Miracle-dz/UniFAR-FTUs huggingface dataset:
Focal Adhesion Kinase (FAK) as a novel therapeutic target in HER2+ breast cancer

Focal Adhesion Kinase (FAK) is an intracellular kinase known to mediate integrin signalling following cell adhesion to the extracellular matrix. It is now emerging as a promising therapeutic target in many tumour types due to its overexpression in tumour cells and is associated with various cellular processes involved in cancer progression. Given that existing literature demonstrating that FAK plays a key role in the transduction of HER2 signalling in HER2+ cells and that the levels of FAK expression strongly correlated with HER2 overexpression in clinical samples, we explored the potential for improvement of current therapies for HER2+ breast cancer by combination treatment strategies with the small molecule FAK inhibitor, PF878. FAK activity was assessed in a panel of cell lines reflecting HER2- (MCF7, T47D) and HER2+ (BT474, MDA-361, SKBr3) disease by Western blotting. FAK activity was relatively increased in HER2+ versus HER2- cell lines with HER2+ cells demonstrating greatest sensitivity to PF878 with respect to suppression of FAK phosphorylation at Y397. The effects of PF878 on cell proliferation as a monotherapy and in combination with Herceptin were assessed using MTT and direct coulter cell counting and by Ki67 immuno-staining. Whilst PF878 did not affect the proliferation as a monotherapy, treatment of HER2+ cells with PF878 and Herceptin combined resulted in synergistic inhibitory action on cell proliferation with an associated suppression in AKT pathway activity. This combination treatment strategy produced the greatest effects in MDA-361 cells which were intrinsically insensitive to Herceptin-monotherapy. Inhibition of FAK activity also suppressed HER2+ cell migration in response to the (1) exogenous ligand Heregulin and (2) conditioned-media derived from fibroblasts (FCM), as assessed in Boyden Chamber migration assays. In this latter context, our data suggests that FAK may act through a STAT3-dependent mechanism to regulate fibroblast-stimulated migratory and invasive responses. Collectively, these data support a role for FAK in HER2+ breast cancer where its targeting has the potential to improve Herceptin response as well as suppress stromal-induced signalling that can contribute to disease progression and spread.
Identification of a decapacitation factor in goat seminal plasma

The seminal plasma is complex mixture of the secretions of the testis, epididymis and the accessory glands. The secretory proteins of the epididymal fluid as well as those of the accessory glands appear along with spermatozoa as semen at the time of ejaculation. Some of these proteins coat the sperm surface and prevent the premature activation of the spermatozoa in the female reproductive tract. The activation of spermatozoa, which requires the removal of sperm- coating proteins, is necessitated for the entry of the spermatozoa into the oocyte at the site of fertilization. The adsorption of radiolabelled seminal plasma proteins on the sperm surface showed an absence of high molecular weight proteins, thus suggesting the reorganization of the sperm surface proteins during the process of capacitation. The effect of lyophilized goat seminal plasma proteins revealed an inhibitory effect on the capacitation after an initial preincubation of 3.5 h. The absorption of radiolabelled seminal plasma proteins on the sperm surface showed an absence of high molecular weight proteins, thus suggesting the reorganization of the sperm surface proteins during the process of capacitation. The amount of protein for a 50% decrease in the acrosome reaction as compared to the control in a dose- dependent response, ID50 is 2.45 mg. The factor is removed by the help of ultracentrifugation for 6 h and the pellet obtained showed an inhibitory effect at an initial preincubation of 3.5 h and the value of ID50 determined is 1.25 mg. An apparent mechanism of capacitation involves the rearrangement of sperm surface proteins and removal of the factor by ultracentrifugation shows that it is a high molecular weight protein.
The waistline of Indian men is expanding faster than women with general obesity and abdominal obesity reaching a epidemic in Indian subject with diabetes

