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The neutral particle temperature in the edge region of the Aditya-U tokamak has been measured by recording the hydrogen Balmer alpha emission spectra at 656.28 nm from different lines of sight in both the high and low field sides. The spatial profile of the H α emission has been recorded using a 1 m multi-track spectrometer. The neutral temperature is estimated from the Doppler broadening of the measured H α spectrum by appropriately removing the contribution from the Zeeman splitting of the spectral lines. A computer simulation code was developed to estimate the neutral temperature by including the broadening mechanisms such as Doppler broadening and the Zeeman effect to simulate the H α emission spectrum along with the proper convolution of the instrumental width of the diagnostic system. It has been observed that the high field side neutral temperature (~4–6 eV) during plasma flat top is almost twice that of the low field side (~2–3 eV) suggesting poloidal asymmetry in the neutral temperature.

The first Indian tokamak ADITYA, operated over 2 decades with circular poloidal limiter has been upgraded to a tokamak named ADITYA Upgrade (ADITYA-U) for attaining shaped-plasma operations with open divertor in single and double-null configurations. The experimental research in ADITYA-U has made significant progress, since last FEC 2016. After installation of PFC and standard tokamak diagnostics in ADITYA-U, the Phase-I plasma operations has been initiated from December 2016 with graphite toroidal belt limiter. Ohmically heated circular plasmas supported by filament pre-ionization with plasma parameters, Ip ~ 80 – 95 kA, duration ~ 80 – 180 ms with maximum toroidal field ~ 1T and chord-averaged electron density ~ 2.5 x 10^19 m^-3 has been successfully obtained. The runaway electron (RE) generation, transport and mitigation experiments along with MHD activities and density enhancement with H2 gas puffing experiments have carried out in Phase-I, which is completed in March 2017. The Phase-II operation preparation in ADITYA-U includes calibration of magnetic diagnostics followed by commissioning of major diagnostics and installation of baking system. After repeated cycles of baking the vacuum vessel up to ~ 135°C, the Phase-II operations resumed from February 2018 and are continuing to achieve plasma parameters close to the design parameters of circular limiter plasmas using real time plasma position control. The plasma current has been raised to ~ 135 kA in phase-II with maximum chord averaged electron density of ~ 4 x 10^19 x m^-3. Hydrogen gas breakdown has been observed in more than ~ 2000 discharges including Phase-I and Phase-II operation without a single failure. Several experiments, including the control of REs with fuelling of Supersonic Molecular Beam Injection as well as sonic H2 gas puffing during current flat-top, MHD modes studies using multiple periodic gas puffs and radiative improved modes using Neon gas puff have been carried out. The experimental results from Phase-I and Phase-II operations of ADITYA-U tokamak are discussed in this paper.

The formation of a density blob in the boundary region of a tokamak plasma is widely believed to be due to the presence of poloidal velocity shear that differentially breaks off a radially elongated streamer structure. However, blobs have also been experimentally detected in the absence of poloidal velocity shear. We ascribe the formation of such blobs to the differential stretching of the streamer arising from a radial velocity shear and thereby present a unified picture of the breaking mechanism that takes into account both the processes in a synergistic manner. Our universal condition for blob formation is validated from detailed numerical simulations of the edge turbulence in a typical L-mode scenario.

Alloying and surface structures of Cu films evaporated onto a Pt(111) single-crystal substrate were studied by X-ray photoelectron diffraction (XPD), low-energy alkali ion scattering spectroscopy (ALISS), and low-energy electron diffraction (LEED). Alloying begins at temperatures above 500 K, and increasing the annealing temperature of deposited films to 900 K caused all Cu atoms to diffuse deep into the subsurface region of the Pt crystal. One particular Cu/Pt(111) bimetallic alloy surface was characterized in detail, and this surface was formed by depositing one monolayer of Cu onto the Pt(111) surface and then annealing to 550 K. Only a diffuse (1 × 1) LEED pattern was observed from this Cu/Pt(111) alloy, which indicates that there was no long-range, ordered intermetallic compound created at the surface for these conditions or any others that we investigated. ALISS and XPS were used to determine that the Cu concentration in the topmost, surface layer of this alloy was 7 atomic percent. XPD and ALISS give consistent results showing that Cu in this alloy was present in the first, second, and third layers at the surface, forming a surface alloy. Cu atoms in the alloy are located at Pt atom lattice sites, and are coplanar with the topmost Pt atomic layer without significant corrugation or buckling. Temperature programmed desorption (TPD) measurements showed that both CO and NO are more weakly adsorbed and have smaller desorption energies on the Cu/Pt(111) surface alloy compared to the Pt(111) surface.

The ephemeral nature of most sedimentation processes and the fragmentary character of the sedimentary record are of first-order importance. Despite a basic uniformity of external controls on sedimentation resulting in markedly similar lithologies, facies, fades associations and depositional elements within the rock record across time, there are a number of secular changes, particularly in rates and intensities of processes that resulted in contrasts between preserved Precambrian and Phanerozoic successions. Secular change encompassed (1) variations in mantle heat, rates of plate drift and of continental crustal growth, the gravitational effects of the Moon, and in rates of weathering, erosion, transport, deposition and diagenesis; (2) a decreasing planetary rotation rate over time; (3) no vegetation in the Precambrian, but prolific microbial mats, with the opposite pertaining to the Phanerozoic; (4) the long-term evolution of the hydrosphere-atmosphere-biosphere system. A relatively abrupt and sharp turning point was reached in the Neoarchaean, with spikes in mantle plume flux and tectonothermal activity and possibly concomitant onset of the supercontinent cycle. Substantial and irreversible change occurred subsequently in the Palaeoproterozoic, whereby the dramatic change from reducing to oxidizing volcanic gases ushered in change to an oxic environment, to be followed at ca. 2.4-2.3 Ga by the "Great Oxidation Event" (GOE); rise in atmospheric oxygen was accompanied by expansion of oxygenic photosynthesis in the cyanobacteria. A possible global tectono-thermal "slowdown" from ca. 2.45-2.2 Ga may have separated a preceding plate regime which interacted with a higher energy mantle from a ca. 2.2-2.0 Ga Phanerozoic-style plate tectonic regime; the "slowdown" period also encompassed the first known global-scale glaciation and overlapped with the GOE. While large palaeodeserts emerged from ca. 2.0-1.8 Ga, possibly associated with the evolution of the supercontinent cycle, widespread euxinia by ca. 1.85 Ga ushered in the "boring billion" year period. A second time of significant and irreversible change, in the Neoproterozoic, saw a second major oxidation event and several low palaeolatitude Cryogenian (740-630 Ma) glaciations. With the veracity of the "Snowball Earth" model for Neoproterozoic glaciation being under dispute, genesis of Pre-Ediacaran low-palaeolatitude glaciation remains enigmatic. Ediacaran (635-542 Ma) glaciation with a wide palaeolatitudinal range contrasts with the circum-polar nature of Phanerozoic glaciation. The observed change from low latitude to circum-polar glaciation parallels advent and diversification of the Metazoa and the Neoproterozoic oxygenation (ca. 580 Ma), and was succeeded by the Ediacaran-Cambrian transition which ushered in biomineralization, with all its implications for the chemical sedimentary record. (C) 2012 International Association for Gondwana Research. Published by Elsevier B.V. All rights reserved.

