Inhibition of monocyte complement receptor enhancement by low molecular weight material from human lung cancers

We have studied the effect of dialysates from lung cancer homogenates to alter both the expression of complement (C3b) receptors per se and also to inhibit leucoattractant-induced enhancement of complement rosettes on monocytes from healthy individuals. Enhancement and enhancement-inhibition by tumour extracts were compared with material derived from normal lung excised from distance from the tumour. There was no significant difference between tumour homogenate (TH) and normal lung homogenate (NLH) in terms of enhancement of complement rosettes per se. In contrast, TH produced a dose- and time-dependent inhibition of leucoattractant-induced enhancement of C3b rosettes which was significantly different from that obtained with NLH. This enhancement-inhibition was observed with four undifferentiated, four squamous and three adenocarcinomas of lung. The degree of enhancement-inhibition was not related to the type of tumour or varying accompanying histological features such as necrosis and the degree of infiltration with inflammatory cells. Following gel filtration on Sephadex G-50 each type of cancer gave a major peak of inhibitory activity which eluted with molecules having an apparent molecular size of approximately 3,000 daltons. A second larger peak (8,000-10,000 daltons) was also detected with extracts from the undifferentiated and adenocarcinomas. These results support previous findings, mainly from experimental animals, indicating that 'anti-macrophage/monocyte principles' are elaborated from certain tumour types

Surface superconducting states in a polycrystalline MgB2_{2} sample

We report results of dc magnetic and ac linear low-frequency study of a polycrystalline MgB$_2$ sample. AC susceptibility measurements at low frequencies, performed under dc fields parallel to the sample surface, provide a clear evidence for surface superconducting states in MgB$_2$.Comment: 4 pages and 5 figure

Star-forming galaxies in low-redshift clusters: Data and integrated galaxy properties

This paper is a continuation of an ongoing study of the evolutionary processes affecting cluster galaxies. Both CCD R band and H alpha narrow-band imaging was used to determine photometric parameters (m_(r), r_(24), H alpha flux and equivalent width) and derive star formation rates for 227 CGCG galaxies in 8 low-redshift clusters. The galaxy sample is a subset of CGCG galaxies in an objective prism survey of cluster galaxies for H alpha emission. It is found that detection of emission-line galaxies in the OPS is 85%, 70%, and 50% complete at the mean surface brightness values of 1.25 x 10^(-19), 5.19 x 10^(-20), and 1.76 x 10^(-20) W m^(-2) arcsec^(-2), respectively, measured within the R band isophote of 24 mag arcsec^(-2) for the galaxy. The CCD data, together with matched data from a recent H alpha galaxy survey of UGC galaxies within 3000 km s^(-1), will be used for a comparative study of R band and H alpha surface photometry between cluster and field spirals.Comment: Accepted for publication in A&A. 11 pages, including 6 figure

Effect of DMSO on Protein Structure and Interactions Assessed by Collision-Induced Dissociation and Unfolding

Given the frequent use of DMSO in biochemical and biophysical assays, it is desirable to understand the influence of DMSO concentration on the dissociation or unfolding behavior of proteins. In this study, the effects of DMSO on the structure and interactions of avidin and Mycobacterium tuberculosis (Mtb) CYP142A1 were assessed through collision-induced dissociation (CID) and collision-induced unfolding (CIU) as monitored by nanoelectrospray ionization–ion mobility–mass spectrometry (nESI-IM-MS). DMSO concentrations higher than 4% (v/v) destabilize the avidin tetramer toward dissociation and unfolding, via both its effects on charge state distribution (CSD) as well as at the level of individual charge states. In contrast, DMSO both protects against heme loss and increases the stability of CYP142A1 toward unfolding even up to 40% DMSO. Tandem MS/MS experiments showed that DMSO could modify the dissociation pathway of CYP142A1, while CIU revealed the protective effect of the heme group on the structure of CYP142A1.D.S.-H.C. acknowledges the Croucher Foundation and the Cambridge Commonwealth, European and International Trust for receipt of a Croucher Cambridge International Scholarship. M.E.K. was supported by a Commonwealth (University of Cambridge) Scholarship awarded in conjunc-tion with the Cambridge Commonwealth Trust and Cam-bridge Overseas Trust. K.J.M. and A.G.C. were supported by grants from the UK BBSRC (Biotechnology and Biological Sciences Research Council (BB/I019669/1 and BB/I019227/1)

Scanning Mechanical Microscopy of Laser Ablated Volumes Related to Inductively Coupled Plasma-Mass Spectrometry

