Rho GTPases and signaling networks

The Rho GTPases form a subgroup of the Ras superfamily of 20- to 30-kD GTP-binding proteins that have been shown to regulate a wide spectrum of cellular functions. These proteins are ubiquitously expressed across the species, from yeast to man. The mammalian Rho-like GTPases comprise at least 10 distinct proteins: RhoA, B, C, D, and E; Rac1 and 2; RacE; Cdc42Hs, and TC10. A comparison of the amino acid sequences of the Rho proteins from various species has revealed that they are conserved in primary structure and are 50%–55% homologous to each other. Like all members of the Ras superfamily, the Rho GTPases function as molecular switches, cycling between an inactive GDP-bound state and an active GTP-bound state. Until recently, members of the Rho subfamily were believed to be involved primarily in the regulation of cytoskeletal organization in response to extracellular growth factors. However, research from a number of laboratories over the past few years has revealed that the Rho GTPases play crucial roles in diverse cellular events such as membrane trafficking, transcriptional regulation, cell growth control, and development. Consequently, a major challenge has been to unravel the underlying molecular mechanisms by which the Rho GTPases mediate these various activities. Many targets of the Rho GTPases have now been identified and further characterization of some of them has provided major insights toward our understanding of Rho GTPase function at the molecular level. This review aims to summarize the general established principles about the Rho GTPases and some of the more recent exciting findings, hinting at novel, unanticipated functions of the Rho GTPases

Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial

Objective To determine the efficacy of a probiotic drink containing Lactobacillus for the prevention of any diarrhoea associated with antibiotic use and that caused by Clostridium difficile. Design Randomised double blind placebo controlled study. Participants 135 hospital patients (mean age 74) taking antibiotics. Exclusions included diarrhoea on admission, bowel pathology that could result in diarrhoea, antibiotic use in the previous four weeks, severe illness, immunosuppression, bowel surgery, artificial heart valves, and history of rheumatic heart disease or infective endocarditis. Intervention Consumption of a 100 g (97 ml) drink containing Lactobacillus casei, L bulgaricus, and Streptococcus thermophilus twice a day during a course of antibiotics and for one week after the course finished. The placebo group received a longlife sterile milkshake. Main outcome measures Primary outcome: occurrence of antibiotic associated diarrhoea. Secondary outcome: presence of C difficile toxin and diarrhoea. Results 7/57 (12%) of the probiotic group developed diarrhoea associated with antibiotic use compared with 19/56 (34%) in the placebo group (P=0.007). Logistic regression to control for other factors gave an odds ratio 0.25 (95% confidence interval 0.07 to 0.85) for use of the probiotic, with low albumin and sodium also increasing the risk of diarrhoea. The absolute risk reduction was 21.6% (6.6% to 36.6%), and the number needed to treat was 5 (3 to 15). No one in the probiotic group and 9/53 (17%) in the placebo group had diarrhoea caused by C difficile (P=0.001). The absolute risk reduction was 17% (7% to 27%), and the number needed to treat was 6 (4 to 14). Conclusion Consumption of a probiotic drink containing L casei, L bulgaricus, and S thermophilus reduce the incidence of antibiotic associated diarrhoea and C difficile associated diarrhoea. This has the potential to decrease morbidity, healthcare costs, and mortality if used routinely in patients aged over 50

A Clinical Study of Blunt Ocular Trauma in a Tertiary Care Centre.

Purpose: To analyze blunt eye injuries with respect to mode of injury, sites involved and outcome. Method: This was a retrospective study of 32 patients with blunt ocular trauma from 2010 to 2012 in a tertiary care centre. Patient data, mode and extent of injury, management and outcome was noted and analyzed. Result: The commonest age of presentation was 10-20 years (28.125%) and the commonest mode of injury was road traffic accident (28.125%). The most commonly involved structure was conjunctiva (84.375%), followed by lid and adnexa (62.5%). Anterior segment involvement included corneal epithelial defect (7 cases), hyphaema (4 cases), iritis (3 cases) and anterior dislocation of lens (1 case). Posterior segment involvement included vitreous haemorrhage (1 case) and commotio retinae (2 cases). Conclusion: This study reinforces that blunt trauma can cause any extent of damage to ocular structures and the final visual outcome is dependent on the structures injured

Rac regulates integrin-mediated spreading and increased adhesion of T lymphocytes