Extensive Cenozoic lignite-bearing sediments in the western part of Kutch, western India provide a unique opportunity to study the floral diversity at a crucial time of early Eocene Climatic Optimum (EECO). Rock samples representing a lignite-bearing sequence from the open cast mine at Matanomadh, Gujarat, western India were collected to study the palynofloral composition and to interpret the palaeoclimate and environment of deposition. The sequence mainly composed of lignites, shales and calcareous mudstones yielded rich assemblage consists of pteridophytic spores (7 genera, 10 species), angiosperm pollens (20 genera, 26 species), fungal remains (14 genera, 16 species) and dinoflagellate cysts. The palynofloral assemblage is marked with dominance of angiospermic pollen, particularly those having affinity with the family Arecaceae. Occurrence of fungal remains in high abundance is also noticed. Based on palynomorph contents, the studied sequence is divisible into two palynozones. It is inferred that lower part of the sequences was deposited in a near-shore environment with intermittent marine incursions whereas the depositional regime of upper part was shallow marine. The climate is found to be tropical-subtropical, humid with heavy precipitation during the deposition of Matanomadh lignite-bearing sequence.

Alloy formation and chemisorption at bimetallic surfaces formed by vapor-depositing Zn on a Pt(111) single crystal were investigated primarily by using X-ray photoelectron diffraction (XPD), X-ray photoelectron spectroscopy (XPS), low-energy alkali ion scattering spectroscopy (ALISS), low electron energy diffraction (LEED), and temperature programmed desorption (TPD). A wide range of conditions were investigated to explore whether deposition and annealing of Zn films could produce well-defined, ordered alloy surfaces, similar to those encountered for Sn/Pt(111) surface alloys. These attempts were unsuccessful, although weak, diffuse (2 × 2) spots were observed under special conditions. The particular PtZn bimetallic alloy created by annealing one monolayer of Zn on Pt(111) at 600 K, which has a Zn composition in the surface layer of about 5 at. %, was investigated in detail by using XPD and ALISS. Only a diffuse (1 × 1) pattern was observed from this surface by LEED, suggesting that no long-range, ordered alloy structure was formed. Zn atoms were substitutionally incorporated into the Pt(111) crystal to form a near-surface alloy in which Zn atoms were found to reside primarily in the topmost and second layers. The alloyed Zn atoms in the topmost layer are coplanar with the Pt atoms in the surface layer, without any "buckling" of Zn, that is, displacement in the vertical direction. This result is expected because of the similar size of Pt and Zn, based on previous studies of bimetallic Pt alloys. Zn atoms desorb upon heating rather than diffusing deep into the bulk of the Pt crystal. Temperature programmed desorption (TPD) measurements show that both CO and NO have lower desorption energies on the PtZn alloy surface compared to that on the clean Pt(111) surface.

Lithiumization of the vacuum vessel wall of the Aditya tokamak using a lithium rod exposed to glow discharge cleaning plasma has been done to understand its effect on plasma performance. After the Li-coating, an increment of ~100 eV in plasma electron temperature has been observed in most of the discharges compared to discharges without Li coating, and the shot reproducibility is considerably improved. Detailed studies of impurity behaviour and hydrogen recycling are made in the Li coated discharges by observing spectral lines of hydrogen, carbon, and oxygen in the visible region using optical fiber, an interference filter, and PMT based systems. A large reduction in O I signal (up to ~40% to 50%) and a 20% to 30% decrease of Hα signal indicate significant reduction of wall recycling. Furthermore, VUV emissions from O V and Fe XV monitored by a grazing incidence monochromator also show the reduction. Lower Fe XV emission indicates the declined impurity penetration to the core plasma in the Li coated discharges. Significant increase of the particle and energy confinement times and the reduction of Zeff of the plasma certainly indicate the improved plasma parameters in the Aditya tokamak after lithium wall conditioning.

The Early Miocene succession in Kutch (western India) is represented by a mixed carbonate-siliciclastic system. A combined sedimentological, trace fossil assemblage and micropaleontological analysis of the succession was carried out to refine sequence stratigraphic architecture. In this mixed carbonate-siliciclastic system, the trace fossil complement the micropaleontological data in the carbonate portion and provide crucial information in the siliciclastic part, particularly in identifying key stratal surfaces. The sedimentary succession records single cycle of third order fluctuation in relative sea-level (~7 Ma.) with higher order fluctuations of million year episodicity. The preserved sequence is asymmetric, consisting of a thick transgressive systems tract (TST) and a relatively thin highstand systems tract (HST). The transgressive systems tract exhibits a gradual change in foraminiferal assemblage indicating deepening upward succession in overall middle shelf environment. The trace fossils change from Psilonichnus ichnogenera to Skolithos assemblage to Thalassinoides assemblage, from the base of the section to the top. The reworked burrow tubes of Psilonichnus ichnogenera concentrated in the lower part of the TST indicates lag concentration, accumulated during onset of the transgression. The recurrence of larger foraminifera and trace fossil attributable to the Thalassinoides assemblage at various stratigraphic levels (i.e. upper part of TST and lower part of HST) marks the higherorder flooding surfaces and base of parasequence. A high abundance of planktonic foraminifera, including Cassigerinella, Globigerina and Globorotalia , characterizes the maximum flooding surface (MFS) corresponding to a maximum bathymetry of ~50m. The progressive shallowing in highstand systems tract exhibit siliciclastic dominated succession with increased coarse clastic sediments towards top and it is marked by a gradual decrease in the abundance of ichnogenera and shallow water foraminifera and their absence in the upper part of the HST.