Scanning mechanical microscopy based on the point by point sampling of the target surface was used to characterize volumes of minerals ablated by laser pulses (Nd: YAG, = 1064 nm, 140 μs pulse-width). Differentiated volumes resulting from vaporization and exfoliation mechanisms were selectively measured. Ablated volumes of natural pyrite (cubic FeS2), marcasite (orthorhombic FeS2) and arsenopyrite AsFeS, were transported into an inductively coupled plasma torch for subsequent mass analysis. The log of the S34 Fe57, and As75 mass intensities was linearly correlated with the log of the dimensions of the vaporized crater induced by the laser shots while large particles had no effect on the measured intensities. A memory effect for As was observed when a nylon tube was used to carry the ablated materials into the plasma torch. The memory effect was decreased by using a copper tube resulting probably from a difference in the electrical properties of the tubing systems leading to a lower adsorption of As within the copper tube than for the case of the nylon tube

Research data supporting "A fragment profiling approach to inhibitors of the orphan M. tuberculosis P450 CYP144A1"

Fragment-based approaches to targeting CYP144 from Mycobacterium tuberculosi

Cognitive manipulation of brain electric microstates

EEG studies of wakeful rest have shown that there are brief periods in which global electrical brain activity on the scalp remains semi-stable (so-called microstates). Topographical analyses of this activity have revealed that much of the variance is explained by four distinct microstates that occur in a repetitive sequence. A recent fMRI study showed that these four microstates correlated with four known functional systems, each of which is activated by specific cognitive functions and sensory inputs. The present study used high density EEG to examine the degree to which spatial and temporal properties of microstates may be altered by manipulating cognitive task (a serial subtraction task vs. wakeful rest) and the availability of visual information (eyes open vs. eyes closed conditions). The hypothesis was that parameters of microstate D would be altered during the serial subtraction task because it is correlated with regions that are part of the dorsal attention functional system. It was also expected that the sequence of microstates would preferentially transition from all other microstates to microstate D during the task as compared to rest. Finally, it was hypothesized that the eyes open condition would significantly increase one or more microstate parameters associated with microstate B, which is associated with the visual system. Topographical analyses indicated that the duration, coverage, and occurrence of microstate D were significantly higher during the cognitive task compared to wakeful rest; in addition, microstate C, which is associated with regions that are part of the default mode and cognitive control systems, was very sensitive to the task manipulation, showing significantly decreased duration, coverage, and occurrence during the task condition compared to rest. Moreover, microstate B was altered by manipulations of visual input, with increased occurrence and coverage in the eyes open condition. In addition, during the eyes open condition microstates A and D had significantly shorter durations, while C had increased occurrence. Microstate D had decreased coverage in the eyes open condition. Finally, at least 15 microstates (identified via k-means clustering) were required to explain a similar amount of variance of EEG activity as previously published values. These results support important aspects of our hypotheses and demonstrate that cognitive manipulation of microstates is possible, but the relationships between microstates and their corresponding functional systems are complex. Moreover, there may be more than four primary microstates

The Importance of Meteorite Collections to Sample Return Missions: Past, Present, and Future Considerations

While much of the scientific community s current attention is drawn to sample return missions, it is the existing meteorite and cosmic dust collections that both provide the paradigms to be tested by these missions and the context for interpreting the results. Recent sample returns from the Stardust and Hayabusa missions provided us with new materials and insights about our Solar System history and processes. As an example, Stardust sampled CAIs among the population of cometary grains, requiring extensive and unexpected radial mixing in the early solar nebula. This finding would not have been possible, however, without extensive studies of meteoritic CAIs that established their high-temperature, inner Solar System formation. Samples returned by Stardust also revealed the first evidence of a cometary amino acid, a discovery that would not have been possible with current in situ flight instrument technology. The Hayabusa mission provided the final evidence linking ordinary chondrites and S asteroids, a hypothesis that developed from centuries of collection and laboratory and ground-based telescopic studies. In addition to these scientific findings, studies of existing meteorite collections have defined and refined the analytical techniques essential to studying returned samples. As an example, the fortuitous fall of the Allende CV3 and Murchison CM2 chondrites within months before the return of Apollo samples allowed testing of new state-of-the-art analytical facilities. The results of those studies not only prepared us to better study lunar materials, but unanticipated discoveries changed many of our concepts about the earliest history and processes of the solar nebula. This synergy between existing collections and future space exploration is certainly not limited to sample return missions. Laboratory studies confirmed the existence of meteorites from Mars and raised the provocative possibility of preservation of ancient microbial life. The laboratory studies in turn led to a new wave of Mars exploration that ultimately could lead to sample return focused on evidence for past or present life. This partnership between collections and missions will be increasingly important in the coming decades as we discover new questions to be addressed and identify targets for for both robotic and human exploration . Nowhere is this more true than in the ultimate search for the abiotic and biotic processes that produced life. Existing collections also provide the essential materials for developing and testing new analytical schemes to detect the rare markers of life and distinguish them from abiotic processes. Large collections of meteorites and the new types being identified within these collections, which come to us at a fraction of the cost of a sample return mission, will continue to shape the objectives of future missions and provide new ways of interpreting returned samples