Cloning, characterization and regulation of the soluble guanylyl cyclase alpha1 and beta1 genes

Cell signaling by nitric oxide (NO) through soluble guanylyl cyclase (sGC) and cGMP production regulates physiological responses such as smooth muscle relaxation, neurotransmission, and cell growth and differentiation. Although the NO receptor, sGC, has been studied extensively at the protein level, information on regulation of the sGC genes remains elusive. In order to understand the molecular mechanisms involved at the level of gene expression, cDNA and genomic fragments of the murine sGCα1 subunit gene were obtained through library screenings. Using the acquired clones, the sGCα 1 gene structure was determined following primer extension, 3 ′RACE and intron/exon boundary analyses. The basal activity of several 5′-flanking regions (putative promoter regions) for both the α1 and β1 sGC subunits were determined following their transfection into mouse N1E-115 neuroblastoma and rat RENE1Δ14 uterine epithelial cells using a luciferase reporter plasmid. Using the sGC sequences, real-time RT-PCR assays were designed to measure mRNA levels of the sGC α1 and β1 genes in rat, mouse and human. Subsequent studies found that uterine sGC mRNA and protein levels decreased rapidly in response to 17β-estradiol (estrogen) in an in vivo rat model. As early as 1 hour following treatment, mRNA levels of both sGC mRNAs decreased, and reached their lowest level of expression after 3 hours. This in vivo response was completely blocked by the pure estrogen receptor antagonist, ICI 182,780, was not seen in several other tissues examined, did not occur in response to other steroid hormones, and was due to a post-transcriptional mechanism. Additional studies ex vivo and in various cell culture models suggested that the estrogen-mediated decreased sGC mRNA expression did not require signals from other tissues, but may require cell communication or paracrine factors between different cell types within the uterus. Using chemical inhibitors and molecular targeting in other related studies, it was revealed that c-Jun-N-terminal kinase (JNK) signaling was responsible for decreased sGC mRNA expression in rat PC12 and RFL-6 cells, two models previously determined to exhibit rapid decreased sGC mRNA expression in response to different stimuli. To further investigate the post-transcriptional gene regulation, the full length sGCα1 3′-untranslated region (3′UTR) was cloned from rat uterine tissue and ligated downstream of the rabbit β-globin gene and expressed as a chimeric mRNA in the rat PC12 and RFL-6 cell models. Expression studies with the chimeric mRNA showed that the sGCα 1 3′UTR was not sufficient to mediate the post-transcriptional regulation of its mRNA by JNK or cAMP signaling in PC12 and RFL-6 cells. This study has provided numerous valuable tools for future studies involving the molecular regulation of the sGC genes. Importantly, the present results identified a novel paradigm and a previously unknown signaling pathway for sGC mRNA regulation that could potentially be exploited to treat diseases such as uterine cancers, neuronal disorders, hypertension or various inflammatory conditions. ^

Aligning Library Strategy and Structure With the Campus Academic Plan: A Case Study

Colleges and universities’ missions are typically comprised of educating students, training professionals, engaging in scholarship and research, promoting creative activity, improving healthcare, and providing public service. Academic libraries exist to support these core functions, yet most academic libraries are organized based on library functions rather than the primary missions of their college or university. This paper describes one academic library’s attempt to align library strategy and structure with its university’s academic plan.

Existence and Uniqueness of Equilibrium in Nonoptimal Unbounded Infinite Horizon Economies

In applied work in macroeconomics and finance, nonoptimal infinite horizon economies are often studied in the the state space is unbounded. Important examples of such economies are single vector growth models with production externalities, valued fiat money, monopolistic competition, and/or distortionary government taxation. Although sufficient conditions for existence and uniqueness of Markovian equilibrium are well known for the compact state space case, no similar sufficient conditions exist for unbounded growth. This paper provides such a set of sufficient conditions, and also present a computational algorithm that will prove asymptotically consistent when computing Markovian equilibrium.