Background & Objectives: People with obesity and overweight are increasing in India. This study aimed at determining the prevalence of generalized and abdominal obesity in diabetics and comparison between genders. Methods: An observational study held at Diabetes centre, betwee n 2013-2014. Classification of obesity was done usi ng WHO and IDF criteria for BMI in Asians, while Waist Circumferen ce and WHR per IDF criteria. WHO Asia Pacific guide lin s were used to define overweight [body mass index (BMI) ≥23 kg/m but <25 kg/m, generalized obesity, BMI ≥25kg/m), abdominal obesity, waist circumference ≥90 cm in men, ≥80cm for women). 4504 subjects (men 2741, women 176 3) with diabetes aged ≥ of 25 were recruited. Results: The prevalence rates were 2, 13, 31 & 54% women an d 3, 23, 48, & 26% men were lean, normal, overweight and obese res pectively. Comparing the waist circumference betwee n m n and women with IDF criteria 65% men (n=9235) and 89% (n =8175) have a WC above the normal. Waist hip ratio, identified higher prevalence rate in men (89%) compared to wom en (76%) and WHR was a sensitive index compared to WC. Interpretation & Conclusions: Higher prevalence of abdominal obesity compared to general obesity in diabetic population affected both genders similarly. Both ge neral and abdominal obesity prevalence are higher i n women than men. Our study found that AO had a higher prevalenc e i men contrary to the belief that women have hig her AO. Abdominal obesity is directly linked to increased m orbidity.
Macroarray for studying chloroplast gene expression profiles associated with the initial development of wheat

Chloroplasts, as photosynthetic carbon assimilating organelles, play an essential role in plants throughout their development. We have previously devised a mitochondrial macroarray using a set of rice and wheat mitochondrial genes to study their expression associated with biogenesis and initial development of this energy supplying organelle in wheat (1). We now report a chloroplast macroarray that can provide us with a useful means for studying chloroplast gene expression in wheat and other cereals. The chloroplast macroarray was constructed using 60 wheat chloroplast genes excluding tRNA and other small sized genes. In addition, five nuclear encoded and chloroplast-targeted genes and two control nuclear genes were included. Primer sets for the target genes were designed based on the published wheat chloroplast genome sequence (2). Changes in gene expression levels were monitored using RNA isolated from germinating seeds and seedlings at three different stages of development, i.e. at 1, 2 and 3 leaf stages. Remarkable differences and dynamic changes were revealed in the amount of individual transcripts during the initial stages of wheat development. The amount of psbA transcript increased until the 3 leaf stage. Those of psaA, psaB and psaC also increased significantly. Heterologous hybridisation was successful with cDNAs constructed from barley and rice seedlings, suggesting the versatility of this macroarray system for studies of chloroplast biogenesis and developmental changes in chloroplast gene expression in Gramineae. This system, after refining detailed protocol, can be utilized to depict chloroplast/plastid gene expression dynamics at different developmental stages and under various environmental conditions in cereals
Nouveaux rôles du régulateur de l'immunité MYB30 dans le développement d'Arabidopsis thaliana

MYB30 est un facteur de transcription d’Arabidopsis thaliana connu pour son role de regulateur positif des defenses via la production d’acides gras a tres longue chaine (VLCFA). La cuticule, une couche hydrophobe protectrice qui recouvre les parties aeriennes de la plante, est composee majoritairement de molecules lipidiques derivees des VLCFA. Dans cette these, nous avons montre que le gene MYB30 est exprime dans les cellules epidermiques de l’embryon, a une etape du developpement qui coincide avec la mise en place de la cuticule embryonnaire. Nos travaux revelent que lors de l’embryogenese, MYB30 controle l’expression de genes de biosynthese de la cuticule et la production de composes cuticulaires. En accord avec cela, nous avons montre que MYB30 est requis pour la formation d’une cuticule embryonnaire fonctionnelle. De plus, l’expression de MYB30 est dependante de GASSHO1 et GASSHO2 (GSO1/2), deux recepteurs de type Receptor Like Kinase (RLK) impliques dans une voie de signalisation specifique a la graine, necessaire pour la formation de la cuticule chez l’embryon. Nos donnees indiquent egalement que MYB30 regule negativement l’expression de GSO2, et que MYB30 pourrait agir en aval des deux RLK pour la formation de la cuticule embryonnaire. D’autre part, nous avons montre que ces deux RLK jouent egalement un role positif dans l’activation des reponses immunitaires de la plante adulte. Enfin, notre etude indique que MYB30 est aussi implique dans l’elongation cellulaire chez les plantules etiolees probablement via la regulation de la production de composes parietaux. En conclusion, ces travaux identifient de nouveaux roles pour MYB30, et le placent a l’interface entre les reponses de defense et le developpement de la plante.
Community level support for the allotonic frequency hypothesis

