Diurnal rhythm of active calcium transport in rat intestine

Summary The active calcium transport along the small intestine of adult rat was shown to exhibit daily rhythmic variations of considerable amplitude. Both the light-dark cycle and the time of food presentation acted as synchronizers of the rhythm observed.This work has been supported by Polish Academy of Sciences within the project MR II.1.1.6.     

Multimodal fast optical interrogation of neural circuitry

Our understanding of the cellular implementation of systems-level neural processes like action, thought and emotion has been limited by the availability of tools to interrogate specific classes of neural cells within intact, living brain tissue. Here we identify and develop an archaeal light-driven chloride pump (NpHR) from Natronomonas pharaonis for temporally precise optical inhibition of neural activity. NpHR allows either knockout of single action potentials, or sustained blockade of spiking. NpHR is compatible with ChR2, the previous optical excitation technology we have described, in that the two opposing probes operate at similar light powers but with well-separated action spectra. NpHR, like ChR2, functions in mammals without exogenous cofactors, and the two probes can be integrated with calcium imaging in mammalian brain tissue for bidirectional optical modulation and readout of neural activity. Likewise, NpHR and ChR2 can be targeted together to Caenorhabditis elegans muscle and cholinergic motor neurons to control locomotion bidirectionally. NpHR and ChR2 form a complete system for multimodal, high-speed, genetically targeted, all-optical interrogation of living neural circuits.     

Spatially asymmetric reorganization of inhibition establishes a motion-sensitive circuit

Spatial asymmetries in neural connectivity have an important role in creating basic building blocks of neuronal processing. A key circuit module of directionally selective (DS) retinal ganglion cells is a spatially asymmetric inhibitory input from starburst amacrine cells. It is not known how and when this circuit asymmetry is established during development. Here we photostimulate mouse starburst cells targeted with channelrhodopsin-2 (refs 6-8) while recording from a single genetically labelled type of DS cell. We follow the spatial distribution of synaptic strengths between starburst and DS cells during early postnatal development before these neurons can respond to a physiological light stimulus, and confirm connectivity by monosynaptically restricted trans-synaptic rabies viral tracing. We show that asymmetry develops rapidly over a 2-day period through an intermediate state in which random or symmetric synaptic connections have been established. The development of asymmetry involves the spatially selective reorganization of inhibitory synaptic inputs. Intriguingly, the spatial distribution of excitatory synaptic inputs from starburst cells is significantly more symmetric than that of the inhibitory inputs at the end of this developmental period. Our work demonstrates a rapid developmental switch from a symmetric to asymmetric input distribution for inhibition in the neural circuit of a principal cell.     

1,2-di-n-butylhydrazine dihydrochloride carcinogenesis in mice

Summary A solution of 0.0625% 1,2-di-n-butylhydrazine dihydrochloride (1,2-DBH) was given continuously in the drinking water of 6-week-old randomly bred albino Swiss mice for the remainder of their lives. The treatment gave rise to tumors of the lungs, lymphoreticular tissue and kidneys.     

Sickle cell vasoocclusion: Many issues and some answers

The pathophysiology of sickle (SS) cell vasoocclusion is derived from the presence of hemoglobin S (HbS) which forms polymeric fibers in the deoxygenated state. Nevertheless, phenotypic expression of sickle cell disease (i.e., clinical severity) shows marked individual variations and is influenced by genetic modifiers such as epistatic effects of linked and unlinked genes. Furthermore, the polymerization of HbS is central but not the only event, and is more likely a consequence of disruptions of the steady state of flow. The available evidence indicates that the vasoocclusive crisis is a microcirculatory event in which multiple factors could be involved. We present a model of vasoocclusion as a two step process in which adhesion of deformable cells occurs first, followed by obstruction induced by less deformable SS cells. This review discusses, in addition, rheologic and microcirculatory behavior of SS erythrocytes and the interacting role of vascular factors, red cell heterogeneity, deoxygenation rates, and red cell-endothelial interactions in the pathophysiology of SS cell vasoocclusion.     

Effect of the rat liver S9 fraction on the mutagenicity of azathioprine in theSalmonella/mammalian microsome assay

Summary Azathioprine is a direct acting mutagen inSalmonella typhimurium TA100 and TA1535. Addition of rat liver S9 fraction with or without co-factors, or glutathione, causes a decrease in the mutagenicity of azathioprine in TA100 and an increase in TA1535, indicating the effect of SH groups.Acknowledgments. This work was supported in part by a grant from SECYT (Argentina).