Drosophila phosphoinositide-dependent kinase-1 regulates apoptosis and growth via the phosphoinositide 3-kinase-dependent signaling pathway

Phosphoinositide-dependent kinase-1 (PDK-1) is a central mediator of the cell signaling between phosphoinositide 3-kinase (PI3K) and various intracellular serine/threonine kinases including Akt/protein kinase B (PKB), p70 S6 kinases, and protein kinase C. Recent studies with cell transfection experiments have implied that PDK-1 may be involved in various cell functions including cell growth and apoptosis. However, despite its pivotal role in cellular signalings, the in vivo functions of PDK-1 in a multicellular system have rarely been investigated. Here, we have isolated Drosophila PDK-1 (dPDK-1) mutants and characterized the in vivo roles of the kinase. Drosophila deficient in the dPDK-1 gene exhibited lethality and an apoptotic phenotype in the embryonic stage. Conversely, overexpression of dPDK-1 increased cell and organ size in a Drosophila PI3K-dependent manner. dPDK-1 not only could activate Drosophila Akt/PKB (Dakt1), but also substitute the in vivo functions of its mammalian ortholog to activate Akt/PKB. This functional interaction between dPDK-1 and Dakt1 was further confirmed through genetic analyses in Drosophila. On the other hand, cAMP-dependent protein kinase, which has been proposed as a possible target of dPDK-1, did not interact with dPDK-1. In conclusion, our findings provide direct evidence that dPDK-1 regulates cell growth and apoptosis during Drosophila development via the PI3K-dependent signaling pathway and demonstrate our Drosophila system to be a powerful tool for elucidating the in vivo functions and targets of PDK-1.

(Table 1) Age and sedimentation rates of Pleistocene/Holocene sequences at DSDP Sites 86-580 and 94-611

The recovery from the North Atlantic (Site 611) of a continuous Pleistocene sedimentary record with a siliceous microfaunal component made it possible to compare the high-latitude abundance pattern of the radiolarian species Cycladophora davisiana in the Atlantic with that produced from analyses of a high-latitude record (Site 580) from the northwest Pacific. Previous studies had shown that the late Pleistocene (0-0.45 Ma) abundance variations of this species in these high-latitude regions were similar. Cycladophora davisiana maxima in the North Atlantic record reach abundance levels three to four times higher than C. davisiana maxima registered in sediments from the northwest Pacific site. This difference in magnitude of abundance peaks is most likely an effect of the more northerly location of Site 611 (53°N) compared with that of Site 580 (42°N), since high-latitude time-slice studies have shown a direct relationship between increasing latitude and C. davisiana abundance. Discontinuous preservation of radiolarians in sediments from North Atlantic Site 611 allows only tentative correlation of the North Atlantic and northwest Pacific C. davisiana abundance curves. These correlations are confined to those portions of the cores where ages are tightly constrained by magnetic boundaries, and to intervals with comparable sedimentation rates.

Age and chemical composition of dredged igneous rocks from the Vityaz Ridge, Pacific slope of the Kuril Island Arc

Original results of igneous rock studies are presented. The rocks were dredged during a marine expedition (cruise 37 of R/V Akademik M.A. Lavrent'ev in August-September, 2005) in the region of the submarine Vityaz Ridge and the Kuril Arc outer slope. Several age complexes (Late Cretaceous, Eocene, Late Oligocene, Miocene, and Pliocene-Pleistocene) are recognizable on the Vityaz Ridge. These complexes are characterized by a number of common geochemical features since all of them represent formations of island arc calc-alkali series. At the same time, they also have individual features reflecting different geodynamic settings. The outer slope of the Kuril Arc demonstrates submarine volcanism. Pliocene-Pleistocene volcanic rocks dredged here are similar to volcanites of the Kuril-Kamchatka Arc frontal zone.