The allotonic frequency hypothesis proposes that some insectivorous bats increase their access to moths that can hear echolocation calls by using frequencies to which the ears of the moths are less sensitive. The hypothesis predicts that the frequencies of bat echolocation calls are positively correlated with the incidence of moths in the diet of these bats. Studies that have provided evidence in support of the allotonic frequency hypothesis have relied on data collected by a number of researchers, in a number of different ways and at different times. The aim of this study was to test the allotonic frequency hypothesis on a single African bat community so that data for the different species could be collected at more or less the same time and in the same way. This community consisted of three high duty cycle species, Cloeotis percivali, Hipposideros caffer, and Rhinolophus simulator, and two low duty cycle species, Miniopterus schreibersii and Scotophilus borbonicus. As predicted by the hypothesis, echolocation frequency was positively correlated with the proportion of moths in the diet of these bats. Echolocation frequency was also a better predictor of diet than wing morphology suggesting that the selection pressure exerted by moth hearing might have acted directly on call frequency and secondarily on wing morphology, as part of the same adaptive complex. These results suggest that structure of bat communities might be determined by prey defenses rather than by competition.
Enterpreneurs’ Characteristics as a Determinant of MSE Growth in Addis Ababa, Ethiopia

The study evaluated owner manager characteristics as a determinant of MSE growth. Utilizing a self administered questionnaire, data were collected from two sub-cities of Addis Ababa (Addis ketema an Arada sub-city) where large number of MSEs are located and 99 MSE owner/managers were proportionally selected. Analysis of variance was carried out and hypothesis tested to examine the variation in the growth of MSEs with respect to the variation in each of the independent variables. As two dependent variables were used to measure growth in this study, the result shows different statistical value for both of them. The ANOVA and t-test result indicates, there was a significant variation on the growth of MSEs in relation to the variations of gender, work experience and family back ground if growth is measured using asset growth. If growth is measured using employment growth, the difference in experience and family back ground brings difference in growth. But the study showed no significant difference between MSE growth with respect to the variation in the level of education of the owner/ managers whether growth is measured using asset and employment growth. The study found no evidence to support a common perception linking formal higher education with higher incidence of business success and growth.
The Roles of Free Fatty Acids and Inflammation in Î˛-Cell Dysfunction

β-cell lipotoxicity refers to the adverse effects of chronically elevated plasma free fatty acids on β-cell function and mass and plays an important role in type 2 diabetes. The objective of my thesis was to investigate the role of inflammation in fat-induced β-cell dysfunction in vivo. I used in vivo models of 48h intravenous fat infusion in mice followed by hyperglycemic clamps or islet secretion studies ex vivo, and in vitro models of 48h exposure to oleate and palmitate in islets. The first study showed the proinflammatory kinase IKKβ is causally involved in fat-induced β-cell dysfunction during hyperglycemic clamps in vivo, ex vivo in isolated islets of fat-infused rodents and in vitro in oleate-exposed islets. This is the first study to show directly that β-cell IKKβ plays a causal role in fat-induced β-cell dysfunction in vivo. Inflammation induces insulin resistance in the classical insulin target tissues muscle, fat and liver and the purpose of the second study was to determine whether β-cell insulin resistance plays a causal role in fat-induced β cell dysfunction. We used models of pharmacologic and genetic upregulation of insulin signaling, which were protected from fat-induced β-cell dysfunction in vivo and ex vivo. These data are the first to show that β-cell insulin resistance plays a causal role in β-cell dysfunction induced selectively by fat. The intracellular NOD1 receptor of innate immunity also affects metabolism, however its role in β-cell function is unknown and was the focus of the third study. Mouse and human islets expressed iii NOD1 mRNA, the NOD1 activator FK565 decreased β-cell function and NOD1-KO islets were protected from palmitate-induced β-cell dysfunction in vitro. In vivo, FK565 decreased β-cell function and NOD1-KO mice were protected from palmitate-induced β-cell dysfunction. These data demonstrate that NOD1 plays a causal role in saturated-fat induced β-cell dysfunction in vivo.
Dispersal ecology : the 42nd Symposium of the British Ecological Society held at the University of Reading, 2-5 April 2001