The early part of the Cenozoic succession of Kutch is still debated for the age of the formations overlying the Deccan basalt. Authors have differed on the question of the presence of marine Palaeocene, Lutetian and Priabonian sediments in Kutch. This paper integrates the larger foraminifer based shallow benthic zones (Serra Kiel et al., 1998) and the planktic foraminiferal zones (Berggren and Pearson, 2005) of the Eocene succession to present a revised chronostratigraphy. It is concluded that there is no evidence of Palaeocene marine sediments in on-land Kutch. The Eocene successions are referred to Ypressian and Bartonian stages. A small thickness of sediments below the Bartonian lacks age-diagnostic taxa and could questionably be of late Lutetian age. There is no evidence of Priabonian sediments in the area. Based on the present biostratigraphic study and the latest Geologic Time Scale (Gradestein et al., 2012), hiatuses of ~7 Myr between the Deccan Trap and Naredi Formation, ~7 Myr between Naredi Formation and Harudi Formation and ~4 Myr between Fulra Limestone and Maniyara Fort Formation are estimated.

A combined sedimentological, stratigraphical, mineralogical and geochemical investigation on Palaeogene glauconites of Kutch address some of the crucial issues related to origin of glauconite and its depositional and stratigraphic significance. Glauconite occurs within fossiliferous green shale units of Naredi, Harudi and Maniyara Fort Formation. It occurs primarily in two modes, either as an altered form of fecal pellets or as infillings within the bioclasts. The origin of glauconite may be best explained by direct precipitation of Fe-rich glauconitic smectite within the pores of bioclasts and fecal pellets followed by its maturation to glauconitic mica by the addition of K. Fecal pellet is a more favourable substrate than bioclasts for glauconitization because of easy percolation of pore water within and availability of relevant ions in pellets. Strong biostratigraphic control allows us to clearly establish that relatively high rate of sedimentation (>27 m/Ma) discourage glauconite formation in the Fulra limestone while low rate of sedimentation rate (

Two depositional sequences are recognized in the Eocene succession of Kutch. The Sequence-I in the lower part is of Ypressian age and 6 Myr duration. A hiatus of about 7 Myr is estimated between the Deccan trap and Sequence-I and a hiatus of equal magnitude exists between sequences I and II. The Sequence-II is of Bartonian (and possibly extending to late Lutetian) age and a major part of it formed during a small interval of planktic foraminiferal zone E12 (0.5 Myr). A hiatus of ~7 Myr is estimated between the two sequences. Five depositional cycles of low amplitude, low frequency and confined to inner shelf are inferred in Sequence-I. In contrast, eight depositional cycles are recognized in Sequence-II and cycles in the lower part are of high amplitude, reaching to middle shelf. The average cyclicity is of > 1 Myr duration in Sequence-I and < 0.1 Myr duration in Sequence-II.

Background Elevated levels of oncostatin M (OSM), an interleukin-6 cytokine family member, have been observed in HIV-1-associated neurocognitive disorders (HAND) and Alzheimer’s disease. However, the function of OSM in these disease conditions is unclear. Since deficient glutamate uptake by astrocytes is instrumental in HAND-associated neurotoxicity, we hypothesized that OSM impairs glutamate uptake in astrocytes and thereby promotes neuronal excitotoxicity. Methods Primary cultures of mouse cortical astrocytes, neurons, microglia, and BV2 cell line were used. The expression of glutamate transporters (GLAST/EAAT1 and GLT-1/EAAT2) was investigated using real-time PCR and Western blot, and their activity was assessed by measuring 3H-d-aspartate uptake. Neuronal toxicity was measured using the colorimetric MTT (3-(4,5-dimethylthiazol-2-yl-) 2,5-diphenyltetrazolium bromide) assay and immunocytochemistry. A chimeric HIV-1 that infects murine cells (EcoHIV/NL4-3-GFP virus (EcoHIV)) was used to investigate whether the virus induces OSM, OSM receptor (OSMR)-β, glycoprotein 130 (gp130), GLT-1, GLAST (mRNA and protein), and OSM release (ELISA) in cultured BV2 cells, primary microglia, or astrocytes. Statistical analyses of the data were performed using one-way ANOVA (to allow multiple comparisons) and two-tailed Student’s t test. Results OSM treatment (10 ng/mL) time-dependently reduced GLAST and GLT-1 expression and inhibited 3H-d-aspartate uptake in cultured astrocytes in a concentration-dependent manner, an effect prevented by the Janus kinase (JAK)/signal transducers and activators of transcription (STAT)3 inhibitor AG490. Down-regulation of astrocytic glutamate transport by OSM resulted in NMDA receptor-dependent excitotoxicity in cortical neurons. Infection with EcoHIV induced OSM gene expression and protein release in BV2 cells and microglia, but not in astrocytes. Conversely, EcoHIV caused a fivefold increase in OSMR-β mRNA (but not gp130) and protein in astrocytes, but not in microglia, which did not express OSMR-β protein. Finally, astrocytic expression of GLAST gene was unaffected by EcoHIV, whereas GLT-1 mRNA was increased by twofold. Conclusions We provide first evidence that activation of JAK/STAT3 signaling by OSM inhibits glutamate uptake in astrocytes, which results in neuronal excitotoxicity. Our findings with EcoHIV suggest that targeting OSMR-β signaling in astrocytes might alleviate HIV-1-associated excitotoxicity. Electronic supplementary material The online version of this article (doi:10.1186/s12974-016-0613-8) contains supplementary material, which is available to authorized users.

Scientific Reports 6: Article number: 21094; published online: 19 February 2016; updated: 20 April 2016. The original version of this Article contained errors in the spelling of the authors Jana Ninkovic, Vidhu Anand, Raini Dutta, Lisa Koodie, Santanu Banerjee and Sabita Roy which were incorrectly given as Ninkovic Jana, Anand Vidhu, Dutta Raini, Koodie Lisa, Banerjee Santanu and Roy Sabita.

Opioid drug abusers have a greater susceptibility to gram positive (Gram (+)) bacterial infections. However, the mechanism underlying opioid modulation of Gram (+) versus Gram (−) bacterial clearance has not been investigated. In this study, we show that opioid treatment resulted in reduced phagocytosis of Gram (+), when compared to Gram (−) bacteria. We further established that LPS priming of chronic morphine treated macrophages leads to potentiated phagocytosis and killing of both Gram (+) and Gram (−) bacteria in a P-38 MAP kinase dependent signaling pathway. In contrast, LTA priming lead to inhibition of both phagocytosis and bacterial killing. This study demonstrates for the first time the differential effects of TLR4 and TLR2 agonists on morphine induced inhibition of phagocytosis. Our results suggest that the incidence and severity of secondary infections with Gram (+) bacteria would be higher in opioid abusers.

