Action ofp-chlorophenylalanine on the synaptic vesicles from rat pineal nerves

Resumen Se demuestra que lap-clorofenilalanina depleciona los componentes de las vesículas sinápticas de los nervios pineales de la rata revelables por la mezcla tetróxido de osmio-yoduro de zinc pero no afecta a los revelables por tetróxido de osmio-yoduro de potasio.

---

---

This work has been supported by grants from the Consejo Nacional de Investigaciones Cientificas y Técnicas, Argentina, and National Institutes of Health, USA, No. 5 R01 NS 06953-05 NEUA.     

Towards an Holistic Framework for Environmental Change: The Role of Normative Behaviour and Informal Networking to Enhance Sustainable Business Practices

The term ‘Sustainable Development’ is brandished by modern businesses as a marketing ploy used to suggest evidence of ethical conduct, innovative thinking and moral superiority. However, when analysing an organisations’ adoption of sustainable practices, it is often clear—within the UK—that there are few activities that have been undertaken as an ethical stance instead of legal obligation (McCormick in Environmental politics and policy in industrialized countries, MIT, London, 2002). Our hypothesis is that most methodologies and practices for environmental management do not adopt a holistic perspective, causing significant problems in implementation from inadequate structures and communication channels (Espinosa et al. in Eur J Oper Res, 187:636–651, 2008). In particular we consider that most organisations are currently stifled with management hierarchies that prevent informal/social networking, which may be one of the most powerful natural forms for self-organisation. It is proposed that sustainable development requires more efficient communication channels that foster self-organisation and self-regulation as a method for more productive change processes. In this paper, we explain the reasons why meta-systemic principles of self-organisation and distributed network management offer clear criteria to design an environmental management system that operates on the basis of self-controlled individuals and communities.     

The cells and logic for mammalian sour taste detection

Mammals taste many compounds yet use a sensory palette consisting of only five basic taste modalities: sweet, bitter, sour, salty and umami (the taste of monosodium glutamate). Although this repertoire may seem modest, it provides animals with critical information about the nature and quality of food. Sour taste detection functions as an important sensory input to warn against the ingestion of acidic (for example, spoiled or unripe) food sources. We have used a combination of bioinformatics, genetic and functional studies to identify PKD2L1, a polycystic-kidney-disease-like ion channel, as a candidate mammalian sour taste sensor. In the tongue, PKD2L1 is expressed in a subset of taste receptor cells distinct from those responsible for sweet, bitter and umami taste. To examine the role of PKD2L1-expressing taste cells in vivo, we engineered mice with targeted genetic ablations of selected populations of taste receptor cells. Animals lacking PKD2L1-expressing cells are completely devoid of taste responses to sour stimuli. Notably, responses to all other tastants remained unaffected, proving that the segregation of taste qualities even extends to ionic stimuli. Our results now establish independent cellular substrates for four of the five basic taste modalities, and support a comprehensive labelled-line mode of taste coding at the periphery. Notably, PKD2L1 is also expressed in specific neurons surrounding the central canal of the spinal cord. Here we demonstrate that these PKD2L1-expressing neurons send projections to the central canal, and selectively trigger action potentials in response to decreases in extracellular pH. We propose that these cells correspond to the long-sought components of the cerebrospinal fluid chemosensory system. Taken together, our results suggest a common basis for acid sensing in disparate physiological settings.     

Platensimycin is a selective FabF inhibitor with potent antibiotic properties

Bacterial infection remains a serious threat to human lives because of emerging resistance to existing antibiotics. Although the scientific community has avidly pursued the discovery of new antibiotics that interact with new targets, these efforts have met with limited success since the early 1960s. Here we report the discovery of platensimycin, a previously unknown class of antibiotics produced by Streptomyces platensis. Platensimycin demonstrates strong, broad-spectrum Gram-positive antibacterial activity by selectively inhibiting cellular lipid biosynthesis. We show that this anti-bacterial effect is exerted through the selective targeting of beta-ketoacyl-(acyl-carrier-protein (ACP)) synthase I/II (FabF/B) in the synthetic pathway of fatty acids. Direct binding assays show that platensimycin interacts specifically with the acyl-enzyme intermediate of the target protein, and X-ray crystallographic studies reveal that a specific conformational change that occurs on acylation must take place before the inhibitor can bind. Treatment with platensimycin eradicates Staphylococcus aureus infection in mice. Because of its unique mode of action, platensimycin shows no cross-resistance to other key antibiotic-resistant strains tested, including methicillin-resistant S. aureus, vancomycin-intermediate S. aureus and vancomycin-resistant enterococci. Platensimycin is the most potent inhibitor reported for the FabF/B condensing enzymes, and is the only inhibitor of these targets that shows broad-spectrum activity, in vivo efficacy and no observed toxicity.