A laboratory scale model technique for investigating pneumatic tire hydroplaning

Laboratory scale model technique for investigating pneumatic tire hydroplanin

Ecto-protein kinases and phosphatases: an emerging field for translational medicine

Progress in translational research has led to effective new treatments of a large number of diseases. Despite this progress, diseases including cancer and cardiovascular disorders still are at the top in death statistics and disorders such as osteoporosis and osteoarthritis represent an increasing disease burden in the aging population. Novel strategies in research are needed more than ever to overcome such diseases. The growing field of extracellular protein phosphorylation provides excellent opportunities to make major discoveries of disease mechanisms that can lead to novel therapies. Reversible phosphorylation/dephosphorylation of sites in the extracellular domains of matrix, cell-surface and trans-membrane proteins is emerging as a critical regulatory mechanism in health and disease. Moreover, a new concept is emerging from studies of extracellular protein phosphorylation: in cells where ATP is stored within secretory vesicles and released by exocytosis upon cell-stimulation, phosphorylation of extracellular proteins can operate as a messenger operating uniquely in signaling pathways responsible for long-term cellular adaptation. Here, we highlight new concepts that arise from this research, and discuss translation of the findings into clinical applications such as development of diagnostic disease markers and next-generation drugs

És possible evitar un col·lapse de la civilització global?

En el número 48 de la revista L'Espill trobaràs un dossier monogràfic sobre "Cap a un col·lapse de la civilització industrial?", amb contribucions d'Antonio Turiel, Luc Semal, Ernest Garcia, Paul R. Ehrlich, Anne H. Ehrlich i Alain Gras. A més, articles d'Antoni Mora, François Rastier, Simona Škrabec, Joan Ramon Resina, Jacobo Muñoz Veiga, Faust Ripoll Domènech, Tobies Grimaltos Mascarós i Narcís Selles Rigat, així com documents del Manifest «Darrera crida», un full de dietari de Vicent Alonso i una conversa amb Tomàs Llorens

Vertebrates on the Brink as Indicators of Biological Annihilation and the Sixth Mass Extinction

The ongoing sixth mass species extinction is the result of the destruction of component populations leading to eventual extirpation of entire species. Populations and species extinctions have severe implications for society through the degradation of ecosystem services. Here we assess the extinction crisis from a different perspective. We examine 29,400 species of terrestrial vertebrates, and determine which are on the brink of extinction because they have fewer than 1,000 individuals. There are 515 species on the brink (1.7% of the evaluated vertebrates). Around 94% of the populations of 77 mammal and bird species on the brink have been lost in the last century. Assuming all species on the brink have similar trends, more than 237,000 populations of those species have vanished since 1900. We conclude the human-caused sixth mass extinction is likely accelerating for several reasons. First, many of the species that have been driven to the brink will likely become extinct soon. Second, the distribution of those species highly coincides with hundreds of other endangered species, surviving in regions with high human impacts, suggesting ongoing regional biodiversity collapses. Third, close ecological interactions of species on the brink tend to move other species toward annihilation when they disappear—extinction breeds extinctions. Finally, human pressures on the biosphere are growing rapidly, and a recent example is the current coronavirus disease 2019 (Covid-19) pandemic, linked to wildlife trade. Our results reemphasize the extreme urgency of taking much-expanded worldwide actions to save wild species and humanity’s crucial life-support systems from this existential threat

Modulation of Neuronal Signal Transduction Systems by Extracellular ATP

The secretion of ATP by stimulated nerves is well documented. Following repetitive stimulation, extracellular ATP at the synapse can accumulate to levels estimated to be well over 100 Μ M. The present study examined the effects of extracellular ATP in the concentration range of 0.1–1.0 m M on second-messenger-generating systems in cultured neural cells of the clones NG108-15 and NIE-115. Cells in a medium mimicking the physiological extracellular environment were used to measure 45 Ca 2+ uptake, changes in free intracellular Ca 2+ levels by the probes aequorin and Quin-2, de novo generation of cyclic GMP and cyclic AMP from intracellular GTP and ATP pools prelabeled with [ 3 H]guanosine and [ 3 H]adenine, respectively, and phosphoinositide metabolism in cells preloaded with [ 3 H]inositol and assayed in the presence of LiCI. Extracelluar ATP induced a concentration-dependent increase of 45 Ca 2+ uptake by intact cells, which was additive with the uptake induced by K + depolarization. The increased uptake involved elevation of intracellular free Ca 2+ ions, evidenced by measuring aequorin and Quin-2 signals. At the same concentration range (0.1–1.0 m M ), extracellular ATP induced an increase in [ 3 H]cyclic GMP formation, and a decrease in prostaglandin E 1 -stimulated [ 3 H]cyclic AMP generation. In addition, extracellular ATP (1 m M ) caused a large (15-fold) increase in [ 3 H]inositol phosphates accumulation, and this effect was blocked by including La 3+ ions in the assay medium. In parallel experiments, we found in NG 108–15 cells surface protein phosphorylation activity that had an apparent K m for extracellular ATP at the same concentration required to produce half-maximal effects on Ca 2+ uptake. Extracellular ATP at concentrations that can be produced in the synaptic cleft by repetitive stimulation but not during routine transmission can thus initiate a unique chain of events, which may play a role in the induction of long-term adaptive changes in neuronal function.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65952/1/j.1471-4159.1988.tb13263.x.pd