(Table 1) Magnetozone boundaries, age and sedimentation rate at DSDP Hole 93-605

Natural Remanent Magnetization (NRM) was measured for regularly spaced samples from the 620-m-thick, lower middle Eocene to upper Maestrichtian section of DSDP Site 605. The total NRM of the Eocene chalks was too low (5-50 µA/m) to establish a reliable magnetic polarity stratigraphy. However, the results from the somewhat more clayrich Paleocene-upper Maestrichtian section are useful. A fourfold quality classification of the results of progressive demagnetization studies aided in determining the polarity of the original remanence. Two types (1 and 2a) showed a Characteristic Remanent Magnetization (ChRM) direction with reversed and normal polarity, respectively; the third type (2b) can be interpreted as having a reversed ChRM, which could not be cleaned, whereas the fourth type (3) is considered to be unreliable. The Site 605 magnetic polarity stratigraphy compares well with published sections, adding important detail to the correlation with planktonic microfossil zones and, hence, to the resolution of this portion of the time scale (C24-C32 on the Berggren et al., 1985, scale). The Cretaceous/Tertiary boundary occurs in a reversed polarity zone that has been correlated with Subchron C29r. We suspect the presence of an unconformity at the boundary between lithostratigraphic Units Va and IV a location which is also the level of Reflection Horizon A*.

Age and chemical composition of volcaniclastic rocks from the Sea of Japan

Petrographic and geochemical studies showed that Oligocene - Early Miocene volcaniclastic rocks from the southern part of the Sea of Japan are ascribed to high-potassium aluminous rocks of sub-alkaline volcanic series from active continental margins. A comparative analysis revealed spatiotemporal relation of Oligocene - Early Miocene subaerial volcanism of the Sea of Japan with Late Cretaceous and Eocene - Early Miocene ignimbrite volcanism of the East Eurasian margin. This allows to refer the volcaniclastic rocks of the Sea of Japan to the stage of ignimbrite volcanism that occurred during relative quiescence against general extension in the continental margin setting.

Investigation of the immunocompetent cells that bind early pregnancy factor and preliminary studies of the early pregnancy factor target molecule

Early pregnancy factor (EPF) is a secreted protein with immunosuppressive and growth factor properties. It has been shown to suppress the delayed-type hypersensitivity response in mice as well as acute and chronic forms of experimental autommume encephalomyelitis in rats and mice, respectively. In previous studies, we have demonstrated that EPF binds to a population of lymphocytes and we hypothesized that it mediates its suppressive effects by binding to CD4(+) T cells. In the present study, we isolated monocytes and subpopulations of lymphocytes and labelled them with fluoresceinated EPF in order to determine which populations bind EPF. We demonstrated that EPF binds specifically to CD4(+), CD8(+), CD14(+) (monocytes) and CD56(+) NK cells but not to CD19(+) B cells. The identity of the molecule(s) on the cell surface that is targeted by EPF is unknown, but as EPF is an extracellular homologue of the intracellular protein chaperonin 10 (Cpn 10), we examined the possibility that the EPF receptor is a membrane-associated form of chaperonin 60 (Cpn60), the functional associate of Cpn 10 within the cell. The EPF target molecule on lymphocytes was visualized by chemical cross-linking of exogenous iodinated Cpn10 to cells and probed with anti-Cpn60. The effect of anti-Cpn60 on activity in the EPF bioassay, the rosette inhibition test, was also examined. In both instances, no specific interaction of this antibody and the putative receptor was observed. It was concluded that the cell surface molecule targeted by EPF is unlikely to be a homologue of Cpn60.

Textural and microstructural studies of zinc sulfide and associated phases in certain base metal deposits

