Expression of the NH(2)-terminal fragment of RasGAP in pancreatic beta-cells increases their resistance to stresses and protects mice from diabetes.

OBJECTIVE: Our laboratory has previously established in vitro that a caspase-generated RasGAP NH(2)-terminal moiety, called fragment N, potently protects cells, including insulinomas, from apoptotic stress. We aimed to determine whether fragment N can increase the resistance of pancreatic beta-cells in a physiological setting. RESEARCH DESIGN AND METHODS: A mouse line, called rat insulin promoter (RIP)-N, was generated that bears a transgene containing the rat insulin promoter followed by the cDNA-encoding fragment N. The histology, functionality, and resistance to stress of RIP-N islets were then assessed. RESULTS: Pancreatic beta-cells of RIP-N mice express fragment N, activate Akt, and block nuclear factor kappaB activity without affecting islet cell proliferation or the morphology and cellular composition of islets. Intraperitoneal glucose tolerance tests revealed that RIP-N mice control their glycemia similarly as wild-type mice throughout their lifespan. Moreover, islets isolated from RIP-N mice showed normal glucose-induced insulin secretory capacities. They, however, displayed increased resistance to apoptosis induced by a series of stresses including inflammatory cytokines, fatty acids, and hyperglycemia. RIP-N mice were also protected from multiple low-dose streptozotocin-induced diabetes, and this was associated with reduced in vivo beta-cell apoptosis. CONCLUSIONS: Fragment N efficiently increases the overall resistance of beta-cells to noxious stimuli without interfering with the physiological functions of the cells. Fragment N and the pathway it regulates represent, therefore, a potential target for the development of antidiabetes tools.

Timing effects of combined radioimmunotherapy and radiotherapy on a human solid tumor in nude mice.

Timing effects of radioimmunotherapy (RIT) combined with external-beam radiotherapy (RT) were assessed in human colon carcinoma xenografts. Initially, dose effects of fractionated RT and RIT were evaluated separately. Then, 30 Gy RT (10 fractions over 12 days) were combined with three weekly i.v. injections of 200 microCi of 131I-labeled anti-carcinoembryonic antigen monoclonal antibodies in four different treatment schedules. RIT was given either prior to, concurrently, immediately after, or 2 weeks after RT administration. The longest regrowth delay (RD) of 105 days was observed in mice treated by concurrent administration of RT and RIT, whereas the RDs of RT and RIT alone were 34 and 20 days, respectively. The three sequential combination treatments produced significantly shorter RDs ranging from 62 to 70 days. The tumor response represented by the minimal volume (MV) also showed that concurrent administration of RT and RIT gave the best result, with a mean MV of 4.5% as compared to MVs from 26 to 53% for the three sequential treatments. The results were confirmed in a second experiment, in which a RT of 40 Gy was combined with an identical RIT as above (three injections of 200 microCi of 131I-labeled monoclonal antibodies). At comparable toxicity levels, the maximum tolerated RT or RIT alone gave shorter RDs and less tumor shrinkage compared to simultaneous RT+ RIT. These results may be useful for designing clinical protocols of combined RIT and RT.

Fact Sheet: Extreme Heat, 2001

Doing too much on a hot day, spending too much time in the sun or staying too long in an overheated place can cause heat-related illnesses. Know the symptoms of heat disorders and overexposure to the sun, and be ready to give first aid treatment.

Kinetic parameters of soil β-glucosidase response to environmental temperature and moisture regimes

Soil β-glucosidase participates in the final step of cellulose biodegradation. It is significant in the soil C cycle and is used as an indicator of the biological fertility of soil. However, the response of its kinetic parameters to environmental temperature and moisture regimes is not well understood. This study tested the β-glucosidase response in the main agricultural soils (black soil, albic soil, brown soil, and cinnamon soil) of Northeast China. Incubation tests were conducted to measure the kinetic parameters Km, Vmax or Vmax/Km of soil β-glucosidase at environmental temperatures of 10, 20 and 30 ºC and at 10, 20 and 30 % soil moisture content. The insensitive response of the kinetic parameters to temperature changes indicates that soil β-glucosidase was present primarily in immobilized form. The significant response of the kinetic parameters of soil β-glucosidase to soil moisture rather than to environmental temperatures suggests that the catalytic ability of soil β-glucosidase was sensitive to changing soil moisture regimes.