Tidal sand bars and tidal sand ridges are extensively developed in the macrotidal Gulf of Khambhat, offshore western India. The inner and outer regions of the gulf are characterised by the development distinct tidal sand bodies with discrete geometries and dimensions. The outer gulf ridges are long, narrow, curvilinear and several metres high (similar to 20 m). They are asymmetric in cross-section and migratory in nature, forming 'ribbon' like sand bodies separated by tidal channels. Active dunes on these ridges indicate the presence of sand and their orientation parallel to palaeo-shorelines supports a tidal origin. In contrast to the outer gulf tidal sand ridges, sand bars associated with macrotidal estuaries flanking the Gulf of Khambhat typically have an elongate to diamond shape and are only hundreds of metres in width and a few kilometres length. These tidal sand bars occur in the estuary mouths and within the tidally influenced fluvial reaches of the rivers flowing into the gulf. The height of these sand bars is in the range similar to 1-3 m. Due to high tidal ranges and bi-directional flow the sand bars do not develop significant height and are formed between the mutually evasive ebb and flow channels. Their bi-directional foresets and the presence of abundant mud drapes associated with the dunes within in-channel sand bars indicate a tidal origin. The Gulf of Khambhat acquired the present configuration in the last few thousand years since the Pleistocene sea-level lowstand (last glacial maximum, similar to 18 Ka) when the entire continental shelf was subaerially exposed and rivers down-cut into the coastal plain. With increasing sea-level rise, the exposed shelf was drowned, flooding parts of the Modern western Indian peninsula, and large tidal sand ridges formed in the outer gulf. After the fall of sea-level at 2 ka the gulf acquired the Modern configuration with multiple estuaries on both coastlines, rivers supplied the embayment with sandy sediment, and tidal sand bars formed in the Modern estuaries. Quantitative data gathered from the Modern Gulf of Khambhat indicates that for the P50 case, a vertical drill hole will encounter tidal sand bodies (ridges and bars combined) of approximate dimensions 1700 m long, 470 m wide and 1.5 m high, with a spacing of 400 m. In subsurface hydrocarbon reservoirs, where data is sparse and only limited amount of core is available, this quantitative dataset can be useful to constrain subsurface geocellular models. Also, the overall geometry, distribution and aspect ratio of the tidal sand ridges and tidal sand bars can be used to identify ancient counterparts through seismic geomorphology or in core. (C) 2016 Elsevier Ltd. All rights reserved.

Three successive subspecies of Nummulites burdigalensis evolved from N. solitarius. These include N. burdigalensis keupperi, N. burdigalensis burdigalensis and N. burdigalensis cantabricus. The evolving lineage is traced in a borehole drilled through the Naredi Formation of Kutch. The associated taxa include N. solitarius and N. fraasi in the lower part and Assilina laxispira and A. spinosa in the upper part of the formation. The better stratigraphic resolution achieved by subspecies identification and the lately redefined Ilerdien Stage in the background of Early Eocene carbon isotope excursion marker, lead to constrain the age of Naredi Formation as Early Eocene, ranging from shallow-benthic zones SBZ6 to SBZ11.

Ambient fluctuations and the generation of coherent convective structures are investigated as a function of vertical to toroidal magnetic field ratio (Bz/Bt) in the spherical tokamak QUEST [K. Hanada et al., Plasma Fusion Research 5, S1007]. Fluctuation signals are obtained at a high spatial and temporal resolution using the fast visible camera. The coherent structures (blobs) were seen to be apparent only beyond a critical Bz/Bt ratio (~ 10). This clearly indicates a shift from the drift to the interchange mode with the increase in vertical magnetic field. The blobs are propagated radially at a high speed ~ 10 m/s which is ~ 1/10 of the ion acoustic speed in QUEST. Lifetime of the blobs is about 700 μs. Second part of the study comprises of the investigation of the finer structures in the current ramp-up phase which is characterized by lower levels of fluctuations. Singular value decomposition (SVD) and principal component analysis (PCA) techniques are applied on the fast camera images to reveal the structures which are otherwise embedded in the overall intensity image. Electron banana orbits were seen to form from the slab annular plasma and grow wider to eventually shape the plasma current front.

An integrated study of the sedimentology, micropalaeontology, mineralogy and geochemistry of glauconites in the Oligocene Maniyara Fort Formation (western Kutch, India), has been undertaken. Authigenic glauconites, mostly of evolved type, formed within a back-barrier lagoonal environment. Foraminifera help constrain the biostratigraphy and along with sedimentological evidence, provide information on the depositional conditions. Glauconite in the Maniyara Fort Formation occurs either as infillings within intra-particle pores of larger foraminifers, or as an altered form of faecal pellets. X-ray diffraction studies reveal the less mature nature of glauconite infillings compared to the glauconite pellets. Electron microprobe investigation confirms a relative enrichment of K2O and total Fe2O3 in the latter. Both varieties of glauconite formed by initial authigenic precipitation of K-poor glauconite and subsequently matured by addition of potassium in the interlayer sites and fixation of total iron in the octahedral sites; calcium, magnesium and aluminum were released from the glauconite structure concomitantly. Alkaline conditions during the entire process of glauconite formation did not allow dissolution of foraminiferal tests. Mineralogical and chemical characteristics of the Maniyara Fort Formation glauconites are more similar to deep marine glauconites than those reported from other shallow or marginal marine settings. A low negative cerium anomaly, as well as abundant pyrite, suggests formation of glauconite in sub-oxic micro-environments, created by decay of organic matter associated with foraminiferal chambers and faecal pellets. Sub-oxic condition apparently prevailed relatively longer within the Maniyara Fort Formation lagoons. Copyright © 2011 John Wiley & Sons, Ltd.

Purpose Unlike other microbiomes of the body, the composition of the ocular surface microbiome (OSM) in children has yet to be thoroughly explored. Our goal was to evaluate the OSM in young infants and compare its composition to older children using both culture dependent and independent methodologies to assess for differences with age. Methods Prospective, observational, cross-sectional study of children 1 species. Culture positive patients were older (43 vs. 29 months, P = 0.19). Additionally, older children had greater diversity than children under 6 months of age by 16S sequencing (P = 0.05). Staphylococcus species were predominant by culture (35/52 isolates) and by 16S sequencing. The OSM was fairly similar to the nose microbiome, whereas the throat microbiome differed significantly and had a higher abundance of Streptococcaceae (P = 0.001). Conclusions The OSM is predominantly composed of Staphylococcus species in children, as demonstrated by both culture dependent and culture independent methods. Older children were more likely to have growth on culture and have more a complex bacterial milieu with 16S sequencing. Translational Relevance 16S sequencing provides more robust information regarding the composition of the microbiomes than culture dependent methods.