AN INVESTIGATION OF THE RELIABILITY AND VALIDITY OF THE CENTER FOR EPIDEMIOLOGIC STUDIES DEPRESSION SCALE IN THREE ETHNIC GROUPS

Epidemiologic studies of mental disorder have called attention to the need for identifying untreated cases and to the inadequacies of the instruments available for this purpose. Accurate case ascertainment devices are the basis of sound epidemiology. Without these, neither case classification nor analytic studies of risk factors is possible.^ The purpose of this research was to examine the reliability and validity of an instrument designed to measure depressive symptoms in community populations--the Center for Epidemiologic Studies Depression Scale (CES-D Scale). Two particular foci of the study were whether or not the scale had the same statistical structure across three ethnic groups and whether or not the magnitude and pattern of rates of symptoms for these groups were affected by one source of response error, that due to response tendencies. The effects of age and education on the pattern and magnitude of rates also were examined. In addition, the reliability and validity of the measures of response tendencies were assessed.^ The study population consisted of residents of Alameda County, California. A stratified sample of approximately 700 whites, blacks and Mexican-Americans was interviewed in the summer and fall of 1978.^ The results of the analysis indicated that the scale was reliable and measured a similar content domain across the three ethnic groups. The unadjusted sex- and ethnic-specific rates of depressive symptoms showed an ethnic pattern for both sexes: rates for whites were lowest, those for Mexican-Americans were highest, and those for blacks were intermediate. Measures of response tendencies--need for social approval, trait desirability, and acquiescence--affected the magnitude of the rates for most comparisons. Likewise, the pattern of rates changed somewhat from that originally observed. The one fairly consistent observation was that rates for Mexican-American women were higher than those for the other two female subgroups in most of the comparisons. These results must be considered in the context of the reliability and validity assessment of the measures of response tendencies which indicated the tenuousness of these measures.^ Age affected the ethnic pattern of rates for men in an inconsistent way; for women, Mexican-Americans continued to have higher rates than whites or blacks in all age categories. Education affected the magnitude of rates for women but not for men. For both men and women, Mexican-Americans had higher rates in all educational strata. Rates for women showed an inverse association with education while those for men did not. ^

COMPARISON OF THE ORGANIZATIONAL STRUCTURES AND EFFECTIVENESS OF THE INVESTOR-OWNED AND VOLUNTARY MULTIHOSPITAL SECTORS

Objectives. The central objective of this study was to systematically examine the internal structure of multihospital systems, determining the management principles used and the performance levels achieved in medical care and administrative areas.^ The Universe. The study universe consisted of short-term general American hospitals owned and operated by multihospital corporations. Corporations compared were the investor-owned (for-profit) and the voluntary multihospital systems. The individual hospital was the unit of analysis for the study.^ Theoretical Considerations. The contingency theory, using selected aspects of the classical and human relations schools of thought, seemed well suited to describe multihospital organization and was used in this research.^ The Study Hypotheses. The main null hypotheses generated were that there are no significant differences between the voluntary and the investor-owned multihospital sectors in their (1) hospital structures and (2) patient care and administrative performance levels.^ The Sample. A stratified random sample of 212 hospitals owned by multihospital systems was selected to equally represent the two study sectors. Of the sampled hospitals approached, 90.1% responded.^ The Analysis. Sixteen scales were constructed in conjunction with 16 structural variables developed from the major questions and sub-items of the questionnaire. This was followed by analysis of an additional 7 structural and 24 effectiveness (performance) measures, using frequency distributions. Finally, summary statistics and statistical testing for each variable and sub-items were completed and recorded in 38 tables.^ Study Findings. While it has been argued that there are great differences between the two sectors, this study found that with a few exceptions the null hypotheses of no difference in organizational and operational characteristics of non-profit and for-profit hospitals was accepted. However, there were several significant differences found in the structural variables: functional specialization, and autonomy were significantly higher in the voluntary sector. Only centralization was significantly different in the investor owned. Among the effectiveness measures, occupancy rate, cost of data processing, total manhours worked, F.T.E. ratios, and personnel per occupied bed were significantly higher in the voluntary sector. The findings indicated that both voluntary and for-profit systems were converging toward a common hierarchical corporate management approach. Factors of size and management style may be better descriptors to characterize a specific multihospital group than its profit or nonprofit status. (Abstract shortened with permission of author.) ^