List of Contributors. History of the British Ecological Society. Preface.Part I: Techniques For Dispersal Studies:1 Measuring And Modelling Seed Dispersal Of Terrestrial Plants: D.F. Greene & C. Calogeropoulos.2 Monitoring Insect Dispersal: Methods And Approaches: J.L. Osborne, H.D. Loxdale & I.P. Woiwod.3 From Marking To Modelling: Dispersal Study Techniques For Land Vertebrates: R.E. Kenward, S.P. Rushton, C.M. Perrins, D.W. Macdonald & A.B. South.4 The Measurement Of Dispersal By Seabirds And Seals: Implications For Understanding Their Ecology: I.L. Boy.5 Inferring Patterns Of Dispersal From Allele Frequency Data: A.F. Raybould, R.T. Clarke, J.M. Bond, R.E. Welters & C.J. Gliddon.Part II: Dispersal In Behavioural And Evolutionary Ecology: 6 Sailing With The Wind: Dispersal By Small Flying Insects: S.G. Compton.7 Density-Dependent Dispersal In Animals: Concepts, Evidence, Mechanisms And Consequences: W.J. Sutherland, J.A Gill & K. Norris.8 Seed Dispersal-The Search For Trade-Offs: K. Thompson, L.C. Rickard, D.J. Hodkinson & M. Rees.9 Manipulating Your Host: Host-Pathogen Population Dynamics, Host Dispersal And Genetically-Modified Baculoviruses: G. Dwyer & R.S. Hails.10 Gene Flow And The Evolutionary Ecology Of Passively Dispersing Aquatic Invertebrates:. Okamura & J. Freeland.Part III: Dispersal And Spatial Processes:11 Niche Colonization And The Dispersal Of Bacteria And Their Genes In The Natural Environment: M.J. Bailey & A.J. Lilley.12 Dispersal Behaviour And Population Dynamics Of Vertebrates: H.P. Andreassen, N.C. Stenseth & R.A. Ims.13 Dispersal And The Spatial Dynamics Of Butterfly Populations: R.J. Wilson & C.D. Thomas.14 Plant Dispersal And Colonisation Processes At Local And Landscape Scales: J.M. Bullock, I.L. Moy, R.F. Pywell, S.J. Coulson, A.M. Nolan & H. Caswell.15 Biogeography And Dispersal: R. Hengeveld & L. Hemerik.Part IV: Applications Of An Understanding Of Dispersal:16 Modelling Vertebrate Dispersal And Demography In Real Landscapes: How Does Uncertainty Regarding Dispersal Behaviour Influence Predictions Of Spatial Population Dynamics? A.B. South, S.P. Rushton, R.E. Kenward & D.W. Macdonald.17 Invasion And Species Range Expansion: Effects Of Long-Distance Dispersal: N. Shigesada & K. Kawasaki.18 Success Factors In The Establishment Of Human-Dispersed Organisms: A.N. Cohen.19 Oases In The Desert: Dispersal And Host Specialization Of Biotrophic Fungal Pathogens Of Plants: J.K. M. Brown, M.S. Hovmoller, R.A. Wyand & D. Yu.20 Climate Change And Dispersal: A.R. Watkinson & J.A. Gill.Part V: Overview:21 Overview And Synthesis The Tale Of The Tail: M. Williamson. Index.
Avancées récentes en biologie moléculaire du virus de la diarrhée virale bovine

RESUME : La recherche sur le virus de la diarrhée virale bovine (BVDV) et les autres pestivirus a récemment abouti à des avancées significatives, en particulier concernant l'organisation du génome et la fonction des protéines virales. Cette revue fait le point sur ces progrès récents qui permettent de mieux comprendre la pathogénie de la diarrhée virale bovine et de la maladie des muqueuses. Les implications sur la vaccination et le diagnostic sont également abordées.
Investigation of varicella zoster virus glycoprotein-specific T cell responses

