H-Ras Nanocluster Stability Regulates the Magnitude of MAPK Signal Output

H-Ras is a binary switch that is activated by multiple co-factors and triggers several key cellular pathways one of which is MAPK. The specificity and magnitude of downstream activation is achieved by the spatio-temporal organization of the active H-Ras in the plasma membrane. Upon activation, the GTP bound H-Ras binds to Galectin-1 (Gal-1) and becomes transiently immobilized in short-lived nanoclusters on the plasma membrane from which the signal is propagated to Raf. In the current study we show that stabilizing the H-Ras-Gal-1 interaction, using bimolecular fluorescence complementation (BiFC), leads to prolonged immobilization of H-Ras.GTP in the plasma membrane which was measured by fluorescence recovery after photobleaching (FRAP), and increased signal out-put to the MAPK module. EM measurements of Raf recruitment to the H-Ras.GTP nanoclusters demonstrated that the enhanced signaling observed in the BiFC stabilized H-Ras.GTP nanocluster was attributed to increased H-Ras immobilization rather than to an increase in Raf recruitment. Taken together these data demonstrate that the magnitude of the signal output from a GTP-bound H-Ras nanocluster is proportional to its stability

Influence of antenatal physical exercise on haemodynamics in pregnant women: a flexible randomisation approach

Background: Normal pregnancy is associated with marked changes in haemodynamic function, however theinfluence and potential benefits of antenatal physical exercise at different stages of pregnancy and postpartumremain unclear. The aim of this study was therefore to characterise the influence of regular physical exercise onhaemodynamic variables at different stages of pregnancy and also in the postpartum period.Methods: Fifty healthy pregnant women were recruited and randomly assigned (2 × 2 × 2 design) to a land orwater-based exercise group or a control group. Exercising groups attended weekly classes from the 20th week ofpregnancy onwards. Haemodynamic assessments (heart rate, cardiac output, stroke volume, total peripheralresistance, systolic and diastolic blood pressure and end diastolic index) were performed using the Task Forcehaemodynamic monitor at 12–16, 26–28, 34–36 and 12 weeks following birth, during a protocol including posturalmanoeurvres (supine and standing) and light exercise.Results: In response to an acute bout of exercise in the postpartum period, stroke volume and end diastolic indexwere greater in the exercise group than the non-exercising control group (p = 0.041 and p = 0.028 respectively).Total peripheral resistance and diastolic blood pressure were also lower (p = 0.015 and p = 0.007, respectively) in theexercise group. Diastolic blood pressure was lower in the exercise group during the second trimester (p = 0.030).Conclusions: Antenatal exercise does not appear to substantially alter maternal physiology with advancinggestation, speculating that the already vast changes in maternal physiology mask the influences of antenatalexercise, however it does appear to result in an improvement in a woman’s haemodynamic function (enhancedventricular ejection performance and reduced blood pressure) following the end of pregnancy

A Density-Dependent Switch Drives Stochastic Clustering and Polarization of Signaling Molecules

Positive feedback plays a key role in the ability of signaling molecules to form highly localized clusters in the membrane or cytosol of cells. Such clustering can occur in the absence of localizing mechanisms such as pre-existing spatial cues, diffusional barriers, or molecular cross-linking. What prevents positive feedback from amplifying inevitable biological noise when an un-clustered “off” state is desired? And, what limits the spread of clusters when an “on” state is desired? Here, we show that a minimal positive feedback circuit provides the general principle for both suppressing and amplifying noise: below a critical density of signaling molecules, clustering switches off; above this threshold, highly localized clusters are recurrently generated. Clustering occurs only in the stochastic regime, suggesting that finite sizes of molecular populations cannot be ignored in signal transduction networks. The emergence of a dominant cluster for finite numbers of molecules is partly a phenomenon of random sampling, analogous to the fixation or loss of neutral mutations in finite populations. We refer to our model as the “neutral drift polarity model.” Regulating the density of signaling molecules provides a simple mechanism for a positive feedback circuit to robustly switch between clustered and un-clustered states. The intrinsic ability of positive feedback both to create and suppress clustering is a general mechanism that could operate within diverse biological networks to create dynamic spatial organization

Philips Oy Healthcaren asiakaspalveluprosessin kehittäminen

Tämän insinöörityön aiheena on parantaa Philips Oy Healthcaren asiakaspalveluprosessia. Työn aiheeseen kuuluu vain pelkästään Suomessa palvelevaa Healthcaren osastoa. Työn tavoitteena oli parantaa Philips Oy Healthcaren asiakaspalveluprosessia työntekijöiden näkökulmasta, koska Philipsin johto näki siinä eniten parannettavaa. Tämän insinöörityön tutkimusmenetelmä oli laadullinen tutkimus, jolloin kaikkia Philips Oy Healthcaren asiakaspalvelijoita haastateltiin sekä myynnin että huollon puolelta. Haastateltavia oli yhteensä kuusi kappaletta ja heitä haastateltiin henkilökohtaisesti. Haastatteluista tehtyjen johtopäätöksien mukaan työtehtävät olivat erittäin epäselkeät. Tämän lisäksi puhelinrinkiin ei saatu sitovuutta ja sähköpostien hoitamisessa oli myös suuria vaikeuksia. Tutkimuksen tulokseksi saatiin uusi prosessikuvaus asiakaspalveluprosessiin, jossa on selitetty eri vaiheet ja tapahtumajärjestykset mahdollisimman selkeästi sekä ratkaisut sähköpostiin ja puhelinrinkiin. Tutkimustulosta eli prosessikuvaus annetaan työntekijöille työtehtävien selkeyttämiseksi, jolloin suurin hyöty aiheutuu työntekijöille työskennellessä