Analysis of Agrobacterium tumefaciens VirB6 and VirB9 of the VirB /D4 type IV secretion system

Agrobacterium tumefaciens uses the VirB/D4 type IV secretion system (T4SS) to translocate oncogenic DNA (T-DNA) and protein substrates to plant cells. Independent of VirD4, the eleven VirB proteins are also essential for elaboration of a conjugative pilus termed the T pilus. The focus of this thesis is the characterization and analysis of two VirB proteins, VirB6 and VirB9, with respect to substrate translocation and T pilus biogenesis. Observed stabilizing effects of VirB6 on other VirB subunits and results of protein-protein interaction studies suggest that VirB6 mediates assembly of the secretion machine and T pilus through interactions with VirB7 and VirB9. Topology studies support a model for VirB6 as a polytopic membrane protein with a periplasmic N terminus, a large internal periplasmic loop, five transmembrane segments, and a cytoplasmic C terminus. Topology studies and Transfer DNA immunoprecipitation (TrIP) assays identified several important VirB6 functional domains: (i) the large internal periplasmic loop mediates interaction of VirB6 with the T-DNA, (ii) the membrane spanning region carboxyl-terminal to the large periplasmic loop mediates substrate transfer from VirB6 to VirB8, and (iii) the terminal regions of VirB6 are required for substrate transfer to VirB2 and VirB9. To analyze structure-function relationships of VirB9, the phenotypic consequences of dipeptide insertion mutations were characterized. Substrate discriminating mutations were shown to selectively export the oncogenic T-DNA and VirE2 to plant cells or a mobilizable IncQ plasmid to bacterial cells. Mutations affecting VirB9 interactions with VirB7 and VirB10 were localized to the C- and N- terminal regions respectively. Additionally, “uncoupling” mutations identified in VirB11 and VirB6 that block T pilus assembly, but not substrate transfer to recipient cells, were also identified in VirB9. These results in conjunction with computer analysis establish that VirB9, like VirB6, is also composed of distinct regions or domains that contribute in various ways to secretion channel activity and T pilus assembly. Lastly, in vivo immunofluorescent studies suggest that VirB9 localizes to the outer membrane and may play a role similar to that of secretion/ushers of types II and III secretion systems to facilitate substrate translocation across this final bacterial barrier. ^

Geochemical parameters of sediments and water of the Black Sea, data of Cruise 8 of R/V Vityaz-2

The book presents results of comprehensive geological investigations carried out during Cruise 8 of R/V "Vityaz-2" to the western part of the Black Sea in 1984. Systematic studies in the Black Sea during about hundred years have not weakened interest in the sea. Lithological and geochemical studies of sediments in estuarine areas of the Danube and the Kyzyl-Irmak rivers, as well as in adjacent parts of the deep sea and some other areas were the main aims of the cruise. Data on morphological structures of river fans, lithologic and chemical compositions of sediments in the fans and their areal distribution, forms of occurrence of chemical elements, role of organic matter and gases in sedimentation and diagenesis are given and discussed in the book.

(Table 1.4) Ratios of petrogenic components in glassy and crystalline basalts from the north part of the Bougault anomaly, Mid-Atlantic Ridge 15°N

Structure and composition of sub-surface bottom sediments from the southwest Barents Sea have been under study. The study has revealed heterogeneity of sediment structure resulted from temporal irregularity and variability of sedimentation processes. The study of the heavy minerals from 0.1-0.01 mm grain size fraction has shown prevalence of green hornblende, epidote, garnet, and ilmenite in all types of sediments; these minerals are the basis of terrigenous-mineralogical province. At the same time in different areas local terrigenous-mineralogical associations have been identified. Clay mineral composition of in the sediments was quite uniform: biotite, chlorite, hydromica, smectite. Despite this, a number of features indicating initial stages of clay mineral transformation has been identified. Differences in material composition and structure of the studied sediments are associated with rapid change in paleogeographic situation on the land - ice cover melting on the Kola Peninsula and subsequent Holocene climatic situation.