T cells are believed to be important in the control of varicella zoster virus (VZV) replication but little is known of T cell epitopes and the relationships between T cell responses, viral load and clinical disease during primary infection. I initially set to investigate the immune responses to two of the main VZV glycoproteins (gE and gI) using ex vivo and cultured IFNγ ELISpot assays. I identified several novel CD4+ T cell epitopes within gE and gI and characterized the phenotype of gE DRB1*1501 tetramer specific responses in healthy immune donors. I then set out to investigate the function and phenotype of VZV specific T cells in primary infection and their relationship to viral loads and clinical disease severity by using glycoprotein E/DRB1*1501 specific MHC class II tetramers, ex vivo IFNγ ELISpot assays and quantitative real time PCR assays. I compared the frequency and phenotype of specific T cells with virological and clinical outcomes in 32 adult individuals with primary VZV infection. In healthy immune donors, the gE specific T cells showed a early intermediate stage of differentiation with evidence of recent activation. Patients with acute primary infection had higher VZV/DRB1*1501 tetramer specific T cell responses and expressed markers of activation and effector differentiation. Viral loads were found to be significantly higher in patients with moderate to severe infection compared to those with mild infection (p ex vivo IFNγ ELISpot responses of the patients (p These data would be compatible with a role for gE and gl-specific T cells in the control of viral replication during both primary infection and re-activation.
Variabilité de l'adaptation à la sécheresse des cèdres méditerranéens (Cedrus atlantica, C. brevifolia et C. libani) : aspects écophysiologiques

Nous avons caracterise et compare le comportement ecophysiologique des cedres mediterraneens (Cedrus atlantica, et C. libani et C. brevifolia) et leur reaction a la secheresse. L'acclimatation a la secheresse a ete realisee en soumettant la moitie d'un ensemble de plants de 3 ans a une longue periode de secheresse moderee, l'autre moitie etant bien irriguee. L'effet d'une secheresse drastique courte a ete etudie sur des plants des 2 traitements hydriques. Plusieurs parametres ecophysiologiques dont la croissance, l'assimilation nette de CO2 (A), la conductance stomatique (gs), la vulnerabilite du xyleme a l'embolie, la resistance du photosysteme II (PSII) aux fortes temperatures et la composition isotopique en 13C (delta 13C) ont ete etudies. C. brevifolia a une faible croissance. Elle est peu sensible a la secheresse (croissance ou echanges gazeux). Son efficience intrinseque d'utilisation de l'eau (WUEi) est faible. C. atlantica presente une forte croissance, une WUEi elevee, mais aussi une forte sensibilite a la secheresse. Son xyleme est le plus vulnerable a l'embolie et elle a un PSII plus sensible aux fortes temperatures.C. libani presente des caracteristiques intermediaires. La secheresse moderee a augmente la thermotolerance du PSII. La variabilite ecophysiologique de C. libani a ete etudiee en comparant, durant 3 ans, la biomasse, la croissance et delta 13C de 19 provenances turques et libanaise. L'effet de la secheresse atmospherique (VPD) sur les echanges gazeux a ete etudie. La hauteur, la biomasse, le rapport entre partie aerienne et partie racinaire ainsi que delta 13C s'averent plus variables que la reponse des echanges gazeux au VPD. Les provenances libanaises sont plus performantes du point de vue croissance. Elles paraissent moins adaptees a la secheresse que les provenances turques. La variabilite de reponse au VPD au sein de l'espece C. libani est faible. La diminution de g. et de A, qui suit l'augmentation du VPD, est plus forte chez les plants acclimates a la secheresse.
Phylogeographic patterns of the Lysianassoidea (Crustacea: Peracarida: Amphipoda)

Phylogeographic patterns on Southern Ocean lysianassoid amphipods are discussed. First, the patterns of genetic structure within and between Antarctic species of Orchomene sensu lato has been investigated by DNA barcoding. Second, phylogeographic studies have been carried out on the assumed cosmopolitan deep-sea species Eurythenes gryllus. Third, DNA barcoding results on other Antarctic lysianassoids are presented. A summary of these studies discusses the geographic and bathymetric distributions, the findings of (pseudo)cryptic lineages and species, circum-Antarctic, bipolar and cosmopolitan species as well as the phenomenon of eurybathy versus vertical segregation. Finally, the observed patterns are linked with the feeding ecology and evolutionary history of the species, which might explain the genetic patterns observed across its distributional range.