Atmospheric effects of the emerging mainland Chinese transportation system at and beyond the regional scale

Local surface travel needs in the People's Republic of China (mainland China) have traditionally been met largely by nonpolluting bicycles. A major automobile manufacturing/importing effort has begun in the country over the last decade, and planning documents indicate that the Chinese may strive to acquire more than 100 million vehicles early in the next century. By analogy with large automotive fleets already existing in the western world, both regional and global scale pollution effects are to be expected from the increase. The present work adopts the latest projections of Chinese automobile manufacture and performs some quantitative assessments of the extent of pollution generation. Focus for the investigation is placed upon the oxidant ozone. Emissions of the precursor species nitrogen oxides and volatile organics are constructed based on data for the current automotive sector in the eastern portion of the United States. Ozone production is first estimated from measured values for continental/oceanic scale yields relative to precursor oxidation. The estimates are then corroborated through idealized two dimensional modeling of the photochemistry taking place in springtime air flow off the Asian land mass and toward the Pacific Ocean. The projected fleet sizes could increase coastal and remote oceanic ozone concentrations by tens of parts per billion (ppb) in the lower troposphere. Influences on the tropospheric aerosol system and on the major greenhouse gas carbon dioxide are treated peripherally. Nitrogen oxides created during the vehicular internal combustion process will contribute to nitrate pollution levels measured in the open Pacific. The potential for soot and fugitive dust increases should be considered as the automotive infrastructure develops. Since the emerging Chinese automotive transportation system will represent a substantial addition to the global fleet and all the carbon in gasoline is eventually oxidized completely, a significant rise in global carbon dioxide inputs will ensue as well. Some policy issues are treated preliminary. The assumption is made that alterations to regional oxidant/aerosol systems and to terrestrial climate are conceivable. The likelihood that the Chinese can achieve the latest vehicle fleet goals is discussed, from the points of view of new production, positive pollution feedbacks from a growing automobile industry, and known petroleum reserves. Vehicular fuel and maintenance options lying before the Chinese are outlines and compared. To provide some perspective on the magnitude of the environmental changes associated with an Asian automotive buildup, recent estimates of the effects of future air traffic over the Pacific Rim are described

Notch Promotes Neural Lineage Entry by Pluripotent Embryonic Stem Cells

A central challenge in embryonic stem (ES) cell biology is to understand how to impose direction on primary lineage commitment. In basal culture conditions, the majority of ES cells convert asynchronously into neural cells. However, many cells resist differentiation and others adopt nonneural fates. Mosaic activation of the neural reporter Sox-green fluorescent protein suggests regulation by cell-cell interactions. We detected expression of Notch receptors and ligands in mouse ES cells and investigated the role of this pathway. Genetic manipulation to activate Notch constitutively does not alter the stem cell phenotype. However, upon withdrawal of self-renewal stimuli, differentiation is directed rapidly and exclusively into the neural lineage. Conversely, pharmacological or genetic interference with Notch signalling suppresses the neural fate choice. Notch promotion of neural commitment requires parallel signalling through the fibroblast growth factor receptor. Stromal cells expressing Notch ligand stimulate neural specification of human ES cells, indicating that this is a conserved pathway in pluripotent stem cells. These findings define an unexpected and decisive role for Notch in ES cell fate determination. Limiting activation of endogenous Notch results in heterogeneous lineage commitment. Manipulation of Notch signalling is therefore likely to be a key factor in taking command of ES cell lineage choice

Influence of surgical approach on component positioning in primary total hip arthroplasty