Abundance and biomass of the benthic infauna of the North Sea

In 1986 participants of the Benthos Ecology Working Group of ICES conducted a synoptic mapping of the infauna of the southern and central North Sea. Together with a mapping of the infauna of the northern North Sea by Eleftheriou and Basford (1989, doi:10.1017/S0025315400049158) this provides the database for the description of the benthic infauna of the whole North Sea in this paper. Division of the infauna into assemblages by TWINSPAN analysis separated northern assemblages from southern assemblages along the 70 m depth contour. Assemblages were further separated by the 30, 50 m and 100 m depth contour as well as by the sediment type. In addition to widely distributed species, cold water species do not occur further south than the northern edge of the Dogger Bank, which corresponds to the 50 m depth contour. Warm water species were not found north of the 100 m depth contour. Some species occur on all types of sediment but most are restricted to a special sediment and therefore these species are limited in their distribution. The factors structuring species distributions and assemblages seem to be temperature, the influence of different water masses, e.g. Atlantic water, the type of sediment and the food supply to the benthos.

Composition and properties of rocks and sediments from the Cape Verde fracture zone

The book presents results of comprehensive geological and geophysical studies, carried out in the Cape Verde fault zone in the 3-rd cruise of R/V Akademik Nikolaj Strakhov (1986). Detailed characterization of bottom relief, thickness and structure of the sedimentary cover, magnetic field, crust structure, lithology and stratigraphy of sediments, petrography and geochemistry of magmatic rocks. Conclusions about tectonic layering of the crust and upper mantle in the fault zone, and about a concurrent structural section of large mantle inhomogeneities have been done. The book is the first monographic description of a major fault structure of the ocean floor.

Taxonomic lists and abundances of the Lower Miocene bivalve assemblages of the Vives quarry (Meilhan, SW France)

Biodiversity estimates through geological times are difficult because of taphonomic perturbations that affect sedimentary records. Pristine shell assemblages, however, allow for calibration of past diversity. Diversity structures of two exceptionally preserved Miocene bivalve assemblages are quantitatively determined, compared with recent communities and used as paleoenvironmental proxy. The extremely rich assemblages were collected in Aquitanian (Early Miocene) carbonate sands of the Vives Quarry (Meilhan, SW France). Both paleontological and sedimentological data indicate a coral patch-reef environment, which deposits were affected by transport processes. Among two samples more than 28.000 shells were counted and 135 species identified. Sample Vives 1 is interpreted as a proximal debris flow and Sample Vives 2 as a sandy shoreface/foreshore environment influenced by storms. The two Vives assemblages have a similar diversity structure despite facies differences. Rarefaction curves level off at ~600 shells. The rare species account for more than 80 % of the species pool. The high values of PIE diversity index suggest a relatively high species richness and an even distribution of abundance of the most common species within the assemblages. The fossil data are compared to death shell assemblages (family level) of a modern reefal setting (Touho area, New Caledonia). The shape of the rarefaction curves and PIE indices of Meilhan fossil assemblages compare well to modern data, especially those of deep (>10 m water depth), sandy depositional environments found downward the reef slope (slope and pass settings). In addition to primary ecological signals, the similarity of the Vives samples and the Recent deep samples derives from taphonomic processes. This assumption is supported by sedimentological and paleontological observations. Sediment transports gather allochthonous and in situ materials leading to mixing of various ecological niches. Such taphonomic processes are recorded in the diversity metrics. Environmental mixing and time-averaging of the shell assemblages disturb the preservation of local-scale diversity properties but favour the sampling of the regional-scale diversity.