Background Unabated use of antibiotics for human diseases, in livestock and aquaculture has resulted in natural selection of multi-drug-resistant organisms (MDROs). The emergence of pan-resistant strains of Pseudomonas spp. pose a major threat to patients appropriately exposed to antibiotics (e.g., cystic fibrosis, lung transplant recipients). This organism evades antibiotics by a combination of efflux pumps, harboring multiple-resistant genes and acquiring low permeability of the outer membrane. Altering the gut microbiome could potentially modify the lung microbiome of patients colonized or infected with MDROs. Methods A 17-year-old patient with CF developed recurrent exacerbations with an extreme drug-resistant Pseudomonas aeruginosa; due to the lack of effective antibiotics to treat her while awaiting a decision to proceed with lung transplantation, sputum cultures were collected as part of clinical care. We modeled patient-derived isolate of predominantly MDR Pseudomonas in C57Bl6/j mice, where we engrafted the isolate into humanized murine lungs and studied host cytokine responses and microbial composition of the gut and lungs to the engraftment. Results Our data shows that there is a dominant IL6- and IL17-mediated immune response to the engraftment, accompanied by measurable changes to the lung and gut microbiota. We also show that some of these changes can be reversed by fecal microbial transplant (FMT) of ‘normal’ microbiota into the gut and lungs. Conclusion This murine model results suggest a potential role and effectiveness of gut FMT as a therapeutic measure for MDR bacterial infection in the lungs. Further studies are required to assess response in humans. Disclosures L. M. Abbo, Roche Diagnostics: Scientific Advisor, Consulting fee.

Plasma flows and their profiles in edge and scrape-off layer (SOL) regions of a tokamak plasma are important as these can modify the interchange plasma turbulence. These flows have been investigated in the presence of neutral gas numerically using the two-dimensional model equations. A reduction of poloidal flows, radial particle, and energy fluxes has been observed in the edge and SOL regions by the presence of the neutral gas. The reduction of radial flux is due to the reduction in the radial velocity of the plasma blob. We have investigated Reynolds stress in the presence of the gas. It is found that in the presence of ion-neutral collisions, the magnitude of the stress decreases. The gas also reduces the diamagnetic drift frequency in the edge and SOL regions.

Dust events are recorded in the SST-1 tokamak with fast visible imaging and infrared imaging systems. The events are analyzed from the image sequences with an in-house developed dust tracking routine in MATLAB called FINDUST. Specific operating scenarios for dust observation and their deleterious effects on discharge evolution are identified. A clear correlation of the dust events frequency and strength with the successful start-up and discharge evolution is observed over eight consecutive experimental campaigns in SST-1. It has been seen that the electron cyclotron resonance heating (ECRH) generated pre-ionization slab annular-plasma around the fundamental layer is most likely to generate dust, while the strongest effect of the ECRH fundamental layer on the plasma facing components is seen when the confined plasma column disrupts by some means while the ECRH pulse is still ON.

Calcium (Ca2+) signaling is known to regulate the development, maintenance and modulation of activity in neuronal circuits that underlie organismal behavior. InDrosophila, intracellular Ca2+signaling by the inositol 1,4,5-trisphosphate receptor and the store-operated channel (dOrai) regulates the formation and function of neuronal circuits that control flight. Here, we show that restoring InsP3R activity in insulin-producing neurons of flightless InsP3R mutants (itpr) during pupal development can rescue systemic flight ability. Expression of the store operated Ca2+entry (SOCE) regulator dSTIM in insulin-producing neurons also suppresses compromised flight ability of InsP3R mutants suggesting that SOCE can compensate for impaired InsP3R function. Despite restricted expression of wild-type InsP3R and dSTIM in insulin-producing neurons, a global restoration of SOCE and store Ca2+is observed in primary neuronal cultures from theitprmutant. These results suggest that restoring InsP3R-mediated Ca2+release and SOCE in a limited subset of neuromodulatory cells can influence systemic behaviors such as flight by regulating intracellular Ca2+homeostasis in a large population of neurons through a non-cell-autonomous mechanism.

"Ln(TePh)(3)" (Ln = Er, Tm, Lu), prepared in situ by the reduction of PhTeTePh with elemental Ln in the presence of Hg catalyst, reacts with elemental Te to give heterometallic clusters with the formula (py)(7)Ln(3)HgTe(4)(TePh)(3). Structural characterization of all three isostructural derivatives reveals a cubane arrangement of metal ions, with a distorted tetrahedral Hg(II) ion coordinated to three mu(3) coordinate Te(2-) and a terminal TePh ligand. There are two chemically inequivalent types of octahedral Ln(III) ions, one bound to three Te(2-) and three pyridine donors, and two that coordinate two pyridine, three Te(2-), and a terminal TePh ligand. The Lu compound decomposes at elevated temperatures to give LuTe.

Contamination of optical signals by reflections from the tokamak vessel wall is a matter of great concern. For machines such as ITER and future reactors, where the vessel wall will be predominantly metallic, this is potentially a risk factor for quantitative optical emission spectroscopy. This is, in particular, the case when bremsstrahlung continuum radiation from the bulk plasma is used as a common reference light source for the cross-calibration of visible spectroscopy. In this paper the reflected contribution to the continuum level in Textor and ITER has been estimated for the detection channels meant for charge exchange recombination spectroscopy (CXRS). A model assuming diffuse reflection has been developed for the bremsstrahlung which is a much extended source. Based on this model, it is shown that in the case of ITER upper port 3, a wall with a moderate reflectivity of 20% leads to the wall reflected fraction being as high as 55-60% of the weak signals in the edge channels. In contrast, a complete bidirectional reflectance distribution function (BRDF) based model has been developed in order to estimate the reflections from more localized sources like the charge exchange (CX) emission from a neutral beam in tokamaks. The largest signal contamination of similar to 15% is seen in the core CX channels, where the true CX signal level is much lower than that in the edge channels. Similar values are obtained for Textor also. These results indicate that the contributions from wall reflections may be large enough to significantly distort the overall spectral features of CX data, warranting an analysis at different wavelengths.

Background: Orthopaedic Outpatient Department (OPD) is an important part of health care system. Patients coming with different illness for treatment. Distribution pattern of illness represents the area from where patients come for treatment.Methods: Cross sectional, Observation Study. The patients who had willingly participated were enrolled on the basis of subject selection criteria. Prescriptions were collected from newly patients attending the Orthopaedics OPD. No follow up visit was done.Results: Male patients attended more than female gender (62% vs 38%). 18-30 years age group attended OPD much than another group (32.5%). Trauma is an important contributing factor (38.5%). History of trauma was seen more in male gender group and among 18-30 years age group. Low back pain is common problem. (29.5%).Conclusions: Low back pain is the common problem among patients attended Orthopaedic OPD. Trauma is an important contributing factor among 18-30 years age group.