Background: Minimal invasive surgery (MIS) has gained growing popularity in total hip arthroplasty (THA) but concerns exist regarding component malpositioning. The aim of the present study was to evaluate femoral and acetabular component positioning in primary cementless THA comparing a lateral to a MIS anterolateral approach. Methods: We evaluated 6 week postoperative radiographs of 52 hips with a minimal invasive anterolateral approach compared to 54 hips with a standard lateral approach. All hips had received the same type of implant for primary cementless unilateral THA and had a healthy hip contralaterally. Results: Hip offset was equally restored comparing both approaches. No influence of the approach was observed with regard to reconstruction of acetabular offset, femoral offset, vertical placement of the center of rotation, stem alignment and leg length discrepancy. However, with the MIS approach, a significantly higher percentage of cups (38.5 %) was malpositioned compared to the standard approach (16.7 %) (p = 0.022). Conclusions: The MIS anterolateral approach allows for comparable reconstruction of stem position, offset and center of rotation compared to the lateral approach. However, surgeons must be aware of a higher risk of cup malpositioning for inclination and anteversion using the MIS anterolateral approach

Fundamental issues in systems biology.

types: Journal Article; Research Support, Non-U.S. Gov'tIn the context of scientists' reflections on genomics, we examine some fundamental issues in the emerging postgenomic discipline of systems biology. Systems biology is best understood as consisting of two streams. One, which we shall call 'pragmatic systems biology', emphasises large-scale molecular interactions; the other, which we shall refer to as 'systems-theoretic biology', emphasises system principles. Both are committed to mathematical modelling, and both lack a clear account of what biological systems are. We discuss the underlying issues in identifying systems and how causality operates at different levels of organisation. We suggest that resolving such basic problems is a key task for successful systems biology, and that philosophers could contribute to its realisation. We conclude with an argument for more sociologically informed collaboration between scientists and philosophers.Funding received from the Economic and Social Research Council (ESRC), UK, and Overseas Conference Funding from the British Academy

Bumblebee foraging rhythms under the midnight sun measured with radiofrequency identification

<p>Abstract</p> <p>Background</p> <p>In the permanent daylight conditions north of the Arctic circle, there is a unique opportunity for bumblebee foragers to maximise intake, and therefore colony growth, by remaining active during the entire available 24-h period. We tested the foraging rhythms of bumblebee (<it>Bombus terrestris </it>and <it>B. pascuorum</it>) colonies in northern Finland during the summer, when the sun stays above the horizon for weeks. We used fully automatic radio-frequency identification to monitor the foraging activity of more than 1,000 workers and analysed their circadian foraging rhythms.</p> <p>Results</p> <p>Foragers did not use the available 24-h foraging period but exhibited robust diurnal rhythms instead. A mean of 95.2% of the tested <it>B. terrestris </it>workers showed robust diurnal rhythms with a mean period of 23.8 h. Foraging activity took place mainly between 08:00 and 23:00, with only low or almost no activity during the rest of the day. Activity levels increased steadily during the morning, reached a maximum around midday and decreased again during late afternoon and early evening. Foraging patterns of native <it>B. pascuorum </it>followed the same temporal organisation, with the foraging activity being restricted to the period between 06:00 and 22:00.</p> <p>Conclusions</p> <p>The results of the present study indicate that the circadian clock of the foragers must have been entrained by some external cue, the most prominent being daily cycles in light intensity and temperature. Daily fluctuations in the spectral composition of light, especially in the UV range, could also be responsible for synchronising the circadian clock of the foragers under continuous daylight conditions.</p

Beyond the Global Brain Differences:Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers

BACKGROUND: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and globalbrain differences compared with noncarriers. However, interpreting regional differences is challenging if a globaldifference drives the regional brain differences. Intraindividual variability measures can be used to test for regionaldifferences beyond global differences in brain structure.METHODS: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n =30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matchednoncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual’sregional difference and global difference, were used to test for regional differences that diverge from the globaldifference.RESULTS: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differedmore than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thicknessin regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal andsomatosensory cortex differed more than the global difference in cortical thickness.CONCLUSIONS: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distaland 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distaland 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanismsinvolved in altered neurodevelopment

Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium

BACKGROUND Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC. METHODS Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals). RESULTS Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation. CONCLUSION This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts

Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies