Distinct functions of integrin alpha and beta subunit cytoplasmic domains in cell spreading and formation of focal adhesions.

Integrin-mediated cell adhesion often results in cell spreading and the formation of focal adhesions. We exploited the capacity of recombinant human alpha IIb beta 3 integrin to endow heterologous cells with the ability to adhere and spread on fibrinogen to study the role of integrin cytoplasmic domains in initiation of cell spreading and focal adhesions. The same constructs were also used to analyze the role of the cytoplasmic domains in maintenance of the fidelity of the integrin repertoire at focal adhesions. Truncation mutants of the cytoplasmic domain of alpha IIb did not interfere with the ability of alpha IIb beta 3 to initiate cell spreading and form focal adhesions. Nevertheless, deletion of the alpha IIb cytoplasmic domain allowed indiscriminate recruitment of alpha IIb beta 3 to focal adhesions formed by other integrins. Truncation of the beta 3 subunit cytoplasmic domain abolished cell spreading mediated by alpha IIb beta 3 and also abrogated recruitment of alpha IIb beta 3 to focal adhesions. This truncation also dramatically impaired the ability of alpha IIb beta 3 to mediate the contraction of fibrin gels. In contrast, the beta 3 subunit cytoplasmic truncation did not reduce the fibrinogen binding affinity of alpha IIb beta 3. Thus, the integrin beta 3 subunit cytoplasmic domain is necessary and sufficient for initiation of cell spreading and focal adhesion formation. Further, the beta 3 cytoplasmic domain is required for the transmission of intracellular contractile forces to fibrin gels. The alpha subunit cytoplasmic domain maintains the fidelity of recruitment of the integrins to focal adhesions and thus regulates their repertoire of integrins

A point mutation of integrin beta 1 subunit blocks binding of alpha 5 beta 1 to fibronectin and invasin but not recruitment to adhesion plaques.

A point mutation in a highly conserved region of the beta 1 subunit, Asp130 to Ala (D130A) substitution, abrogates the Arg-Gly-Asp (RGD)-dependent binding of alpha 5 beta 1 to fibronectin (FN) without disrupting gross structure or heterodimer assembly. The D130A mutation also interferes with binding to invasin, a ligand that lacks RGD sequence. In spite of the lack of detectable FN binding by alpha 5 beta 1(D130A), it was recruited to adhesion plaques formed on FN by endogenous hamster receptors. Thus, intact ligand binding function is not required for recruitment of alpha 5 beta 1 to adhesion plaques. Overexpression of beta 1(D130A) partially interfered with endogenous alpha 5 beta 1 function, thus defining a dominant negative beta 1 integrin mutation

Updating DL-Lite ontologies through first-order queries

In this paper we study instance-level update in DL-LiteA, the description logic underlying the OWL 2 QL standard. In particular we focus on formula-based approaches to ABox insertion and deletion. We show that DL-LiteA, which is well-known for enjoying first-order rewritability of query answering, enjoys a first-order rewritability property also for updates. That is, every update can be reformulated into a set of insertion and deletion instructions computable through a nonrecursive datalog program. Such a program is readily translatable into a first-order query over the ABox considered as a database, and hence into SQL. By exploiting this result, we implement an update component for DLLiteA-based systems and perform some experiments showing that the approach works in practice.Peer ReviewedPostprint (author's final draft

Superconductivity of the Sr2Ca12Cu24O41Sr_2 Ca_{12} Cu_{24} O_{41} spin ladder system: Are the superconducting pairing and the spin-gap formation of the same origin?

Pressure-induced superconductivity in a spin-ladder cuprate Sr$_2$Ca$_{12}$Cu$_{24}$O$_{41}$ has not been studied on a microscopic level so far although the superconductivity was already discovered in 1996. We have improved high-pressure technique with using a large high-quality crystal, and succeeded in studying the superconductivity using $^{63}$Cu nuclear magnetic resonance (NMR). We found that anomalous metallic state reflecting the spin-ladder structure is realized and the superconductivity possesses a s-wavelike character in the meaning that a finite gap exists in the quasi-particle excitation: At pressure of 3.5GPa we observed two excitation modes in the normal state from the relaxation rate $T_1^{-1}$. One gives rise to an activation-type component in $T_1^{-1}$, and the other $T$-linear component linking directly with the superconductivity. This gapless mode likely arises from free motion of holon-spinon bound states appearing by hole doping, and the pairing of them likely causes the superconductivity.Comment: to be published in Phys. Rev. Let

Perinatal and long term effects of maternal uterine artery adenoviral VEGF-A165 gene therapy in the growth restricted guinea pig fetus

