou pas subdivisee. Six des 7 caracteres meristiques etudies ne presentent pas de differences significatives entre les echantillons. L'echantillon de population de la sous-espece soufia du Var differe des autres echantillons seulement par sa frequence allelique, son faible taux d'heterozygotie et le nombre de branchiospines. Il est evident que ses caracteres sont insuffisants et entrainent un doute sur la validite du rang de sous-espece de cette population.
Integrin signalling regulates YAP and TAZ to control skin homeostasis

The skin is a squamous epithelium that is continuously renewed by a population of basal layer stem/progenitor cells and can heal wounds. Here we show that YAP and TAZ are nuclear localised in the basal layer of skin and are elevated upon wound healing. Skin-specific deletion of both YAP and TAZ in adult mice slows proliferation of basal layer cells, leads to hair loss and impairs regeneration after wounding. Contact with the basal extracellular matrix and consequent Integrin-Src signalling is a key determinant of YAP/TAZ nuclear localisation in basal layer cells and in skin tumours. Contact with the basement membrane is lost in differentiating daughter cells, where YAP and TAZ become mostly cytoplasmic. In other types of squamous epithelia and squamous cell carcinomas, a similar control mechanism is present. In contrast, columnar epithelia differentiate an apical domain that recruits CRB3, MERLIN, KIBRA and SAV to induce Hippo signalling and retain YAP/TAZ in the cytoplasm despite contact with the basal layer extracellular matrix. When columnar epithelial tumours lose their apical domain and become invasive, YAP/TAZ becomes nuclear and tumour growth becomes sensitive to the Src inhibitor Dasatinib. (CYR61, CTGF), and EGFR ligands (AREG), we propose that a positive feedback loop drives basal layer stem/progenitor cell identity, and that this loop is broken when daughter cells lose contact with the basement membrane and differentiate – forming a bistable system of cell fate determination. Our findings provide an explanation
Preferential survivorship of brooding corals in a regional extinction

Approximately half of the Caribbean Oligocene reef coral fauna became locally extinct during the Early Miocene; roughly two thirds of the genera driven to local extinction still survive in the Indo-Pacific. Coral genera with lecithotrophic larvae (brooders) preferentially survived, over those with planktotrophic larvae (broadcasters). Among 37 genera for which we inferred reproductive mode, 73% of brooding genera survived the Oligocene/Miocene extinction events, while only 29% of the broadcasting genera survived. The proportion of brooders to broadcasters also increased markedly. During the late Oligocene, 47% of Caribbean reef coral genera were broadcasters, but in the middle Miocene, only 32% of the genera were broadcasters. Survivorship in Puerto Rican reefs was correlated with tolerance of cold and turbid conditions. Genera tolerant of both cold water and turbidity had much higher survival rates than those tolerant of turbidity alone. Only 25% of the genera that could tolerate neither cold water nor turbidity survived. Most of the eurytopic genera were brooders, while most of the stenotypic genera were broadcasters. We present two hypotheses that may account for the preferential survivorship of brooders: the recruitment hypothesis, and the dispersal hypothesis. The recruitment hypothesis holds that brooders survive preferentially because lecithotrophic larvae have higher recruitment success than do planktotrophic larvae in marginal habitats, such as upwelling zones. This is supported by the correlation of brooding and eurytopy. The dispersal hypothesis suggests that brooders survive preferentially because lecithotrophic larvae, which typically inherit zooxanthellae from the egg, have a longer larval lifespan and, hence, a wider potential dispersal range, than planktotrophic larvae, which typically capture zooxanthellae from the water column. Biogeographic range data, however, do not support this second hypothesis: modern Indo-Pacific brooding and broadcasting genera have nearly identical ranges, and many brooding species have narrower longitudinal ranges than do broadcasting species. Preferential survivorship of brooding corals contrasts sharply with survivorship patterns among molluscs during extinction events; among molluscs, broadcasters are favored over brooders. A major increase in upwelling at the Oligocene/Miocene boundary was probably responsible for this extinction/geographic restriction event. Preferential survival of brooding and mixed mode coral genera appears to be a product of their being better able to recruit and survive in marginal conditions such as upwelling zones.
Phylogenetic Placement of Foot and Mouth Disease Virus during 2014 in Buffaloes, Egypt -

