Role of Chk1 in the differentiation program of hematopoietic stem cells

Hematopoietic stem cells (HSC) isolated from umbilical cord blood (UCB) were treated with ionizing radiation (IR) and sensitivity and IR induced checkpoints activation were investigated. No difference in the sensitivity and in the activation of DNA damage pathways was observed between CD133+ HSC and cells derived from them after ex vivo expansion. Chk1 protein was very low in freshly isolated CD133+ cells, and undetectable in ex vivo expanded UCB CD133+ cells. Chk1 was expressed only on day 3 of the ex vivo expansion. This pattern of Chk1 expression was corroborated in CD133+ cells isolated from peripheral blood apheresis collected from an healthy donor. Treatment with a specific Chk1 inhibitor resulted in a strong reduction in the percentage of myeloid precursors (CD33+) and an increase in the percentage of lymphoid precursors (CD38+) compared to untreated cells, suggesting a possible role for Chk1 in the differentiation program of UCB CD133+ HSC.     

Transiting extrasolar planetary candidates in the Galactic bulge

More than 200 extrasolar planets have been discovered around relatively nearby stars, primarily through the Doppler line shifts owing to reflex motions of their host stars, and more recently through transits of some planets across the faces of the host stars. The detection of planets with the shortest known periods, 1.2-2.5 days, has mainly resulted from transit surveys which have generally targeted stars more massive than 0.75 M(o), where M(o) is the mass of the Sun. Here we report the results from a planetary transit search performed in a rich stellar field towards the Galactic bulge. We discovered 16 candidates with orbital periods between 0.4 and 4.2 days, five of which orbit stars of masses in the range 0.44-0.75 M(o). In two cases, radial-velocity measurements support the planetary nature of the companions. Five candidates have orbital periods below 1.0 day, constituting a new class of ultra-short-period planets, which occur only around stars of less than 0.88 M(o). This indicates that those orbiting very close to more-luminous stars might be evaporatively destroyed or that jovian planets around stars of lower mass might migrate to smaller radii.     

Kelletinin I and kelletinin A from the marine molluscBuccinulum corneum are inhibitors of eukaryotic DNA polymeraseα

Summary The inhibitory effect of esters of p-hydroxybenzoic acid (kelletinins I and A), extracted from the marine gastropodBuccinulum corneum, have been tested on eukaryotic and prokaryotic enzymes of DNA metabolism such as DNA polymerases and , DNA polymerase I, Exo III, pancreatic DNAse I, micrococcal DNAse andE. coli RNA polymerase. Kelletinin I and kelletinin A inhibit preferentially DNA polymerase. The inhibitory effect of kelletinin I involves the hydroxyl group of p-hydroxybenzoic acid.     

Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism

In degenerative disorders of the central nervous system (CNS), transplantation of neural multipotent (stem) precursor cells (NPCs) is aimed at replacing damaged neural cells. Here we show that in CNS inflammation, NPCs are able to promote neuroprotection by maintaining undifferentiated features and exerting unexpected immune-like functions. In a mouse model of chronic CNS inflammation, systemically injected adult syngeneic NPCs use constitutively activated integrins and functional chemokine receptors to selectively enter the inflamed CNS. These undifferentiated cells survive repeated episodes of CNS inflammation by accumulating within perivascular areas where reactive astrocytes, inflamed endothelial cells and encephalitogenic T cells produce neurogenic and gliogenic regulators. In perivascular CNS areas, surviving adult NPCs induce apoptosis of blood-borne CNS-infiltrating encephalitogenic T cells, thus protecting against chronic neural tissue loss as well as disease-related disability. These results indicate that undifferentiated adult NPCs have relevant therapeutic potential in chronic inflammatory CNS disorders because they display immune-like functions that promote long-lasting neuroprotection.     

Simulating micrometre-scale crystal growth from solution

Understanding crystal growth is essential for controlling the crystallization used in industrial separation and purification processes. Because solids interact through their surfaces, crystal shape can influence both chemical and physical properties. The thermodynamic morphology can readily be predicted, but most particle shapes are actually controlled by the kinetics of the atomic growth processes through which assembly occurs. Here we study the urea-solvent interface at the nanometre scale and report kinetic Monte Carlo simulations of the micrometre-scale three-dimensional growth of urea crystals. These simulations accurately reproduce experimentally observed crystal growth. Unlike previous models of crystal growth, no assumption is made that the morphology can be constructed from the results for independently growing surfaces or from an a priori specification of surface defect concentration. This approach offers insights into the role of the solvent, the degree of supersaturation, and the contribution that extended defects (such as screw dislocations) make to crystal growth. It also connects observations made at the nanometre scale, through in situ atomic force microscopy, with those made at the macroscopic level. If extended to include additives, the technique could lead to the computer-aided design of crystals.     

Guggulsterol-like steroids from the Mediterranean gorgonianLeptogorgia sarmentosa

Summary Several polyoxygenated steroids (1, 2, 3) have been isolated from the marine gorgonianLeptogorgia sarmentosa. One of these (1) is the known guggulsterol III, previously found in the pharmacologically active resin from the treeCommiphora mukul; the others,2 and3, have not been found before in nature, and are closely related to1. During the structural work apparent anomalies in the CMR-spectra of1 were observed.The authors are grateful to Prof. Sukh Dev for the PMR-spectra of guggulsterol III. Thanks are also due to Zoological Station (Naples), for the collection of the gorgonian, to Centro Metodologie Chimico-Fisiche, Università di Napoli, for recording PMR-spectra on WH-270 Superconducting Spectrometer-Bruker, to Mr C. Di Pinto for the CMR-spectra and to Mr A. Milone for the MS spectral measurements.     

Methionine enkephalin inhibits the bursting activity of the Br-type neuron inHelix pomatia L.

Summary The present study demonstrates that methionine enkephalin can inhibit the normal bursting activity pattern of the RPal or Br-type neuron and this inhibition can be blocked by prior treatment with naloxone, the selective opiate antagonist. The study demonstrates indirectly the presence of opiate-like receptors inHelix pomatia.Acknowledgments. This work was funded by grant RR 08171 Division of Research Resources and NIMH, and a National Academy of Sciences Travel grant and a Hungarian Academy of Sciences research support award to G.B.S. We also gratefully acknowledge thoughtful comments from Dr J. Salanki.