Phyto- and zooplankton of the southeastern Barents Sea in April 2000

Spring bloom of cold-water centric and pennate diatoms was observed in two different areas of the southeastern Barents Sea in April 2000: ice-free waters off the Kolguev Island northern shelf and the eastern Pechora Sea near the Karskie Vorota (Kara Gate) Straight in polynyas and ice-free patches in one-year-old ice. Maximal values of phytoplankton abundance and biomass were found at the ice edge. The bloom was localized in shallow water areas with depths less than 50 m in mixing zones of waters of different origin: warm Atlantic, cold coastal, and Arctic (Litke current) waters. Ice melting was among factors inducing the phytoplankton bloom. Each area had a specific phytocoenosis, whose structure was determined by water origin and ice conditions. In the western Kara Sea, under a solid (up to 30 cm thick) ice cover (i.e., under conditions of a hydrological winter), a spring phytoplankton succession was observed from its initial stage. In areas located close to the ice-cover edge, simultaneously with the mass phytoplankton bloom, the early spring zoocoenosis development manifested itself in mass spawning of euphausiids and mass appearance of Cirripedia nauplii and bottom polychaete larvae.

Histological structure of the facial skin in the bald uakari (Cacajao calvus), compared to other non-red Neotropical primates

In social species, such as primates, facial appearances transmit a variety of social signals. Although it is suggested that the intense red colour of the face of the bald uakari monkey might be an indicator of health, this hypothesis still has not been verified. This study describes the histological structure of the skin of the face in the bald uakari, compared with other non-red neotropical primates, to better understand the maintenance of its colour. The facial skin of the bald uakari monkey is characterized by a thinner epidermis, absence of melanin pigments and a high density of vascular capillaries that spread below the epidermis. These vascular capillaries are larger and more tortuous than in other neotropical primates. The skin of the face of the bald uakari monkey allows a direct external assessment of haematological status, suggesting that the colour of the face would be an honest indicator of health, but could also signal sexual or behavioural states.

Elevated CO2 levels do not affect the shell structure of the bivalve Arctica islandica from the western Baltic

Shells of the bivalve Arctica islandica are used to reconstruct paleo-environmental conditions (e.g. temperature) via biogeochemical proxies, i.e. biogenic components that are related closely to environmental parameters at the time of shell formation. Several studies have shown that proxies like element and isotope-ratios can be affected by shell growth and microstructure. Thus it is essential to evaluate the impact of changing environmental parameters such as high pCO2 and consequent changes in carbonate chemistry on shell properties to validate these biogeochemical proxies for a wider range of environmental conditions. Growth experiments with Arctica islandica from the Western Baltic Sea kept under different pCO2 levels (from 380 to 1120 µatm) indicate no affect of elevated pCO2 on shell growth or crystal microstructure, indicating that A. islandica shows an adaptation to a wider range of pCO2 levels than reported for other species. Accordingly, proxy information derived from A. islandica shells of this region contains no pCO2 related bias.

Species name, classification (WORMS), abundance and biomass of the megabenthic communities of the Algarve

The present study analysed the megabenthic diversity in subtidal soft bottoms and assessed the main environmental drivers of megabenthic community organisation along the Algarve coast (southern Portugal). We tested the hypothesis that megabenthic communities respond to the same environmental drivers than macrofauna. We found that similar to macrofauna, megafaunal communities were organised in relation to the depth of closure, light reaching the bottom, and the hydrodynamic conditions related with exposure within the shallower areas. The influence of the main river outflow prevailed over other drivers, but only up to 9 m depth. We found that seven different spatial units should be considered, each characterised by different indicator species. Additionally, among a total of 412 taxa collected between 4 and 50 m depth, we provide the characteristics of the 64 commonest species in terms of occurrence, frequency, distribution, abundance, bathymetric and sedimentary preferences, which constitutes most valuable information for ecosystem modelling. Megabenthic alpha diversity decreased with depth, contrary to evenness and was higher in the proximity of the river Guadiana and in highly exposed shores. We conclude that the megafauna, which is significantly quicker to collect and analyse, can provide an accurate alternative to macrofauna sampling, as their communities are shaped by the same drivers.