A textural and microstructural study of a variety of zinc sulfide-containing ores has been undertaken, and the possible depositional and deformational controls of textural and microstructural development considered. Samples for the study were taken from both deformed and undeformed zinc ores of the Central U.S. Appalachians, and deformed zinc ores of the English Pennines. A variety of mineralogical techniques were employed, including transmitted and reflected light microscopy of etched and unetched material, transmission electron microscopy and electron microprobe analysis. For the Pennine zinc sulfides, spectroscopic, x-ray diffraction and fluid inclusion studies were also undertaken. Optical and electron optical examination of the Appalachian material confirmed the suitability of zinc sulfide for detailed study with such techniques. Growth and deformation-related microstructures could be distinguished from specimen-preparation induced artifacts. A deformationally-mduced lamelliform optical anisotropy is seen to be developed in areas hosting a dense planar microstructure of {111} twin- and slip-planes. The Pennine zinc sulfide texturally records a changing depositional environment. Thus, for example, delicately growth- zoned crystals are truncated and cross-cut by solution disconformities. Fluid inclusion studies indicate a highly saline (20-25 wt. % equiv. NaCl), low temperature (100-150°C.) fluid. Texturally, two varieties of zinc sulfide can be recognised; a widely developed, iron- banded variety, and a paragenetically early variety, banded due to horizons rich in crystal defects and microscopic inclusions. The zinc sulfide takes the form of a disordered 3C-polytype, with much of the disorder being deformational in origin. Twin- and slip-plane fabrics are developed . A deformation-related optical anisotropy is seen to overprint growth-related anisotropy, along with cuprian alteration of certain {111} deformation planes.

Objective and psychophysical studies of infant visual development

Distortion or deprivation of vision during an early `critical' period of visual development can result in permanent visual impairment which indicates the need to identify and treat visually at-risk individuals early. A significant difficulty in this respect is that conventional, subjective methods of visual acuity determination are ineffective before approximately three years of age. In laboratory studies, infant visual function has been quantified precisely, using objective methods based on visual evoked potentials (VEP), preferential looking (PL) and optokinetic nystagmus (OKN) but clinical assessment of infant vision has presented a particular difficulty. An initial aim of this study was to evaluate the relative clinical merits of the three techniques. Clinical derivatives were devised, the OKN method proved unsuitable but the PL and VEP methods were evaluated in a pilot study. Most infants participating in the study had known ocular and/or neurological abnormalities but a few normals were included for comparison. The study suggested that the PL method was more clinically appropriate for the objective assessment of infant acuity. A study of normal visual development from birth to one year was subsequently conducted. Observations included cycloplegic refraction, ophthalmoscopy and preferential looking visual acuity assessment using horizontally and vertically oriented square wave gratings. The aims of the work were to investigate the efficiency and sensitivity of the technique and to study possible correlates of visual development. The success rate of the PL method varied with age; 87% of newborns and 98% of infants attending follow-up successfully completed at least one acuity test. Below two months monocular acuities were difficult to secure; infants were most testable around six months. The results produced were similar to published data using the acuity card procedure and slightly lower than, but comparable with acuity data derived using extended PL methods. Acuity development was not impaired in infants found to have retinal haemorrhages as newborns. A significant relationship was found between newborn binocular acuity and anisometropia but not with other refractive findings. No strong or consistent correlations between grating acuity and refraction were found for three, six or twelve months olds. Improvements in acuity and decreases in levels of hyperopia over the first week of life were suggestive of recovery from minor birth trauma. The refractive data was analysed separately to investigate the natural history of refraction in normal infants. Most newborns (80%) were hyperopic, significant astigmatism was found in 86% and significant anisometropia in 22%. No significant alteration in spherical equivalent refraction was noted between birth and three months, a significant reduction in hyperopia was evident by six months and this trend continued until one year. Observations on the astigmatic component of the refractive error revealed a rather erratic series of changes which would be worthy of further investigation since a repeat refraction study suggested difficulties in obtaining stable measurements in newborns. Astigmatism tended to decrease between birth and three months, increased significantly from three to six months and decreased significantly from six to twelve months. A constant decrease in the degree of anisometropia was evident throughout the first year. These findings have implications for the correction of infantile refractive error.

SMEs in a globalised world:survival and growth strategies on Europe's geographical periphery

This insightful book shows how small and medium enterprises (SMEs) from some of the traditionally less dynamic peripheral economies of the 'old' EU - namely Ireland, Italy, Portugal and Spain - have responded to the twin challenges of globalisation and industrial restructuring. Through a series of unique case studies the contributing authors discuss how these economies, and in particular the SME sector, can be transformed. The book begins by examining the key drivers of the globally competitive SME sector in the EU, before moving on to explore the relationship between multinational enterprises (MNEs), SMEs and industrial development. The authors investigate important policy implications and provide lessons for SME development and growth. With empirical and theoretical contributions on SMEs in both the manufacturing and the services sectors, this essential book will be invaluable for researchers and policymakers in small business economics and management. Postgraduate students of entrepreneurship, business economics, industrial economics and European studies will appreciate this unique set of insights.