Foot-and-mouth disease virus (FMDV) SAT2 serotype is endemic in Egypt since 2012. The objectives of the present study were to investigate strain identification of FMDV infecting water buffaloes (Bubalus bubalis) in April, 2014, Qalyubia, Egypt. Therefore partial sequences were generated after detection by real time RT-PCR and subsequent gel purification of RT-PCR amplified products of VP1 gene of FMDV- SAT2. Partial sequencing of purified virus revealed that SAT2serotype of FMD was circulating in this region. Sequences were further examined by sequence analysis and subsequent phylogeny to compare these sequences from known strains of FMDV-SAT2 circulating globally and retrieved from GenBank. Nucleotide substitution generates polymorphism at position 13 nucleotide, where a Cytosine replaced a Thymine and at the levels of 22 nucleotide where Guanine substituted Adenosine. A partial sequence of SAT2 showed the highest level of homology 99.4% similarity with sequences from Egypt 2012 with diversion 0.6 but it is variable from its neighbor countries isolates. Phylogenetic analysis showed a robust tree clustering all samples with sequences belonging to the FMDV-SAT2 variant with strong bootstrap values at relevant nodes and the evolutionary distance between groups is very short. There is a substitution in the sequences of amino acids at the position of 8, where an Alanine is changed to a Threonine. These findings demonstrate the recent picture of FMDV-SAT2 which incriminated for buffalo infectivity and responsible for its persistence in the endemic areas. Such epidemiological data could guide the application of efficient control strategies of FMDV in Egypt.
Evaluation of the effectiveness of supplementing micro-encapsulated organic acids and essential oils in diets for sows and suckling piglets

Abstract This study was conducted to evaluate the effect of microencapsulated organic acids and essential oils (MOE) on reproductive performance, nutrient digestibility, piglet diarrhoea score, and blood profiles in sows and suckling piglets. A total of 60 multiparous sows (Landrace × Yorkshire) with an average initial body weight (BW) of 249.47 ± 11. 62 kg were used and randomly subjected to three treatments such that 20 replicates per treatment were maintained in this trial. Dietary treatments consisted of a basal diet supplemented with 0, 500, 1000 mg MOE/kg respectively. The BW of sows increased (linear, p = .014) before farrowing; after farrowing and weaning showed both linear and quadratic (p = <.001) effects with the increase in the dose of MOE in the diet. Further, results showed that tendency of reduced (p = .063) BW loss and increased (linear, p = .046) digestibility of dry matter in sows fed with MOE in the diet. The back fat loss and blood profiles were unaffected (p > .05) both in the sows and suckling piglets by the dietary treatment. Dietary inclusion of increasing level of MOE in sows’ diet increased (p < .05) BW, average daily gain, faecal score of suckling piglets and reduced the number of diarrheal piglets. Therefore, the addition of MOE can be considered as safe and effective enhancement in both farrowing and lactating sows as it favours the growth, nutrient digestibility and helps in avoidance of diarrhoea among suckling piglets.
Influence of Agitation Intensity and Aeration Rate on Production of Antioxidative Exopolysaccharides from Submerged Mycelial Culture of Ganoderma resinaceum

The present study investigated the influence of the aeration rate and agitation intensity on the production of the mycelial biomass and antioxidative exopolysaccharide (EPS) in Ganoderma resinaceum. In submerged cultures with varying agitation speeds and aeration rates in a stirred-tank reactor, the maximum mycelial biomass and maximum EPS concentration were achieved at 50 rpm and 300 rpm, respectively. Under varying aeration rates, the highest amount of mycelial biomass (18.1 g/l) was accumulated at the lowest aeration rate (0.5 vvm) and the maximum EPS production (3.0 g/l) obtained at 1.0 vvm. A compositional analysis revealed that the five different EPSs were protein-bound heteropolysaccharides, consisting of 87.17-89.22% carbohydrates and 10.78-12.83% proteins. The culture conditions had a striking affect on the carbohydrate composition of the EPS, resulting in different antioxidative activities. All the EPSs showed strong scavenging activities against superoxide and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radicals, whereas no clear trend in antioxidative activity was observed against hydroxyl radicals and lipid peroxides. Although the precise reason for this difference is still unclear, the high glucose moiety of EPS is probably linked to its broad spectrum of antioxidative activity.
Germination In Vitro, Micropropagation, and Cryogenic Storage for Three Rare Pitcher Plants: Sarracenia oreophila (Kearney) Wherry (Federally Endangered), S. leucophylla Raf., and S. purpurea spp. venosa (Raf.) Wherry

The genus Sarracenia forms a group of carnivorous pitcher plants native to North America. Habitat destruction and overcollection have caused pitcher plants to become rare, including U.S. federally endangered S. oreophila as well as S. leucophylla and S. purpurea spp. venosa (Raf.) Wherry, both listed as endangered in several states. Protocols for in vitro germination, sustainable shoot micropropagation, shoot establish- ment in soil, and seed cryopreservation are presented. Six-min sulfuric acid scarification treatments coupled with appropriate tissue culture media resulted in germination in vitro within 3 weeks, often reaching greater than 50%. Best germination for S. leucophylla and S. purpurea occurred on one-third strength Murashige and Skoog (MS) salts, whereas S. oreophila germinated best on one-sixth strength MS salts. Adjustment of pH to 4.5 to simulate a bog environment further increased germination for S. leucophylla . S hoot multiplication occurred at optimal levels when explants were placed on media in the presenceofacytokininwithoutauxinwithgreatestmultiplicationon6-benzylaminopurine (BAP) or trans-zeatin and best shoot quality on trans-zeatin. Plant establishment in soil required both an in vitro rooting treatment and use of shoot clusters resulting in greater than 80%survivalin soil. Seedcryopreservationtests withall three species suggeststorage in liquid N2 followed by in vitro micropropagation and plant establishment can be used to preserve material long term.
Better Match, Better Career: Comparing the Mediating Effects of Demands-Abilities Fit and Needs-Supplies Fit Between Career Exploration and Career Satisfaction