Homozygous mutations in fibroblast growth factor (FGF23) have recently been described as the genetic cause of one form of hyperphosphatemic tumoral calcinosis (HFTC). However, it remained unclear to date how these mutations lead to loss of biologically active FGF23 in the circulation.We here report a novel homozygous mutation, c.385TC in FGF23 exon 2, which changes codon 129 from serine to proline (S129P) in a previously described individual affected by HFTC. The S129P mutation as well as two known FGF23 mutations, S71G and S129F, were introduced into an expression vector encoding wild-type (wt) human (h) FGF23 to yield [P129]hFGF23, [F129]hFGF23, and [G71]hFGF23; whole lysates, glycoprotein fractions, and conditioned media from HEK293 and COS-7 cells expressing these constructs were subjected to Western blot analysis using affinity-purified goat anti-hFGF23(51-69) and anti-hFGF23(206-222) antibodies.We detected 25- and 32-kDa protein species in total lysates of HEK293 cells expressing wt-hFGF23. The 32-kDa band, representing O-glycosylated hFGF23, was not detectable in the glycoprotein fraction of lysates from HEK293 cells expressing [P129]hFGF23, and in comparison with wt-FGF23 only small amounts of [P129]hFGF23 were secreted into the medium. Similar results were obtained for cells expressing [G71]hFGF23 and [F129]hFGF23.Our data for the first time directly show that FGF23 mutations associated with HFTC impair O-glycosylation in vitro resulting in poor secretion of the mutant hormone thereby explaining the characteristic hyperphosphatemic phenotype of homozygous carriers in vivo.

The Early Miocene succession of Kutch represents a mixed carbonate-siliciclastic depositional system. The carbonate part of the succession, characterized by high abundance of shallow marine benthic fauna, hosts typical shell concentrations (also referred as shell beds). The thickness of shell concentrations vary in scale from 5 cm to 100 cm and are separated by poorly fossiliferous to barren silty shales/siltstones. Based on taphonomic and sedimentological observations, shell concentrations are classified as lag, event, composite/multi-event and hiatal types. The occurrence of different types of shell concentrations in the background of sequence stratigraphic framework is the main theme for the present study. Overall, the shell concentrations occupy the middle part of the sequence i.e. upper part of the transgressive systems tract and lower part of the highstand systems tract. Lag concentrations are found in the lower part of the sequence while composite concentrations, the major contributors in the sequence, occur in upper part of the transgressive systems tract and in the lower part of the highstand systems tract. The hiatal concentrations are associated with maximum flooding surface while the position of event concentrations is independent of sequence stratigraphic framework. The shell concentrations occupy marine flooding surface or marine ravinement surface, thus mark parasequence boundaries.

Incorporation of the Kaapvaal craton within a speculative Neoarchaean–Palaeoproterozoic supercontinent has long been debated, and this idea provides a potential solution to solving the apparently enigmatic provenance of the huge quantities of gold within the famous Witwatersrand auriferous deposits of Kaapvaal. Within a framework of a postulated Neoarchaean “Kenorland” (“northern”; present-day reference) supercontinent, we examine possible “southern” cratons that may have been contiguous with Kaapvaal: Pilbara, Zimbabwe, Dharwar, Sao Francisco, Amazon, Congo. Brief reviews of their basic geology and inferred evolution in syn-Witwatersrand basin times (c. 3.1–2.8 Ga) show no obvious support for any such supercontinental amalgamations. An alternative idea to explain a measure of gross similarity amongst several Neoarchaean cratons is through global events, such as a c. 3125–3000 Ma cratonic-scale erosive event interpreted for both Pilbara and Kaapvaal, and a much more widespread magmatic event at c. 2760–2680 Ma. We postulate that a global superplume event at c. 3.0 Ga included a plume beneath the Kaapvaal cratonic nucleus, thus halting any subduction around that terrane due to the thermal anomaly. Such a speculative global magmatic event is assumed to have enhanced production of juvenile oceanic crust at mid-ocean ridges, including those “offshore” of the thermally elevated Kaapvaal nucleus. Intra-oceanic obduction complexes may have built up fairly rapidly under such conditions, globally, and once the plume event had abated, “normal” plate tectonics would have resulted in composite (greenstone-tonalite, possibly also including granite) terranes accreting with nuclei such as Kaapvaal. This enhanced plume-related cratonic growth can be seen as a rapid accretion event. Formation of the envisaged ophiolite complexes possibly encompassed deformation-related first-order concentration of gold, and once accretion occurred around Kaapvaal's nucleus, from north and west (present-day frame of reference), a second-order (deformation-related) gold concentration may have resulted. The third order of gold concentration would logically have occurred once placer systems reworked detritus derived from the orogens along the N and W margins of Kaapvaal. Such conditions and placer gold deposits are known from many Neoarchaean cratons. The initial source of gold was presumably from the much hotter Mesoarchaean mantle and may have been related to major changes in Earth's tectonic regime at c. 3.0 Ga. The unique nature of Kaapvaal is probably its early stabilization, enabling formation of a complex flexural foreland basin system, in which vast quantities of placer sediments and heavy minerals could be deposited, and preserved from younger denudation through a unique post-Witwatersrand history.

An ordered (√19 × √19)R23.4°-Ge/Pt(1 1 1) surface alloy can be formed by vapor depositing one-monolayer Ge on a Pt(1 1 1) substrate at room temperature and subsequently annealing at 900–1200 K. The long-range order of this structure was observed by low energy electron diffraction (LEED) and confirmed by scanning tunneling microscopy (STM). The local structure and alloying of vapor-deposited Ge on Pt(1 1 1) at 300 K was investigated by using X-ray Photoelectron Diffraction (XPD) and low energy alkali ion scattering spectroscopy (ALISS). XPS indicates that Ge adatoms are incorporated to form an alloy surface layer at ∼900 K. Results from XPD and ALISS establish that Ge atoms are substitutionally incorporated into the Pt surface layer and reside exclusively in the topmost layer, with excess Ge diffusing deep into the bulk of the crystal. The incorporated Ge atoms at the surface are located very close to substitutional Pt atomic positions, without any corrugation or “buckling”. Temperature Programmed Desorption (TPD) shows that both CO and NO adsorb more weakly on the Ge/Pt(1 1 1) surface alloy compared to that on the clean Pt(1 1 1) surface.