Suppression of scroll wave turbulence by noise

Rotating scroll waves are dynamical spatiotemporal structures characteristic of three-dimensional active media. It is well known that, under low excitability conditions, scroll waves develop an intrinsically unstable dynamical regime that leads to a highly disorganized pattern of wave propagation. Such a ¿turbulent¿ state bears some resemblance to fibrillation states in cardiac tissue. We show here that this unstable regime can be controlled by using a spatially distributed random forcing superimposed on a control parameter of the system. Our results are obtained from numerical simulations but an explicit analytical argument that rationalizes our observations is also presented.

Parvalbumin interneurons mediate neuronal circuitry-neurogenesis coupling in the adult hippocampus.

Using immunohistology, electron microscopy, electrophysiology and optogenetics, we found that proliferating adult mouse hippocampal neural precursors received immature GABAergic synaptic inputs from parvalbumin-expressing interneurons. Recently shown to suppress adult quiescent neural stem cell activation, parvalbumin interneuron activation promoted newborn neuronal progeny survival and development. Our results suggest a niche mechanism involving parvalbumin interneurons that couples local circuit activity to the diametric regulation of two critical early phases of adult hippocampal neurogenesis.

Cinema Roads to the Platonic Image of the Cave

The aim of this article is to prove the real possibility of travelling intellectually to the Platonic image of the cave from different films. In this sense, one can speak of explicit references as in The Conformist by B. Bertolucci or in Shadowlands by R. Attenborough -if one bears in mind the Chronicles of Narnia by C. S. Lewis- or The Picture of Dorian Gray ¿if one bears in mind the well-known O. Wilde¿s novel-, but, on other occasions, although the Platonic influence cannot be proved, for instance in The Truman Show, A Room with a View or Brideshead Revisited, one can perfectly think of these films in order to guide the contemporary audiences to that Platonic image, since Plato himself affirms that it deals with an image which can be easily applied and, in first place, to his idealistic philosophy.

Leaving the cave in search of life (A Platonic reading of R. Sirera's La caverna (The Cave)

The aim of this article is to show how a contemporary playwright thinks once more of the Platonic image of the cave in order to reflect on the necessary existential journey of men and women as in the case of a Bildungsroman. Sooner or later men and women must abandon the protection that any sort of cavern such as home, the family garden or family itself can offer. In spite of writing from a by no means idealistic or metaphysical point of view, thanks to R. Sirera and to the very applicability of Platonic images, Plato becomes once again a classical reference which is both useful and even unavoidable if one bears in mind the Platonic origin of all the literary caverns.

John Addington Symonds. A Problem in Greek Ethics. Plutarch's Eroticus quoted only in some footnotes? Why?

It is certainly astonishing that an innovating study about the Greek pederasty in England like the one by John Addington Symonds does not quote Plutarch's Eroticus -in fact, it is only cited in some footnotes-, if one bears in mind that this dialogue is an accurate philosophical reflection on Greek eros, in which very often significant ethical themes are approached. The aim of this article is just to reveal the different reasons for such an omission.

Epidemiologie und Prävention des Hautmelanoms in der Schweiz: Update 2010. [Epidemiology and prevention of melanoma in Switzerland: 2010 update]