Two-photon absorption and broadband optical limiting with bis-donor stilbenes

Large two-photon absorptivities are reported for symmetrical bis-donor stilbene derivatives with dialkylamino or diphenylamino groups. These molecules exhibit strong optical limiting of nanosecond pulses over a broad spectral range in the visible. Relative to bis(di-n-butylamino)stilbene, bis(diphenylamino)stilbene exhibits a 90-nm red shift of its optical limiting band but only a minimal shift of ~13 nm of its lowest one-photon electronic absorption band. Mixtures of these compounds offer an unprecedented combination of broad optical limiting bandwidth and high linear transparency

Therapies for bleomycin induced lung fibrosis through regulation of TGF-Β1 induced collagen gene expression

This review describes normal and abnormal wound healing, the latter characterized by excessive fibrosis and scarring, which for lung can result in morbidity and sometimes mortality. The cells, the extracellular matrix (ECM) proteins, and the growth factors regulating the synthesis, degradation, and deposition of the ECM proteins will be discussed. Therapeutics with particular emphasis given to gene therapies and their effects on specific signaling pathways are described. Bleomycin (BM), a potent antineoplastic antibiotic increases TGF-Β1 transcription, TGF-Β1 gene expression, and TGF-Β protein. Like TGF-Β1, BM acts through the same distal promoter cis -element of the COL1A1 gene causing increased COL1 synthesis and lung fibrosis. Lung fibroblasts exist as subpopulations with one subset predominately responding to fibrogenic stimuli which could be a specific cell therapeutic target for the onset and development of pulmonary fibrosis. J. Cell. Physiol. 211: 585–589, 2007. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55994/1/20972_ftp.pd

Atrial-Selective Approaches for the Treatment of Atrial Fibrillation

Atrial-selective pharmacologic approaches represent promising novel therapeutic options for the treatment of atrial fibrillation (AF). Medical treatment for AF is still more widely applied than interventional therapies but is hampered by several important weaknesses. Besides limited clinical efficacy (cardioversion success and sinus-rhythm maintenance), side effects like ventricular proarrhythmia and negative inotropy are important limitations to present class I and III drug therapy. Although no statistically significant detrimental survival consequences have been documented in trials, constitutional adverse effects might also limit applicability. Cardiac targets for novel atrial-selective antiarrhythmic compounds have been identified, and a large-scale search for safe and effective medications has begun. Several ionic currents (IKACh, IKur) and connexins (Cx-40) are potential targets, because atrial-selective expression makes them attractive in terms of reduced ventricular side-effect liability. Data on most agents are still experimental, but some clinical findings are available. Atrial fibrillation generates a specifically remodeled atrial milieu for which other therapeutic interventions might be effective. Some drugs show frequency-dependent action, whereas others target structurally remodeled atria. This review focuses on potential atrial-selective compounds, summarizing mechanisms of action in vitro and in vivo. It also mentions favorable interventions on the milieu in terms of conventional (such as antifibrotic effects of angiotensin-system antagonism) and innovative gene-therapy approaches that might add to future AF therapeutic options

Rigid Singularity Theorem in Globally Hyperbolic Spacetimes

We show the rigid singularity theorem, that is, a globally hyperbolic spacetime satisfying the strong energy condition and containing past trapped sets, either is timelike geodesically incomplete or splits isometrically as space $\times$ time. This result is related to Yau's Lorentzian splitting conjecture.Comment: 3 pages, uses revtex.sty, to appear in Physical Review