Glauconitic minerals are considered as one of the valuable input parameters in sequence stratigraphic analysis of a basin. In the present study glauconitic minerals are reported from subtidal green shale facies in the lower part of the Late Paleocene-Early Eocene Naredi Formation of western Kutch. On the basis of the foraminiferal assemblage the glauconite bearing beds are interpreted to have formed in a mid shelf depositional settings of an unstable marine conditions. XRD studies confirm the glauconite mineralogy of the green pellets and provide an estimation of glauconite maturity. Textural attributes of the glauconites confirm their derivation by different degrees of alteration of precursor feldspar grains. Because of the authigenic origin and autochthonous nature, these glauconites hold promise for understanding sequence stratigraphy of the Palaeogene succession of the western Kutch.

Helicoverpa armigera causes massive yield loss of various crops globally. Bacillus thuringiensis coded Cry1Ac toxin is effective against the pest. Through the present investigation, an alkaline phosphatase type putative receptor of the toxin was identified in the target insect gut BBMV. Lectin-ligand immunoblot assay detected the presence of alpha-GalNAc residue at the nonreducing terminal of the glycan structure in the membrane bound HaALP protein which mediates the toxin-receptor interaction.

Molecular (DME)2Tm(SC6F5)3 and tetrametallic (DME)4(µ2-SPh)8Tm4(SPh)4 have been isolated in high yield and characterized by conventional methods. The fluorinated thiolate has an eight-coordinate Tm(III) ion bound to three sulfur atoms from the thiolates, four oxygen donors from the THF ligands, and a relatively weak dative Tm-F interaction with a 2.842(3)A Tm-F separation. The benzenethiolate compound crystallizes as a tetramer with an alternating number (3, 2, 3) of thiolates connecting the nearly linear array of Tm(III) ions. Emission properties of both thiolates and the chalcogen-rich cluster (THF)6Tm4Se9(SC6F5)2 have been established. The Ph compound is significantly more emissive than either of the fluorinated species.

This paper focusses upon two glauconitic sandstones in the Paleoproterozoic Deoland Formation and Chorhat Sandstone, both belonging to the Semri Group, central India. In both the cases glauconitic minerals occur in sandstones deposited in the marine realm, within a transgressive systems tract (TST) for the former unit and within a highstand systems tract (HST) for the latter. The proportion of glauconitic minerals increases in the paleo-offshore direction. Petrography reveals selective early glauconitization of detrital K-feldspars along their fringes, cleavages and the fractures created by volume expansion during progressive alteration, leading to the generation of peloids with small relics of the precursors. XRD and mineral chemistry reveal a structure typical of glauconite, and more akin to Mg-rich ferric illite. The mineral chemistry of the glauconitic mineral phases remains the same whether the glauconitization process was incipient or at an advanced stage. These findings contrast with the previously held belief that ferric illite is confined to terrestrial or marginal marine sediments, and concurs with recent observations that the mineral can form in the open sea, but with high Mg. Since there are no ferro-magnesian minerals in association with these Vindhyan glauconitic sandstones, the seawater appears to be the only source for the Mg and Fe required. The general low rate of sedimentation on Proterozoic open shelves would have permitted ferric illite formation even within a HST, as represented by the Chorhat Sandstone. (C) 2007

Major, trace and rare earth element (REE) concentrations were measured for eighty eight shale samples from the Paleoproterozoic to Neoproterozoic Vindhyan Supergroup in central India. The major and trace element data of the Vindhyan shales are compared with North American Shale Composite, upper crust, mid-oceanic ridge basalts and many other shale standards of Archean, Proterozoic and Phanerozoic age. REE concentrations of the Vindhyan shales are comparable to the upper continental crust. Various discriminant diagrams were used to reveal the inferred provenance, tectonics and paleoweathering conditions. A predominantly granitic source rock is inferred for the Lower Vindhyan shales, whereas partial contribution from basaltic source is evident during deposition of the Upper Vindhyan shales. Existing paleocurrent data and the present geochemical investigations together suggest Archean-Paleoproterozoic basement rocks, exposed beyond the southern basin margin of the Vindhyan outcrops as the possible source rocks. The deposition of the Vindhyan shales took place in an intracratonic basin where sediments were primarily derived from stable continental areas. Moderate climatic conditions are inferred during the deposition of the shales. The Upper Vindhyan shales, however, reflect more intense weathering compared to the Lower Vindhyan shales, which may be attributed to relative tectonic stability and more humid conditions during deposition of Upper Vindhyan shales. (C) 2007

Although the principle of uniformitarianism may be applied to the Precambrian sedimentary record as a whole, certain periods of the Archaean and Palaeoproterozoic witnessed a changing pattern of prime influences controlling the depositional systems. This paper examines the major controls on sedimentation systems and environments during the Archaean and Palaeoproterozoic within the broader perspective of Earth evolution. Earth's earliest sedimentary system (4.4?-3.7 Ga) was presumably comprised of deep oceanic realms and probably influenced primarily by bolide impacts, major tsunamis, localized traction and global contour current patterns, and bathymetry. As continental crust began to form, the impact-dominated, tsunami type sedimentation gave way to wider varieties of sedimentary environments, known from the oldest sedimentary records. During early continental crustal evolution (c. 3.7–2.7 Ga), sedimentation was essentially of greenstone-type. Volcanic and volcaniclastic rocks were the major components of the greenstone belts, associated with thin carbonates, stromatolitic evaporites, BIF, pelites and quartzites and lesser synorogenic turbidites, conglomerates and sandstones. Volcanism and active tectonism (reflecting dynamic depositional settings during island arc and proto-continental nucleus formation) were the predominant factors

The optical properties of the nanoscale neodymium ceramic cluster (THF)8Nd8O2Se2(SePh)16 (Nd8) and molecular (DME)2Nd(SC6F5)3 (Nd1) were studied by optical absorption, photoluminescence, and time-resolved spectroscopy. Both complexes exhibited emission characteristic of solid-state materials with bands centered at 927, 1078, 1360, and 1843 nm for Nd8 and 897, 1071, 1347, and 1824 nm for Nd1. The observed red-shift in the absorption and emission bands of Nd8 is attributed to the increased covalency and nephelauxetic effect. Using the calculated radiative decay time, the quantum efficiency of the 4 F3/2 f 4 I11/2 transition is calculated to be 16% in Nd8 and 9% in Nd1 with corresponding stimulated emission cross sections of 3.04 10 -20 cm 2 in Nd8 and 1.61 10 -20 cm 2 in Nd1 that are comparable to those of solid-state inorganic systems. This efficiency is the highest reported value for “molecular” neodymium compounds. This finding, along with the novel 1.8 Im emission, is attributed to the absence of direct Nd 3+ coordination with fluorescence quenching vibrational groups such as hydrocarbon or hydroxide groups. The direct coordination of S, Se, and F accounts for the improved fluorescence spectral properties, because these heavy anions facilitate a low phonon energy host environment for neodymium. Monte Carlo simulation permitted analysis of energy transfer processes to show the primary source of fluorescence quenching. Cross relaxation is responsible for the quenching of the 4 F3/2 f 4 I15/2 emission whereas excitation migration quenches the 4 F3/2 f 4 I9/2 emission. These processes are mediated by a dipole-dipole interaction for Nd8 and a quadrupole-quadrupole interaction for Nd1.