Zusammenfassung] Die Inzidenz des malignen Melanoms steigt seit über 50 Jahren bei der weißen Bevölkerung stark an. Die Schweiz ist mit ungefähr 1900 neu diagnostizierten Fällen pro Jahr das am stärksten betroffene Land Europas (16/100 000 Welt-standardisierte Rate). In letzter Zeit sind regionale Unterschiede mit höherer Inzidenz in den Westschweizer Kantonen festzustellen. Änderungen in Wissen und Verhalten der Schweizer Bevölkerung gegenüber dem Schutz vor Sonnenexposition bestehen noch zu wenig lange und sind zu bescheiden, als dass sie schon einen Einfluss auf die Inzidenz hätten haben können. Dank der seit 20 Jahren betriebenen Früherfassung sind Überlebensrate und Anteil an dünnen Melanomen gestiegen, allerdings bei gleichbleibender Inzidenz dicker Läsionen. Die Mortalität aufgrund des malignen Melanoms ist neuerdings rückläufig, vor allem bei den Frauen. Werden die gegenwärtigen Präventionsbemühungen weitergeführt, dürften sich bald noch mehr Erfolge zeigen. [Abstract] The incidence of cutaneous malignant melanoma has steadily increased in Caucasian populations over the last decades. With around 1900 new cases each year, Switzerland has one of the highest melanoma rates in Europe (16/100 000 world-standardised rate). Regional differences are emerging within Switzerland, with a higher incidence in the western (French-speaking) region. Observed changes in sun protection attitudes and knowledge in the Swiss population have yet no impact on the incidence trend. Early detection, carried out since the mid 1980s in Switzerland, has led to a substantial increase in survival and rates of thin melanoma, without material change in rates of thick melanoma. Mortality from melanoma has recently decreased, earlier in women than men. The efficacy of prevention campaigns should soon become more blatant if current efforts persist.

Dark energy equation of state and anthropic selection

We explore the possibility that the dark energy is due to a potential of a scalar field and that the magnitude and the slope of this potential in our part of the Universe are largely determined by anthropic selection effects. We find that, in some models, the most probable values of the slope are very small, implying that the dark energy density stays constant to very high accuracy throughout cosmological evolution. In other models, however, the most probable values of the slope are such that the slow roll condition is only marginally satisfied, leading to a recollapse of the local universe on a time scale comparable to the lifetime of the Sun. In the latter case, the effective equation of state varies appreciably with the redshift, leading to a number of testable predictions.

Nanotechnology: balancing benefits and risks to public health and the environment : expert paper

Nanotechnology has been heralded as a "revolution" in science, for two reasons: first, because of its revolutionary view of the way in which chemicals and elements, such as gold and silver, behave, compared to traditional scientific understanding of their properties. Second, the impact of these new discoveries, as applied to commerce, can transform the daily life of consumer products ranging from sun tan lotions and cosmetics, food packaging and paints and coatings for cars, housing and fabrics, medicine and thousands of industrial processes.9 Beneficial consumer use of nanotechnologies, already in the stream of commerce, improves coatings on inks and paints in everything from food packaging to cars. Additionally, "Nanomedicine" offers the promise of diagnosis and treatment at the molecular level in order to detect and treat presymptomatic disease,10 or to rebuild neurons in Alzheimer's and Parkinson's disease. There is a possibility that severe complications such as stroke or heart attack may be avoided by means of prophylactic treatment of people at risk, and bone regeneration may keep many people active who never expected rehabilitation. Miniaturisation of diagnostic equipment can also reduce the amount of sampling materials required for testing and medical surveillance. Miraculous developments, that sound like science fiction to those people who eagerly anticipate these medical products, combined with the emerging commercial impact of nanotechnology applications to consumer products will reshape civil society - permanently. Thus, everyone within the jurisdiction of the Council of Europe is an end-user of nanotechnology, even without realising that nanotechnology has touched daily life.

Less Risk, More Effort : Demand Risk Allocation in Incomplete Contracts

This article investigates the allocation of demand risk within an incomplete contract framework. We consider an incomplete contractual relationship between a public authority and a private provider (i.e. a public-private partnership), in which the latter invests in non-verifiable cost-reducing efforts and the former invests in non-verifiable adaptation efforts to respond to changing consumer demand over time. We show that the party that bears the demand risk has fewer hold-up opportunities and that this leads the other contracting party to make more effort. Thus, in our model, bearing less risk can lead to more effort, which we describe as a new example of âeuro~counter-incentivesâeuro?. We further show that when the benefits of adaptation are important, it is socially preferable to design a contract in which the demand risk remains with the private provider, whereas when the benefits of cost-reducing efforts are important, it is socially preferable to place the demand risk on the public authority. We then apply these results to explain two well-known case studies.