Trichloroethylene fate and transport studies and biodegradation kinetics in the saturated zone

Permeable reactive barriers (PRB) are constructed from soil solid amendments to support the growth of bacteria that are capable of degrading organic contaminants. The objective of this study was to identify low-cost soil solid amendments that could retard the movement of trichloroethylene (TCE) while serving as long-lived carbon sources to foster its biodegradation in shallow groundwater through the use of a PRB. The natural amendments high in organic carbon content such as eucalyptus mulch, compost, wetland peat, organic humus were compared based on their geophysical characteristics, such as pHw, porosity and total organic carbon (TOC), and as well as TCE sorption potentials. The pHw values were within neutral range except for pine bark mulch and wetland peat. All other geophysical characteristics of the amendments showed suitability for use in a PRB. While the Freundlich model showed better fit for compost and pine bark mulch, the linear sorption model was adequate for eucalyptus mulch, wetland peat and Everglades muck within the concentration range studied (0.2-0.8 mg/L TCE). According to these results, two composts and eucalyptus mulch were selected for laboratory column experiments to evaluate their effectiveness at creating and maintaining conditions suitable for TCE anaerobic dechlorination. The columns were monitored for pH, ORP, TCE degradation, longevity of nutrients and soluble TOC to support TCE dechlorination. Native bacteria in the columns had the ability to convert TCE to DCEs; however, the inoculation with the TCE-degrading culture greatly increased the rate of biodegradation. This caused a significant increase in by-product concentration, mostly in the form of DCEs and VC followed by a slow degradation to ethylene. Of the tested amendments eucalyptus mulch was the most effective at supporting the TCE dechlorination. The experimental results of TCE sequential dechlorination took place in eucalyptus mulch and commercial compost from Savannah River Site columns were then simulated using the Hydrus-1D model. The simulations showed good fit with the experimental data. The results suggested that sorption and degradation were the dominant fate and transport mechanisms for TCE and DCEs in the column, supporting the use of these amendments in a permeable reactive barrier to remediate the TCE.

Defining Fluid Restriction in the Management of Infants Following Cardiac Surgery and Understanding the Subsequent Impact on Nutrient Delivery and Growth Outcomes

Adequacy of nutritional intake during the postoperative period, as measured by a change in weight-for-age z-scores from surgery to the time of discharge, was evaluated in infants (n = 58) diagnosed with a congenital heart defect and admitted for surgical intervention at Miami Children’s Hospital using a prospective observational study design. Parental consent was obtained for all infants who participated in the study. Forty patients had a weight available at hospital discharge. The mean preoperative weight-for-age z-score was -1.3 ±1.43 and the mean weight-for-age z-score at hospital discharge was -1.89 ±1.35 with a mean difference of 0.58 ±0.5 (P Nutritional intake during the postoperative period was inadequate based on a decrease in weight-for-age z-scores from the time of surgery until discharged home. Our findings suggested that limited fluid volume for nutrition likely contributes to suboptimal nutritional delivery during the postoperative period; however, inadequate nutrition prescription may also be an important contributing factor. Development of a nutrition protocol for initiation and advancement of nutrition support may reduce the delay in achieving patient’s nutritional goals and may attenuate the observed decrease in z-scores during the postoperative period.