Leukocyte adhesion to the extracellular matrix (ECM) is tightly controlled and is vital for the immune response. Circulating lymphocytes leave the bloodstream and adhere to ECM components at sites of inflammation and lymphoid tissues. Mechanisms for regulating T-lymphocyte-ECM adhesion include (i) an alteration in the affinity of cell surface integrin receptors for their extracellular ligands and (ii) an alteration of events following postreceptor occupancy (e.g., cell spreading). Whereas H-Ras and R-Ras were previously shown to affect T-cell adhesion by altering the affinity state of the integrin receptors, no signaling molecule has been identified for the second mechanism. In this study, we demonstrated that expression of an activated mutant of Rac triggered dramatic spreading of T cells and their increased adhesion on immobilized fibronectin in an integrin-dependent manner. This effect was not mimicked by expression of activated mutant forms of Rho, Cdc42, H-Ras, of ARF6, indicating the unique role of pac in this event. The Rac-induced spreading was accompanied by specific cytoskeletal rearrangements; Also, a clustering of integrins at sites of cell adhesion and at the peripheral edges of spread cells was observed. We demonstrate that expression of RacV12 did not alter the level of expression of cell surface integrins or the affinity state of the integrin receptors. Moreover, our results indicate that Rac plays a role in the regulation of T-cell adhesion by a mechanism involving cell spreading, rather than by altering the level of expression or the affinity of the integrin receptors. Furthermore, we show that the Rac-mediated signaling pathway leading to spreading of T lymphocytes did not require activation of c-Jun kinase, serum response factor, or pp70(S6) (kinase) but appeared to involve a phospholipid kinase

Testing equivalence of pure quantum states and graph states under SLOCC

A set of necessary and sufficient conditions are derived for the equivalence of an arbitrary pure state and a graph state on n qubits under stochastic local operations and classical communication (SLOCC), using the stabilizer formalism. Because all stabilizer states are equivalent to a graph state by local unitary transformations, these conditions constitute a classical algorithm for the determination of SLOCC-equivalence of pure states and stabilizer states. This algorithm provides a distinct advantage over the direct solution of the SLOCC-equivalence condition for an unknown invertible local operator S, as it usually allows for easy detection of states that are not SLOCC-equivalent to graph states.Comment: 9 pages, to appear in International Journal of Quantum Information; Minor typos corrected, updated references

The power of choice in network growth

The "power of choice" has been shown to radically alter the behavior of a number of randomized algorithms. Here we explore the effects of choice on models of tree and network growth. In our models each new node has k randomly chosen contacts, where k > 1 is a constant. It then attaches to whichever one of these contacts is most desirable in some sense, such as its distance from the root or its degree. Even when the new node has just two choices, i.e., when k=2, the resulting network can be very different from a random graph or tree. For instance, if the new node attaches to the contact which is closest to the root of the tree, the distribution of depths changes from Poisson to a traveling wave solution. If the new node attaches to the contact with the smallest degree, the degree distribution is closer to uniform than in a random graph, so that with high probability there are no nodes in the network with degree greater than O(log log N). Finally, if the new node attaches to the contact with the largest degree, we find that the degree distribution is a power law with exponent -1 up to degrees roughly equal to k, with an exponential cutoff beyond that; thus, in this case, we need k >> 1 to see a power law over a wide range of degrees.Comment: 9 pages, 4 figure

Predictors of dental visits among primary school children in the rural Australian community of Lithgow

Background: Regular dental attendance is significant in maintaining and improving children’s oral health and well-being. This study aims to determine the factors that predict and influence dental visits in primary school children residing in the rural community of Lithgow, New South Wales (NSW), Australia. Methods: All six primary schools of Lithgow were approached to participate in a cross-sectional survey prior to implementing water fluoridation in 2014. Children aged 6–13 years (n = 667) were clinically examined for their oral health status and parents were requested to complete a questionnaire on fluoride history, diet, last dental visit, and socio-demographic characteristics. Multiple logistic regression analyses were employed to examine the independent predictors of a 6-monthly and a yearly dental visit. Results: Overall, 53% of children visited a dentist within six months and 77% within twelve months. In multiple logistic regression analyses, age of the child and private health insurance coverage were significantly associated with both 6-monthly and twelve-month dental visits. In addition, each serve of chocolate consumption was significantly associated with a 27% higher odds (OR = 1.27, 95% CI: 1.05-1.54) of a 6-monthly dental visit. Conclusion: It is imperative that the socio-demographic and dietary factors that influence child oral health must be effectively addressed when developing the oral health promotion policies to ensure better oral health outcomes.James Rufus John, Haider Mannan, Subrat Nargundkar, Mario D’Souza, Loc Giang Do and Amit Aror