Uterine artery application of adenoviral vascular endothelial growth factor gene therapy (Ad.VEGF-A165) increases uterine blood flow and fetal growth in experimental animals with fetal growth restriction (FGR). Whether Ad.VEGF-A165 reduces lifelong cardiovascular disease risk imposed by FGR remains unknown. Here, pregnant guinea pigs fed 70% normal food intake to induce FGR received Ad.VEGF-A165 (1x1010 viral particles, n=15) or vehicle (n=10), delivered to the external surface of the uterine arteries, in mid-pregnancy. Ad libitum fed controls received vehicle only (n=14). Litter size, gestation length, and perinatal mortality were similar in control, untreated FGR and FGR+Ad.VEGF-A165 animals. Compared to controls, birth weight was lower in male but higher in female pups following maternal nutrient restriction, whilst both male and female FGR+Ad.VEGF-A165 pups were heavier than untreated FGR pups (P<0.05 ANOVA). Postnatal weight gain was 10-20% greater in female FGR+Ad.VEGF-A165 than untreated FGR pups, depending on age, although neither group differed from controls. Maternal nutrient restriction reduced heart weight in adult female offspring, irrespective of Ad.VEGF-A165 treatment, but did not alter ventricular wall thickness. In males, postnatal weight gain and heart morphology were not affected by maternal treatment. Neither systolic, diastolic nor mean arterial pressure, adrenal weight, basal or challenged plasma cortisol were affected by maternal undernutrition or Ad.VEGF-A165 in either sex. Therefore, increased fetal growth conferred by maternal uterine artery Ad.VEGF-A165 is sustained postnatally in FGR female guinea pigs. In this study we did not find evidence for an effect of maternal nutrient restriction or Ad.VEGF-A165 therapy on adult offspring blood pressure

Specifics of impurity effects in ferropnictide superconductors

Effects of impurities and disorder on quasiparticle spectrum in superconducting iron pnictides are considered. Possibility for occurrence of localized energy levels due to impurities within the superconducting gap and the related modification of band structure and of superconducting order parameter are discussed. The evolution of superconducting state with impurity doping is traced.Comment: 9 pages, 8 figure

Twitter-based analysis of the dynamics of collective attention to political parties

Large-scale data from social media have a significant potential to describe complex phenomena in real world and to anticipate collective behaviors such as information spreading and social trends. One specific case of study is represented by the collective attention to the action of political parties. Not surprisingly, researchers and stakeholders tried to correlate parties' presence on social media with their performances in elections. Despite the many efforts, results are still inconclusive since this kind of data is often very noisy and significant signals could be covered by (largely unknown) statistical fluctuations. In this paper we consider the number of tweets (tweet volume) of a party as a proxy of collective attention to the party, identify the dynamics of the volume, and show that this quantity has some information on the elections outcome. We find that the distribution of the tweet volume for each party follows a log-normal distribution with a positive autocorrelation of the volume over short terms, which indicates the volume has large fluctuations of the log-normal distribution yet with a short-term tendency. Furthermore, by measuring the ratio of two consecutive daily tweet volumes, we find that the evolution of the daily volume of a party can be described by means of a geometric Brownian motion (i.e., the logarithm of the volume moves randomly with a trend). Finally, we determine the optimal period of averaging tweet volume for reducing fluctuations and extracting short-term tendencies. We conclude that the tweet volume is a good indicator of parties' success in the elections when considered over an optimal time window. Our study identifies the statistical nature of collective attention to political issues and sheds light on how to model the dynamics of collective attention in social media.Comment: 16 pages, 7 figures, 3 tables. Published in PLoS ON

Association of Over-The-Counter Pharmaceutical Sales with Influenza-Like-Illnesses to Patient Volume in an Urgent Care Setting

We studied the association between OTC pharmaceutical sales and volume of patients with influenza-like-illnesses (ILI) at an urgent care center over one year. OTC pharmaceutical sales explain 36% of the variance in the patient volume, and each standard deviation increase is associated with 4.7 more patient visits to the urgent care center (p<0.0001). Cross-correlation function analysis demonstrated that OTC pharmaceutical sales are significantly associated with patient volume during non-flu season (p<0.0001), but only the sales of cough and cold (p<0.0001) and thermometer (p<0.0001) categories were significant during flu season with a lag of two and one days, respectively. Our study is the first study to demonstrate and measure the relationship between OTC pharmaceutical sales and urgent care center patient volume, and presents strong evidence that OTC sales predict urgent care center patient volume year round. © 2013 Liu et al

Test of exotic scalar and tensor interactions in K_e3 decay using stopped positive kaons

The form factors of the decay K+ --> pi0 e+ nu (K_e3) have been determined from the comparison of the experimental and Monte Carlo Dalitz distributions containing about 10^5 K_e3 events. The following values of the parameters were obtained: lambda_+ = 0.0278 +- 0.0017(stat) +- 0.0015(syst), f_S/f_+(0) = 0.0040 +- 0.0160(stat) +- 0.0067(syst) and f_T/f_+(0) = 0.019 +- 0.080(stat) +- 0.038(syst). Both scalar f_S and tensor f_T form factors are consistent with the Standard Model predictions of zero values.Comment: 10 pages, 5 figures, contributed to the proceedings of NANP Conference, Dubna, June 19-23, 200