Variations of carbon and oxygen isotopic ratios in response to cyclical sea level fluctuations have been documented from a Paleoproterozoic peritidal stromatolite succession. The upper division of the Kajrahat Limestone, Vindhyan Supergroup of central India consists of several shallowing upward stromatolite cycles identified by regular and systematic changes in stromatolite size. Normally, larger stromatolites are followed upward in the succession by smaller stromatolites and microbial laminites that occupy the top of the cycle. Desiccation cracks are found in all the facies indicating subaerial exposure. We investigated the stable isotope compositional variations across nine complete stromatolite cycles showing frequent subaerial emergence. Carbon and oxygen isotopic values of the limestones, in general, are comparable to contemporary marine values available from earlier studies but show regular depletion in response to shallowing of the water level. The δ13C and δ18O values of the limestones vary within an individual stromatolite cycle; depleted values characterize the topmost part of the cycles. The isotope pattern is explained by micritic carbonate deposition in different sub environments of the shallow marine domain having different salinity and variable duration of exposure. These variations also probably caused the observed scatter in δ13C and δ18O values of supratidal microbial laminites., © Elsevier

Opportunistic lung infection and inflammation is a hallmark of chronic recreational/clinical use of morphine. We show that early induction of IL17 from the bronchial epithelium, following pathogenic encounter is a protective response, which contributes to pathogenic clearance and currently attributed to TLR2 activation in immune cells. Concurrent activation of TLR2 and IL17R in bronchial epithelium results in the sequestration of MyD88 (TLR2 adapter) by Act1/CIKS (IL17R adapter), thereby turning off TLR2 signaling to restore homeostasis. Morphine inhibits the early IL17 release and interaction between Act1 and MyD88, leading to decreased pathogenic clearance and sustained inflammation. Hence, we propose that therapeutically targeting either TLR2 or IL17 in bronchial epithelia, in the context of morphine, can restore inflammatory homeostasis.

Sepsis is the predominant cause of mortality in ICUs and opioids are the preferred analgesic in this setting. However, the role of opioids in sepsis progression has not been well characterized. The present study demonstrated that morphine alone altered the gut microbiome and selectively induced the translocation of Gram-positive gut bacteria in mice. Using a murine model of poly-microbial sepsis, we further demonstrated that morphine treatment led to predominantly Gram-positive bacterial dissemination. Activation of TLR2 by disseminated Gram-positive bacteria induced sustained up-regulation of IL-17A and IL-6. We subsequently showed that overexpression of IL-17A compromised intestinal epithelial barrier function, sustained bacterial dissemination and elevated systemic inflammation. IL-17A neutralization protected barrier integrity and improved survival in morphine-treated animals. We further demonstrated that TLR2 expressed on both dendritic cells and T cells play essential roles in IL-17A production. Additionally, intestinal sections from sepsis patients on opioids exhibit similar disruption in gut epithelial integrity, thus establishing the clinical relevance of this study. This is the first study to provide a mechanistic insight into the opioid exacerbation of sepsis and show that neutralization of IL-17A might be an effective therapeutic strategy to manage Gram-positive sepsis in patients on an opioid regimen.

Neural connectivity between the spinal cord and paired appendages is key to the superior locomotion of tetrapods and aquatic vertebrates. In contrast to nerves that innervate axial muscles, those innervating appendages converge at a specialized structure, the plexus, where they topographically reorganize before navigating towards their muscle targets. Despite its importance for providing appendage mobility, the genetic program that drives nerve convergence at the plexus, as well as the functional role of this convergence, are not well understood. Here, we show that in zebrafish the transcription factor foxc1a is dispensable for trunk motor nerve guidance but is required to guide spinal nerves innervating the pectoral fins, equivalent to the tetrapod forelimbs. In foxc1a null mutants, instead of converging with other nerves at the plexus, pectoral fin nerves frequently bypass the plexus. We demonstrate that foxc1a expression in muscle cells delineating the nerve path between the spinal cord and the plexus region restores convergence at the plexus. By labeling individual fin nerves, we show that mutant nerves bypassing the plexus enter the fin at ectopic positions, yet innervate their designated target areas, suggesting that motor axons can select their appropriate fin target area independently of their migration through the plexus. Although foxc1a mutants display topographically correct fin innervation, mutant fin muscles exhibit a reduction in the levels of pre- and postsynaptic structures, concomitant with reduced pectoral fin function. Combined, our results reveal foxc1a as a key player in the development of connectivity between the spinal cord and paired appendages, which is crucial for appendage mobility.

Parathyroid hormone (PTH) regulates calcium, phosphorous and skeletal homeostasis via interaction with the G protein-coupled PTH/PTHrP receptor, which is fully activated by the amino-terminal 34 amino-acid portion of the hormone. Recent evidence points to the existence of another class of receptors for PTH that recognize the carboxyl (C)-terminal region of intact PTH (1-84) (CPTHRs) and are highly expressed by osteocytes. Here we report the synthesis and characterization of two novel bifunctional CPTH ligands that include benzoylphenylalanine (Bpa) substitutions near their amino-termini and carboxyl-terminal biotin moieties, as well as a tyrosine(34) substitution to enable radioiodination. These peptides are shown to bind to CPTHRs with affinity similar to that of PTH (1-84) and to be specifically and covalently crosslinked to CPTHRs upon exposure to ultraviolet light. Crosslinking to osteocytes or osteoblastic cells generates complexes of 80 and 220 kDa, of which the larger form represents an aggregate that can be resolved into the 80 kDa. The crosslinked products can be further purified using immunoaffinity and avidin-based affinity procedures. While the molecular structure of the CPTHR(s) remains undefined, these bifunctional ligands represent powerful new tools for use in isolating and characterizing CPTHR protein(s).