Effects of in situ CO2 enrichment on structural characteristics, photosynthesis, and growth of the Mediterranean seagrass Posidonia oceanica

Seagrass is expected to benefit from increased carbon availability under future ocean acidification. This hypothesis has been little tested by in situ manipulation. To test for ocean acidification effects on seagrass meadows under controlled CO2/pH conditions, we used a Free Ocean Carbon Dioxide Enrichment (FOCE) system which allows for the manipulation of pH as continuous offset from ambient. It was deployed in a Posidonia oceanica meadow at 11 m depth in the Northwestern Mediterranean Sea. It consisted of two benthic enclosures, an experimental and a control unit both 1.7 m**3, and an additional reference plot in the ambient environment (2 m**2) to account for structural artifacts. The meadow was monitored from April to November 2014. The pH of the experimental enclosure was lowered by 0.26 pH units for the second half of the 8-month study. The greatest magnitude of change in P. oceanica leaf biometrics, photosynthesis, and leaf growth accompanied seasonal changes recorded in the environment and values were similar between the two enclosures. Leaf thickness may change in response to lower pH but this requires further testing. Results are congruent with other short-term and natural studies that have investigated the response of P. oceanica over a wide range of pH. They suggest any benefit from ocean acidification, over the next century (at a pH of 7.7 on the total scale), on Posidonia physiology and growth may be minimal and difficult to detect without increased replication or longer experimental duration. The limited stimulation, which did not surpass any enclosure or seasonal effect, casts doubts on speculations that elevated CO2 would confer resistance to thermal stress and increase the buffering capacity of meadows.

Seawater carbonate chemistry and growth rate of Emiliania huxleyi in lab experiment

Predicting the impacts of environmental change on marine organisms, food webs, and biogeochemical cycles presently relies almost exclusively on short-term physiological studies, while the possibility of adaptive evolution is often ignored. Here, we assess adaptive evolution in the coccolithophore Emiliania huxleyi, a well-established model species in biological oceanography, in response to ocean acidification. We previously demonstrated that this globally important marine phytoplankton species adapts within 500 generations to elevated CO2. After 750 and 1000 generations, no further fitness increase occurred, and we observed phenotypic convergence between replicate populations. We then exposed adapted populations to two novel environments to investigate whether or not the underlying basis for high CO2-adaptation involves functional genetic divergence, assuming that different novel mutations become apparent via divergent pleiotropic effects. The novel environment "high light" did not reveal such genetic divergence whereas growth in a low-salinity environment revealed strong pleiotropic effects in high CO2 adapted populations, indicating divergent genetic bases for adaptation to high CO2. This suggests that pleiotropy plays an important role in adaptation of natural E. huxleyi populations to ocean acidification. Our study highlights the potential mutual benefits for oceanography and evolutionary biology of using ecologically important marine phytoplankton for microbial evolution experiments.

Barriers and facilitators to asthma self-management in adolescents:a systematic review of qualitative and quantitative studies

BACKGROUND: Many adolescents have poor asthma control and impaired quality of life despite the availability of modern pharmacotherapy. Research suggests that poor adherence to treatment and limited engagement in self-management could be contributing factors. OBJECTIVE: To conduct a systematic review of the barriers and facilitators to self-management of asthma reported by adolescents using a narrative synthesis approach to integrate the findings. DESIGN: MEDLINE, EMBASE, CINAHL, and PsycINFO were searched for all types of study design. Full papers were retrieved for study abstracts that included data from participants aged 12-18 years referring to barriers or facilitators of asthma self-management behaviors. RESULTS: Sixteen studies (5 quantitative and 11 qualitative) underwent data extraction, quality appraisal, and thematic analysis. Six key themes were generated that encompassed barriers and/or facilitators to self-management of asthma in adolescents: Knowledge, Lifestyle, Beliefs and Attitudes, Relationships, Intrapersonal Characteristics, and Communication. CONCLUSIONS: There is a pressing need to prepare adolescents for self-management, using age-appropriate strategies that draw on the evidence we have synthesized. Current clinical practice should focus on ensuring adolescents have the correct knowledge, beliefs, and positive attitude to self-manage their illness. This needs to be delivered in a supportive environment that facilitates two-way communication, fosters adolescents' self-efficacy to manage their disease, and considers the wider social influences that impinge on self-management. Pediatr Pulmonol. 2016; 9999:XX-XX. © 2016 Wiley Periodicals, Inc.