: In the boundaryless career era, employees tend to focus on their own needs and what they can obtain from jobs to make wise career choices and achieve a high level of career satisfaction. Using a sample of 230 Chinese employees, this study investigated the mediating effect of demands-abilities fit and needs-supplies fit in the relationship between career exploration and career satisfaction and compared the mediating effects of these two types of person-job fit. This study found that: 1) employees could achieve a higher level of career satisfaction by conducting more career exploration behaviors; 2) both demands-abilities fit and needs-supplies fit mediated the relationship between career exploration and career satisfaction; 3) the mediating effect of needs-supplies fit was stronger than that of demands-abilities fit. Theoretical and practical applications were also discussed.
Specific Detection of Klebsiella variicola and K. oxytoca by Loop-Mediated Isothermal Amplification

Klebsiella spp. are opportunistic pathogens with clinical, veterinary and plant-associated isolates. A previous study showed that bacterial ooze from wetwood of severely declined ironwood trees in Guam contained Ralstonia solanacearum, Klebsiella variicola and K. oxytoca. In this study, Loop-Mediated Isothermal Amplification (LAMP) detected K. variicola and K. oxytoca specifically, using unique primer sets designed individually for each organism. Each LAMP detected its target specifically, while showing negative results for non-target bacteria and negative controls. LAMP detected Klebsiella in inoculated-ironwood stem tissues and bacterial ooze. Due to the presence of plant inhibitors, different sampling protocols were tested. Soaking plant tissue samples to allow diffusion of bacteria into solution, followed by boiling, provided optimum detection of Klebsiella directly from plant samples. False negatives obtained when using crushed plant samples were eliminated by including an enrichment step, involving plating and 12-h incubation. DGGE (denaturing gradient gel electrophoresis) and a colony-blot immunoassay using a Klebsiella-specific antibody also detected Klebsiella in inoculated ironwood. DGGE bands and antibody crossreactions from closely related enterobacters showed the potential for false positive results. The nature of LAMP makes it ideal for point-of-care testing, and when combined with the specificity of the LAMP primers developed in this study, demonstrates its potential as a routine field test for Klebsiella in ironwood in Guam, as well as clinical and veterinary diagnosis of Klebsiella infection. Additionally, the regions targeted for detection in this study have application across all forms of molecular-based diagnostics.
A CONTRIBUTION TO THE PHYSIOLOGY OF WING DEVELOPMENT IN APHIDS

Results of the observations and experiments reported above may briefly be summarized as follows:1. Either an apterous or an alate parthenogenetic female may bear young larvae, some of which may finally attain the winged condition, while the others may remain wingless throughout life.2. When newly born aphids were reared on rose twigs planted in tumblers, containing washed and sterilized sand which had previously been saturated with the solution of a certain substance, nearly one hundred per cent. of winged individuals appeared on the twigs, while either none or few winged forms developed on the twigs charged with any one of another set of chemicals. For the sake of making a distinction between these two groups of substances, we may call the former the "wing-developing" substances, and the latter, the "non-wing-developing" substances.3. As far as the tests go, the salts of the alkalis (Na, Cl, K, etc.) and alkaline earths (Ca, Br) with the exception of magnesium, distilled water, urea, alum and others were .
Quantitative proteomics of human chromatin

The work presented in this thesis aims at unravelling human chromatin composition by quantitative proteomics to outline the functional and structural changes occurring during the life of human cells. Chromatin is the structure formed by proteins and RNAs interacting with the genetic material. At present, chromatin is not well defined. It is not easy to investigate either the composition of its constituent proteins or how this arrangement changes. We set out to analyse the chromatin composition changes occurring during the cell cycle. Our procedure couples a SILAC mass spectrometry-based approach with a newly developed biochemical chromatin purification method, which involves fixation of proteins to DNA. By testing two different fixation times (5 and 10 minutes) and three phases of the cell cycle (G1/S, G2, M), we quantified ∼3000 proteins providing a broad picture of the global changes on chromatin protein composition. Surprisingly, chromatin seems to be occupied by many unexpected proteins (40%) that appear to be increased during mitosis. We hypothesized that these unexpected proteins come into contact with DNA during mitosis when the nuclear envelope breaks down and the highly negatively charged DNA can be found in proximity to extra nuclear proteins. We used Pulse-SILAC technique that allows to distinguish newly synthesized proteins to test this possibility. By comparing in a single cell cycle and during G0 arrest the incorporation of new proteins into chromatin with their synthesis in the cytoplasm and in the whole cell, we could not find a different behaviour for the unexpected proteins as result of mitosis. Despite the efforts in tracking down the origin of these unexpected proteins, it is still uncertain whether their presence on chromatin is the result of a biological process or, in part, a drawback of the purification methods adopted. However, proving their genuine presence on chromatin will be important to elucidate how chromatin functions.